A randomized controlled clinical trial to evaluate a new xenograft for ...

Monica Calasans-MaiaRodrigo ResendeGustavo FernandesJose Calasans-MaiaAdriana Terezinha AlvesJos�e Mauro Granjeiro

A randomized controlled clinical trialto evaluate a new xenograft foralveolar socket preservation

Authors’ affiliations:Monica Calasans-Maia, Rodrigo Resende,Department of Oral Surgery, Fluminense FederalUniversity, Niteroi, BrazilGustavo Fernandes, Cell and Molecular BiologyDepartment, Fluminense Federal University,Niteroi, BrazilJose Calasans-Maia, Department of Orthodontics,Fluminense Federal University, Nova Friburgo,BrazilAdriana Terezinha Alves, Department of OralPathology, Gama Filho University, Rio de Janeiro,BrazilJos�e Mauro Granjeiro, Fluminense FederalUniversity, Niteroi, BrazilBioengineering Program, National Institute ofMetrology Standardization and Industrial Quality,Duque de Caxias, Brazil

Corresponding author:Monica Calasans-MaiaDepartment of Oral SurgeryFluminense Federal UniversityRua Mario Santos Braga30. CentroNiteroiRio de janeiroCEP: 24020-140Brazile-mail: [email protected]

Key words: bone implant interactions, bone substitutes, clinical research, clinical trials

Abstract

Objective: The aim of this clinical trial was to compare the effect of Bio-Oss� and a new bovine

xenograft (Osseus�) in alveolar sockets after a 24-week healing period.

Materials and methods: A total of 20 adult volunteers ages 30–60 were subjected to single tooth

extraction. A tooth extraction was performed at the baseline. All sites were randomly allocated to

two test groups (TG1: grafted using a new bovine xenograft, Osseus�, and TG2: grafted using

commercially available bovine xenograft-Bio-Oss�). Six months later, a sample of the grafted area

was obtained and implants were inserted in the same site. Histological sections were examined

focusing on the presence of fibrous connective tissue (CT), and newly formed bone in direct

contact with the graft. The HE-stained sections were subjected to histomorphometrical evaluation

using Image Pro-Plus� software (Release 7.0). The definitive crown was placed 3 months later.

Results: Upon completion of the study, no patients were removed from the study and all inserted

implants (10 in each group) were eventually integrated. After 6 months, in the TG1, the mean

value of new bone formation was 33.7 (�7.1), for CT was 32.3 (�8.9) and for the remaining

biomaterial was 10.7 (�16.2). In the TG2, the mean value of new bone formation was 19.3 (�22.6),

of the CT was 49.9 (�14.1) and of the remaining biomaterial was 22.6 (�7.9).

Conclusions: No statistically significant difference was observed between TG1 and TG2 after

6 months (P > 0.05), and both biomaterials afforded a more favorable implant position.

The aim of implant dentistry is to restore

missing or extracted teeth by placing implants

in anatomical, esthetical, and long-term

functional restorative positions (Kutkut et al.

2012). The amount of hard tissue resorption

following tooth extraction occasionally

involves prosthetically driven implant place-

ment; therefore, the development of ridge

preservation techniques that result in less

alveolar bone loss is of great interest (Sisti

et al. 2012). Extraction socket wound healing

is characterized by resorption of the alveolar

bone at the extraction site, which reduces

the bone volume available for implant place-

ment. Major changes in the extraction socket

occur during the first year after tooth extrac-

tion, with two-thirds of the bone loss occur-

ring within the first 3 months (Schropp et al.

2003; Ara�ujo et al. 2008; Van der Weijden

et al. 2009), although dimensional changes

are observed up to 1 year after tooth extrac-

tion, resulting in a 50% reduction in the buc-

colingual dimension of the alveolar ridge

(Schropp et al. 2003), primarily due to the

resorption of the buccal bone plate (Ara�ujo &

Lindhe 2011). The ridge preservation proce-

dures facilitate the preservation of the alveo-

lar architecture to prevent hard and soft

tissue collapse and minimize or eliminate

the necessity for future augmentation proce-

dures (Tan et al. 2012). Many graft materials,

such as autogenous bone grafts (Pelegrine

et al. 2010), allografts (Wood et al. 2012;

xenografts (Calasans-Maia et al. 2009; Fernan-

des et al. 2011; Spinato et al. 2012; Festa

et al. 2011), and alloplasts (Gonshor et al.

2011; Ruga et al. 2011; Brkovic et al. 2012),

have been used to maintain the dimensions

of the alveolar ridge after extraction in

humans. Although some of these graft mate-

rials preserved the post-extraction alveolar

ridge dimensions to some extent, the quan-

tity and the quality of the bone tissue forma-

tion in the socket varied and the presence

of these materials has often affected the

usual healing process (Heberer et al. 2011).

Date:Accepted 3 July 2013

To cite this article:Calasans-Maia M, Resende R, Fernandes G, Calasans-Maia J,Alves AT, Granjeiro JM. A randomized controlled clinicaltrial to evaluate a new xenograft for alveolar socketpreservation.Clin. Oral Impl. Res. 00, 2013, 1–6doi: 10.1111/clr.12237

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1

Xenografts are obtained from a species that is

different from that of the recipients, and as

osteoconductors, these grafts are predomi-

nantly made from the inorganic portion of

animal bone tissue (Granjeiro et al. 2005;

Munhoz et al. 2006; Calasans-Maia et al.

2009; Accorsi-Mendonc�a et al. 2011; Zam-

buzzi et al. 2012). The processing of bovine

bone results in two distinct types of materi-

als: inorganic and organic (predominantly col-

lagen type I). Inorganic material is free of

proteins and cells because it only consists of

hydroxyapatite. The proteins are removed

through heat treatment at temperatures

above 300°C or alkali treatment, followed by

neutralization, thus eliminating the risk of

disease transmission. However, the bioab-

sorption of these materials is reduced with

increasing temperature (Wenz et al. 2001).

Indeed, bovine materials obtained from Brazil

are regarded favorably, as Brazilian cattle are

free of spongiform encephalopathy (BSE or

mad cow disease). A new Brazilian bone sub-

stitute (Osseous�; SIN, S~ao Paulo, SP, Brazil),

comprising an inorganic bovine bone matrix,

has been used as an alternative graft material

for ridge preservation after tooth extraction

prior to implant placement. In previous in

vivo studies, we confirmed that this bovine

xenograft is a biocompatible, bioabsorbable

osteoconductor (Calasans-Maia et al. 2009;

Jardelino-Lima et al. 2008). The aim of this

study was to compare the effects of two

deproteinized bovine bone minerals in the

healing of fresh extraction sockets using

clinical, histological, and histomorphometric

analyses.

Material and methods

This study was performed in compliance

with the principles outlined in the Declara-

tion of Helsinki concerning experimentation

involving human subjects. Quality assess-

ment was carried out based on the RCT-

checklist of the CONSORT-statements

(Schulz et al. 2010). All procedures and mate-

rials in the present study were approved

through the relevant independent committee

on the Ethics of Human Research of Flumin-

ense Federal University (CEP/HUAP nº 118),

and the volunteer subjects were informed

about the study protocol and required to sign

a consent form. Twenty patients (ten women

and 10 men) participated in this randomized,

controlled clinical trial, which took place in

the Dental Clinical Research Center at Flu-

minense Federal University, Rio de Janeiro,

Brazil (Table 1, Data S1). A minimum sample

size (10 subjects per group) was established

in an attempt to minimize the publication

bias (Vignoletti et al. 2012, Sisti et al. 2012).

Patient selection

All the patients were in general good health.

Any patient requiring one tooth extraction

(hopeless tooth for periodontal, traumatic, or

caries reasons) and showing a bone defect

between 3 and 5 mm at the buccal wall and

no soft tissue recession was eligible for this

study according to specific exclusion and

inclusion criteria (Table 2). The recruitment

of the volunteers was carried out during

6 months, and all volunteers were followed

up for a period of 12 months after prosthetic

rehabilitation. The volunteer subjects were

randomly assigned to the tests groups using

an envelope system distribution provided by

the principal investigator.

Presurgical procedures

The medical and dental histories of the

patients were reviewed, and each patient

was evaluated using periapical radiographs,

clinical photographs, study casts, and clinical

examinations of the extraction sites. Sub-

sequently, the volunteers were provided

with detailed oral hygiene instructions, and

customized surgical splints were fabricated

on the study casts for use in reentry proce-

dures to accurately obtain bone biopsies from

the center of the grafted sockets.

Surgical procedures

The following implant procedure was used at

all extraction sites. The extraction was

performed under local anesthesia, without the

elevation of a mucoperiosteal flap (Fig. 1a,b,

Data S1). A periotome and the appropriate

dental forceps were used to minimize surgical

trauma of the surrounding tissue. The thor-

ough curettage of all soft tissue debris in the

alveolus was performed during the extraction

at all extraction sites to ensure the removal of

all granulation tissue and stimulate bleeding

from the osseous base to promote healing. A

caliper (Dentaurum�; Dentaurum Dental

Technology, Ispringen, Germany) was subse-

quently used to measure the horizontal ridge

width (buccolingually) at the midpoint of the

alveolar crest using the mid-buccal and mid-

palatal marks on the cervical bone surface as

published before (Mardas et al. 2011, Vigno-

letti et al. 2012). After completion of the mea-

surements, the randomization envelope was

opened and the assigned treatment test Osse-

ous� (SIN) or control (Geistlich Biomaterials,

Wollhusen, Switzerland) was revealed to the

surgeon. The implant did not exceed the

height of the alveolar crest, and the site was

visually inspected to ensure that the biomate-

rial was saturated with blood (Fig. 1c). Pri-

mary wound closure was performed following

the elevation and rotation of the mucoperio-

steal flap (Fig. 1d,e). Postoperative antibiotic

therapy (500-mg Azithromycin) was adminis-

tered once a day for the first postoperative

week, and a disinfectant mouth rinse (0.12%

Chlorhexidine) was prescribed two times per

day, for the first two postoperative weeks.

Postoperative clinical evaluations of the

patients were performed at 1, 7, 30, and

Table 1. List of volunteer subjects investigated

Patient Gender Age ToothExperimentalgroups

1 Female 30 46* 12 Female 52 37* 23 Female 53 37* 24 Male 44 21‡ 15 Female 34 46* 26 Male 58 46‡ 17 Male 50 47‡ 28 Female 51 46* 29 Female 34 36* 110 Female 34 16* 111 Female 53 22† 112 Male 50 27‡ 213 Male 60 15† 214 Male 52 36‡ 215 Male 23 47* 216 Female 56 36† 117 Female 48 26* 118 Female 45 24† 119 Female 33 34† 220 Female 31 36† 1

*Extraction due to periodontal reason.†caries.‡tooth/root fracture.

Table 2. Inclusion and exclusion criteria

Inclusion criteria Exclusion criteria

Age between 30 and 60 yearsGood general healthPresence of a hopeless tooth requiringextraction

The extraction site would be suitable forreplacement by a dental implant

Volunteer subjects had voluntarily signedthe informed consent

Pregnancy or lactating periodSmokingChronic treatment with any medication knownto affect oral status and bone turnover

Contraindicate surgical treatmentSuffering from a known psychological disorder

2 | Clin. Oral Impl. Res. 0, 2013 / 1–6 © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Calasans-Maia et al �Alveolar socket preservation with xenograft

90 days to determine the presence of compli-

cations, such as infection with inflammation,

wound dehiscence, or loss of graft material.

After 6 months, all sockets were evaluated

through clinical and radiographic examination

(Fig. 1f,g).

Surgical reentry

At 24 weeks after extraction, the implants

were placed. A mucoperiosteal flap was

raised, and the site of extraction was identi-

fied using a customized surgical splint. A

caliper was used to measure the horizontal

ridge width buccolingually. A core biopsy

with a depth of 6 mm was obtained from the

center of the extraction site. A trephine bur

(2 mm in diameter, SIN) was used to collect

the biopsy specimen (Fig. 2a), followed by

dental implant placement according to the

manufacturer’s surgical protocol. Try-On or

Strong implants (SIN) were used (Fig. 2b,c).

The mucoperiosteal flaps were closed with

interrupted sutures (Silk suture 4-0, Ethi-

con�). After 6 months, the implants were

successfully placed at all sites in the control

and test groups (Fig. 2d).

Histological evaluation

Bone biopsy specimens (6 9 2 mm) obtained

from the grafted and ungrafted sockets were

fixed in 10% formalin for 2 days and subse-

quently decalcified in bone decalcification

solution (Alkimia�; Allkimia, Campinas, Bra-

zil) for 48 h. After routine processing, the tis-

sues were embedded in paraffin, sectioned

longitudinally into multiple 4lm-thick sec-

tions and stained with Hematoxylin and

Eosin (H&E) and Masson’s trichrome stain.

The two most central sections were obtained

from each specimen. For the qualitative and

morphologic analysis of the remodeling pro-

cess, the stained preparations were examined

under a light microscope (Zeiss Axioplan) at a

minimum 209 magnification and the entire

section was evaluated. Ten digital images of

each section were acquired and used to trace

the areas identified as vital bone, biomaterial

particles, and connective tissue (CT)/other

non-bone components. Image analysis soft-

ware (Image ProPlus�, Release 7.0; MediaCy-

bernetics, Silver Spring, MD, USA) was used

to create individual layers of newly formed

bone, biomaterial particles, and CT/other non-

bone components, which were assessed by a

single observer blinded to the clinical data.

Statistical analysis

The results were expressed as the means �95%CI. The Mann–Whitney unpaired test were

performed, considering significant differences if

P < 0.05.

Results

Clinical findings

Clinical healing was uneventful and free of

infection or symptoms in all volunteers from

both groups. Age and gender did not signifi-

cantly affect the clinical outcomes of this

study.

Almost complete soft tissue closure was

observed at 10 days after extraction in both

test groups. After 6 months of healing, when

the bone specimen sample was obtained, both

groups exhibited the same bone density and

showed the same resistance on trephine appli-

cation. Bone core samples were retrieved, and

implants were placed in all sockets. The hori-

zontal ridge width (buccolingually) was mea-

sured at the midpoint of the alveolar crest

using the mid-buccal and mid-palatal marks

on the cervical bone crest before the tooth

extraction and after 6 months of socket heal-

ing, and the results are showed in Table 3.

Statically significant differences were not

observed between the groups.

(a) (b)

(c)

(d)

(e)

(f)

(g)

Fig. 1. (a, b) Clinical and radiographic aspects of the hopeless tooth; (c) socket filled with the osseus xenograft; (d)

The flap was advanced coronally for primary closure; (e) radiographic aspect of the immediate area post grafting; (f,

g) clinical and radiographic aspects at 6 months after grafting.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 3 | Clin. Oral Impl. Res. 0, 2013 / 1–6


Histological observations

Test sites

One experienced blinded pathologist performed

the histological evaluation. Histological slides

were prepared, and the cores were examined at

209 and 409 magnification, revealing new

bone formation in all grafted sockets. The for-

mation of new well-mineralized vital trabecu-

lar bone was observed in all examined sections.

The new bone showed trabecular organization,

with collagen fibers arranged in a meshwork

pattern and osteocytes randomly distributed

(a)

(b)

(c)

(d)

Fig. 2. (a) Before implant installation a 2-mm specimen was removed using a trephine; (b, c) Clinical and

radiographic images of the installed implant; (d) Prosthetic rehabilitation.

Table 3. Clinical outcomes with respect towidth in millimeters (standard deviation inparentheses)

Tooth Group Baseline EndChange inwidth (mm)

46 1 11 10.6 0.437 2 10 9.5 0.537 2 9.5 9.1 0.421 1 8.0 7.8 0.246 2 11.2 10.9 0.346 1 12.1 11.6 0.547 2 12.3 12 0.346 2 11 10.4 0.636 1 11.5 11.1 0.416 1 11 10.8 0.222 1 7.0 6.8 0.227 2 12.0 11.7 0.315 2 6.5 6.3 0.236 2 11.5 11.2 0.347 2 12.4 12 0.436 1 11.8 11.6 0.226 1 12.1 12 0.124 1 9.0 8.8 0.234 2 7.0 6.4 0.636 1 11.9 11.4 0.5

(a) (b)

Fig. 3. (a, b) Photomicrographs of the interface between xenograft and the new formed bone, Stain HE, 109 and

409 augmentation.

(a)

(b)

(c)

Fig. 4. Histomorphometric evaluation of the alveolar

sockets grafted with Bio-Oss� and Osseus�, consider-

ing the volume density of (a) newly-formed bone; (b)

connective tissue and (c) residual biomaterial particles.

Points in the plot represent all data, mean 95% of confi-

dence interval (bars).



within the trabeculae in large spindle-shaped

lacunae (Fig. 3a,b). Loose fibrous tissue with

thin vessels filled the trabecular spaces. Dense,

trabecular bone patterns were observed in both

test groups. The overall mean value of the

newly formed vital bone area fraction for TG1

was 33.6% (�7.1) and 19.3% (�22.5) for TG2.

For TG1, the mean value of the newly formed

CT was 32.3% (�8.8), and the mean value

of the remaining biomaterial was 10.6%

(�16.2). For TG2, the mean value of the CT

was 49.9% (�14.0), and the mean value of the

remaining biomaterial was 22.5% (�7.9)

(Fig. 4).

Discussion

The present randomized clinical trial com-

pared two bovine xenografts (Bio-Oss� and

Osseus�) for the preservation of the alveolar

ridge dimensions following tooth extraction.

The clinical, histological, and histomorpho-

metrical evaluations did not show significant

differences between the two materials. In the

present study, biopsy specimens were

obtained and dental implants were placed

after a 6-month healing period. A healing

period of 6 months was selected because this

time point was used in two previously

reported systematic reviews. The first sys-

tematic review showed 29–63% horizontal

bone loss and 11–22% vertical bone loss

after 6 months following tooth extraction

and demonstrated rapid reductions in the

first 3–6 months, followed by gradual reduc-

tions in the dimensions (Tan et al. 2012).

The second systematic review showed a

3.8 mm horizontal reduction in width and a

1.24 mm vertical reduction in height of the

alveolar ridge within 6 months after tooth

extraction (H€ammerle et al. 2012). These

studies demonstrated rapid reductions in the

first 3–6 months, followed by gradual reduc-

tions in the dimensions. A previous study

discussed so-called ridge preservation tech-

niques, which are categorized into two differ-

ent groups: techniques for maintaining the

ridge profile (ridge preservation) and tech-

niques for enlarging the ridge profile (ridge

augmentation). The reasons for ridge preser-

vation include the maintenance of the exist-

ing soft and hard tissue envelope,

maintenance of a stable ridge volume for

optimizing the functional and esthetic out-

comes, and the simplification of treatment

procedures subsequent to ridge preservation

(Vignoletti et al. 2012). Contraindications for

ridge preservation were considered in patients

irradiated in the area planned for ridge preser-

vation, patients taking biphosphonates and

when general contraindications against oral

surgical interventions and infections at the

site planned for ridge preservation were

observed, which could not be treated during

ridge preservation surgery (H€ammerle et al.

2012). The volunteer subjects included in the

present clinical trial did not present contrain-

dications for ridge preservation. In the pres-

ent study, mucoperiosteal flaps were raised

to preserve the ridge profile and facilitate

primary wound closure. The primary closure

of the wound is beneficial with respect to

the volume gained as a result of this

approach (H€ammerle et al. 2012). Cellular

differentiation, augmentation material break-

down, and bone replacement were evidenced

at the grafted sites, largely preserving the

dimensions of the alveolar ridge after

6 months of healing. In the present study, a

very small horizontal resorption of the bone

crest after the two types of treatments was

observed in both groups, confirming previous

clinical and preclinical reports that post-

extraction healing is always characterized by

osseous resorption and significant contour

changes especially in the horizontal plane of

the residual alveolar ridge (Schropp et al.

2003; Ara�ujo & Lindhe 2011). These changes

may be limited because our sample is mainly

composed by molars. A shorter 3-month

healing period should be evaluated in future

studies. A recent systematic review evalu-

ated bone healing after tooth extraction,

with or without an intervention, and the

histological evaluation revealed a large pro-

portion of residual graft material that might

account for some of the differences in the

alveolar ridge dimensions observed during

the follow-up exam (Morjaria et al. 2012).

Another recent systematic review evaluated

the effectiveness of bone preservation using

graft materials in non-molar alveolar regions

and suggested that the graft materials might

not prevent physiological resorptive bone

processes after tooth extraction, although

these materials might reduce changes in the

resulting bone dimensions (Ten Heggeler

et al. 2011).

Conclusions

The alterations in the dimension of the alve-

olar ridge following tooth extraction were

similar between the groups, affording a more

favorable implant position.

Acknowledgements: The authors

thank Sistema de Implantes Nacional, S~ao

Paulo, Brazil (SIN) for providing financial

support for this study. We also want to

express our thanks to Dr. Alfredo Schnetzler

Neto and Frederico, Prosthodontists, Rio de

Janeiro, Brazil for his significant

contributions to developing the

prosthodontic rehabilitation.

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REVIEW

Alveolar ridge preservation. A systematic review

Attila Horváth & Nikos Mardas & Luis André Mezzomo &

Ian G. Needleman & Nikos Donos

Received: 31 December 2011 /Accepted: 14 May 2012 /Published online: 20 July 2012# Springer-Verlag 2012

AbstractObjective The objective of this paper is to examine theeffect of alveolar ridge preservation (ARP) compared tounassisted socket healing.Methods Systematic review with electronic and hand searchwas performed. Randomised controlled trials (RCT), controlledclinical trials (CCT) and prospective cohort studies wereeligible.Results Eight RCTs and six CCTs were identified. Clinicalheterogeneity did not allow for meta-analysis. Average changein clinical alveolar ridge (AR) width varied between −1.0and −3.5±2.7 mm in ARP groups and between −2.5and −4.6±0.3 mm in the controls, resulting in statisticallysignificantly smaller reduction in the ARP groups in five outof seven studies. Mean change in clinical AR height variedbetween +1.3±2.0 and −0.7±1.4 mm in the ARP groups andbetween −0.8±1.6 and −3.6±1.5 mm in the controls. Heightreduction in the ARP groups was statistically significantly less

in six out of eight studies. Histological analysis indicatedvarious degrees of new bone formation in both groups. Somegraft interfered with the healing. Two out of eight studiesreported statistically significantly more trabecular bone for-mation in the ARP group. No superiority of one technique forARP could be identified; however, in certain cases guidedbone regeneration was most effective. Statistically, signifi-cantly less augmentation at implant placement was neededin the ARP group in three out of four studies. The strength ofevidence was moderate to low.Conclusions Post-extraction resorption of the AR might belimited, but cannot be eliminated by ARP, which at histolog-ical level does not always promote new bone formation. RCTswith unassisted socket healing and implant placement in theARP studies are needed to support clinical decision making.Clinical relevance This systematic review reports not only onthe clinical and radiographic outcomes, but also evaluates thehistological appearance of the socket, along with site specificfactors, patient-reported outcomes, feasibility of implantplacement and strength of evidence, which will facilitate thedecision making process in the clinical practice.

Keywords Tooth extraction . Bone resorption . Implant sitedevelopment . Bone substitute . Bone regeneration .

Human histology

Introduction

Periodontal disease, periapical pathology and mechanical trau-ma often result in bone loss prior to tooth removal [1]. Further-more, traumatic extraction has also been associated withadditional loss of bone. In the healing phase after extraction,alveolar bone undergoes additional atrophy as a result of thenatural remodelling process [2–7]. This begins immediately

A. Horváth :N. Mardas : L. A. Mezzomo : I. G. Needleman :N. Donos (*)Unit of Periodontology, Department of Clinical Research,UCL Eastman Dental Institute,256 Gray’s Inn Road,London WC1X 8LD, UKe-mail: [email protected]

A. HorváthDepartment of Periodontology, Semmelweis University,Budapest, Hungary

L. A. MezzomoPontifical Catholic University of Rio Grande do Sul,Porto Alegre, Brazil

I. G. NeedlemanInternational Centre for Evidence-Based Oral Health,UCL Eastman Dental Institute,London, UK

Clin Oral Invest (2013) 17:341–363DOI 10.1007/s00784-012-0758-5

after extraction and may result in up to 50 % resorption of thealveolar ridge (AR) width even in 3 months [1]. Post-extractionAR resorption may have an impact on dental implant place-ment, since sufficient vertical and horizontal volume of alveolarbone should ideally be present at the site of insertion [8].

Alveolar ridge preservation (ARP) procedures have beenintroduced to maintain an acceptable ridge contour in areasof aesthetic concern, as well as to prevent alveolar ridgeatrophy and maintain adequate dimensions of bone in orderto facilitate implant placement in prosthetically driven posi-tions [9, 10]. Several methods have already been investigat-ed for ARP in preclinical models [11–14] and clinicalstudies, such as socket grafting with autogenous bone[15], demineralised freeze-dried bone allograft (DFDBA)[15–17], xenografts, like deproteinized bovine-bonemineral (DBBM) [18], alloplasts [19] and bone morpho-genic proteins (BMP) [20]. Guided bone regeneration(GBR) with or without bone grafts has also been evaluated[9, 10, 21–25].

Although some of the above bone substitutes wereable to limit the resorption of post-extraction alveolarridge up to a certain extent, the quality of the newtissue in the socket varied broadly. The remnants ofthe grafts often interfered with the normal healing pro-cess in line with preclinical results [15–17, 26]. Anumber of review articles on ARP have been publishedin the last decade [27–32]. However, a systematic as-sessment of the nature and quality of the newly formedtissue alongside methodological quality and risk of biasof the studies has not been carried out. Furthermore,non-controlled prospective and retrospective studies aswell as case series were also included in most of theprevious reviews without the comparison to the controlgroup of unassisted socket healing [33–36].

Therefore, the objective of the present systematic reviewwas to investigate the effect of ridge preservation on theresidual alveolar ridge dimensions and on histological char-acteristics, compared to unassisted socket healing.

Methods

Prior to commencement of the study, a detailed protocol wasdeveloped and agreed upon by the authors based on theCochrane Collaboration guidelines and previous reviewspublished by our group [37–41].

Focused question

Following tooth/root extraction in humans, what is the effectof ridge preservation on the residual alveolar ridge dimensionand on histological characteristics, compared to unassistedsocket healing?

Definition

Whilst ‘socket preservation’ has widely been employed todepict a certain procedure, we believe that the objective ofthese interventions is to preserve the dimension of the AR.Therefore, we have used the term ‘Alveolar Ridge Preser-vation’ to define such procedures.

Types of studies

Longitudinal prospective studies were included, i.e. RCTs,CCTs and cohort studies with control group.

Populations of studies

Healthy individuals, without any age limit, who underwentany type of ridge preservation following permanent toothextraction, were included. Smokers and patients with historyof periodontal disease were not excluded. The minimumnumber of subjects per group was five. However, no limitwas set for study follow-up period.

Types of interventions

Test groups

Studies reporting on any of the following types of interven-tions were included: socket grafting (autograft, allograft,xenograft, alloplastic materials); socket sealing (soft tissuegrafts); GBR (resorbable/non-resorbable barriers); biologicalactive materials (growth factors) and combinations of theabove techniques/materials.

Control groups

The control groups of the included studies comprised emptysockets, i.e. unassisted socket healing.

Outcome variables

The primary outcomewas the change in oro-facial (horizontal)and apico-coronal (vertical) AR dimensions. Secondary out-comeswere the following: (1) change in buccal plate thickness;(2) bone volume alteration following extraction; (3) complica-tions; (4) histological healing characteristics; (5) site eligibilityfor placement of an adequate size dental implant with orwithout further augmentation; (6) patient-reported outcomes,such as quality of life and (7) health economics.

Risk of bias and methodological quality assessment

In order to evaluate the methodological quality and risk ofbias of individual studies, we used a combination of

342 Clin Oral Invest (2013) 17:341–363

parameters from the Cochrane Collaboration and Consoli-dated Standards of Reporting Trials (CONSORT) statement.The following parameters were assessed and taken intoconsideration in the final analysis: sample size calculation,statement of eligibility criteria, ethics approval, informedconsent, baseline homogeneity, randomisation method, allo-cation concealment, masking, calibration, follow up, protocolviolation, method of statistics, unit of analysis, CONSORTimplementation, International Standard Randomised Con-trolled Trial Number Register (ISRCTN) and funding disclo-sure. Methodology unique to RCTs was not assessed in CCTs,i.e. randomisation and concealment of allocation.

Randomisation was accepted as adequate, in case theallocation sequence was correctly generated either bycomputer, toss of a coin, throwing dice, etc. Quasirandomisation, e.g. birth dates, hospital numbers werenot accepted. Adequacy of allocation concealment wasaccepted if the sequence was concealed, until interven-tion was assigned (e.g. in sequentially numbered andsealed opaque envelopes, remote computer or centraltelephone). Statistical analysis was judged as adequateif appropriate statistical method was selected to accom-modate to the characteristic of the each individual data(e.g. number of groups and investigated categories, sizeof samples, normally distributed or skewed data, para-metric or non-parametric, paired or unpaired, numericalor categorical variables). Statistical significance was ac-cepted in case of confidence interval (CI) >95 % (p<0.05), while ‘statistically highly significant’ referred toCI>99.9 % (p<0.001).

Based on the above, we attempted to categorize thepossible risk of bias as low, moderate or high. Low riskreferred to studies with adequate randomisation method,sequence concealment and masking of examiner. Studieswere classified as moderate, if one of the above keycategories were missing, or high risk of bias, if morethan one were lacking.

Inclusion criteria

1. All prospective longitudinal studies (i.e. RCTs, CCTsand cohort studies) were included, where one of theabove mentioned types of interventions were carriedout in the test group, whereas unassisted socket healingserved as control.

2. Studies on healthy individuals, without any age limit,who underwent ARP following tooth extraction, wereincluded.

3. Studies had to report on minimum of five patients pergroup.

4. Studies, performing clinical or three-dimensional (3D)radiographic evaluation of hard tissue or histologicalassessment, were included.

Exclusion criteria

1. Case reports, case series, retrospective analyses wereexcluded.

2. Studies without a control group comprising unassistedsocket healing were excluded.

3. Studies on medically compromised patients, e.g. uncon-trolled diabetes mellitus or cancer were excluded.

4. Studies reporting on immediate placement of dentalimplant were excluded.

5. Studies describing extraction of third molars wereexcluded.

Search strategy

A sensitive search strategy was designed as we anticipatedthat relevant studies might be difficult to locate. The searchstrategy incorporated both electronic and hand searches. Thefollowing electronic databases were utilised in Apr 2010: (1)MEDLINE In-Process & Other Non-Indexed Citationsand MEDLINE 1950 to present via Ovid interface; (2)EMBASE Classic + EMBASE 1947 to present via Ovidinterface; (3) The Cochrane Central Register of ControlledTrials (CENTRAL); (4) LILACS.

The electronic search strategy used the following combi-nation of key words and MeSH terms: (“tooth extraction”OR “tooth removal” OR “socket” OR “alveol$” OR “ridge”OR “crest” OR “tooth socket” OR “alveolar bone loss” OR“bone resorption” OR “bone remodeling”) AND (“preserv$” OR “reconstruct$” OR “augment$” OR “fill$” OR “seal$” OR “graft$” OR “repair$” OR “alveolar ridge augmen-tation” OR “bone regeneration” OR “bone substitutes” OR“transplantation”).

Cochrane search filters for RCTs and CCTs were imple-mented. In addition, cohort trials were also searched. Theresults were limited to humans only.

An extensive hand search was also performed encom-passing the bibliographies of the included papers and reviewarticles. Furthermore the following journals were screenedfrom 2001 to April 2010: Clinical Oral Implants Research,Clinical Implant Dentistry and Related Research, EuropeanJournal of Oral Implantology, Implant Dentistry, Interna-tional Journal of Oral and Maxillofacial Implants, Interna-tional Journal of Periodontics and Restorative Dentistry,Journal of Clinical Periodontology, Journal of Dental Re-search, Journal of Oral and Maxillofacial Surgery, Journalof Periodontology, Oral Surgery, Oral Medicine, Oral Ra-diology, Oral Pathology and Endodontics, Periodontology2000. No language restrictions were applied. Translationswere carried out as necessary by two reviewers (AH, LAM).

The extracted data were copied into Reference Manager10 software (Thomson Reuters, New York, NY, USA). Thusthe further steps of screening were performed on this

Clin Oral Invest (2013) 17:341–363 343

interface. A three-stage selection of the resulted hits wasperformed independently and in duplicate by two reviewers(AH and LAM). In order to reduce errors and bias, a cali-bration exercise was performed with the first 500 titles,resulting in 96.4 % agreement. In case of disagreement atthe title selection stage, the trial was included in the abstractstage. At the abstract and full text selection any disagree-ments between the above reviewers were resolved by dis-cussion. If unresolved, a third reviewer (NM) was involvedfor arbitration. The reasons for exclusion were recordedeither in the Reference Manager (abstract stage) or in aspecific data extraction form (full text stage). The level ofagreement was determined by Kappa score calculation.

Research synthesis

Studies were grouped by research design and their chiefcharacteristics. Outcomes were recorded in evidence tables.In view of the marked heterogeneity, no meta-analysis wasconducted. Instead, a narrative synthesis was undertaken.

Results

Search sequence

The electronic search yielded 6,216 relevant hits after re-moval of duplicates (Fig. 1). Subsequently, 157 titles wereselected for the abstract stage. Following investigation ofthe abstracts, 42 articles qualified for full text evaluation.Four extra papers were then added as a result of the handsearch. Assessment of these articles resulted in the following

14 publications eligible for the review [17, 19–21, 23–25,42–48]. The excluded full text papers along with the reasonsfor exclusion are listed in Table 1. The most typical reasonsfor exclusion were lack of control group with unassistedsocket healing; use of retrospective design; assessment ofdimensional changes of the AR only on periapical two-dimensional radiographs, or on casts taken from soft tissuelevel; and surgical removal of third molars.

The Kappa score for agreement between the reviewers (AH,LAM) at the abstract and full text selection level, was 0.96 and0.90, respectively, indicating a high level of agreement.

Study characteristics

In the 14 included articles (eight RCTs and six CCTs) theefficacy of ARP techniques was evaluated clinically bymeans of direct measurements of the residual alveolar ridgedimensions during re-entry procedures, radiographically bymeans of computer tomography or histologically from tre-phine biopsies taken at re-entry during osteotomies forimplant placement (Tables 3 and 4). No cohort studies wereindentified. Limited data were reported on confoundingfactors, such as periodontitis, smoking, systemic diseaseand medication. The extraction site distribution was fairlyheterogeneous. In some studies ARP was performed only inmaxillary anterior sockets [42, 46, 47], whereas such restric-tion was not employed in other studies. The residual bonevolume around the investigated sockets, e.g. the presence/absence and width of the buccal bone plate varied fromseverely compromised [20, 46], to completely intact, buccalbone (Table 3) [17, 21, 42].

Intervention characteristics

With regard to the techniques or materials used for ARP, theincluded studies were grouped into three categories (Table 3);

1. Bone grafts/substitutes2. GBR3. Biological active materials.

In the majority of the included studies, various bonegrafts were utilised, such as autologous bone marrow [47],plasma rich in growth factor (PRGF) with or without autol-ogous bone [43], DFDBA [17], DBBM [46], calcium sul-phate hemihydrates [42, 45] and bioactive glass [17].Alloplastic polyglycolide/polylactide (PGPL) sponge wasalso employed [19, 48]. GBR technique was applied usingnon-resorbable expanded polytetrafluoroethylene (e-PTFE)[24] or resorbable (PGPL) [25] barrier. Resorbable collagenmembrane was also employed in combination with FDBA[23] or corticocancellous porcine bone [21]. Biological ac-tive material, namely bone morphogenic protein (rhBMP-2)was used on a collagen sponge carrier in one study [20].

Electronic search6.216 titles

Included publications14

Relevantabstracts

Full-text analysis 45

Relevant full-texts42

6,059 Excluded based

on the title

115Excluded based on the abstract

32Excluded based on the full-text

3 Included as a result of hand search

Kappa score 0.96

Kappa score 0.90

1 Included as a result of final search

Fig. 1 Flow chart of the screening process

344 Clin Oral Invest (2013) 17:341–363

Table 1 List of excluded full text papers and reasons for exclusion

First author(year of publication)

Journal Reasons for exclusion

Bianchi (2004) Int J Periodont Rest Dent Retrospective analysis

Single-arm of the included Fiorellini et al. (2005)

Bolouri (2001) Comp Cont Educ Dent Reported on optical density on two-dimensional radiographs

Brawn (2007) Impl Dent Case report

Brkovic (2008) J Can Dent Assoc Case report

Carmagnola (2003) Clin Oral Impl Res Lack of real control group, resembles to a retrospective analysis(extreme difference in follow-up period between tests and controls.T1: 4 months; T2: 7 months; C: 1-15 years, mean: 7.8 years)

Cranin (1988) J Biomed Mat Res Case series without control group

De Coster (2009) Clin Impl Dent Relat Res Case series

Retrospective study as stated by the authors in the discussion

Healing period varied between 1.5 months and 1.5 years

Neither histomorphometry nor clinical or radiographic measurementsreported in the results

Graziani (2008) J Cranofac Surg Extraction of fully impacted third molars

Linear measurements on OPG

Gulaldi (1998) Oral Surg Oral MedOral Pat Oral Rad End

Extraction of fully impacted third molars

Linear measurements on OPG and scintigraphy

Primary outcome was to analyze bone metabolism

Heberer (2008) Clin Oral Impl Res Case series without control group

Hoad-Reddick (1994) Eur J Prosth Rest Dent Two-dimensional linear measurements obtained from OPG and cephalometry

Lack of defined landmarks

Surgical procedure was not described

Hoad-Reddick (1999) Eur J Prosth Rest Dent Description of a method for measurements on casts

Neither socket preservation procedure nor the results were described.Soft tissue punch technique only

Howell (1997) Int J Periodont Rest Dent Case series without control group

Jung (2004) Int J Periodont Rest Dent Case series without control group

Primary outcome was soft tissue healing

Kangvonkit (1986) Int J Oral Maxillofac Surg Based on OPG and lateral cephalogram only

Evaluation method remains unclear

Primary outcome was the biocompatibility of HA cones

Karapataki (2000) J Clin Periodontol Extraction of fully impacted third molars

Primary outcome was to assess the periodontal status ofsecond molars after extraction of third molars

Kerr (2008) J Periodontol No biomaterials were used to preserve the ridge dimensions,therefore did not address the focused question

Kwon (1986) J Oral Maxillofac Surg Based on OPG and lateral cephalogram only

Evaluation method remains unclear

Lack of description of the measurement methods

Molly (2008) J Periodontol Control group was covered by an e-PTFE membrane,thus lack of unassisted control sockets

Munhoz (2006) Dento Maxillofac Radiol Extraction of fully impacted third molars

Two-dimensional evaluation of periapical radiographs

Norton (2002) Int J Oral Maxillofac Impl Case series without control group

Resembles to a retrospective design(healing period ranged from 3 to 11 months)

Page (1987) J Oral Maxillofac Surg Case report

Pape (1988) Deutsche ZahnarztlicheZeitschrift

Augmentation of a resorbed ridge

Clin Oral Invest (2013) 17:341–363 345

None of the included studies used the socket sealing tech-nique. Primary flap closure was achieved in 9 out of 14studies, while the sockets left uncovered in the rests. Varioustypes and amounts of antibiotics and antiseptic rinses wereadministered for different duration in studies reporting onpostoperative care. Finally, average healing period rangedfrom one to nine months.

Outcome characteristics

Clinical outcomes

Eight out of the 14 included studies investigated the efficacyof various ARP techniques to preserve the pre-extractionridge dimensions using intra-surgical hard tissue measure-ments taken during re-entry procedure [19, 21, 23–25, 42,44, 47]. In these studies, ARP was performed in 137 socketsof 119 patients and compared to 120 sockets that left to healwithout any treatment in a total of 92 patients (Table 3).

Bone ‘graft’ Four studies evaluated changes in AR dimen-sions following grafting of the socket. Two studies were RCTs[42, 47] and two were CCTs [19, 44]. Healing time variedfrom 3 to 6 months [19, 42, 44, 47].

The horizontal (bucco-lingual) changes of the alveo-lar ridge were assessed in three studies [42, 44, 47].The AR reduced in width from baseline to re-entrybetween −1.0 mm and −3.5±2.7 mm following ARP(p<0.05) and between −2.5 mm and −3.2±1.8 mm in

the control groups (p<0.05). In two out of the three studies,the width reduction was statistically significantly smaller inthe test groups compared to the controls [42, 47].

Four studies investigated the mean change in ridge heightat the mid-buccal aspect [19, 42, 44, 47]. The AR heightchanged from baseline to re-entry between +1.3±1.9 mmand −0.5±1.1 mm following ARP, and between −0.8±1.6 mm and −1.2±0.6 mm in the control groups. The heightreduction between baseline and re-entry was not statisticallysignificant in one study in both test and control groups [44],while one study reported an increase in height instead ofloss following ARP with a PGPL sponge (p<0.05) [19]. Intwo out of the four studies, the height reduction was statis-tically significantly smaller in the test groups compared tothe controls [42, 47].

The vertical dimension changes at the mesial and distalaspects of the socket were measured in two studies [19, 42]and did not present any statistically significant difference forboth groups.

Three studies captured data on socket fill and reportedstatistically significant differences between baseline and re-entry in both groups [42, 44, 47], but only one reportedstatistically significantly higher socket fill, where bioactiveglass was covered by calcium sulphate, compared to theunassisted healing [44].

GBR Four studies evaluated changes in AR dimensionsfollowing ARP with GBR alone [24, 25], or in combinationwith bone graft [21, 23]. Three studies were RCTs [21, 23,

Table 1 (continued)

First author(year of publication)

Journal Reasons for exclusion

Case series without control group

Penteado (2005) Braz J Oral Sci Immunohistochemical analysis

Did not address the focused question

Quinn (1985) J Am Dent Assoc Clinical measurements at soft tissue level only based on tattoo points,thus failed to address the focused question

Resembles to a retrospective analysis

Schepers (1993) Impl Dent Retrospective case series without control group

Simon (2004) Ind J Dent Res Extraction of fully impacted third molars

Evaluated soft tissue healing and radiographic analysis basedon the two-dimensional periapical radiographs

Simion (1994) Int J Periodont Rest Dent Titanium implants placed simultaneously

No control group

Primary outcome was microbiological analysis

Smukler (1999) Int J Oral Maxillofac Impl Healed edentulous ridge as control instead of empty socket

No compatibility of the follow-up periods of the different groups

Svrtecky (2003) J Prosth Dent Case report

Throndson (2002) Oral Surg Oral MedOral Pat Oral Rad End

Extraction of fully impacted third molars

Measurements based on two-dimensional periapical radiographs

Yilmaz (1998) J Clin Periodontol Measurement at soft tissue level on study casts

346 Clin Oral Invest (2013) 17:341–363

25] and one was CCT [24]. Healing time varied between 4and 9 months.

Horizontal (bucco-lingual) changes of the AR wereassessed in all four studies. AR width reduction from base-line to re-entry varied between −1.2±0.9 mm and −2.5±1.2 mm in the GBR-treated sockets and between −2.6±2.3 mm and −4.6±0.3 mm in the control groups. With theexception of one study [23], a statistically significantlysmaller reduction of the alveolar ridge width was observedwhen e-PTFE [24], PGPL [25], or collagen membranes incombination with xenograft [21] were used.

All the four studies investigated the mean change in ARheight at the mid-buccal aspect. The AR height changedfrom baseline to re-entry between +1.3±2.0 mm and −0.7±1.4 mm in the ARP groups and between −0.9±1.6 mmand −3.6±1.5 mm in the control groups. The resorption inthe ARP group was not statistically significant in three outof four studies [23–25]. All studies reported a statisticallysignificantly less post-extraction reduction in AR heightwhen the socket was treated by GBR compared to unassistedhealing.

Vertical dimension changes at mesial and distal aspectsof the socket were measured in two studies [21, 23]. Theobserved differences between baseline and re-entry were notstatistically significant in both groups. In one out of the twostudies the height reduction was statistically significantlysmaller in the test group compared to the control [23].

Two studies captured data on the socket fill [24, 25] andreported statistically significant socket fill in both groupsbetween baseline and re-entry, as well as between tests andcontrols.

No data were found on either initial buccal plate thick-ness or alteration of bone volume. However, one studymeasured the buccal bone thickness loss and reported sta-tistically significantly less reduction in the ARP group [47].

Radiographic measurements

Two RCTs, reporting on 3D radiographic assessment, metthe inclusion criteria [20, 46]. The healing time varied from1 to 4 months. In one study, where the post-extraction socketwas grafted with a radiopaque material (DBBM), treatmentresulted in significantly less reduction in radiographic ARheight compared to unassisted socket healing [46]. The testgroup in the other study, where the higher concentration(1.5 mg/ml) of RhBMP-2 was utilised [20], resulted in amean increase of the radiographic AR width by 3.27±2.53 mm at the most coronal part, compared to the 0.57±2.56 mm increase in the group of unassisted healing. ARheight was reduced by 0.02±1.2 mm in the same test groupand by 1.17±1.23 mm in the control group (Table 3). Thedifferences between test and control were statisticallysignificant.

Histological results

Eleven studies carried out a histological analysis based ontrephine biopsies retrieved at re-entry [17, 19–21, 23, 42,43, 45–48]. Seven studies were RCTs [17, 20, 21, 23, 46,47] and four were CCTs [19, 43, 45, 48]. In these studies,ARP was performed in 181 sockets of 158 patients andcompared to 149 sockets that left to heal without anytreatment in 131 patients (Table 4). Only two out ofeight studies reported statistically significantly higher tra-becular bone volume following ARP in comparison to unas-sisted socket healing [21, 42] and two studies reportedstatistically significantly more connective tissue in the post-extraction socket when no ARP was performed [17, 21]. Onthe contrary, one study reported more vital bone in theunassisted socket healing group compared to the ARPgroup [23]. None of the differences of the investigatedhistomorphometric parameters reached statistical signifi-cance in other studies.

Bone ‘grafts’ Eight studies evaluated histologically thehealing of post-extraction sockets following the applicationof some type of bone grafts/substitutes [17, 19, 42, 43,45–48]. Four studies were RCTs [17, 42, 46, 47] and fourwere CCTs [19, 43, 45, 48]. New mineralised bone wasobserved at various levels in all studies in both ARP andcontrol groups in a healing period from 2.5 to 8 months.Connective tissue occupied a portion of the socket in bothgroups. When DFDBA, bioactive glass or DBBM wereused, the graft particles were embedded either in new boneor in connective tissue. In most studies, there was no sig-nificant difference in the type of healing, or amount of boneformation between bone grafts and unassisted sockethealing.

GBR in combination with graft GBR in combination withgraft was utilised in two RCTs. ARP with a collagen mem-brane and deproteinized porcine bone resulted in statisticallysignificantly higher new bone and lower connective tissueformation after 7 to 9 months of healing in comparison tounassisted socket healing [21]. However, residual graftmaterials were present in the ARP biopsies. FDBA andcollagen membrane resulted in similar amounts of new boneformation to untreated sockets, although more vital bonewas observed in the untreated sockets at 4 to 6 months ofhealing (p>0.05) [23].

Biological active material RhBMP-2 in a collagen spongecarrier was completely resorbed at 4 months following ARPregardless of the concentration of the growth factor [20].Mineralised tissue was found and trabecular bone formationwas noticed in two third of both the test and control biopsiesin the RCT.

Clin Oral Invest (2013) 17:341–363 347

Adverse events, complications

Adverse events were reported in six RCTs [17, 20, 21, 25,42, 47] and four CCTs [19, 24, 44, 48] including oedema,pain, erythema and membrane exposure/infection. In twostudies, more adverse events, i.e. oedema, erythema [20] ormembrane exposure [24] were observed in the ARP groupcompared to the natural socket healing. No comparisonbetween tests and controls were reported in the other studies(Table 3).

Feasibility of implant placement

Seven studies [17, 19, 23, 42, 45, 46, 48] reported thatimplant placement in the previous sockets were successful,but no differences between the ARP and untreated sites wererevealed. The outcome of implant placement remained un-clear in one article [43] and only re-entry without implanta-tion was performed in three trials [24, 44]. Four studiesreported the need of further augmentation at the stage ofimplant placement. Three of them favoured the ARP groupover the controls, since less [20] or no sites [21, 47] in theARP group presented with residual dehiscence or fenestra-tion defects around the inserted implants (Table 3).

Patient-reported outcome and health economics

No data were found for patient-reported outcome measuresor health economic evaluation.

Quality assessment

Considerable heterogeneity was found among the studies interms of methodological quality. Detailed description of thequality assessment of the included studies is presented inTable 2. Among the 14 included controlled studies, eightwere randomised [17, 20, 21, 23, 25, 42, 46, 47] although infour of them the randomisation technique was not reported[20, 42, 46, 47]. None of the RCTs reported the method ofallocation concealment. Masking of the examiner wasreported at the clinical level in two out of eight [23, 25], atradiological level in one out of two [20] and at histologicallevel in four out of 11 studies [17, 21, 42, 43]. Examinercalibration was declared in three papers [20, 23, 42], whilstinclusion and exclusion criteria were defined in seven pub-lications [17, 21, 23, 42, 43, 46, 47]. Apart from threestudies [21, 43, 46] all the other reported the approval ofthe ethical committee. Three studies were funded by indus-try [17, 20, 44], two studies by academic institution [45, 48]and the remaining nine did not report the source of funding.

Nine trials implemented patient-based analysis [20, 21,23–25, 42, 44, 47, 48], whilst the extraction site served asunit of analysis in the rest of the five investigations [17, 19,

43, 45, 46]. Sample size calculations were reported only inthree studies [20, 23, 42], although with insufficient data toevaluate the validity of the calculations. Statistical analysiswas appropriately carried out and described in one studyonly [47]. Appropriate statistics were either not carried out[17, 19–21, 43, 45, 46], or the reported data were insuffi-cient to determine the validity [23–25, 42, 43, 48]. In addi-tion, no RCTs were either registered with ISRCTN orreported using the CONSORT guidelines (Table 3).

Risk of bias

Four studies were classified as moderate risk of bias [17, 21,23, 25] and the rest were categorised as high risk of bias(Table 2).

Discussion

Key findings

This systematic review has demonstrated that different ARPtechniques do not totally eliminate post-extraction alveolarridge resorption or predictably promote new bone forma-tion. However, the reduction in ridge width and heightfollowing ARP may be less than that which occurs follow-ing natural socket healing. The clinical data suggest that thehorizontal ridge contraction was most successfully limitedin the two studies applying GBR without additional bonegrafts [24, 25], whereas the vertical shrinkage was mostefficiently limited by employing GBR with additional bonegraft [21, 23].

Strengths of the review

The present systematic review was limited to randomisedcontrolled trials, controlled clinical trials and prospectivecohort studies with a control group of empty untreatedsockets. Furthermore, the inclusion criteria of our systematicreview were based on the fact that the clinical merit ofapplying the different ARP techniques could only be vali-dated, if the clinical and histological outcomes following theapplication of a technique are superior to that of unassistedsocket healing.

In comparison to the previous systematic reviews [28,32] the present review has evaluated the histological char-acteristics of the alveolar socket healing with or withoutARP. The amount and the quality of the newly formedosseous tissues in the socket area are essential, especiallywhen the justification of ARP is to facilitate the placementof a dental implant in the position of a previously extractedtooth. It is doubtful, whether an ARP technique should beclaimed successful, if it only preserves the external contour

348 Clin Oral Invest (2013) 17:341–363

Tab

le2

Qualityassessmentof

theinclud

edstud

ies

Study

QualityCriteria

Estim

ated

risk

ofbias

Firstauthor

Randomisation

Masking

Calibratio

nElig

ibility

Criteria

Follow

upEthical

considerations

Funding

Statistical

analysis

Miscellaneous

Yearof

publication

1.Randomised

1.Therapist

1.Intra-exam

iner

1.Inclusion

criteriadefined

1.Percentage

ofcompleted

follo

wups

1.Ethicsapproval

Sourceof

Funding

1.Appropriate

samplesize

calculationandpower

1.Com

parable

experimentalgroups

2.CONSORT

implem

ented

2.Inform

edconsent

3.ISRCTN

registered

2.Unitof

analysis

4.Other

comments

3.Appropriate

statisticsapplied

2.Exclusion

criteriadefined

2.Adequate

correctio

n

2.Patient

2.Inter-exam

iner

2.Adequate

sequence

generatio

n3.

Examiner

Type

4.Statistician

3.Allo

catio

nconcealm

ent

Reference

number

4.Concealment

adequate

Aim

etti

1.Yes

1.N/R

1.Yes

(histo),

N/R

(clin

)1.

Yes

1.N/R

1.Yes

N/R

1.Insufficient

data

todeterm

ine

1.Yes

High

2.N/R

2009

2.N/R

2.N/R

2.N/A

2.Yes

2.N/A

2.Yes

2.Patient

3.N/R

3.Insufficient

data

todeterm

ine

RCT

3.N/R

3.Yes

(histo),

N/R

(clin

).#42

4.N/A

4.N/R

*Reportedas

‘doubleblind’

Anitua

1.Yes

(btw

T-C)

No(w

ithin

T)

1.N/R

1.N/R

1.Yes

1.100%

1.N/R

N/R

1.N/R

1.N/R

High

1999

2.N/A

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

+site

2.N/R

CCT

3.N/R

3.Yes

3.Nostatistical

analysis

was

carriedout

3.N/R

#43

4.N/A

4.N/R

4.Atsevere

defects

autogenous

bone

was

addedto

PRGF.

Different

healingperiods.

Barone

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.N/R

N/R,declared

noconflict

ofinterest

1.N/R

1.Yes

Moderate

2008

2.Yes

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.Yes

(histo),

N/R

(clin

)3.

No

3.N/R

#21

4.N/A

4.N/R

4.Different

healing

periods.

Cam

argo

N/A

1.N/R

1.N/R

1.Yes

1.100%

1.Yes

Industry

1.N/R

1.N/R

High

2000

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

CCT

3.N/R

3.Insufficient

data

todeterm

ine

3.N/R

#44

4.N/R

Fiorellini

1.Yes

1.N/R

1.N/R

1.No

1.100%

1.Yes

Industry

1.Insufficient

data

1.N/R

High

2005

2.N/R

2.N/R

2.Yes

2.No

2.Unclear

2.Yes

todeterm

ine

2.N/R

RCT

3.N/R

3.Yes

(CTscans)

2.Patient

3.N/R

#20

4.N/A

4.N/R

*Reported

as‘double

blind’

3.No

4.Standardisatio

nof

CTscansN/R.

Final

number

ofsockets,patients

remainunclear.

Froum

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.Yes

Industry

1.N/R

1.N/R

Moderate

2002

2.Yes

2.N/R

2.N/A

2.Yes

2.Unclear

2.Yes

2.Site

2.N/R

RCT

3.N/R

3.Yes

3.No

3.N/R

#17

4.N/A

4.N/R

4.Different

healingperiods.

Enrolmentof

sitesof

subjectsinconsistent.

Clin Oral Invest (2013) 17:341–363 349

Tab

le2

(con

tinued)

Study

QualityCriteria

Estim

ated

risk

ofbias

Firstauthor

Randomisation

Masking

Calibratio

nElig

ibility

Criteria

Follow

upEthical

considerations

Funding

Statistical

analysis

Miscellaneous

Yearof

publication

1.Randomised

1.Therapist

1.Intra-exam

iner

1.Inclusion

criteriadefined

1.Percentage

ofcompleted

follo

wups

1.Ethicsapproval

Sourceof

Funding

1.Appropriate

samplesize

calculationandpower

1.Com

parable

experimentalgroups

2.CONSORT

implem

ented

2.Inform

edconsent

3.ISRCTN

registered

2.Unitof

analysis

4.Other

comments

3.Appropriate

statisticsapplied

2.Exclusion

criteriadefined

2.Adequate

correctio

n

2.Patient

2.Inter-exam

iner

2.Adequate

sequence

generatio

n3.

Examiner

Type

4.Statistician

3.Allo

catio

nconcealm

ent

Reference

number

4.Concealment

adequate

Guarnieri

N/A

1.N/R

1.N/R

1.Yes

1.N/R

1.Yes

Governm

ent;

institu

tion

1.N/R

1.N/R

High

2004

2.N/R

2.N/A

2.No

2.N/A

2.Yes

2.Site

2.N/R

CCT

3.N/R

3.No

3.N/R

#45

4.N/R

Iasella

1.Yes

1.N/R

1.Yes

1.Yes

1.100%

1.Yes

N/R

1.Insufficient

data

todeterm

ine

1.Yes

Moderate

2003

2.Yes

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.Yes

3.Insufficient

data

todeterm

ine

3.N/R

#23

4.N/A

4.N/R

Lekovic

N/A

1.N/R

1.N/R

1.No

1.70%

(premature

exposure

ofe-PTFE

barrierin

3/10)

1.Yes

N/R

1.N/R

1.Yes

High

1997

2.N/R

2.N/A

2.No

2.N/R

2.Patient

2.N/R

CCT

3.N/R

2.Yes

3.Insufficient

data

todeterm

ine

3.N/R

#24

4.N/R

Lekovic

1.Yes

1.N/R

1.N/R

1.No

1.100%

1.Yes

N/R

1.N/R

1.Yes

Moderate

1998

2.Yes

2.N/R

2.N/A

2.No

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.Yes

3.Insufficient

data

todeterm

ine

3.N/R

#25

4.N/A

4.Yes

Nevins

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.N/R

N/R

1.N/R

1.Yes

High

2006

2.N/R

2.N/R

2.N/A

2.Yes

2.Yes

2.N/R

2.Site

2.N/R

RCT

3.N/R

3.N/R

3.No

3.N/R

#46

4.N/A

4.N/R

4.Standardisationof

CT

scansN/R.T

estm

aterial

radiopaque.D

ifferent

healingperiods.

Pelegrine

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.Yes

N/R

1.N/R

1.N/R

High

2010

2.N/R

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.N/R

3.Yes

3.N/R

#47

4.N/A

4.N/R

Serino

N/A

1.N/R

1.N/R

1.Yes

1.80%

1.Yes

N/R

1.N/R

1.N/R

High

2003

2.N/R

2.N/A

2.No

2.Unclear

2.Yes

2.Site

2.N/R

CCT

3.N/R

3.No

3.N/R

#19

4.N/R

4.Molarsonly

inT.

350 Clin Oral Invest (2013) 17:341–363

of the AR, but the newly formed tissue is of inferior qualityand quantity (percentage of matured trabecular bone) towhat is normally achieved following a tooth extraction.

Finally, the quality of the included studies has also beenmeticulously assessed in this review. Such a quality evalu-ation of the retrieved data is essential to estimate the sourceand magnitude of potential bias that may lead to delusiveconclusions.

Strength of evidence—risk of bias

The quality assessment of the included studies in this sys-tematic review revealed that none of the trials have qualifiedfor a low risk of bias category. Ten out of the 14 studiespresented with high risk of bias thus their results must beevaluated with caution. The lack of clear reporting of re-search methodology elements, such as adequate randomiza-tion and concealment and/or masking of the therapist andthe examiner were among the primary reasons for the highrisk of bias [49]. We did not contact authors for clarificationof unclear methodology. Therefore, it is possible that actualstudy conduct was better than that reported in the publica-tion. Statistical considerations played important role as well,since appropriate analytical statistics was completed andreported merely in one study [47]. Power calculation wasconducted in three trials only [21, 23, 42], nevertheless thereported data were insufficient to determine the validity ofthe calculation.

Dimensional changes and histological characteristics

Sufficient ridge width and height have been considered asone of the key requirements for successful implant therapyand for the establishment of an aesthetically pleasing emer-gence profile at fixed partial dentures [8, 50, 51]. Therefore,the alterations in oro-facial (horizontal) and apico-coronal(vertical) AR dimensions were selected as the primary out-comes of the present review. Direct intra-surgical measure-ments on the AR at re-entry are considered as the mostprecise method to evaluate the bone volume changes fol-lowing ARP. It is desirable though to establish and validate asurrogate measure that avoids the need for re-entry surgery,while providing the clinician with a reliable measure. Two-dimensional radiographs, such as periapical or panoramicradiographs, are not ideal to estimate the 3D changes of theAR [52]. Also, measurements of the alveolar mucosa levelor study casts incorporate not only the alveolar bone, butalso the overlaying soft tissue. For these reasons onlystudies performing clinical or 3D radiographic evaluationof hard tissue were included in this review. Cone-beamcomputerised tomography (CBCT) appears to offer a validtechnique to assess alveolar ridge changes, with newer mod-els greatly reducing radiation exposure [53]. However, aT

able

2(con

tinued)

Study

QualityCriteria

Estim

ated

risk

ofbias

Firstauthor

Randomisation

Masking

Calibratio

nElig

ibility

Criteria

Follow

upEthical

considerations

Funding

Statistical

analysis

Miscellaneous

Yearof

publication

1.Randomised

1.Therapist

1.Intra-exam

iner

1.Inclusion

criteriadefined

1.Percentage

ofcompleted

follo

wups

1.Ethicsapproval

Sourceof

Funding

1.Appropriate

samplesize

calculationandpower

1.Com

parable

experimentalgroups

2.CONSORT

implem

ented

2.Inform

edconsent

3.ISRCTN

registered

2.Unitof

analysis

4.Other

comments

3.Appropriate

statisticsapplied

2.Exclusion

criteriadefined

2.Adequate

correctio

n

2.Patient

2.Inter-exam

iner

2.Adequate

sequence

generatio

n3.

Examiner

Type

4.Statistician

3.Allo

catio

nconcealm

ent

Reference

number

4.Concealment

adequate

Serino

N/A

1.N/R

1.N/R

1.Yes

1.80%

1.Yes

Governm

ent;

institu

tion

1.N/R

1.N/R

High

2.Patient

2.N/R

3.Insufficient

data

todeterm

ine

3.N/R

2008

2.N/R

2.N/A

2.No

2.Unclear

2.Yes

CCT

#48

3.N/R

4.N/R

N/A

notapplicable;N/R

notrepo

rted,Ttest;C

control;RCTrand

omised

controlledtrial;CCTcontrolledclinical

trial;PRGFplatelet-richgrow

thfactor;CONSO

RTCon

solid

ated

Stand

ards

ofReportin

gTrials;ISRCTNInternationalStand

ardRando

mised

Con

trolledTrial

Num

berRegister

Clin Oral Invest (2013) 17:341–363 351

Tab

le3

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessityof

simultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Type

offlap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Aimetti

1.Italy

1.36-68

(51.27

±8.4)

1.No

1.Maxillary

anterior

Calcium

sulphate

Empty

(18/18)

1.Flapless

1.3months

1.T:-2.0±1.1**

1.T:

-0.5±1.1*,

C:-1.2±0.6**,***

1.Im

plants

were

inserted

2009

2.1

RCT

Parallel

2.N/R

3.University

Clin

+Histo

Hem

ihydrate

(22/22)

#42

2.40

(40)

2.Noprim

ary

closure

2.4-wall

configuration

2.N/R

C:-3.2±1.8**,

***

3.Uneventful

healing

3.Amoxicillin

2g/day

for

5days,

Chlorexidine

0.12%

for

2weeks

2.N/R

2.T:-0.2±0.6,

C:-0.5±0.9

3.T:-0.4±0.9,

C:-0.5±1.1

4.T:

11.3±2.8**,

C:10.0±2.3**

(Acrylic

stent)

2.N/R

Anitua1999

1.Spain

1.T:35-55

(41)

1.Yes

1.Any

T1:

PRGF

(5+3/5+3)

Empty

(10+3/

10+3)

1.Full-thickness

1.2.5–4

months

N/A

N/A

1.N/R

2.N/R

2.Variable

2.Yes

2.Primary

closure

2.0

3.N/R

T2:

PRGF+

Autologous

bone

(5/5)

3.Amoxicillin

1.5g/day

for

5days

2.1

C:38-54(42)

CCT

3.Private

practice

2.23

(26)

Parallel+Split-

mouth

Histo

#43

Barone

2008

1.Italy

1.26-69

1.<10/day

1.Non-m

olars

Corticocancellous

porcinebone+

collagen

mem

brane

(20/20)

Empty

(20/20)

1.Full-thickness

1.7-9months

1.T:-2.5±1.2*,

C:-4.5±0.8*,***

1.T:-0.7±1.4*,

C:-3.6±1.5*,***

1.‘Implantswere

inserted

inboth

groups’

2.1

2.Primaryclosure

2.0

2.T:-0.2±0.8,

C:-0.4±1.2

2.Som

eGBR

wereneeded

dueto

buccal

dehiscence

inthecontrol

group

2.N/R

3.T:-0.4±0.8,

C:-0.5±1.0

3.Amoxicillin

2g/day

for

4days+

Chlorexidine

0.12%

for

3weeks

3.Uneventful

healing

(pain,

swellin

g)

2.Yes

(treated)

2.4-wall

configuration

4.N/R

2.40

(40)

(Acrylic

stent)

3.Hospital

RCT

Parallel

Clin

+Histo

#21

Cam

argo

2000

1.USA,

Yugoslavia

1.28-60

(44±15.9)

1.N/R

1.Maxillary

anterior,

prem

olars

Bioactiv

eglass+

coveredby

calcium

sulphate

layer(16/8)

Empty

(16/8)

1.Full-thickness

with

4vertical

releasing

incisions

1.6months

1.T:-3.48

±2.68**,

C:-3.06

±2.41**

1.T:-0.38

±3.18,

C:-1.00

±2.25

(titanium

tack)

1.Reentry

only

2.N/R

2.Noprim

ary

closure

3.N/R

2.N/R

4.T:

6.43

±2.78**,

C:4.00±2.33**,***

(tobuccal

bone

crest)

2.N/A

3.Penicillin

1.5g/day

for

7days+

Chlorexidine

0.12%

for

2weeks

2.N/R

2.N/R

2.16

(32)

3.Uneventful

healing

2.N/R

CCT

2.N/R

3.University

Split-mouth

Clin

#44

352 Clin Oral Invest (2013) 17:341–363

Tab

le3

(con

tinued)

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessity

ofsimultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Typeof

flap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Fiorellini

2005

1.USA

1.47.4

1.N/R

1.Maxillary

anterior,

prem

olars

T1:

1.5m

g/ml

rhBMP-2

(?/21?)

Empty

(?/20?)

1.Full-thickness

with

vertical

incisions

1.4months

1.Coronal:

T1:+3

.27±2.53*,

T2:+1

.76±1.67*,

T3:+0

.82±1.40,

C:+

0.57

±2.56,***

(T1vs

T2/T3/C)

1.T1:-0.02±1.2,

T2:-0.62±1.39*,

T3:-1.00±1.40*,

C:-1.17

±1.23*,

***(T1vs

C)

1.N/R

2.Noneed

for

augm

entatio

n2.

Nodrop-outs

reported.

(3patients

incorrectly

random

ized,

1patient

received

different

graft)

T1:

18/21(86%

)T2:

0.75mg/ml

rhBMP-2

(?/22?)

T2:

12/22(55%

)

2.Primary

closure

2.N/R

T3:

10/17(59%

)

2.N/R

3.N/R

C:9/20

(45%

)

3.250(T

>C)

4.N/R

(T1vs

T2/C)***

3.Penicillin

(?mg)

for7-10

days+

Chlorexidine

0.12%

T3:

Collagen

sponge

(?/17?)

2.≥5

0%buccal

bone

loss

2.8centres

2.80

(95)

2.N/R

RCT

3.University

Parallel

Radiogr+

Histo

#20

Froum 2002

1.USA

1.35-77

(54.9±11.9)

1.No

1.Any

T1:

Bioactiv

eglass(10/8)

Empty

(10/10)

1.Full-thickness

with

outvertical

incisions

1.6-8months

N/A

N/A

1.‘A

nim

plant

ofappropriate

size

was

placed

inthehealed

sockets.’

2.0

3.Uneventful

healing

T2:

DFDBA

(10/8)

2.Primary

closure

2.N/R

3.Doxycyclin

e100m

g/day

for13

days+

Chlorexidine

0.12%

for

30days

2.N/R

2.4-wall

configuration,

≤2mm

buccal

plateloss

2.19

(30)

2.Single

centre

RCT

Splitmouth

3.University

Histo

#17

Guarnieri

2004

1.Italy

1.35-58

1.N/R

1.Maxillary,

mandibular

anteriors,

prem

olars

Calcium

sulphate

Empty

(5/5)

1.Full-thickness

with

outvertical

incisions

1.3months

N/A

N/A

1.‘Bucco-lingual

dimensionsof

thealveolar

ridge

enabled

safeinsertion

oftitanium

implant.’

2.socket

with

ridge

resorptio

n≥5

0%were

excluded

2.Primaryclosure

3.Amoxicillin

(?mg)

for

1week+Chlorexidine

0.2%

for2weeks

2.N/R

Hem

ihydrate

(10/10)

2.N/R

2.Yes

3.N/R

2.10

(25)

2.N/R

3.N/R

CCT

Parallel+

Split

mouth

Histo

#45

Iasella

2003

1.USA

1.28-76

(51.5±13.6)

1.Yes

1.Maxillary

anteriors,

prem

olars

and

mandibular

prem

olars

Tetracycline

hydrated

FDBA

+

Empty

(12/12)

1.Full-thickness

with

outvertical

incisions

1.4or

6months

(com

bined)

1.T:-1.2±0.9*,

C:-2.6±2.3*

1.T:

+1.3±2.0,

C:-0.9±1.6***

1.Im

plants

successfully

placed

atall

sites

2.N/R

2.N/R

2.T:

-0.1±0.7,

C:-1

.0±0.8***

2.Somesiteshad

slightdehiscence

andrequired

furth

eraugm

entation

2.Noprim

aryclosure

2.N/R

3.T:

-0.1±0.7,

C:-0.8±0.8***

3.Doxycyclin

200m

g/dayfor

1week+

Chlorexidine

0.12%

for

2weeks

collagen

mem

brane

(12/12)

2.0

4.N/R

3.N/R

(Acrylic

stent)

3.N/R

2.24

(24)

RCT

2.N/R

Parallel

Clin

+Histo

#23

Clin Oral Invest (2013) 17:341–363 353

Tab

le3

(con

tinued)

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessity

ofsimultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Typeof

flap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Lekovic

1997

1.Yugoslavia

/USA

1.(49.8)

1.N/R

1.Maxillary

and

mandibular

anteriors,

prem

olars

e-PTFE

mem

brane

(10/10)

Empty

(10/10)

1.Full-thickness

with

4vertical

releasing

incisions

1.6months

1.10/10:,

T:-1.80±0.51,

C:-4.40±0.61**,

***

1.10/10:

T:-0.5±0.22,

C:-1.2±0.13**,

***

1.Reentry

only

7/10:T:-1.71±0.75,

C:-4.43±0.72**,

***

7/10:

T:-0.28±0.18,

C:-1.0±0.0**,

***

3/10:T:-2.00±0.00,

C:-4.33±0.88*

3/10:T:-1.0±0.58,

C:-1.66±0.33

(titanium

tack)

2.N/R

3.N/R

4.10/10:

T:4.9±0.86*,

C:3.0±0.63,

***

2.N/R

7/10:T

:5.43±1.1*,

C:2.92±1.61,***

3/10:T

:3.66±1.20,

C:4

.33±1.45

(tobuccalbone

crest)

2.Primaryclosure

3.Penicillin

1g/day

for

7days+

Chlorexidine

0.2%

2.N/A

2.3/10

drop-outs

dueto

prem

ature

mem

brane

exposure

3.3/10

exposed,

7/10

noinfection

2.10

(20)

2.N/R

CCT

2.N/R

(presumably

singlecentre)

Split-mouth

2.N/R

Clin

3.University

#24

Lekovic

1998

1.Yugoslavia

1.(52.6±11.8)

1.N/R

1.Maxillary

and

mandibular

anteriors,

prem

olars

PG/PL

mem

brane

(16/16)

Empty

(16/16)

1.Full-thickness

with

4vertical

releasingincisions

1.6months

1.T:-1.31±0.24*

1.T:-0.38

±0.22,

C:-1.50

±0.26*,

***(titanium

tack)

1.Reentry

only

2.N/A

2.0

C:-4.56

±0.33*,

***

3.Uneventful

healing

2.N/R

2.Primaryclosure

2.N/R

3.Penicillin1g/day

for7days+

Chlorexidine0.12%

for2weeks

3.N/R

2.Yes

(treated)

2.N/R

4.T:5.81

±0.29*,

C:3.94

±0.35*,

***

(tobuccal

bone

crest)

2.16

(32)

2.1

3.University

RCT

Split-mouth

Clin

#25

Nevins2006

1.USA

/Italy

1.N/R

1.N/R

1.Maxillaryanterior

DBBM

(19/9)

Empty(17/9)

1.Partial

thickness

1.1–3months

(biopsiesat6M

)N/A

1.T:-2.42±2.58,

C:-5.24±3.72***

1.Im

plantswere

placed,but

number

unknow

n

2.Buccalplatewas

comprom

ised

2.Primary

closure

2.0

3.N/R

2.N/R

2.N/R

3.N/R

3.N/R

4.N/R

(At6mm

ridgewidth)

2.Yes

RCT

2.N/R

Split-mouth

3.N/R

Radiogr+

Histo

#46

2.9(36)

354 Clin Oral Invest (2013) 17:341–363

Tab

le3

(con

tinued)

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessity

ofsimultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Typeof

flap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Pelegrine

2010

1.Brazil

1.28-70

(47.5±10.3)

1.No

1.Maxillary

anteriors

Autologous

bone

marrow

(15/7)

Empty

(15/6)

1.Full-thickness

with

2buccal

vertical

releasing

incisions

1.6months

1.T:-1.0*,

C:-2.5*,***

1.T:

-0.5*,

C:-1.0*,***

(Titanium

screw)

1.Allimplants

osseointegrated

2.N/R

2.13

(30)

2.N/R

2.Primaryclosure

3.N/R

2.1

2.0

3.University

2.T:-0.75,

C:-1.75,***

4.T:10.33*,C:10.32*

(tobuccal

bone

crest)

2.T:with

out

further

augm

entatio

n,C:At5sites

augm

entatio

nor

expansion

carriedout

3.N/R

3.Uneventful

healing

RCT

2.Socketswith

severe

bone

loss

were

excluded

Parallel

Clin

+histo

#47

Serino

2003

1.Italy

1.35-64

1.N/R

1.Any

PG/PLsponge

(26/24)after

drop-out

Empty

(13/12)

afterdrop-out

1.Full-thickness

buccally

and

lingually

1.6months

N/A

1.T:+1.3±1.9*,

C:-0.8±1.6

1.Placementof

implantsin

all

CandTsites

with

good

prim

arystability

2.Buccalplate

couldbe

partially

orcompletely

lost

2.1

CCT

Parallel+

split-m

outh

2.45

(39)

before

drop-out

3.N/R

2.Yes

(treated)

Clin

+Histo

#19

2.Noprim

ary

closure

2.9drop-outs

forreasons

unrelatedto

thetherapy

2.T:-0.2±1.0,

C:-0.6±1.0

3.T:-0.1±1.1,

C:-0.8±1.5

3.No

antib

iotics;

Chlorexidine

0.2%

for

2weeks

3.Uneventful

healing

4.N/R

(Acrylic

stent)

2.N/R

Serino

2008

1.Italy

1.32-64

1.N/R

1.Any

non-molars

PG/PLsponge

(7/7)

Empty(9/9)

afterdrop-out

1.Full-thickness

buccally

and

lingually

1.3months

N/A

N/A

1.Placementof

implantsin

all

CandTsites

with

good

prim

arystability

2.1

2.Yes

(treated)

2.4drop-outs

forreasons

unrelatedto

thetherapy

afterdrop-out

CCT

2.Alveolar

bone

height

≥8mm

2.Noprim

ary

closure

Parallel

2.N/R

Histo

3.NoAntibiotics;

Chlorexidine

0.2%

for2weeks

3.Uneventful

healing

2.20

(20)

before

drop-out

#48

3.N/R

*p<0.05;statistically

sign

ificantintra-grou

pdifference,baselin

eto

final;**

p<0.00

1statistically

high

lysign

ificantintra-grou

pdifference,baselin

eto

final;**

*p<0.05

statistically

sign

ificant

inter-groupdifference,betweentestandcontrol;

N/A

notapplicable;N/R

notrepo

rted;Ttest;C

control;M=mon

th(s);Clin

clinical

analysis;Histo

histolog

ical

analysis;Rad

iogr

radiog

raph

icanalysis;RCTrand

omised

controlledtrial;CCT

controlledclinicaltrial;PRGFplasmarich

ingrow

thfactors;DFDBAdemineralised

freeze-dried

bone

allograft;FDBAfreeze-dried

bone

allograft;e-PTFEexpand

ed-polytetrafluo

rethylen;PG/PL

polyglycolide/po

lylactide;

DBBM

demineralised

bovine-bon

emineral

Clin Oral Invest (2013) 17:341–363 355

Tab

le4

Firstauthor

Num

berof

biopsies

Histomorphology

Histomorphom

etry

Statistical

difference

betweentestand

control

Test

Control

(meanor

median%)

Yearof

publication

(testmaterial)

Type

Healin

gperiod

Reference

number

Aimetti2009

T:N/R

22?

(MGCSH)

Noresidual

graftmaterial.Noinflam

matory

infiltrate.New

bone

form

ationin

all

specim

ens,100%

livingtrabecular

bone

with

woven

andlamellarstructure.

100%

livingbone

(mostly

woven)

inallbiopsies.Lam

ellarbone

remodelingwas

starting.

Trabecular

bone:

Residual

substitute

material:

Woven

bone:

Lam

ellar

bone:

Tvs

C*

T:58.8±3.5

Coronal:

Coronal:

T:0.0

T:83.6±6.6

T:16.4±6.6

C:11.1±7.6

C:88.9±7.6

Middle:

T:40.4±13.2

Middle:

T:59.6±13.2

C:18.9±7.6

C:81.1±7.6

Apical:

Apical:

T:56.4±10.9

T:43.6±10.9

C:77.8±8.1

RCT

C:N/R

18?

C:22.2±8.1

C:N/A

C:47.2±7.7

3M

#42

Anitua

1999

T:N/R

(PRGF±

autogenbone)

Com

pact

maturebone

with

well-organized

trabeculae

andmorphologyin

8/10

patients.

Connectivetissuewith

non-organized

trabeculae

in2/10

patients.Significant

intra-groupdifferences10

vs.16

weeks!

Connectivetissuefills

themain

partof

thedefect.Nomature

bone.

N/R

CCT

2.5–4M

C:N/R

#43

Barone2008

T:20 (Corticocancellous

porcinebone+

collagen

mem

brane)

Residualgraftmaterialem

bedded

innewly

form

edbone

inallspecim

ens.Com

plete

bone

fill.

Typically

trabecular

bone

pattern.

Large

marrow

spaces

filledwith

adipocytes.Lam

ellarbone

was

also

presentwith

inthebone

marrow.

Totalbone

volume:

Connective

tissue:

Residualgraft

material:

Bone:

T>C*

Connectivetissue:

T<C*

RCT

T:35.5±10.4

T:36.6±12.6

T:29.2±10.1

C:25.7±9.5

C:59.1±10.4

C:N/A

7–9M

C:20

#21

Fiorellini

2005

T1:16

(rhB

MP-2

1.5m

g/ml)

Noevidence

ofinflam

mationor

residualgraft.Trabecularbone

form

ationin

2/3

ofthesamples.M

ineralized

tissueform

ationpresentedwith

differentlevelof

remodeling.Minor

osteoclasticactiv

ity.N

ocomparisonreported

between

TandC!

N/R

T2:

15(0,75m

g/ml)

T3:11

(Collagensponge)

RCT

C:14

4M

#20

Froum

2002

T1:

10(Bioactiv

eglass)

T1:

New

bone

form

ation.

Osteoid

surrounded

andpenetrated

thebioactiveglassparticles.

N/R

Vitalbone:

Connective

tissue:

Residualbone

substitute:

Connectivetissue:

T1<T2or

C*

T1:

59.5

T1:

35.3

T1:

5.5

T2:

13.5

T2:

34.7

T2:

51.6

C:N/A

C:67.0

C:32.4

T2:

Varying

degreesof

reossificatio

naround

DFDBA.

RCT

T2:

10(D

FDBA)

C:10

6–8M

#17

356 Clin Oral Invest (2013) 17:341–363

Tab

le4

(con

tinued)

Firstauthor

Num

berof

biopsies

Histomorphology

Histomorphom

etry

Statistical

difference

betweentestand

control

Test

Control

(meanor

median%)

Yearof

publication

(testmaterial)

Type

Healin

gperiod

Reference

number

Guarnieri2004

T:10

(MGCSH)

Alm

ostcompleteabsenceof

MGCSH.

Absence

ofconnectiv

etissueand

inflam

matorycells.In

allsections

trabecular

bone

form

ationwith

nodifferencesbetweentheapical,middle

andcoronallevels.

Lessbone

form

ationcompared

totestsites.

Trabecular

bone

area:

Nostatisticalsignificance

couldbe

draw

ndue

tosm

allnum

berof

controlspecimens.

CCT

C:5

T:Coronal:58.6±9.2

3M

Middle:

58.1±6.2

Apical:58.3±7.8

C:≤46

#45

Iasella

2003

T:4M

:5,

6M:7

Residualgraftparticlessurrounded

bywoven

bone

orby

connectiv

etissue.

Similaram

ount

oftotalb

oneand

trabecular

spaces

asin

test.

Vitalbone:

Non-vitalbone:

N/R

(Tetracycline

hydrated

FDBA+

Collagen

mem

brane)

(Nobiopsy

from

2Csitesdue

tominim

albone

fill)

4M4M

T:31

±9

T:32

±19

C:58

±11

C:N/A

6M T:41

±18

C:N/A

Com

bined

6M

T:37

±18

C:N/A

T:25

±17

C:50

±14

Com

bined

RCT

T:28

±14

C:54

±12

4–6M

#23

C:4M

:5,

6M:5

Nevins2005

T:5(D

BBM)

DBBM

granules

present.Apically

integrated

incancellous

bone

butcoronally

insoft

tissue.Nosignsof

inflam

mationor

foreignbody

reactio

n.

New

bone

form

ation

Nocomparisonmade.

RCT

6M

#46

C:5

Pelegrine

2010

T:7

(Autologous

bone

marrow)

Mineralized

bone:

Nosignificantdifference.

T:45.0

RCT

C:43.75

C:6

6M

#47

Serino

2003

T:10 (PG/PLsponge)

Noresidual

graftmaterial.Presenceof

matured,mineralized

bone.Lackof

coronalsofttissueingrow

th.

Presenceof

mineralized

bone.

Widemarrow

spaces.

Mineralized

bone:

Statisticalcomparison

cannotbe

madedue

tothesm

allnum

ber

ofcontrolspecimens.

T:66.7

C:3

C:43.7

CCT

6M

#19

Serino

2008

T:7 (PG/PLsponge)

Noresidualgraftm

aterial.Scarce

presence

ofinflammatorytissue.Coronal:new

lyform

edtrabecularbone

with

largemarrowspaces.

Apical:morematureandcompactbone.

Coronal:trabecularbone

with

wide

marrowspaces

with

connective

tissue.Apical:morematureand

compactbone.

Mineralized

bone:

Nosignificant

difference.

T:59.9±22.4

CCT

C:9

C:48.8±14.4

3M

#48

*p<0.05

;statistically

sign

ificantdifference

betweentestandcontrol

Ttest;Ccontrol;M

mon

th(s);N/R

notrepo

rted;N/A

notapplicable;vs.v

ersus;TBVtotalbo

nevo

lume;MGCSH

medicalgradecalcium

sulphatehemihyd

rate;DFDBAdemineralised

freeze-dried

bone

allograft;FDBAmineralised

freeze-dried

bone

allograft;DBBM

demineralised

bovine-bon

emineral;PG/PLpo

lyglycolide/po

lylactide

Clin Oral Invest (2013) 17:341–363 357

prerequisite of this technique would be some type of stand-ardisation, so that the captured image is being always takenfrom exactly identical positions [54]. None of the two includedradiographic studies reported on such standardisation [20, 46].

For the interpretation of the results we attempted tocluster the studies in respect to the type of intervention.

Unassisted sockets In the present review, the mean reduc-tion of the AR width of the untreated sites varied between2.6±2.3 mm and 4.6±0.3 mm and the mean reduction of theAR height was between 0.8±1.6 mm and 3.6±1.5 mm after1 to 9 months of healing. This corroborates the result of aprevious clinical study which indicated that 95 % of ARreduction should be expected after three months of extrac-tion [1]. Furthermore, it is in agreement with a recent sys-tematic review, which reported that the average reduction ofthe AR width seemed to be higher (3.87 mm), than thereduction in AR height (1.67 mm) [55].

Even though both AR width and height present resorp-tion, histologically, new bone formation up to a variableextent was also observed in some studies as result of unas-sisted socket healing [19–21, 23, 42, 45, 46, 48]. In addi-tion, a large area was occupied by bone marrow [19, 21, 48],as reported in preclinical studies [11, 13, 56]. Only a singlestudy reported on connective tissue fill and lack of maturebone [43].

Bone grafts and substitutes Effective grafting procedures forbone augmentation have been associated with the osteocon-ductive, osteoinductive or osteogenetic properties of the graft[56–59]. This led to the assumption that the placement of thesematerials in the extraction socket may accelerate new boneformation by the above biological properties and may alsoreduce AR resorption by stabilising the blood clot, providing ascaffold and external source of minerals and/or collagen [11,12, 60, 61]. The placement of DBBM with collagen in freshextraction sockets resulted in limited reduction of the ARdimensions, although delayed initial socket healing in termsof new bone formation was also observed [11, 12]. Humanstudies reported similar unfavourable histological observa-tions when DFDBAwas employed for ARP [15, 16].

In the present review of human experiments, two out ofthree studies reported that socket grafting with autologousbone marrow [47] or alloplastic material [42] have signifi-cantly limited the reduction of the AR width compared tothe unassisted socket healing. Three out of five studiesreported that reduction of the resorption in AR height wassignificant [42, 46, 47], while the ridge height was evenincreased in one study, where sockets were grafted withpolymer sponge [19]. We should emphasise though thatsince the graft material (DBBM) in a CT study possessedradiopaque characteristic, the alteration of the AR contouron the CT image should be interpreted with caution [46].

Based on the histological evaluation of these studies, theabove AR dimensional changes were not necessarily accom-panied by higher amount of new bone formation in thesocket, since the quality of newly formed tissue in theARP sites was comparable to that in the control sites.Furthermore, the sockets were occupied by a mixture ofnew bone and connective tissue which in many occasionswas surrounding the graft particles [17, 21, 46] (Table 4).

GBR (membrane alone or in combination with ‘graft’) Theconception of guided bone and tissue regeneration [62] wastranslated to ARP procedures in order to exclude epithelialcells from the extraction socket by the use of barrier mem-brane in four studies of the present review [21, 23–25].

(a) GBR with membrane aloneARP with GBR resulted in statistically significantly

less resorption in ridge width and height compared tounassisted socket healing, regardless of the type ofmembrane [24, 25]. It should be noted that in one study[24], in three out of 10 cases, the exposed non-resorbable e-PTFE barrier had to be removed prema-turely, highlighting the importance of sufficient softtissue closure and timing of removal of the barrier.The outcomes in these three cases were similar to thecontrol sites. Where healing was uncompromised, astatistically significant difference was found after6 months in width and height changes in favour ofthe ARP group.

(b) GBR with membrane and ‘graft’ARP resulted in statistically significantly less re-

sorption in width [21, 23] and height [23] in compar-ison to unassisted socket healing. The histologicalevaluation of the GBR procedures in the includedstudies demonstrated new bone formation [21, 23],but the presence of graft particles was also evident inboth studies, embedded either in newly formed bone[21] or in connective tissue [23]. This is in agreementwith a recent trial, where a collagen membrane incombination with DBBM or a biphasic bone substitutewas used for ARP [9, 10].

Biological active materials The potential benefit of biologi-cal active molecules was investigated in periodontal and boneregeneration through fostering the proliferation and differen-tiation of different mesenchymal cells in various preclinicalmodels [63, 64]. The safety and feasibility of rhBMP-2 onhuman ARP or ridge augmentation was evaluated and shownto be safe in a two-centre clinical study [35]. Dimensionalchanges of the alveolar ridge were measured on CTscans in anRCT [20]. Treatment with recombinant BMP-2 resulted in anincrease in ridge width which was statistically significantlygreater than controls. However, this observation needs to be

358 Clin Oral Invest (2013) 17:341–363

interpreted in light of the surprise finding of an increase inridge width of the untreated controls. This was a uniquefinding amongst the studies that we reviewed. Histologically,no comparison between ARP and controls sites was reported.

The human histological results of the included papers ofthe present review were generally found to be comparable topreclinical studies [11–13, 60, 65]. There are a number ofaspects to consider in the interpretation of the results. First-ly, it has to be kept in mind that whilst the biopsies of theanimal model incorporate the cross section of the whole AR,the biopsy retrieval at human studies is limited to a trephinecore sample of part of the former socket. This location maynot necessarily coincide with the exact position of the pre-vious extraction, thus making interpretation of the resultschallenging. Furthermore, the differentiation between api-cal, mid and coronal, as well as the central and lateralaspects of the biopsies was not always apparent.

Another important parameter when considering a histo-logical overview of the studies was the variation in healingtime. Due to the nature of post-extraction healing, the directcomparison of the new tissue formation in studies between 1and 9 months of healing could be misleading. This washighlighted in three studies which did not make a distinctionbetween the variable healing times within the groups, rang-ing from 2.5 months to 9 months [17, 21, 43]. It has to bekept in mind also that the only study, which completed andreported appropriate statistical methodology [47], did notobserve statistically significant difference between the testand control biopsies.

Furthermore, small sample sizes in the majority of thestudies may also limit the generalisability of the histologicalfindings.

Two studies found statistically significant histologicaldifferences in new bone formation favouring the test group[21, 42]. Drawing conclusions across the studies is difficultsince the test groups differed in many respects comparedwith each other, including different technique (bone sub-stitute only [42]/GBR + graft [21]), different material(MGCSH [42]/porcine bone with collagen membrane[21]), different flap management (flapless, no primary clo-sure [42]/mucoperiosteal flap, primary closure [21]), dif-ferent healing time (3 months [42]/7–9 months [21]). Onecommon feature was that both groups limited their inter-vention to sockets with four intact walls. It is noteworthythat all three studies that included intact socket walls only,reported statistically significant differences both on ARwidth and height in favour of ARP [21, 42, 47], while onlyone [20] out of two studies [19, 20] with initial buccal boneloss reported similar significant difference between testand control. Therefore, socket morphology could be animportant predicator of improved ARP. The need forARP in such sockets, in terms of future clinical success/implant placement needs further investigation.

Flap management All studies reporting statistically signifi-cant inter-group differences in both horizontal and verticalclinical measurements achieved either primary flap closure[21, 24, 25, 47], or did not detach the periosteum in aflapless procedure [42]. Furthermore, none of the studieswithout primary closure demonstrated statistically signifi-cant differences between test and control in terms of bothhorizontal and vertical clinical measurements [19, 23, 44].Therefore, both achieving and maintaining the epithelialseal above the socket may be crucial to improving ARP.Further corroboration of this concept was suggested wheree-PTFE barriers were prematurely exposed. The healing ofthese three exposed cases demonstrated no statistically sig-nificant differences compared to the control sites [24].

Other factors affecting interpretation of the findings

Healing time

The optimal timing of re-entry following ARP is determinedby the implant insertion. Since the volume of the AR isgradually decreasing, while the quality of the newly formedtissue is gradually increasing during the post-extractionremodelling [1, 6] the implant placement could be consid-ered as early as possible, but as late as necessary, in order tomaintain AR volume, as well as to achieve complete epi-thelial seal with some extent of osseous fill. The healingperiods of the trials in the present review varied consider-ably (one to nine months). Therefore, interpretation of theresults was complicated by the heterogeneity present in theincluded studies.

Antimicrobials

Improvement of clinical parameters was demonstrated as aresult of regular rinsing with chlorhexidine following toothextraction [66]. Subjects of the included trials in the presentreview were prescribed various types of antibiotics andinstructed to rinse with chlorhexidine for 2 to 3 weeks.Therefore, no conclusion could be drawn on the necessityor benefit of employment of antibiotics/antimicrobials fol-lowing ARP.

Smoking

Smoking is associated with delayed socket healing andincreased reduction in post-extraction alveolar width [67].Three trials in this review included smokers [21, 23, 43] andthe half of the studies did not report on smoking as anexclusion factor, thus any conclusions about the impact ofthis well-recognised risk factor for impaired healing aredifficult to draw [68].

Clin Oral Invest (2013) 17:341–363 359

Periodontal treatment/health

Four studies included patients whose periodontal treatmentwas carried out prior to the ARP [19, 21, 25, 48]. ARPresulted in statistically significant difference between testsand controls in clinical [21, 25] and in histological param-eters [21]. In addition, in the studies where periodontitis waspresent, but periodontal treatment was not reported, nostatistically significant histological differences were demon-strated [43, 44, 46]. This suggests that treated periodontitismay not hinder the success of ARP.

Hard and soft tissue morphology

No data were reported on factors, such as gingival biotype,width of the keratinised gingiva, thickness of buccal plate ortotal volume of AR that may modify the outcome of ARP.Therefore, the possible impact of these factors on ARPcannot be determined.

Clinical relevance

The clinical rationale for ARP is to minimise the necessityfor one or two stage alveolar ridge reconstruction to allowsuccessful implant placement. If the ARP procedure failsto meet this requirement, it may be considered as an un-necessary or even unsuccessful procedure. Therefore, astatistical significance favouring ARP does not necessarilylead to a clinical benefit, unless the whole treatment issimplified or made more successful [9]. In the presentsystematic review, seven out of ten studies did not reportdifferences in feasibility of implant insertion at re-entry[17, 19, 23, 42, 45, 46, 48]. Only two studies reported thatthere was no need for further reconstruction in the ARPgroup, whilst GBR or ridge expansion were carried out insome of the control sites alongside implant insertion [21,47]. One study reported that statistically significantly lessaugmentation had to be performed in the ARP group,compared to the control [20]. In relation to illuminatingthe understanding of possible long term benefits of ARP,the success rate of the inserted dental implants in theformer test, versus control sites should be examined. Nostudies have yet reported this.

Patient-reported outcome and health economics

It would be helpful to understand patient experiences suchas concomitant discomfort at/following ARP in order toavoid a further, extensive reconstructive surgery. On theother hand, the additional costs of ARP at the time ofextraction may not be desirable if the outcome and benefitof such extra treatment were not predictable. There are nodata yet to inform on these questions.

Conclusions

Within the limits of the above findings the following con-clusions can be drawn:

1. The results of the control groups confirm that toothextraction results in a statistically significant horizontaland vertical resorption of the AR, as part of the naturalremodelling.

2. The magnitude of the horizontal shrinkage is morepronounced than the vertical.

3. The resorption of the AR cannot be totally preventedby ARP.

4. Dimensional changes of the AR may be limited bysome of the ARP techniques.

5. No evidence was identified to inform on the possibleimpact of the following factors on ARP outcomes: (a)site location, (b) buccal plate thickness, (c) healingtime, (d) antibiotic regime, (e) light smoking, (f) his-tory of treated periodontitis.

6. The presence of intact socket walls and primary flapclosure are often associated with favourable results.

7. Conflicting evidence exists on the benefit of ARPat the histological level. ARP does not appear topromote de novo hard tissue formation routinely.In addition, some graft materials may interfere withhealing.

8. Due to the broad variety of employed materials, tech-niques, defect morphologies, healing periods, as wellas the relatively small sample sizes, meta-analysis orcomparative assessment of ARP cannot be made. Con-sequently no material or method can be claimed toserve superior to another. However, in certain casesGBR appeared to be most effective.

9. Only limited evidence supports the clinical benefit ofARP, namely the reduction of necessity of furtheraugmentation in conjunction with implant placement.

10. No evidence exists on comparison of the survival orsuccess rate of implants, placed in the former ARP orcontrol sites.

11. No evidence exists on cost-effectiveness, patient’spreference or quality of life following ARP.

12. The case selection criteria for performing ARP remainstill undetermined.

13. The strength of evidence ranges from weak to moder-ate and therefore, the conclusions of this review shouldbe interpreted with caution.

Recommendations for further research

& Randomised controlled trials on adequately poweredsample sizes are needed where unassisted socket healingserves as the negative control.

360 Clin Oral Invest (2013) 17:341–363

& Appropriate follow-up periods are required. Ideally, thisshould reflect implant insertion protocols, such as sixweeks (Type 2), three to four months (Type 3) or>6 months (Type 4) placement following extraction.

& Clinical studies should be designed to perform not onlyclinical (quantitative), but also histological (qualitative)assessment.

& The role of additional factors like smoking, reason forextraction, tooth location, initial buccal plate thickness,flap reflection and closure, antimicrobial regime shouldalso be investigated.

& Comparative studies should also be designed in order toidentify the most successful treatment options.

& It may be beneficial to seek for a cell occlusive barriermembrane that does not require extensive soft tissuemobilization for flap approximation.

& Necessity of re-augmentation at implant placementshould be investigated.

& Survival and success rates of implants, placed in formerARP sites should be evaluated.

& Outcome evaluation should ideally incorporate patient’spreference, quality of life, as well as treatment economy.

Acknowledgments The authors wish to express their gratitude toAviva Petrie for her invaluable contribution to the statistical assessment.

Conflict of interest and source of funding There was no known conflictof interest among the review team. The trial was self funded and supportedby the Research Discretionary Account of the Unit of Periodontology, UCLEastman Dental Institute. This work was undertaken at UCLH/UCL whoreceived a proportion of funding from the Department of Health’s NIHRBiomedical Research Centres funding scheme.

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Clin Oral Invest (2013) 17:341–363 363

Ren E. WangNiklaus P. Lang

Ridge preservation after tooth extrac-tion

Authors’ affiliations:Ren E. Wang, Niklaus P. Lang, The University ofHong Kong, Prince Philip Dental Hospital,

Corresponding author:Prof. Niklaus P. Lang, DDS, MS, PhD, Dr, odont.hc.mult.The University of Hong Kong Faculty of DentistryPrince Philip Dental Hospital,34 Hospital Road, Sai Ying Pun, Hong Kong SARPR ChinaTel.: +852 2859 0526Fax: +852 2559 9013Mobile: + 41 79 301 5505e-mail: [email protected]

Conflicts of interest:The authors declare no potential conflicts.

Key words: bone substitutes, GBR, implant dentistry, membrane, ridge preservation, tooth

extraction

Abstract

Background: Following tooth extraction, the alveolar ridge will undergo dimensional changes.

This change may complicate the subsequent restorative procedure when oral implants are chosen.

“Alveolar ridge preservation” has been assessed in various studies.

Aim: To evaluate the more recent studies on this topic and to explore new insights under this

topic.

Material and methods: Animal studies and clinical studies have addressed different techniques.

Results and conclusions: Implants placed into the fresh extraction sockets do not prevent the

resorption of the alveolar bone. Simultaneous guided bone regeneration could partially resolve

alveolar bone resorption. The use of root-formed implants does not preserve alveolar ridges.

Moreover, various bone substitutes have been tested: magnesium-enriched hydroxyapatite, human

demineralized bone matrix, and deproteinized bovine bone mineral have been shown to be

effective in ridge preservation. Applying the guided bone regeneration principle using bone

substitutes together with a collagen membrane has shown clear effects on preserving alveolar

ridge height as well as ridge width. Soft tissue grafts or primary closure did not show beneficial

effect on preserving the alveolar bone.

Following tooth extraction, the alveolar ridge

will undergo structural changes. These

changes in extraction sockets were amply

demonstrated with histological observations

in dog studies (Cardaropoli et al. 2003). At

day 1 after extraction, the socket was occupied

by a coagulum; this coagulum was comprised

mainly of erythrocytes and platelets that were

trapped in a fibrous matrix. Immediately adja-

cent to the hard tissue wall was the “bundle

bone”, and principal fibers from periodontal

ligament (Sharpey’s fibers) could be found

invested in the bundle bone. These were also

in direct contact with the coagulum. At day

3, the coagulum had been replaced by a richly

vascularized granulation tissue. At day 7,

newly formed blood vessels were evident in

the primary matrix. Various types of leuko-

cytes and collagen fibers had taken the place

of the residual periodontal ligament as well as

the granulation tissue. At day 14, most of the

bundle bone had disappeared, and instead,

adjacent to the newly formed blood vessels,

“woven bone” started extending from the old

bone of the socket walls toward the center of

the socket. At day 30, woven bone underwent

resorption, suggesting that the remodeling

process had begun. At day 60, hard tissue

bridges separated the marginal mucosa from

the socket, and bone marrow replaced woven

bone at the center of the previous socket. At

day 90, woven bone was replaced by lamellar

bone. At days 120 and 180, most of the woven

bone had been replaced by lamellar bone.

The role of bundle bone in the dimensional

change in the alveolar ridge was investigated in

several dog studies (Araujo & Lindhe 2005;

Araujo et al. 2005) At 1 week after extraction

(Araujo & Lindhe 2005), the buccal bony crest

was 0.3 mm coronal to the lingual bony crest,

but at 2 weeks after extraction, the buccal crest

became 0.3 mm apical to the lingual crest.

This relative distance was increased to 0.9 and

1.9 mm at 4 and 8 weeks after extraction,

respectively. It was also observed that the cres-

tal region of the buccal bone wall was made up

exclusively of bundle bone, whereas the corre-

sponding region of the lingual bone was made

of a combination of bundle bone and lamellar

bone. Obviously, the function of bundle bone

is to anchor the tooth in the alveolar bone

through the invested periodontal ligament. As

the tooth is extracted, the bundle bonewill lose

its function, and subsequently, will resorb.

This may explain the more pronounced resorp-

tion of the buccal than the lingual bony crest.

Date:Accepted 03 July 2012

To cite this article:Wang RE, Lang NP. New insights into ridge preservation aftertooth extractionClin. Oral Implants Res. 23(Suppl. 6), 2012, 147–156doi: 10.1111/j.1600-0501.2012.02560.x

© 2012 John Wiley & Sons A/S 147

A recent systematic review evaluated the

dimensional changes in the hard and soft tis-

sues of the alveolar process up to 12 months

following tooth extraction (Tan et al. 2012).

It was concluded that after 3 months of

healing, the horizontal resorption of the

alveolar bone was 2.2 mm at the crest, and

1.3, 0.59, and 0.3 mm at 3, 6, and 9 mm api-

cal to the crest, respectively; after 6 months

of healing, the vertical resorption of the

alveolar bone was 11–22%, whereas the hori-

zontal resorption of the alveolar bone was 29

–63%. When soft tissue was included

together with the hard tissue in the dimen-

sional assessments at 3 months of healing,

there was even an increase of 0.4 mm in the

vertical dimension. At 12 months of healing,

the vertical resorption of the alveolar ridge

was 0.8 mm. Horizontally, the resorption of

the soft and hard tissue together was 1.3mm

and 5.1mm after 3 and 12 months of heal-

ing, respectively.

This vertical as well as horizontal dimen-

sional changes of the alveolar ridge may com-

plicate the subsequent restorative procedures

when dental implants are chosen. Over the

past 20 years, increasing interest has arisen

regarding a concept called “alveolar ridge

preservation”, which was defined as “any

procedure undertaken at the time of or fol-

lowing an extraction that is designed to mini-

mize external resorption of the ridge and

maximize bone formation within the socket”

(Darby et al. 2008). As suggested by that

review, studies promoting various techniques

have been performed. Most of the studies

included the measurements of dimensional

changes of the alveolar ridge after a ridge

preservation procedure.

The purpose of this review was to evaluate

these more recent studies and to explore new

insights under this topic. Within the context

of exploring new insights for ridge preserva-

tion, also studies of lower levels in the

evidence hierarchy may be of interest to shed

some light on the techniques designed to pre-

serve the alveolar ridge after tooth extraction.

These low evidence papers are generally case

series that combine various protocols. How-

ever, this approach, should lead to clinical

validation before recommendable for routine

clinical application.

Animal studies

Implants for ridge preservation

Immediate implants alone

A decade ago, it was proposed that “early

implantation may preserve the alveolar anat-

omy and that the placement of a fixture in a

fresh extraction socket may help to maintain

the bony crest structure” (Paolantonio et al.

2001). However, this statement has been

scrutinized later in a dog study (Araujo et al.

2005). In the right jaw of five dogs, implants

were placed into the fresh extraction sockets,

while in the left jaw, fresh sockets were left

for spontaneous healing. After 3 months of

healing, histological sections were obtained

to assess the distance from the SLA level to

the first bone-to-implant contact under

microscope. On the buccal aspect, this dis-

tance was 2.6 mm at implant sites and

2.2 mm at the corresponding extraction

socket sites. Hence, the immediate place-

ment of dental implants clearly failed to pre-

vent the resorption of the buccal bone walls.

To further study the modeling of the buc-

cal bony plate, the same group of researchers

designed another dog study (Araujo et al.

2006). In that study, the implants were

placed into the fresh extraction sockets in

the right jaw and 2 months later, the same

procedure was performed again in the left

jaw. Following another 1 month, the dogs

were sacrificed, and it was observed that after

1 month of healing, at the buccal aspect,

good osseointegration had been achieved

above the first thread of the implant. How-

ever, after 3 months of healing, the level of

this osseointegration had receded to below

the first thread as a result of the modeling of

the buccal bone. In the molar regions, the

degree of this modeling was much less

compared with the premolar regions, most

likely because of the wider original combined

defect and bone wall dimensions in the molar

regions. This study provided strong evidence

for the continued modeling process of the

buccal bony wall leading to buccal bone loss

despite the good osseointegration that had

already been achieved in early healing

phases. Obviously, this phenomenon was less

pronounced in sites with thicker buccal bony

walls. Again, immediate implant installation

failed to preserve the alveolar bone.

In a study aimed at observing bone-

to-implant contact of orthodontic implants

subjected to horizontal loading (Wehrbein

et al. 1998), immediately placed implants

with simultaneous horizontal loading

achieved better osseointegration than those

with delayed loading. Moreover, it was sug-

gested in another dog study that “a static

load may stimulate bone mineralization adja-

cent to titanium implants” (Gotfredsen et al.

2001). Finally, the hypothesis was tested

whether or not immediate implant place-

ment together with simultaneous loading

would help to preserve the buccal bone

(Blanco et al. 2011). In a dog model, two

implants were placed into the fresh extrac-

tion sockets at the premolar sites on each

side of the mandible. At the time of the

implantation, the implants on one side of the

jaw received a prosthesis with occlusal con-

tacts, while the implants on the other side

remained unloaded during the whole experi-

mental period. Three months later, the dogs

were sacrificed. The histomorphometric

results showed that the vertical distance

from the implant shoulder to the first bone-

to-implant contact was on average 3.66 mm

in the simultaneously loaded group and

4.11 mm in the unloaded group. This

difference was not statistically significant,

and hence it was concluded that “immediate

implant placement with or without loading

does not prevent bone resorption that occurs

following tooth extraction.”

Immediate implant with bone grafts

The effect of bone fillers (magnesium-

enriched hydroxyapatite) on preservation of

the alveolar bone around immediate implants

was evaluated in a dog study (Caneva et al.

2011). Implants with a sandblasted acid

etched surface (Zirti®, Sweden & Martina,

Due Carrare, PD, Italy) were placed into the

fresh extraction sockets bilaterally in the

dogs’ jaws. The margin of the rough surface

was placed at the level of the buccal bony

crest. On one side of the jaw, the bone filler

was applied into the gaps around the

implants. The contralateral sites were left

unfilled as controls. After 4 months of sub-

merged healing, the dogs were sacrificed. His-

tomorphometric evaluations showed that the

vertical distance from the junction between

rough and smooth surface to the buccal bony

crest was on average 0.7 mm in the group

with the bone filler and 1.2 mm in the

control group with no statistically significant

differences between the groups. Obviously,

the use of bone fillers around implants

immediately placed into extraction sockets

did not contribute significantly to the preser-

vation of the buccal bone. In a recent experi-

ment (Araujo et al. 2011), it has been

demonstrated that the use of Bio-Oss� col-

lagen as a bone substitute filler in the space

between the implant and the buccal bony

wall resulted in the prevention of buccal soft

tissue recession and a reduction in peri-

implant bone loss and allowed the buccal

bone to be thicker at the marginal level.

However, another similar animal study

(Favero et al. 2012) was not able to confirm

these differences in outcomes.

148 | Clin. Oral Implants Res. 23, 2012 / 147–156 © 2012 John Wiley & Sons A/S

Wang & Lang �Ridge preservation revisited

Immediate implant with GBR

In an AAP-commissioned review on bone

augmentation techniques, it was recom-

mended that immediate implant placement

together with GBR techniques may yield out-

comes comparable to delayed placed implants

(McAllister & Haghighat 2007). Recently,

a dog study was conducted to evaluate the

influence of absorbable membranes on hard

tissue alterations around the immediately

placed implants (Caneva et al. 2010a,b,c).

Implants with a rough surface (zirconium

sandblasted acid etched) were placed immedi-

ately following extraction on both sides of

the mandibles, on the test side of the jaw,

collagen resorbable membranes were placed

to cover the implants. On the control side of

the jaw, the implants were left without

membranes.

After 4 months of intended submerged

healing, all implants were found exposed to

the oral cavity because of soft tissue dehi-

scences. The dogs were sacrificed and biop-

sies were obtained. The distance between the

most coronal margin of the implant and the

bone crest were measured. At the buccal

aspect, this distance was 1.7 mm on the

implants placed with GBR procedures, and

2.2 mm on the implants placed without

GBR, and this difference was statistically sig-

nificant. At the lingual aspect, this distance

was 0.6 and 0.4 mm on the test sites and

control sites, the difference not reaching sta-

tistical significance. There was no difference

between the groups regarding the level of

first bone-to-implant contact and the percent-

age of bone-to-implant contact. This study

provided evidence that the use of collagen

resorbable membranes at immediate implant

sites contributed partially (23%) to the pres-

ervation of the buccal bony wall.

Further studies of the same group of

researchers (Caneva et al. 2011, 2012)

explored the effect of GBR based on deprotei-

nized bovine bone mineral on alveolar ridge

preservation and the reparation of defects

around osseointegrated implants. After

hemi-sectioning the third mandibular premo-

lars and extracting the distal roots, a recipi-

ent site was prepared for an implant. This

was placed lingually, leaving a defect of

about 0.6mm in width and 3mm in depth at

the buccal aspect. While the other side of

the jaw was used as control without GBR,

deproteinized bovine bone mineral (DBBM)

was place into the defects of the test site and

covered with a collagen membrane. This

treatment contributed to improved bone

regeneration in the defects. However, regard-

ing the buccal bony crest preservation only a

limited contribution of DBBM particles was

obtained (Caneva et al. 2011).

In the second study on the same material

the dimensional changes of the alveolar bony

crest following the placement of DBBM parti-

cles into sockets immediately after tooth

extraction, in conjunction of the placement

of a collagen membrane, were addressed

(Caneva et al. 2012). After 4 months of heal-

ing, no differences in soft tissue dimensions

were found based on histological evaluations.

Yet, the location of the soft tissue at the buc-

cal aspect was more coronally at the test

compared to the control sites. Hence, it was

concluded that the application of DBBM con-

comitantly with the placement of a collagen

membrane at implant sites placed in the

socket immediately after tooth extraction

contributed positively to the preservation of

the alveolar process.

In a similar study recently published (Park

et al. 2011), immediate implants (Institute

Straumann AG, Basel, Switzerland) were

placed bilaterally in the dogs’ jaws in the pre-

molar region. On the experimental side, a

non-resorbable ePTFE membrane (Tefgen®,

Lifecore Biomedical, Chaska, MN, USA) was

placed on the buccal plate of the implant

sites without coverage of the bone crest and

was fixed with mini screws. In the control

site, no membrane was placed. After

3 months of non-submerged healing, no

membrane exposure occurred. The dogs were

sacrificed and after histometric observation,

the vertical distance from the rough and

smooth surface interface to the buccal bone

crest was on average 1.72 mm in the control

group and 0.92 mm in the experimental

group. This difference was statistically signif-

icant. Moreover, at the level 2 mm below the

buccal bony crest, the mean thickness of the

buccal bone walls was 0.4 mm in the control

group and 1.49 mm in the test group. Again,

this difference was statistically significant.

From the above two animal studies, it

appeared that the outcomes of using non-

resorbable ePTFE membranes is superior to

that achieved by resorbable collagen mem-

branes. It should be realized that the tech-

niques applied in the two studies were

different. In the first study, the resorbable

collagen membranes were placed on top of

the implants without fixation, and primary

closure was achieved at the completion of

the surgery. However, during the healing per-

iod, all implants were exposed because of soft

tissue dehiscences. In the later study, the

non-resorbable membrane was placed on the

buccal bone wall and fixed with mini screws

to avoid membrane exposure. The mem-

branes were placed below the buccal bony

crests, and no primary closure was intended,

which meant that the flaps healed without

tension. Consequently, membrane exposure

was absent during healing.

Shape of implants and implant positioning

Tapered or root-formed implants were

designed to reduce the gaps around implants

that were placed immediately into the fresh

extraction sockets, thus filling the defect par-

tially with titanium. The question arises if

this type of implant design will help in pre-

venting alveolar bone resorption around such

implants. In a split-mouth design, mandibles

of dogs received cylindrical implants 3.3 mm

in diameter (Premium®, Sweden & Martina,

Due Carrare, PD, Italy) immediately after

tooth extraction (control) (Caneva et al.

2010c). A similar procedure was carried out

with root-formed implants 5 mm in diameter

(Kohno®, Sweden & Martina, Due Carrare,

PD, Italy) on the test sites. After 4 months of

non-submerged healing, the dogs were sacri-

ficed and histomorphometric evaluations

were performed. The mean vertical buccal

bone resorption was significantly greater in

the test group (2.7 mm) than in the control

group (1.5 mm). In essence, the filling of gaps

with root-formed implants failed to preserve

the buccal bone. On the contrary, the bone

resorption was more pronounced around the

root-formed immediate implants that filled

the extraction socket to a greater extent than

did the cylindrical implants. The root-formed

implants with a wider diameter occupied the

entire socket, leaving no space between the

implant and the buccal bony wall. In other

words, the implant body was located closer

to the outer surface of the buccal bony wall.

Consequently, a greater portion of the

implant was exposed in the supracrestal

region after modeling and remodeling pro-

cess, as the distance between the implant

outline and the outer surface of the buccal

bone appears to be a crucial factor for the

preservation of the buccal bone.

To evaluate the influence of implant posi-

tioning into extraction sockets on the main-

tenance of the buccal bone level (Caneva

et al. 2010a), implants (Premium®, Sweden &

Martina, Due Carrare, PD, Italy) were placed

in the center of the sockets in control sites

of mandibles, whereas in the test sites, the

same implants were placed 0.8 mm deeper

and more lingually. After 4 months of non-

submerged healing, the histometric evalua-

tions showed that the mean vertical distance

from the rough and smooth surface interface

to the buccal bone crest was significantly less

© 2012 John Wiley & Sons A/S 149 | Clin. Oral Implants Res. 23, 2012 / 147–156


in the test group (0.6 mm) compared with

the control group (2 mm). Hence, the posi-

tion of the implant had a greater impact on

the preservation of the buccal bone resorp-

tion than the shape of the implant.

Bone substitutes

Bone substitutes alone

The effectiveness of ridge preservation with

bone grafting in the extraction sockets alone

was evaluated in a dog study (Boix et al.

2006). The maxillary and mandibular premo-

lars were extracted. The sockets of the distal

roots were filled with an injectable bone sub-

stitute (a polymer solution and granules of a

biphasic calcium phosphate ceramic), and the

sockets of the mesial roots were left unfilled

as controls. Primary closure was achieved by

overlapping hermetic sutures. After 3 months

of healing, a tangent vector was drawn con-

necting the buccal and lingual crests, and the

distance from the highest point of the alveo-

lar ridge and this tangent vector was mea-

sured. There was a significant difference

between the groups in the mandible (0.5mm

and �0.4mm in test and control, respectively)

and the maxilla (�0.3 and �0.5 in the test

and control, respectively).

In another dog study (Shi et al. 2007), man-

dibular premolars and molars were extracted,

the extraction sockets on the test side were

treated with Surgical-Grade Calcium Sulfate

(SGCS) + platelet-rich plasma (PRP) or with

SGCS alone. On the control side, the sockets

were left unfilled. Primary closure was

achieved by periosteal releasing incisions and

coronally advanced flaps. At baseline and

2 months after healing, CT scans were taken.

Alveolar bone height was assessed on CT

scans as the distance from the midpoint of

the cortical bone to the inferior border of the

mandible. It was found that the reduction in

the ridge height was significantly greater in

the control group compared with the test

group (2.77, 1.39 mm, respectively), although

no difference was found between SGCS +

PRP treatment and SGCS treatment alone.

In five beagle dogs (Fickl et al. 2008a,b),

the 3rd and 4th mandibular premolars were

extracted. In the test sites, the sockets were

filled with Bio-Oss® collagen (Geistlich

Biomaterials, W olhusen, LU, Switzerland).

The collagen was fixed with sutures. The

control sites were left untreated. After

4 months of healing, the histomorphometric

evaluation documented a mean vertical buc-

cal bone loss that was significantly lower in

the test (2.8 mm) than in the control sites

(3.2 mm). At 1 mm below the crest, the

untreated group had a significantly narrower

ridge width than the test group (3.7 mm vs.

4.4 mm). However, at 3 mm/5 mm below

the crest, the ridge width was similar

between the groups. Using digital image anal-

ysis on study casts for the same material

(Fickl et al. 2008a,b) at the buccal aspect, the

volumetric differences from baseline to after

4 months of healing was significantly greater

in the control group (-2.2mm) than the test

group (-1.5mm). These results showed small

benefits toward using Bio-oss® collagen.

A similarly designed study (Araujo & Lind-

he 2009) compared sockets healing without

treatment (control) and sockets treated with

Bio-oss® collagen (test). Flaps were coronally

replaced and primary closure was achieved in

both types of sockets. After 6 months of

healing, biopsies were obtained. Histometric

analysis revealed that the dimensional

changes in the apical and middle portion of

the sockets were moderate in both sites, but

in the coronal portion, the ridge width reduc-

tion was three times greater in the control

sockets (�35%) compared with the test sock-

ets (�12%). However, the composition

between two sites was similar. The xenograft

(Bio-Oss®, Geistlich Biomaterials, W olhusen

LU, Switzerland)) only served as a scaffold and

did not stimulate new bone formation.

Another histometric study (Rothamel et al.

2008) compared sockets treated by Nanocrys-

talline hydroxyapatite paste (test) with un-

filed sockets (control). Primary closure was

achieved in both groups. After 3 and

6 months of healing, the dogs were sacrificed.

Histometric analysis on lingual and buccal

bone height, alveolar wall, and total bone

width showed no difference for any parame-

ters between groups. It could be concluded

that Nanocrystalline hydroxyapatite paste

does not appear to be effective for ridge pres-

ervation.

Xenografts versus autografts

For many years, the use of autologous bone

was regarded as a “gold standard” for augmen-

tation procedures. To evaluate its efficacy in

ridge preservation, a dog study was conducted

(Araujo & Lindhe 2011). Extraction sockets in

the mandibles of dogs were filled with either

anorganic bovine bone or autogenous bone

chips. After 3 months of healing, a histomet-

ric analysis was performed. The cross-sec-

tional area of the ridge alteration was

estimated by subtracting the cross-sectional

ridge area identified after extraction from the

corresponding area at the adjacent root. In the

apical and middle portions of the sockets, no

resorption was observed. However, in the

coronal portions, the ridge underwent resorp-

tion (�25%) in the autogenous bone graft

group. In the xenograft group, there was a posi-

tive change (3.6%). The residual grafting mate-

rial was found to be 24.4%. Non-vital

autogenous bone chips were found to be 1.9%.

It seemed that autologous bone did not pre-

serve the alveolar ridge.

Primary flap closure

Soft tissue grafts versus no soft tissue grafts

In five beagle dogs, the 3rd and 4th mandibu-

lar premolars were extracted (Fickl et al.

2008a). In the test group, the sockets were

filled with Bio-oss® collagen, and free gingi-

val grafts were obtained to cover the sockets.

The control sites were also filled with

Bio-oss® collagen (Geistlich Biomaterials, W

olhusen, LU, Switzerland). The collagen was

fixed with sutures, but no soft tissue grafts

were applied. After 4 months of healing, the

histomorphometric evaluation showed a

mean vertical buccal bone loss that was sig-

nificantly lower in the control group

(2.8 mm) than in the test group (3.3 mm). At

1mm below the crest, the control group had

significantly narrower ridge width than the

test group (4.4 mm vs. 4.8 mm). But at

3 mm/5 mm below the crest, the ridge width

was similar between the test and control

groups. In another study digital image analy-

sis on study casts from the same material

(Fickl et al. 2008b), the remodeling process at

the buccal aspect from baseline to after

4 months of healing was similar between the

control and test groups (�1.5 mm vs. �1.6

mm). These results, therefore, indicate the

need for further human research using free

gingival grafts to obtain primary closure for

alveolar ridge preservation in well preserved

alveoli.

Clinical trials

Implants for ridge preservation

Immediate implants alone

To observe the alteration of hard tissues fol-

lowing tooth extraction and immediate

implant placement, a clinical study was con-

ducted (Botticelli et al. 2004). In 18 patients,

21 SLA surface implants were placed. After

4 months of non-submerged healing without

loading, a re-entry surgery was performed.

The differences between the clinical mea-

surements made before implant placement

and after 4 months of healing yielded a hori-

zontal resorption of the buccal bone of about

56%. The corresponding resorption of the lin-



gual/palatal bone was 30%, whereas the ver-

tical bone resorption was on average 0.3 mm

at the buccal aspect and 0.6 mm at the lin-

gual/palatal aspect. This amount of resorp-

tion is very similar with the resorption at

human alveolar ridges after extraction

reported recently in a systematic review (Tan

et al. 2012). This, in turn, means that

implants immediately placed into extraction

sockets, also in humans, do not prevent the

resorption of the alveolar bony ridge.

Immediate implant with bone GBR

The effect of membrane placement in con-

junction with or without bone substitutes for

preserving the alveolar bony around implants

immediately placed into extraction sockets of

the anterior region (Chen et al. 2007) was

studied in 30 patients that randomly received

immediate implants (SLA surface, Institute

Straumann AG, Basel, Switzerland) with Bio-

oss® + collagen membrane (Geistlich Bioma-

terials, W olhusen, LU, Switzerland), Bio-oss®

alone, or were left un-grafted. The dimen-

sions of the alveolar bony crest were assessed

at baseline and at the re-entry surgery after

6 months of healing. The implants were

loaded after further 2 months, and the

patients were followed up to 3 years after

completion of restoration delivery. Standard-

ized peri-apical radiographs and peri-implant

examinations were performed every year. At

the re-entry surgery, there was no significant

difference between the groups on the vertical

and horizontal defect reduction around the

implants. On the other hand, the reduction

in the horizontal distance from the outer sur-

face of the buccal bony ridge to the implant

surface was significantly greater in the con-

trol group (48.3 ± 9.5%) than in the bone

graft alone group (15.8 ± 16.9%) and the bone

graft with membrane group (20 ± 21.9%).

During the 3-year post-restorative follow-up,

all patients kept excellent oral hygiene. No

difference was found regarding the peri-

implant or radiographic parameters between

baseline and 1-year/3-year follow-ups or

among the groups. This clinical study dem-

onstrated that the bone defect around the

immediately placed implants will heal pre-

dictably irrespective of the usage of mem-

branes or bone grafts. However, the

membrane or bone graft treatment may

reduce the horizontal resorption of the buccal

bony plate by 25% of the original dimension.

Another clinical study was performed in

the molar region, to examine the alteration

of the alveolar bony ridge around implants

immediately placed into molar extraction

sockets after 6 months of healing (Matarasso

et al. 2009); 12 immediate transmucosal

implants with an sandblasted acid etched

surface were placed in 12 patients. GBR was

performed by placing a resorbable collagen

membrane supported by a bone substitute

(Bio-oss®). The alveolar bone dimensions

around the implants were assessed at the

time of implant surgery and at the re-entry

surgery after 6 months of healing. The gaps

around the implants healed as expected.

However, the horizontal distance from the

outer surface of the alveolar ridge to the

implant surface at the buccal aspect was

reduced by 58% on average. Unfortunately,

no control group was provided in this study.

An interesting aspect of this study was the

influence of bone thickness on the buccal

bone resorption. If the buccal bony wall was

initially 1-mm thick, the buccal bone resorp-

tion was as high as 52%. However, when the

buccal bone wall was initially 2-mm thick,

the buccal bone resorption was significantly

reduced to 33%.

Shape of implants and implant positioning

As one of the proposed benefits of using root-

formed implants was to avoid the need for

bone augmentation, a multi-center random-

ized controlled clinical trial was conducted to

test this hypothesis (Lang et al. 2007). In nine

centers, 216 patients received either cylindri-

cal or tapered implants (Institute Straumann

AG, Basel, Switzerland) installed into the

extraction sockets in non-molar regions. Dur-

ing the surgery, the type of implants was allo-

cated at random and the need for guided bone

regeneration was assessed. Whenever the gap

around the implants was more than 0.5 mm

or whenever buccal bony plate was thin (less

than 1 mm), augmentation procedures were

performed. Questionnaires were given to both

patients and the operators to assess the prefer-

ence to these two types of implants. The

results revealed that 90% of both implant

designs required GBR procedures. Patient-

reported outcomes did not show any prefer-

ence toward any type of the implants. How-

ever, the surgeons’ perception was in favor of

the tapered implants. Therefore, it is evident

that root-formed implants do not offer an

advantage in the need for avoiding GBR

procedures.

Another multi-center study aimed to a com-

parison of the dimensional bony changes

around the two types of implants (Sanz et al.

2010). The hypothesis of the study was that,

by providing more space for the coagulum

around the implants, the cylindrical implants

(test) should have a positive effect in preserv-

ing the alveolar bone and to reduce the hori-

zontal bone resorption by 20% when

compared with the tapered implants (control).

In three centers, 93 patients were included in

the study. Forty-five cylindrical implants

(Astra Tech AB, Molndal, Sweden) were

installed into extraction sockets in the test

group, and 48 tapered implants (Astra Tech

AB, Molndal, Sweden) were placed in the con-

trol group. At baseline and at the re-entry sur-

gery after 4 months healing, the results

indicated that there was a marked reduction

in the distance from the outer surface of the

ridge to the implant in both groups (43% and

30%, respectively), although this difference

was not statistically significant. Once again, it

was evidenced that tapered implants cannot

preserve the alveolar bony ridge. On the con-

trary, tapered implants were associated with

more bone resorption.

Non-surgical treatment

Ultrasonic non-surgical treatment

The effect of ultrasonic application on bone

healing has been studied in the orthopedic lit-

erature. In vitro experiments showed a signifi-

cant influence of ultrasound on the

proliferation of mandibular osteoblasts. Clini-

cal evidence has also demonstrated that ultra-

sound treatment may accelerate the healing

process of tibial diaphysis fractures by 38% in

time (Kerr et al. 2008). In a randomized con-

trolled split-mouth clinical trial, 12 patients

who were scheduled for tooth extraction on

both sides of the jaw were enrolled. At 7–

10 days following extraction, ultrasound ther-

apy was delivered on the alveolar ridge of the

test site for 20 min using a piezoelectric

transducer for 10 sessions over the subsequent

4 weeks. Standardized cone-beam volumetric

tomography (CBVT) scans were acquired at

baseline (7–10 days post extraction), comple-

tion of ultrasound therapy (4 weeks after ther-

apy), and 3 months post extraction.

Dimensional changes of the buccal and lin-

gual bony plates were analyzed through

CBVT. However, given the limitations of

small sample size and a short observational

period with CBVT scans in this study, no sig-

nificant differences could be found in absolute

bony dimensional changes.

Bone substitutes

Bone fillers alone

In a randomized controlled clinical trial (Nei-

va et al. 2008), the effectiveness of an

anorganic bovine-derived hydroxyapatite

matrix delivered in a putty-form combined

with a synthetic cell-binding peptide P-15



(Putty P15) on ridge preservation was investi-

gated. Comparisons were made between

untreated control sockets and sockets treated

with this putty-form matrix (test). Collagen

dressing material was applied in both groups.

After 4 months of healing, at the re-entry

surgery, no difference was found between the

groups in ridge width reduction (�1.31 and

�1.43mm in test and control, respectively).

However, significantly less ridge height

reduction was found in the test group

(0.15 mm) compared with the control group

(�0.56 mm). The bone density assessed dur-

ing implant surgery was found significantly

higher in the test group as well.

Another biomaterial, medical-grade calcium

sulfate hemihydrates (MGCSH) was evaluated

in a randomized controlled clinical trial (Ai-

metti et al. 2009). In the test group, 22

patients received this material in their sock-

ets. As control group, 18 patients did not

receive any treatment after extraction at all.

Clinical measurements were performed at

baseline and at the re-entry surgery (implant

surgery). After 3 months of healing, signifi-

cantly greater reduction in ridge height was

found in the control group (1.2 mm) compared

with test group (0.5 mm). Moreover, signifi-

cantly greater ridge width reduction was found

in the control group (3.2 mm) compared with

the test group (2.0 mm). A histological analy-

sis also found less lamellar bone and more

woven bone in the control group.

Two new materials were evaluated in a

split-mouth clinical trial (Crespi et al. 2009).

In 15 patients, three teeth were extracted in

each patient. One of the sockets was treated

with magnesium-enriched hydroxyapatite

(Test 1). Another socket was treated with

Calcium sulfate (Test 2). The third socket

was left unfilled (control). The filling materi-

als in the two test groups were secured with

a collagen sheet covering and sutures to affix

the membrane. Applying standardized intra-

oral radiographs obtained at baseline and

3 months later at the re-entry surgery, signif-

icant differences in ridge height reduction

was found among all groups (�0.48, �2.48,

and �3.75 mm in the Test 1, Test 2, and

control group, respectively). In histological

analyses, the amount of vital bone was found

to be significantly different among all groups

(40.0, 45.0, and 32.8% in the Test 1, Test 2,

and control group, respectively). The amount

of connective tissue was not different

between the test groups, but it was signifi-

cantly different between the test and control

groups. Significantly, less residual grafting

material was found in sockets treated with

Calcium sulfate. Based on this study, magne-

sium-enriched hydroxyapatite was found to

be more useful in alveolar ridge preservation

than calcium sulfate.

In a recent clinical split-mouth design

study (Fernandes et al. 2011), sockets treated

with anorganic bovine bone matrix (ABM)

+ synthetic cell-binding peptide P-15 (Test)

were compared with unfiled sockets (control).

The sockets in both groups were covered

with Acellular dermal matrix (ADM). Clini-

cal measurements were made at baseline and

after 6 months of healing. No statistically

significant differences could be found on

ridge height reduction between the groups

(1.5 and 1.2 mm in the control and test

groups, respectively). But the ridge width

resorption was significantly greater in the

control (3.40 mm) compared with the test

group (2.52 mm).

The effectiveness of an allograft material

in ridge preservation was recently tested in a

randomized controlled clinical trial (Brown-

field & Weltman 2012). Twenty patients

were divided into two groups. The extraction

sockets in the test group were treated with

an allograft paste composed of “osteoinduc-

tive” demineralized bone matrix and cancel-

lous bone chips, and the sockets in the

control group were left unfilled. The sockets

in both groups were covered with an absorb-

able collagen wound dressing. No significant

difference on ridge resorption was found

between the two groups as studied by CBCT/

Micro CT and histological analysis, although

CBCT analysis found a significant correlation

between initial buccal bony plate thickness

and loss of ridge height.

Different particle size

In general, smaller particles of bone substi-

tutes are preferred because they may be

resorbed more rapidly. They may enhance

osteogenesis because of a greater surface area.

On the other hand, the optimal particle size

may depend on the bony defect to be grafted.

Extraction sockets may benefit more using

larger particles, as the sockets are usually lar-

ger than the periodontal defects.

To elaborate on the most appropriate parti-

cle size to be used in extraction sockets, a

randomized controlled clinical trial was

conducted (Hoang & Mealey 2012) in 20

patients. One molar was extracted in each

patient. The sockets were either filled with

human demineralized bone matrix (DBM)

putty with a single particle size (2–4 mm) or

with multiple particle sizes (125–710 lm).

Clinical assessments of the ridge dimensions

were made at baseline and at re-entry surgery

after 4–5 months of healing. No difference

was found on ridge width reduction between

the single particle size group (1.4 mm) and

multiple particle size group (1.3 mm). The

vertical buccal and lingual bone loss was less

than 0.5 mm in both groups. Histological

analysis did not find any difference between

the groups. Obviously, ridge preservation

using this grafting material irrespective of its

particle sizes was effective.

Demineralized allografts versus mineralized allografts

Although both demineralized freeze-dried

bone allograft (DFDBA) and mineralized

freeze-dried bone allograft (FDBA) are claimed

to be osteoconductive; only DFDBA has been

proven to be osteoinductive. Both DFDBA

and FDBA contain bone morphogenic pro-

teins (BMP). As the process of demineraliza-

tion facilitates the release of soluble factors

like BMP, evidence suggested that a maxi-

mum of osteoinduction was observed when

there was approximately 2% residual calcium

in DFDBA. However, FDBA may serve as a

superior scaffold compared with DFDB for

space maintenance and may also be more os-

teoconductive. When osteoclasts break down

the mineral content in FDBA until it is also

demineralized, there could be a prolonged os-

teoinductive effect. To evaluate the clinical

effectiveness of these two materials on ridge

preservation, a randomized controlled clinical

trial was performed (Wood & Mealey 2011).

Forty patients were randomly allocated into

two groups. The extraction sockets of the

patients were filled with FDBA or DFDBA,

respectively. All grafting materials were

obtained from a single donor. Clinical mea-

surements were performed at baseline and at

re-entry surgery after 4–5 months of healing.

No difference between the groups was found

on ridge height reduction (1 mm in both

groups) or ridge width reduction (2 mm in

both groups). However, histological analysis

yielded that the vital bone content was signif-

icantly higher in the DFDB group (38.42% vs.

24.63%), while the residual graft content was

significantly lower in DFDBA group (8.88%

vs. 25.42%). Although DFDBA may seem to

be more osteoinductive, its effect on ridge

preservation is similar to that of FDBA.

Synthetic bone substitutes versus xenografts

Bone Ceramic® is a biphasic ceramic bone

substitute. It is composed of a combination

of hydroxyapatite (HA) and b-tricalcium

phosphate (b-TCP). HA is insoluble.

Although it is well tolerated in bone, its os-

teoconductive properties have been ques-

tioned. To be osteoconductive, the material

should leave space for new bone to be depos-



ited. Unlike HA, b-TCP is soluble. When it

slowly resorbs, it is replaced by new bone.

The objective of combining the insoluble HA

with b-TCP, therefore, is that HA would

maintain the space (scaffold function), while

the b-TCP would resorb and promote new

bone formation.

A randomized controlled clinical trial was

conducted to compare the ability of preserving

alveolar ridges with this synthetic material

(Bone Ceramic®,Institute Straumann AG,

Basel, Switzerland) and a xenograft material,

deproteinized bovine bone mineral (DBBM)

(Mardas et al. 2010). Thirty patients were ran-

domly assigned to two groups. One non-molar

tooth in each patient was extracted, and the

sockets in one group were filled with Bone

Ceramic®, whereas in the other group, the

sockets were filled with DBBM. A resorbable

bi-layer collagen membrane was applied to

cover each socket. Flaps were coronally

advanced to close the wound as well as possi-

ble. Clinical assessments on ridge dimensions

were made at baseline and at re-entry surgery

after 8 months of healing. The reduction in

the ridge width was significantly less in the

Bone Ceramic® group (�1.1 mm) than in

DBBM group (�2.1 mm). The reduction in the

ridge height was negligible in both groups.

Both materials partially preserved the width

and interproximal bone height of the alveolar

ridge. Bone Ceramic® achieved a better out-

come in preserving the alveolar ridge. In a

clinical study (De Coster et al. 2011), whereby

bone regeneration in healing extraction sock-

ets substituted with Bone Ceramic� was com-

pared with unfilled sockets, biopsies were

obtained from the sites during later performed

implant bed preparation. Healing was evalu-

ated using transmitted light microscopy after

6–74 weeks (mean 22 weeks). 15 Bone cera-

mic� sites were compared with 10 naturally

healed sockets. During implant placement it

was clinically observed that bone at the sub-

stituted sites was softer than in control sites

and large amount of loose biomaterial were

found requiring thorough debridement. Con-

sequently, some of the recipient beds were too

large to get normal diameter implants initially

stable. Hence, wider implants were necessary,

and in 4 substituted sites, implants could not

be installed at all. Additionally, it was

reported that 2 out of ten implants installed in

substituted sockets failed within 3 months

after insertion. The histology showed that 5/

15 substituted sites showed clearly incom-

plete healing. Overall, new bone formation

was consistently poorer than in controls and

presented with predominantly loose connec-

tive tissue and less woven bone. The grafting

material appeared to interfere with the normal

healing process. Hence, using this material for

crestal bone preservation when implants are

considered, even after long healing time,

should be revised and based on additional

scientific studies.

Collagen plugs

Ideally, ridge preservation procedures should

be easy and should not involve additional

surgery. The use of collagen plug was intro-

duced, as it has the mentioned advantages.

To test its effectiveness on preserving alveo-

lar ridges, a randomized controlled clinical

trial was conducted (Kim et al. 2011).

Twenty patients were divided into two

groups. After the extraction of one molar in

each patient, the sockets in one group were

grafted with Bio-oss® and a collagen plug.

Sutures were applied to fix the material. The

sockets in the other group were left unfilled

as controls. Study casts were obtained imme-

diately at baseline and after 3 months of

healing. Assessments of the bony height and

ridge width were performed. After calcula-

tion, the average resorption rate of the bone

height was 6.8% in the control group and

5.8% in the test group. There was no signifi-

cant difference between the groups. The aver-

age resorption rate of the alveolar ridge width

at 3 mm below the crest was 20.7% in the

control group and 14.3% in the test group.

Although this technique may be advanta-

geous in preserving the alveolar ridge, no def-

inite recommendations may be made.

Collagen plugs with soft tissue grafts

To evaluate the effectiveness of a collagen

plug together with soft tissue graft on ridge

preservation (Oghli & Steveling 2010), 125

patients were divided into three groups. After

tooth extraction, the sockets were treated

with either a cone comprised of collagen (Test

1), a cone comprised of collagen and impreg-

nated with gentamicin (Test 2), or left unfilled

(control). In the two test groups, soft tissue

grafts were harvested from the palate, and the

sockets were covered with the sutured grafts.

Study casts were obtained at baseline and after

3 months of healing. Assessments of the verti-

cal dimension of the alveolar ridge were made

on the casts. No difference was found among

the three groups on vertical ridge resorption

(0.8, 0.1, and 0.3 mm in Test 1, Test 2, and

control groups, respectively). However, cau-

tion should be taken while interpreting these

results. While using study casts to measure

the ridge dimensions, soft and hard tissue

alterations are included as indicated in a sys-

tematic review (Tan et al. 2012). Soft tissue

may increase in dimension to partially com-

pensate the hard tissue resorption, especially

in vertical direction. Hence, the assessment of

study casts may not be appropriate to evaluate

the effectiveness of ridge preservation proce-

dures.

Guided Bone Regeneration (GBR)

Ridge preservation with or without GBR

A cohort study was performed to follow 30

patients who received ridge preservation pro-

cedures with resorbable b-TCP of small parti-

cle size and resorbable collagen barriers after

tooth extraction (Horowitz et al. 2009). Eval-

uating clinically the alveolar ridge width at

baseline and at re-entry surgery 6 months

later, a mean reduction in the ridge width of

12.4% was reported. Although there was no

control group, it could be estimated from his-

torical controls of a systematic review that

reported on horizontal ridge resorption at

6 months after extraction (29–63%) (Tan

et al. 2012) that this ridge preservation proce-

dure applying the guided tissue regeneration

principle was certainly effective.

In a randomized controlled clinical trial (Ba-

rone et al. 2008), 40 patients were randomly

allocated into two groups. After tooth extrac-

tion, the sockets of the patients in test group

received guided bone regeneration procedures

with cortico-cancellous porcine bone and col-

lagen membranes. The sockets of the patients

in the control group were left to heal sponta-

neously. Clinical measurements were per-

formed at baseline and at re-entry surgery

after 7 months of healing. It was found that

the reduction in ridge width and height were

significantly lower in the GBR group com-

pared with control group (2.5 mm vs. 4.5 mm;

0.4 mm vs. 3 mm, respectively). Histological

analysis revealed that the amount of cancel-

lous bone was significantly greater in the GBR

group (35.5% vs. 25.7%), and the amount of

connective tissue was significantly less in the

GBR group (36.6% vs. 59.1%).

Membranes versus no membranes

To evaluate the adjunctive effect of resorb-

able collagen membranes to bone substitutes,

a randomized clinical study was conducted

(Brkovic et al. 2012). Twenty patients were

randomly allocated into two groups. After

tooth extraction, each socket was filled with

a cone that is comprised of b-tricalcium

phosphate (b-TCP) and type I collagen. The

sockets in the test group were covered with

collagen membranes, whereas the sockets in

the control group were not. Primary closure

was achieved in both groups by muco-perio-



steal flaps. Clinical assessments were per-

formed at baseline and at re-entry surgery

after 9 months of healing. No statistical sig-

nificant differences were found between the

test and control groups on horizontal ridge

resorption (�0.86 mm vs. �1.29 mm, respec-

tively) or on vertical dimensional changes

(0.12 mm vs. 0.5 mm, respectively). Histo-

metric analysis showed that there was no dif-

ference between the test and control groups

regarding the amount of new bone (45.3% vs.

42.4%, respectively). Obviously, applying the

cone material with or without membranes

was effective in preserving the alveolar bone.


Primary closure versus no primary closure

Primary closure can also be attained by

means of an implant-supported provisional

prostheses, or using a customized healing

abutment. In a recent split-mouth clinical

trial (Engler-Hamm et al. 2011), molars or

premolars were extracted bilaterally in 11

patients. The sockets on both sides were

filled with an inorganic bovine-derived

hydroxyapatite matrix, cell-binding peptide

P-15 (ABM/P-15), DFDBA, and covered with

collagen membranes. Primary closure was

achieved on one side (control). On the other

side, the membranes were left uncovered

(test). Clinical assessments of the ridge width

were made using a caliper through a stent at

baseline and at after 6 month of healing. In

addition, questionnaires regarding the post-

operative discomfort were filled by the

patients. No significant differences were

found on the ridge width changes (3 mm vs.

3.42 mm). However, the post-operative dis-

comfort was significantly lower in the group

without primary closure. The mucogingival

junction was significantly more coronally

displaced in the group with primary closure.

Conclusions

Implants and associated techniques for alveolarridge preservation

• Implants placed into the fresh extraction

sockets do not prevent the resorption of

the alveolar bone. Although osseointegra-

tion is achieved in the early stage

(1 month in dogs), modeling of the bone

may cause this level to recede apically.

• Immediate loading of the implants in dogs

as well as in humans does not preserve the

alveolar bone ridge. The use of bone fillers

in residual defects around immediate

implants placed in well preserved, intact

alveoli in dogs may reduce soft tissue

recession as well as vertical and horizontal

resoprtion of the buccal bony plate.

• Simultaneous guided bone regeneration

procedures could partially resolve alveolar

bone resorption. However, this is

depended on the type of membrane as

well as the techniques applied.

• The use of root-formed implants, aiming

at closing the space between the implant

surface and alveolar bone of the extrac-

tion socket, does not preserve alveolar

bone ridges. On the contrary, their use

with this association was associated with

accentuated bone resorption.

• It was demonstrated that thicker bony

walls results in less resorption.

• The position of the implants was also an

essential factor for the alveolar bone ridge

preservation. Placing the immediate

implant 0.8mm deeper and more lingually

led to a reduction in the vertical buccal

bone resorption by 70% in dogs after

4 months of healing.

Non-surgical treatment

• There is not enough evidence to recom-

mend ultrasonic instrumentation for

alveolar ridge preservation and no conclu-

sions on its clinical benefits can be made.

Bone substitutes

• The only relevant dog study showed that

unfilled sockets underwent three times

the amount of horizontal resorption as

sockets filled with xenograft (Bio-oss®).

However, the xenograft only served as a

scaffold and did not stimulate new bone

formation.

• Various bone substitute materials have

been tested in clinical trials for their

effects on ridge preservation.

• Ridge preservation using human deminer-

alized bone matrix was effective in ridge

preservation irrespective of the particle

sizes used, but allograft paste showed no

effect.

• Although DFDBA may be claimed to be

more osteoinductive, its effect on ridge

preservation is similar to that of FDBA.

• A combination of hydroxyapatite and b-tri-

calcium phosphate (Bone Ceramic®) was

twice as effective on preserving the alveo-

lar ridge width when compared with de-

proteinized bovine bone mineral (Bio-

oss®). However, the use of BoneCeramic®

as a grafting material in fresh extraction

sockets appears to interfere with normal

healing processes of the alveolar bone, and

hence its indication as a material for bone

augmentation, when implant placement is

considered, should be reconsidered (De

Coster et al. 2011).

• Although collagen plugs were claimed to

have an advantage in avoiding surgery, no

definite recommendations can be made

based on their poor outcome on preserv-

ing the alveolar ridge.

Guided bone regeneration

• Applying the guided bone regeneration

principle using bone substitutes together

with a collagen membrane has shown

clear effects on preserving alveolar ridge

height as well as ridge width.


• A dog study revealed that using free gingi-

val grafts in combination with bone sub-

stitutes did not provide additional effects

on ridge preservation compared with bone

substitutes alone.

• A clinical trial showed that achieving pri-

mary flap closure did not present addi-

tional beneficial effects on preserving the

ridge width. On the other hand, patients

experienced more discomfort with pri-

mary closed flaps. Moreover, the muco-

gingival junction was significantly more

coronally displaced in the primary closed

flap sites.

Acknowledgements: This manuscript

was supported by a grant of the Clinical

Research Foundation (CRF) for the Promotion

of Oral Health, Brienz, Switzerland. The

senior author was an ITI Scholar 2010–2012

at the University of Hong Kong.

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Wah Lay TanTerry L. T. WongMay C. M. WongNiklaus P. Lang

A systematic review of post-extrac-tional alveolar hard and soft tissuedimensional changes in humans

Authors’ affiliations:Wah Lay Tan, Terry L. T. Wong, May C. M. Wong,Niklaus P. Lang, Implant Dentistry, The Universityof Hong Kong, Prince Philip Dental Hospital,Implant Dentistry, Hong Kong, China

Corresponding author:Prof. Niklaus P. Lang, DMD, MS, PhD, Dr odont.h.c. mult.The University of Hong Kong Faculty of DentistryPrince Philip Dental Hospital34 Hospital Road, Sai Ying PunHong Kong, ChinaTel.:+852 2859 0526Fax: +852 2858 6114e-mail: [email protected]

Conflicts of interestThe authors declare no conflict of interest.

Key words: alveolar bone, dimensional change, extraction, hard tissue, human, removal of

teeth, resorption, soft tissue, systematic review

Abstract

Background: Removal of teeth results in both horizontal and vertical changes of hard and soft

tissue dimensions. The magnitude of these changes is important for decision-making and

comprehensive treatment planning, with provisions for possible solutions to expected

complications during prosthetic rehabilitation.

Objectives: To review all English dental literature to assess the magnitude of dimensional changes

of both the hard and soft tissues of the alveolar ridge up to 12 months following tooth extraction

in humans.

Methods: An electronic MEDLINE and CENTRAL search complemented by manual searching was

conducted to identify randomized controlled clinical trials and prospective cohort studies on hard

and soft tissue dimensional changes after tooth extraction. Only studies reporting on undisturbed

post-extraction dimensional changes relative to a fixed reference point over a clearly stated time

period were included. Assessment of the identified studies and data extraction was performed

independently by two reviewers. Data collected were reported by descriptive methods. Weighted

means and percentages of the dimensional changes over time were calculated where appropriate.

Results: The search provided 3954 titles and 238 abstracts. Full text analysis was performed for 104

articles resulting in 20 studies that met the inclusion criteria. In human hard tissue, horizontal

dimensional reduction (3.79 ± 0.23 mm) was more than vertical reduction (1.24 ± 0.11 mm on

buccal, 0.84 ± 0.62 mm on mesial and 0.80 ± 0.71 mm on distal sites) at 6 months. Percentage

vertical dimensional change was 11–22% at 6 months. Percentage horizontal dimensional change

was 32% at 3 months, and 29–63% at 6–7 months. Soft tissue changes demonstrated 0.4–0.5 mm

gain of thickness at 6 months on the buccal and lingual aspects. Horizontal dimensional changes of

hard and soft tissue (loss of 0.1–6.1 mm) was more substantial than vertical change (loss 0.9 mm to

gain 0.4 mm) during observation periods of up to 12 months, when study casts were utilized as a

means of documenting the changes.

Conclusions: Human re-entry studies showed horizontal bone loss of 29–63% and vertical bone

loss of 11–22% after 6 months following tooth extraction. These studies demonstrated rapid

reductions in the first 3–6 months that was followed by gradual reductions in dimensions

thereafter.

The periodontium is an important structure

that supports the tooth and is affected by any

changes that the tooth may undergo, includ-

ing eruption and extraction (Cohn 1966; Pie-

trokovski & Massler 1967, 1971). The

alveolar process is a tooth-dependent tissue;

the shape and volume of the alveolar process

is influenced by tooth form, as well as the

direction of eruption of the tooth (Marks

1995; Marks & Schroeder 1996), and the pres-

ence or absence of teeth (Tallgren 1972). Sim-

ilarly, gingival tissues undergo changes

together with eruption and eventual exfolia-

tion or extraction of the tooth. Subsequent to

removal of a tooth, the periodontium under-

goes atrophy (Cohn 1966; Schropp et al.

2003), with the complete loss of attachment

apparatus including cementum, periodontal

ligament fibres and bundle bone (Araujo &

Lindhe 2005).

Tooth extraction is one of the most widely

performed dental procedures. In general, post-

extraction healing of both the hard and soft

tissues proceeds uneventfully. However, the

removal of a tooth will generally result in

some alveolar bone loss, as well as structural

Date:Accepted 15 October 2011

To cite this article:Tan WL, Wong TLT, Wong MCM, Lang NP. A systematicreview of post-extractional alveolar hard and soft tissuedimensional changes in humans.Clin. Oral. Impl. Res. 23(Suppl. 5), 2012, 1–21doi: 10.1111/j.1600-0501.2011.02375.x


Daniel Jiménez Cabeza





and compositional changes in the overlying

soft tissue (Schropp et al. 2003). Both hori-

zontal and vertical changes in dimensions are

expected in hard tissue (Van der Weijden

et al. 2009) as well as soft tissue. Studies in

the canine model (Araujo & Lindhe 2005;

Araujo et al. 2005) have demonstrated that

there are marked dimensional changes of the

alveolar ridge in the first 2–3 months post-

extraction, with the changes more pro-

nounced on the buccal (Araujo et al. 2005).

Critically, horizontal buccal bone resorption

has been shown reach as much as 56% while

lingual bone resorption has been reported to

be up to 30% (Botticelli et al. 2004); the over-

all reduction in width of the horizontal ridge

has been reported to reach 50% (Schropp

et al. 2003).

A narrower and shorter ridge can be an

expected sequelae of the resorptive process

(Pinho et al. 2006), and in effect, the process

of resorption often results in the relocation of

the ridge to a more lingual position (Botticelli

et al. 2004). The process of ridge remodelling

is further complicated if the buccal bone wall

is lost (Iasella et al. 2003) as a result of

inflammatory processes or the extraction

itself.

Extraction of one or more teeth results

not only in changes of the bony architec-

ture, but also affects the overlying soft tis-

sues of the alveolus (Schropp et al. 2003).

Immediately following tooth extraction,

there is absence of soft tissue covering over

the socket entrance, and hence the socket

defect is left to heal by secondary intention.

In the subsequent weeks, cell proliferation

will result in an increase in soft tissue vol-

ume, and a soft tissue covering will seal the

socket entrance. The changes in the muco-

sal contours are dependent on the corre-

sponding changes in the external profile of

the alveolar bone surrounding the extraction

site.

The magnitude of these dimensional

changes are important for informed decision-

making and comprehensive treatment plan-

ning, with provisions for possible solutions

to expected complications during prosthetic

rehabilitation. In addition, with the advent of

greater emphasis on aesthetics in the last

decade, a thorough understanding of the

resorptive pattern and alterations in bony and

mucosal contours post-extraction would

greatly enhance our ability to reconstruct our

patients to a level of optimal function cou-

pled with satisfactory aesthetics.

There have been numerous studies that

have researched the magnitude of hard tissue

changes post-extraction, with the consensus

that alveolar bone loss can be quite marked

after tooth removal (Araujo & Lindhe 2009),

especially in the horizontal dimension (Botti-

celli et al. 2004). Soft tissue changes

post-extraction have largely been described

qualitatively, and usually as a single entity

together with the hard tissue changes

assessed using serial study casts (e.g. Schropp

et al. 2003).

In recent years, there has been one system-

atic review addressing the dimensional

changes of the alveolar ridge after tooth

extraction (Van der Weijden et al. 2009);

however, there is as yet no systematic review

addressing the dimensional changes of both

the hard and soft tissues after tooth extrac-

tion.

This study aims to review all existing liter-

ature published between 1st January 1960

and 30th January 2011, to assess the magni-

tude of dimensional change of both the hard

and soft tissues of the alveolar ridge after

tooth extraction.


The Preferred Reporting Items for Systematic

Reviews and Meta-Analyses (PRISMA) state-

ment was consulted throughout the process

of this systematic review.

Focused question

What is the magnitude of dimensional

changes in the hard and soft tissues of the

alveolar process, up to 12 months following

tooth extraction?

Search strategy

A comprehensive and systematic electronic

search of both the MEDLINE–Pubmed data-

base and the Cochrane Central Register of

Controlled Trials (CENTRAL) was con-

ducted, for articles published in English

between 1st January 1960 and 30th June

2010 in the dental literature. The search

was performed again at a later stage, to

include any relevant new studies published

between 1st July 2010 and 31st Janu-

ary 2011. The following key words were

used:

Intervention:

(<[MeSH terms/all subheadings] “Tooth

Extraction”>

OR

<[text words] Tooth Extraction OR Dental

Extraction OR Tooth Removal OR Tooth

Pulling OR Tooth Loss OR Exodontia OR

Surgery OR Surgical Tooth Extraction OR

Surgical Tooth Removal>

OR

<[text words] Tooth AND Extraction>)

AND

Outcome:

(<[MeSH terms/all subheadings] “Bone

Resorption “ OR “Alveolar Bone Loss” OR

“Periodontal Atrophy”>

OR

<[text words] Bone Defect OR Bone Resorp-

tion OR Alveolar Bone Loss OR Alveolar

Resorption OR Alveolar Healing OR Ridge

Changes OR Ridge Alterations OR Ridge

Resorption OR Ridge Healing OR Mucosal

Alterations OR Mucosal Changes OR Muco-

sal Atrophy OR Mucosal Healing OR Gingi-

val Alterations OR Gingival Changes OR

Gingival Atrophy OR Gingival Healing OR

Socket Healing OR Socket>)

The following journals between 2004 and

2010 inclusive, were hand-searched for rele-

vant articles: Clinical Oral Implants

Research, International Journal of Oral &

Maxillofacial Implants, Implant Dentistry,

Journal of Periodontology, Journal of Clinical

Periodontology and Journal of Oral Implan-

tology.

Furthermore, the bibliographies of all pub-

lications selected for inclusion in this review

were also scanned for potentially relevant

articles.

Selection criteria

Studies were included if they were published

in English and conducted on human subjects,

with the intervention being tooth extraction,

and the outcome to be assessed in the form

of changes in the clinical or radiographic

alveolar bone dimensions, as well as dimen-

sional soft tissue changes. Similarly, exclu-

sion criteria were applied; letters and

narrative or retrospective reviews, single case

reports, case series with less than three cases,

and third molar extraction cases were all

excluded. Only studies reporting on undis-

turbed post-extraction dimensional changes

relative to a fixed reference point over a

clearly stated time period were included. In

addition, in the event of duplicate publica-

tions, the study with the most inclusive data

was preferentially selected.

Selection of studies

Screening was performed independently by

two reviewers (L. T. Wong and W. L. Tan);

any disagreement between the reviewers was

resolved by discussion. The initial electronic

search resulted in the identification of 2843

titles from the MEDLINE–Pubmed database

and 1111 titles from the Cochrane Central

2 | Clin. Oral. Impl. Res. 23(Suppl. 5), 2012/1–21 © 2011 John Wiley & Sons A/S

Tan et al !Dimensional tissue changes post extraction

Register of Controlled Trials (CENTRAL).

After careful independent screening of the

titles and elimination of duplicate titles by

both the examiners, a total of 238 titles were

considered for possible inclusion. Retrieval of

the 238 abstracts and further perusal led to

104 full-text articles being selected. From

these full-text articles, 19 were identified for

inclusion in the review.

Another article was deemed suitable from

the secondary electronic search, but no addi-

tional publications from the hand-search or

the bibliography search of the selected arti-

cles were identified for inclusion.

In total, 20 articles were identified for

eventual inclusion in this review (Fig. 1).

A j-score of 0.84 was obtained, for consen-

sus between the two reviewers.

Exclusion of studies

Of the 104 full-text articles examined, 85

were excluded from the final analysis

(Table 1). The main reasons for exclusion

were that there were no actual measure-

ments of the dimensional changes of the

alveolar ridge, the reported parameters were

not useful for this review and that there was

the presence of a foreign material in the

extraction site during the healing phase,

among other reasons.

Data collection

From the selected papers that met the crite-

ria, data addressing dimensional changes

Potentially relevantpublications identified from

electronic search ofCochrane Central Register of Controlled Trials (CENTRAL)

database from 1st January1960 to 30th June 2010

(n = 1111)

Potentially relevantpublications identified from

electronic search of MEDLINE-Pubmed databasefrom 1st January 1960 to 30th

June 2010(n = 2843)

Publications excluded on the basis of titleand summary evaluation; also excluded

duplicate publications(n = 3716)

Potentially relevant full textsretrieved for detailed

evaluation(n = 104)

Publications excluded on the basis of fulltext evaluation

(n = 85)

Studies included based onthe initial electronic search ofthe MEDLINE-Pubmed and

CENTRAL database from 1st

January 1969 to 30th June2010

(n = 19) Publications included based on the hand-

search and bibliography search ofrelevant articles

(n = 0)

Publications included based on thesecondary electronic search of theMEDLINE-Pubmed and CENTRALdatabase from 1st July 2010 to 31st

January 2011(n = 1)

Studies included in thepresent systematic review

(n = 20)

Fig. 1. Search strategy. Post-extraction dimensional changes.

Table 1. Studies failing to meet inclusion criteria

Reference Rationale for exclusion

Richardson 1965; Guglielmotti & Cabrini 1985; Guglielmotti et al. 1985; Mathai et al. 1989;Ubios et al. 1991; Boyne 1995; Gauthier et al. 1999; Teofilo et al. 2001; Brandao et al. 2002;Indovina & Block 2002; Magro-Ernica et al. 2003; Altundal & Guvener 2004; Bianchi et al. 2004;Gorustovich et al. 2004; Nevins et al. 2006; Ortega et al. 2007; Araujo et al. 2008; Iino et al. 2008;Agbaje et al. 2009; Puia et al. 2009; Alissa et al. 2010; Normando et al. 2010

Reported parameters not relevant or not useful

Pietrokovski & Massler 1967a; Matsumoto 1968 Length of observation period not reportedAmemori 1966; Mizutani & Ishihata 1976; Olson & Hagen 1982; Hahn et al. 1988; Oltramari et al.2007; Shi et al. 2007; Fickl et al. 2008a; Fickl et al. 2008b

Studies carried out on animals

Loo 1968; Ashman & Bruins 1985; Ashman & Bruins1987; Scheer & Boyne 1987; Sclar 1999;Minsk 2005

Descriptive report on procedure/ technique;commentary

Guglielmotti et al. 1986; Hsieh et al. 1995; Fickl et al. 2008c; Rothamel et al. 2008; Araujo &Lindhe 2009a; Pessoa et al. 2009

No baseline data available for comparison, thus unableto arrive at an estimate of dimensional change overtime

Carlsson & Persson 1967; Pietrokovski & Massler 1967b; Pietrokovski 1967; Green et al. 1969;Huebsch & Hansen 1969; Berkovitz 1971; Pietrokovski & Massler 1971; Hars & Massler 1972;Librus et al. 1973; Thilander & Astrand 1973; Horn et al. 1979; Olson et al. 1982; Quinn &Kent 1984; Lavelle 1985; Boyes-Varley et al. 1988; Magro-Filho & de Carvalho 1990; Dayanet al. 1992; Alves-Rezende & Okamoto 1997; Anitua 1999; Pinto et al. 2002; Carmagnolaet al. 2003; Cardaropoli et al. 2005; Smith 1974; Ahn & Shin 2008; Serino et al. 2008; Sharan &Madjar 2008; Luvizuto et al. 2010; Teofilo et al. 2010

No measurements of alveolar dimensional changes (e.g.description of healing process or bony shape change,or histology only)

Bergstedt et al. 1973; Michael & Barsoum 1976; Kangvonkit et al. 1986; Sattayasanskul et al.1988

Study subjects had immediate dentures after extraction,hence they did not have undisturbed healingpost-extraction

Bahat et al. 1987; Iizuka et al. 1992; Yugoshi et al. 2002; Araujo et al. 2005; Lindeboom et al.2006; Wu et al. 2008; Araujo & Lindhe 2009b; Nevins et al. 2009

Sample did not include untreated/undisturbed extractionsockets left to heal spontaneously

Araujo & Lindhe 2005 Only measured relative difference in height betweenbuccal and lingual plates of the alveolus

© 2011 John Wiley & Sons A/S 3 | Clin. Oral. Impl. Res. 23(Suppl. 5), 2012/1–21


of both soft and hard tissues of the alveolar

ridge were retrieved for analysis. Mean

values and standard deviations, where

available, were extracted in duplicate by

the two reviewers (L. T. Wong and W. L.

Tan).

Quality assessment

Assessment of study quality was performed

for all the included papers. The Cochrane

Collaboration’s tool for assessing risk of bias

was used in the case of randomized con-

trolled clinical trials and controlled clinical

trials. Methodological quality assessment of

cohort studies was based on the Newcastle–

Ottawa Quality Assessment Scale for Cohort

studies (Tables 2 and 3).

Data synthesis

Preliminary evaluation of the selected publi-

cations revealed that there was considerable

heterogeneity between the studies with

regard to study design, study population,

study period, method of assessment of

dimensional change of the alveolar ridge as

well as reference point from which the

changes were measured. Taking this into

consideration, it was not appropriate to con-

duct a quantitative data synthesis for all

studies, leading to a meta-analysis. In this

case, we attempted to report the data by

applying descriptive methods. In addition,

as a selected few of the included studies

demonstrated some similarity in measure-

ment methods and reference points, we pre-

sented weighted means of the dimensional

change of the alveolar ridge over time as

appropriate, taking into account the values

of the relevant standard deviation and

applying inverse variance weighting (Meier

1953).

Inverse variance weighting

For the weighted mean of the list of data for

which each mean xi comes from a different

probability distribution with a known

variance ri2, the weight for each study is

given by:

Wi "1

ri2

The weighted mean in this case is:

!x "Pn

i"1#xi=r2i $Pni"1#1=r2i $

and the variance of the weighted mean is:

r2!x " 1Pni"1#1=r2i $

Assessment of heterogeneity

Statistical heterogeneity between all the

included studies was not assessed because all

the studies had different observation time

points as well as measurement methods,

making a statistical comparison impossible.

However, assessment of heterogeneity

between studies with similar characteristics

were performed using Cochran’s Q-test:

Q "X

wi#xi % !x$

The P-value was then calculated for the Q

statistic and a value of P < 0.05 would indi-

cate significant statistical heterogeneity

between the studies.

When Q > df, where df is its degree of free-

dom, the I2 index was also calculated using

the following formula:

I2 " Q% df

Q

! "& 100%

where, I2 = 0% to 40% would indicate

there is little to no heterogeneity

I2 = 30% to 60% would indicate there is

moderate heterogeneity

I2 = 50% to 90% would indicate there is

substantial heterogeneity

I2 = 75% to 100% would indicate consider-

able heterogeneity

Similarly, the P-value was calculated for

the I2 statistic, and a value of P < 0.05 would

indicate a result that is statistically signifi-

cant.

Results

Collectively, a total of 20 studies satisfied

the inclusion criteria and were included in

this systematic review.

The 20 studies included 11 randomized

controlled clinical trials, five controlled clini-

cal trials and four cohort studies (Tables 2

and 3). The majority of studies did not state

the reasons for tooth extraction, but in the

studies that did, they included fractures, car-

ies, trauma, endodontic, prosthodontic,

orthodontic and periodontal reasons. Thirteen

papers only studied non-molar extraction

sites (Carlsson & Persson 1967; Lekovic et al.

1997, 1998; Yilmaz et al. 1998; Camargo

et al. 2000; Iasella et al. 2003; Serino et al.

2003; Fiorellini et al. 2005; Saldanha et al.

2006; Rodd et al. 2007; Barone et al. 2008;

Aimetti et al. 2009; Pelegrine et al. 2010),

while six studies (Bragger et al. 1994; Schropp

et al. 2003; Kerr et al. 2008; Crespi et al.

2009; Moya-Villaescusa & Sanchez-Pérez

2010; Rasperini et al. 2010) reported on data

including molar extraction sites and one

study (Oghli & Steveling 2010) did not spec-

ify where the extractions were performed.

Most of the data extracted concerned teeth in

control groups of studies that evaluated vari-

ous ridge preservation procedures (Lekovic

et al. 1997, 1998; Yilmaz et al. 1998; Camar-

go et al. 2000; Iasella et al. 2003; Serino et al.

2003; Fiorellini et al. 2005; Barone et al.

2008; Aimetti et al. 2009; Crespi et al. 2009;

Oghli & Steveling 2010; Pelegrine et al. 2010;

Rasperini et al. 2010), but other studies were

either designed specifically to evaluate post-

extraction alveolar changes (Carlsson & Pers-

son 1967; Schropp et al. 2003; Rodd et al.

2007; Moya-Villaescusa & Sanchez-Perez

2010) or the effect of smoking (Saldanha

et al. 2006) or ultrasound treatment (Kerr

et al. 2008) on these changes. In addition,

one included study (Bragger et al. 1994) was

actually designed to test the effect of

chlorhexidine mouthrinse on post-extraction

healing. Each paper that was included in

this review contributed a number of extrac-

tion sites, ranging from three to over a

hundred sites. The age range of the patients

in these studies was between 10.8 and

53.3 years.

Included studies

There were a total of 20 studies addressing

the hard and soft tissue dimensional changes

of the alveolar ridge in humans, with sponta-

neous undisturbed healing. The studies were

grouped according to the reported changes in

hard tissue, soft tissue, or a combination of

both hard and soft tissue.

Hard tissue changes

Vertical and horizontal linear hard tissue

changes in humans were reported indepen-

dently or in combination by 17 studies

(Tables 4 and 7).

Vertical linear hard tissue alteration

All 17 studies that reported on post-extrac-

tion hard tissue changes looked into the ver-

tical linear dimensional change of the

alveolus. Eight studies (Lekovic et al. 1997,

1998; Camargo et al. 2000; Iasella et al. 2003;

Serino et al. 2003; Barone et al. 2008; Aimetti

et al. 2009; Pelegrine et al. 2010) utilized

re-entry procedures with stents or titanium

pins as reference points (Fig. 2), one other

study (Rasperini et al. 2010) did not carry out

a re-entry procedure but nevertheless utilized

a stent for reference. An additional eight

studies (Carlsson & Persson 1967; Bragger

et al. 1994; Schropp et al. 2003; Fiorellini

et al. 2005; Saldanha et al. 2006; Kerr et al.



Table 2. Cochrane Collaboration’s tool for assessing risk of bias

Study design

Carlsson & Persson (1967) Bragger et al. (1994)Controlled clinical trial Randomized controlled clinical trialParallel Parallel

Adequate sequence generation No UnclearRemark Quote “alternate patients were assigned to respective

groups”Quote “then randomly assigned”

Insufficient information about sequence generationAllocation concealment Unclear UnclearRemark No information provided. No information provided.Blinding Unclear YesRemark Study did not address this outcome. Quote “ double-blind clinical trial”Incomplete outcome data addressed Yes NoRemark Quote “one patient from each group had to be

discarded….one had moved…other case first radiographunsuccessful and could not be repeated..”

Initially mentioned that 40 patients were enrolled instudy, but subsequently only obtained radiographs for23 patients with no explanation

Free of selective reporting Yes NoRemark Initially mentioned that 40 patients were enrolled in

study, but subsequently only obtained radiographs for23 patients with no explanation

Free of other sources of bias Yes YesRemarkOverall risk of bias High High

Study design

Lekovic et al. (1997) Lekovic et al. (1998)Controlled clinical trial Randomized controlled clinical trialSplit-mouth Split-mouth

Adequate sequence generation Unclear YesRemark No information provided Quote “ control and experimental sites were assigned by

the flip of a coin”Allocation concealment Unclear UnclearRemark No information provided No information providedBlinding Unclear YesRemark Study did not address this outcome Quote “clinical measurements were performed by one

clinician who did not have knowledge of control andexperimental sites”

Incomplete outcome data addressed Yes YesRemark Mentioned that three patient had dehiscence in test

group, hence did not measure values at 6 months;re-entry was planned at 6 months, but if membraneexposure occurred, re-entry and measurements wasdone at 3 months. Refer to Tables 3–5 and will see thatthey analysed the results with various combinations,including with or without the patients that exited early,suggesting an intention-to-treat analysis

No missing outcome data

Free of selective reporting Yes YesRemarkFree of other sources of bias Yes YesRemarkOverall risk of bias Unclear Unclear

Study design

Camargo et al. (2000) Iasella et al. (2003) Serino et al. (2003) Fiorellini et al. (2005)

Controlled clinical trialRandomized controlledclinical trial Controlled clinical trial

Randomized controlled clinicaltrial

Split-mouth Parallel Parallel and split-mouth Parallel

Adequate sequencegeneration

Unclear Yes Unclear Unclear

Remark No information provided Quote “randomly selectedusing a coin toss”

No information provided Quote “ cohorts of 40 patientrandomized in a double-blindmanner”

Insufficient information aboutsequence generation

Allocationconcealment

Unclear Unclear Unclear Unclear

Remark No information provided No information provided No information provided No information providedBlinding Unclear Yes Unclear YesRemark Study did not address this

outcomeQuote “measurements weretaken by 2 maskedexaminers”

No information provided Quote “all the patients in the studyunderwent the same surgicalprocedure, regardless of thetreatment

Incomplete outcomedata addressed

Yes Yes Yes Yes



Table 2. (continued)

Study design

Camargo et al. (2000) Iasella et al. (2003) Serino et al. (2003) Fiorellini et al. (2005)

Controlled clinical trialRandomized controlledclinical trial Controlled clinical trial

Randomized controlled clinicaltrial

Split-mouth Parallel Parallel and split-mouth Parallel

Remark No missing outcome data Quote “implants weresuccessfully placed at allsites….none have beensubsequently lost”

Quote “nine subjectsdropped out from thestudy for reasons unrelatedto the therapy”

Quote “ No subjects werewithdrawn or lost to follow-up”

Free of selectivereporting

Yes Yes Yes Yes

RemarkFree of other sourcesof bias

Yes Yes Yes Yes

RemarkOverall risk of bias Unclear Unclear Unclear Unclear

Study design

Barone et al. (2008) Kerr et al. (2008) Aimetti et al. (2009)

Randomized controlled clinical trial Randomized controlled clinical trialRandomized controlled clinicaltrial

Parallel Split-mouth Parallel

Adequate sequence generation Yes Unclear UnclearRemark Quote “using a

computer-generatedrandomisation list…”

Quote “ one site was assignedrandomly as test, whereas theother site was assigned as control”

Quote “ were consecutivelyselected..” and “ all sockets weremeasured and assigned randomlyto test or control”



Allocation concealment Unclear Unclear NoRemark No information provided No information provided Assignment not explicitly

concealedBlinding Yes Yes YesRemark Quote “all measurements were

taken by one examiner who wasnot involved in performing thesurgical treatment…”

Quote “examiner was masked as towhether sites were test or control”

Quote “recorded by the sameexaminer, who was not involvedin providing therapy”

Incomplete outcome data addressed Yes Yes UnclearRemark No loss to follow-up in test and

control groupNo missing outcome data Study did not address this

outcomeFree of selective reporting Yes Yes YesRemarkFree of other sources of bias Yes Yes YesRemarkOverall risk of bias Unclear Unclear High

Study design

Crespi et al. (2009) Pelegrine et al. (2010) Rasperini et al. (2010)

Controlled clinical trial Randomized controlled clinical trialRandomized controlled clinicaltrial

Split-mouth Parallel Parallel

Adequate sequence generation No Unclear YesRemark Quote “sockets on right side of jaw

received MHA….sockets on leftside received CS…”

Quote “teeth to be extracted wererandomized into two groups”

Quote “treatment regimens wereassigned randomly to the subjectswith a balanced random permutedblock approach”

Allocation by left or right sideof jaw


Allocation concealment Unclear Unclear YesRemark No information provided. No information provided. Quote “treatment regimens

assigned randomly…communicated to the operatorimmediately after toothextraction”

Blinding Yes Unclear YesRemark Quote “a masked examiner

measured the bone level changes.”Study did not address this outcome Quote “tubes included into the

stent by a blind examiner…..aftersurgery, blinded examinerpositioned the stent.”

Incomplete outcome data addressed Yes Unclear YesRemark No missing outcome data Study did not address this outcome. Missing outcome data balanced in

numbers across groupsFree of selective reporting Yes Yes YesRemarkFree of other sources of bias Yes Yes YesRemarkOverall risk of bias High Unclear Low



2008; Crespi et al. 2009; Moya-Villaescusa &

Sanchez-Perez 2010) utilized imaging meth-

ods to obtain the required information.

Only one re-entry study (Aimetti et al.

2009) addressed the vertical linear change of

the alveolar hard tissue post-extraction at

3 months. In this study, 3 months after

extraction of anterior maxillary teeth, a mean

vertical reduction of 1.2 ± 0.8 mm on the

buccal, 0.9 ± 1.1 mm on the palatal and

0.5 ± 0.9 mm on the mesial and distal sites

were reported when an acrylic stent was used

as a fixed reference during re-entry.

A total of six re-entry studies (Lekovic et al.

1997, 1998; Camargo et al. 2000; Iasella et al.

2003; Serino et al. 2003; Pelegrine et al. 2010)

reported data on 6-month post-extraction ver-

tical linear hard tissue changes of the alveolus;

four studies (Lekovic et al. 1997, 1998; Camar-

go et al. 2000; Pelegrine et al. 2010) utilized a

titanium screw or pin, while two studies (Ia-

sella et al. 2003 and Serino et al. 2003) used an

acrylic stent as a fixed reference point.

Six months following the extraction of

anterior teeth or premolars, Lekovic et al.

(1997) reported a mean reduction of

1.2 ± 0.13 mm in buccal vertical ridge height,

while Lekovic et al. (1998) and Camargo

et al. (2000) reported a mean reduction of

1.50 ± 0.26 mm and 1.00 ± 2.25 mm respec-

tively. Later, Pelegrine et al. (2010) showed

that 6 months after extraction of maxillary

anterior teeth, the mean buccal vertical alve-

olar ridge height reduction was

1.17 ± 0.26 mm. All the four studies men-

tioned above measure changes relative to a

titanium pin or screw at re-entry.

Iasella et al. (2003) and Serino et al. (2003)

utilized re-entry procedures and acrylic stents

as fixed references, 6 months after extraction

of non-molar teeth. The former study reported

an average alveolar vertical hard tissue reduc-

tion of 0.9 ± 1.6 mm at the mid-buccal,

0.4 ± 1.0 mm at the mid-lingual, 1.0 ± 0.8

mm at the mesial and 0.8 ± 0.8 mm on the

distal sites; the latter study recorded a mean

reduction of 0.7 ± 1.2 mm on the buccal.

Taking into consideration the similarities

between these six re-entry studies that

reported 6-month data (Lekovic et al. 1997,


Serino et al. 2003; Pelegrine et al. 2010), the

weighted mean was calculated for the rele-

vant sites, using the inverse variance

method, to give a more robust value of the

6-month post-extraction vertical change

(Fig. 3). On the buccal, all six studies were

included to give a weighted mean reduction

of 1.24 ± 0.11 mm (Q = 1.3, P = 0.94). Only

two studies (Iasella et al. 2003; Serino et al.

2003) were included when mesial and distal

sites were investigated; the respective

weighted reductions were 0.84 ± 0.62 mm on

the mesial (Q = 0.10, P = 0.75) and

0.80 ± 0.71 mm on the distal (Q = 0, P = 1).

After a 7-month undisturbed healing period

in non-molar extraction sites, Barone et al.

(2008) observed vertical linear reduction of

3.6 ± 1.5 mm, 3.0 ± 1.6 mm, 0.4 ± 1.2 mm

and 0.5 ± 1.0 mm on the mid-buccal, mid-lin-

gual, mesial and distal sites respectively, at re-

entry. A stent was used as a fixed reference.

Rasperini et al. (2010) reported on 3- and 6-

month dimensional changes of the alveolar

ridge after extraction of maxillary molar

teeth, using a custom acrylic stent and a peri-

odontal probe or endodontic file to obtain the

measurements; measurements were made

from the surface of the bone to the external

surface of the stent. The observed reduction

in height of the buccal plate at 3 and

6 months were 2.2 and 5.7 mm respectively,

when the buccal plates were intact after

extraction. However, when the buccal plates

were lost at time of extraction, there was a

corresponding gain of buccal bone height of 1

and 0.6 mm at 3 and 6 months respectively.

Radiographic methods used for the relevant

studies were: lateral cephalometric radiogra-

phy in one study (Carlsson & Persson 1967),

cone beam computed tomography in two

studies (Fiorellini et al. 2005 and Kerr et al.

2008), linear tomography in one study (Salda-

nha et al. 2006), and intraoral peri-apical radi-

ography in four studies (Bragger et al. 1994;

Schropp et al. 2003; Crespi et al. 2009 and

Moya-Villaescusa & Sanchez-Perez 2010).

Carlsson & Persson (1967) attempted to

use lateral cephalometric radiography to dem-

onstrate the longitudinal height change in

the mandibular alveolar ridge after extraction

of at least five to six lower anterior teeth and

loading with conventional full dentures

2 months post-extraction. The study had

observation time points at 2, 4, 6, 12, 24 and

60 months. The reductions in alveolar height

were 2.0 mm at 2 months, 2.9 mm at

4 months, 3.4 mm at 6 months and 4.1 mm

at 12 month, compared to baseline. From this

study, we can see a trend where there is a

large reduction in alveolar bone height in the

first 2 months post-extraction, followed by a

continual gradual resorption thereafter. Take

note that we should interpret the values

obtained in this study, with observation time

points greater than 2 months, with caution;

2 months after teeth extraction, full dentures

were inserted in the conventional group, and

we cannot with full confidence, state that

insertion and use of denture prostheses did

not have an impact on the resorptive pattern

and extent of the alveolar hard and soft tis-

sues in this case.

Two studies (Fiorellini et al. 2005; Kerr

et al. 2008) utilized computed tomography to

detect vertical height changes in the alveolar

Table 2. (continued)

Study design

Yilmaz et al. (1998) Oghli & Steveling (2010)Controlled clinical trial Randomized controlled clinical trialParallel Parallel

Adequate sequence generation Unclear UnclearRemark No information provided Quote “patients were divided randomly into three groups”

Insufficient information about sequence generationAllocation concealment Unclear UnclearRemark No information provided No information providedBlinding Unclear UnclearRemark Study did not address this outcome Study did not address this outcomeIncomplete outcome data addressed Unclear YesRemark Study did not address this outcome All exclusions accounted forFree of selective reporting Yes YesRemarkFree of other sources of bias Yes YesRemarkOverall risk of bias Unclear Unclear



hard tissue. Fiorellini et al. (2005) reported a

4-month mean height reduction of

1.17 ± 1.23 mm in patients after extraction

of maxillary non-molar teeth; of note is that

all the patients in this sample had a buccal

defect of ' 50% bone loss of the extraction

socket at baseline. In the study by Kerr et al.

(2008), following extraction of a permanent

tooth, the corresponding vertical resorption

of the alveolar ridge were 1.01 ± 0.39 mm on

the buccal, 0.62 ± 0.28 mm on the lingual at

1 month and 0.95 ± 0.39 on the buccal,

1.12 ± 0.28 on the lingual at 3 months.

Six months after extraction of upper ante-

rior teeth, Saldanha et al. (2006) observed a

vertical resorption of 1.5 mm in smokers and

1.0 mm in non-smokers when using linear

tomography.

Assessing interproximal bone height

change on intraoral periapical radiographs,

Bragger et al. (1994) demonstrated a vertical

reduction of 0.61 ± 0.67 mm, 0.67 ±

0.66 mm, 1.19 ± 1.50 mm and 0.93 ± 0.74

mm at 1, 2, 3 and 6 months respectively,

while Schropp et al. (2003) documented a

0.3 mm loss at 12 months. Crespi et al.

(2009) went on to show an overall 3-month

Table 3. Newcastle–Ottawa Quality Assessment Scale for Cohort Studies (max 9*)

Study designSchropp et al. (2003) Saldanha et al. (2006)Cohort Cohort

SelectionRepresentativeness of the exposedcohort

Truly representative of the average implantpatient in the community

Representative of the average patientrequiring extraction in the community

Rating * *Selection of non exposed cohort No description of the derivation of non-exposed

cohortNo description of the derivation of the non-exposedcohort

RatingAscertainment of exposure Secure record (radiograph, study model, clinical

exam)Secure record (radiograph, linear tomography, clinicalexam)

Rating * *Demonstration that outcome ofinterest was not present atstart of study

Yes Yes

Rating * *ComparabilityComparability of cohorts on thebasis of the design or analysis

No mention of control of any confounding factors (e.g.smoking, health)

Controlled for confounding factors (smoking, oralhygiene, ethnicity, systemic health)

Rating **OutcomeAssessment of outcome Records (radiograph, study models) Independent blind assessmentRating * *Was follow-up long enough foroutcomes to occur

Yes; 12 months follow up (early soft/hard tissue healingusually 6–8 weeks)

Yes; 6 months (early hard tissue healing usually6–8 weeks)

Rating * *Adequacy of follow up of cohorts Description of those lost to follow-up No statementRating *Overall 6* 7*

Study designRodd et al. (2007) Moya-Villaescusa & Sanchez-Perez (2010)Cohort Cohort

SelectionRepresentativeness of the exposedcohort

Truly representative of the average young patientwith dental trauma in the community

Representative of the average patient requiringextraction in the community

Rating * *Selection of non exposed cohort No description of the derivation of non-exposed

cohortNo description of the derivation of non-exposedcohort

RatingAscertainment of exposure Secure record (study model, photograph, clinical

exam)Secure record (radiograph, clinical exam)

Rating * *Demonstration that outcome of interestwas not present at start of study

Yes Yes

Rating * *ComparabilityComparability of cohorts on the basisof the design or analysis

Sample size too small to allow statisticaladjustment of confounders

Controlled for confounding factors (smoking, numberof roots, oral hygiene, periodontal disease)

Rating **OutcomeAssessment of outcome Records (study model, photograph) Records (radiograph)Rating * *Was follow-up long enough foroutcomes to occur

Yes; 4–61 months follow up (early soft/hard tissuehealing usually 6–8 weeks)

Yes; 3 months follow up (early hard tissue healingusually 6–8 weeks)

Rating * *Adequacy of follow up of cohorts No statement No statementRatingOverall 5* 7*



loss of 3.75 ± 0.63 mm when the buccal plate

was lost during extraction. One study (Moya-

Villaescusa & Sanchez-Pérez 2010) further

discerned between the bone loss at 3 months

after extraction of single-rooted teeth

(4.16 ± 0.32 mm) vs. multiple-rooted teeth

(4.48 ± 0.39 mm loss), although the differ-

ence was not statistically significant. The

average bone loss when both groups were

combined was 4.32 ± 0.24 mm.

Percentage change of vertical linear hard tissuealteration

All the four re-entry studies (Lekovic et al.

1997, 1998; Camargo et al. 2000; Pelegrine

et al. 2010) utilizing a titanium pin or screw

had data on the baseline internal socket

height. This facilitated a calculation of the

percentage reduction of the vertical dimen-

sion of the alveolus post-extraction as fol-

lows:

%vertical linear change #hard tissue$

" vertical linear resortion #hard tissue$baseline internal socket height

The calculated percentage vertical change

of the alveolar hard tissue ranged from 11%

to 22% (Fig. 4) at buccal sites, 6 months

post-extraction.

Horizontal linear hard tissue alteration

A total of eight studies (Lekovic et al. 1997,


Barone et al. 2008; Kerr et al. 2008; Aimetti

et al. 2009; Pelegrine et al. 2010) reported on

horizontal changes over time in the hard tis-

sue at the level of the alveolar crest (Fig. 5).

Two studies (Kerr et al. 2008; Aimetti et al.

2009) reported 3-month horizontal reduction

to be between 2.20 and 3.20 mm; another

study (Barone et al. 2008) reported 7-month

reduction to be 4.5 ± 0.8 mm. Lekovic et al.

(1997, 1998), Camargo et al. (2000), Iasella

et al. (2003) and Pelegrine et al. (2010) docu-

mented 6-month horizontal reduction in the

hard tissue of the alveolar ridge to be 4.40,

4.56, 3.06, 2.63 and 2.46 mm respectively.

The five latter studies (Lekovic et al. 1997,

1998; Camargo et al. 2000; Iasella et al. 2003

and Pelegrine et al. 2010) have quite a few

methodological similarities, however, results

of the heterogeneity testing reveal that there

is considerable heterogeneity between the

Table 4. Characteristics of studies included for hard tissue change only

TitleAuthor,publishing year Species QA Tissue Methods

Samplesize

No. ofextractionsites

Morphologic changes of the mandible after extractionand wearing of denture

Carlsson 1967 human CCT Hard Radio 17 5–6 per pt

Effect of chlorhexidine(0.12%) rinses on periodontaltissue healing after tooth extraction(II)radiographicparameters

Bragger 1994 Human RCCT Hard Radio 12 21

A bone regeneration approach to alveolar ridgemaintenance following tooth extraction. Report of10 cases

Lekovic 1997 Human CCT Hard Re-entry (pin) 10 10

Preservation of alveolar bone in extraction socketsusing bioabsorbable membranes

Lekovic 1998 Human RCCT Hard Re-entry(pin 2–5 mm)

16 16

Influence of bioactive glass on changes in alveolarprocess dimensions after exodontia

Camargo 2000 Human CCT Hard Re-entry(pin 1–8 mm)

16 16

Ridge preservation with freeze-dried bone allograftand a collagen membrane compared to extractionalone for implant site development: a clinical andhistological study in humans

Iasella 2003 Human RCCT Soft+ hard

Re-entry(stent)

12 12

Ridge preservation following tooth extraction usinga polylactide and polyglycolide sponge as space filler:a clinical and histological study in humans

Serino 2003 Human CCT Hard Re-entry(stent)

12 13

Bone healing and soft tissue contour changesfollowing single-tooth extraction: a clinical andradiographic 12-month prospective study

Schropp 2003 Human Cohort Hard Radio 46 46

Randomized study evaluating recombinant humanbone morphogenetic protein-2 for extraction socketaugmentation

Fiorellini 2005 Human RCCT Hard CT scan 20 ?

Smoking may affect the alveolar process dimensionsand radiographic bone density in maxillary extractionsites: a prospective study in humans

Saldanha 2006 Human Cohort Hard Radio 21 21

Xenograft vs. extraction alone for ridge preservationafter tooth removal: a clinical and histomorphometricstudy

Barone 2008 Human RCCT Hard Re-entry(stent)

20 20

The effect of ultrasound on bone dimension changesfollowing extraction: a pilot study

Kerr 2008 Human RCCT Hard CBVT (refplate)

12 12

Clinical and histological healing of human extractionsockets filled with calcium sulphate

Aimettl 2009 Human RCCT Hard Re-entry(stent)

18 18

Magnesium-enriched hydroxyapatite compared tocalcium sulphate in the healing of human extractionsockets: radiographic and histomorphometricevaluation at 3 months

Crespi 2009 Human RCCT Hard Radio 15 15

Measurement of ridge alterations following toothremoval:a radiographic study in humans

Moya-Villaescusa2010

Human Cohort Hard Radio 100 100

Clinical and histomorphometric evaluation ofextraction sockets treated with an autologous bonemarrow graft

Pelegrine 2010 Human RCCT Hard Re-entry (pin) 6 15

Socket grafting in the posterior maxilla reduces theneed for sinus augmentation

Rasperini 2010 Human RCCT Hard Stent 3 3



studies (Q = 17.8, P < 0.05; I2 = 77.6%,

P < 0.05). In this case, although the weighted

mean was calculated by applying the inverse

variance method to arrive at a value of

3.79 ± 0.23 mm horizontal reduction at

6 months (Fig. 6) across all five studies, the

robustness and applicability of this value

should be questioned.

Saldanha et al. (2006) reported the horizon-

tal reduction of the alveolar bone at 0% and

50% the distance from the crest. This study

demonstrated a 6-month reduction of 0.6 and

1.3 mm for non-smokers and smokers respec-

tively at 0% from the alveolar crest and cor-

responding values of 0.1 and 0.8 mm at 50%

from the crest. This study utilized linear

tomography to track the changes.

Of note, Kerr et al. (2008) demonstrated

beautifully that 3 months after tooth extrac-

tion, there was a relative decrease in horizon-

tal ridge reduction as the distance from the

alveolar crest increased (Fig. 7).

Percentage change of horizontal linear hard tissuealteration

All but one study (Kerr et al. 2008) reporting

changes in the ridge width also reported the

baseline ridge width immediately post-extrac-

tion. This facilitated a calculation of the per-

centage reduction of the horizontal dimension

of the alveolus post-extraction as follows:

%horizontallinear change#hard tissue$

" horizontal linear resortion#hard tissue$baseline internal socket height

The calculated percentage horizontal

change of the alveolar hard tissue at the alve-

olar crest ranged from 32% at 3 months, and

between 29% and 63% after 6–7 months

post-extraction (Fig. 8).

Overall hard tissue changes

In general, with regard to vertical dimen-

sional change, we can see a trend where

there is a greater reduction on the buccal and

lingual sites as compared to the mesial and

distal sites. Looking at the horizontal dimen-

sional change, there is a distinct pattern of

resorption where the resorption decreases

with increased distance from the alveolar

crest. Overall, the observed horizontal resorp-

tion of the hard tissues (29–63%) is far

greater than the resorption in the vertical

dimension (11–22%), over an observation per-

iod of 3–7 months. It can be seen that the

bulk of the resorption occurs in the first

3 months post-extraction, and the changes

are much more subtle thereafter.

Fig. 2. Vertical (linear) hard tissue change for re-entry

studies only.

Fig. 3. Vertical (linear) hard tissue change for re-entry

studies only; weighted means shown.

Fig. 4. Vertical (linear) hard tissue percentage change in

four studies.

Fig. 5. Horizontal (linear) hard tissue change for re-

entry studies only.

Fig. 6. Horizontal (linear) hard tissue change for re-

entry studies only; weighted means shown.



Soft tissue changes

Only a single study (Iasella et al. 2003)

reported on longitudinal changes of soft tis-

sue dimensions in the alveolus post-extrac-

tion (Tables 5 and 7). This study

demonstrated a 0.4–0.5 mm gain of soft tis-

sue thickness at 6 months, measured at buc-

cal and lingual sites 3 mm from the alveolar

crest. Occlusally, soft tissue with thickness

of 2.1 mm developed after 6 months to com-

plete soft tissue coverage of the wound

(Fig. 9).

Combined hard and soft tissue changes

To date, a total of five studies (Carlsson &

Persson 1967; Yilmaz et al. 1998; Schropp

et al. 2003; Rodd et al. 2007; Oghli & Stevel-

ing 2010) presented data on the longitudinal

change in the combined hard and soft tissue

dimension of the alveolus post-extraction

(Tables 6 and 7). One study (Carlsson & Pers-

son 1967) utilized lateral cephalometric radi-

ography whereas study casts were employed

in the other four studies (Yilmaz et al. 1998;

Schropp et al. 2003; Rodd et al. 2007; Oghli

& Steveling 2010). Vertical and horizontal

linear tissue alterations were reported inde-

pendently or in combination; in one study

(Rodd et al. 2007) the overall areal change of

the alveolar hard and soft tissue combined,

was reported.

Vertical linear combined hard and soft tissuealteration

Three studies (Carlsson & Persson 1967; Yil-

maz et al. 1998 and Schropp et al. 2003)

addressed the combined hard and soft tissue

changes in the vertical dimension of the alve-

olus.

With the aid of lateral cephalometric radi-

ography, Carlsson & Persson (1967) was able

to demonstrate the combined hard and soft

tissue changes of the mandibular alveolus in

the vertical dimension over time. The verti-

cal reductions of the conjugated tissue

dimension from baseline were 2.1 mm at

2 months, 2.9 mm at 4 months, 3.4 mm at

6 months and 4.0 mm at 12 month. This

degree of resorption of the combined hard

and soft tissues followed a similar trend as

that of hard tissue alone.

Utilizing sectioned study casts, Yilmaz

et al. (1998) demonstrated a vertical reduc-

tion of 0.1 ± 0.52 mm and 0.5 ± 0.76 mm at

Fig. 7. Horizontal (linear) hard tissue change with

respect to distance from alveolar crest.

Fig. 8. Horizontal (linear) hard tissue percentage

change.

Table 5. Characteristic of study included for soft tissue change only

TitleAuthor,Publishing Year Species QA Tissue Methods Sample size

No. ofextraction site

Ridge preservation with freeze-dried bone allograftand a collagen membrane compared to extractionalone for implant site development: a clinical andhistological study in humans

Iasella 2003 Human RCCT Soft + hard Re-entry (stent) 12 12

Table 6. Characteristics of studies included for both hard and soft tissue changes combined

Title Authors Species QA Tissue Method Sample sizeNo. ofextraction sites

Morphologic changes of the mandible after extractionand wearing of denture

Carlsson 1967 Human CCT Soft + hard Radio 17 5/6 per pt

Alveolar ridge reconstruction and/or preservationusing root form bioglass cones

Yilmaz 1998 Human CCT Soft + hard Cast 5 10

Bone healing and soft tissue contour changesfollowing single-tooth extraction: A clinical andradiographic 12-month prospective study

Schropp 2003 Human CCT Soft + hard Cast 46 46

Change in supporting tissue following loss of apermanent maxillary incisor in children

Rodd 2007 Human Cohort Soft + hard Cast 16 16

Ridge preservation following tooth extraction:A comparison between atraumatic extraction andsocket seal surgery

Oghli 2010 Human RCCT Soft + hard Cast 72 101

Fig. 9. Change in soft tissue dimensions over time.



3 and 12 months respectively, post-extrac-

tion of maxillary incisor teeth (Fig. 10).

Schropp et al. (2003) took measurements

from study casts taken immediately after as

well as 3, 6 and 12 months after extraction

of maxillary posterior teeth. Taking the

occlusal surfaces of adjacent teeth as refer-

ence, a reduction of 0.1 mm at 3 months

was followed by a net gain of 0.1 mm at

6 months and 0.4 mm at 12 months of the

buccal sites. Lingual sites demonstrated a

loss of 0.8–0.9 mm between 3 and 6 months,

Table 7. Overall results from all studies

Author,Publishing Year Species Tissue Methods

Samplesize

No. ofextractionsites

Vertical dimensionalchange

Horizontal dimensionalchange

Carlsson 1967 Human Hard Radio 17 5–6 per pt 2 month: %2.0(0.9) 2 month: %2.2(1.1)4 month: %2.9(1.7) 12 month: %3.6(0.5)6 month: %3.4(2.1) 60 month: %4.0(1.5)12 month: %4.1(2.7)24 month: %4.9(3.7)60 month: %7.3(3.7)

Bragger 1994 Human Hard Radio 12 21 1 month: %0.61(0.67)2 month: %0.67(0.66)3 month: %1.19(1.50)6 month: %0.93(0.74)

Lekovic 1997 Human Hard Re-entry (pin) 10 10 6 month: %1.2(0.13) 6 month: %4.4(0.61)Lekovic 1998 Human Hard Re-entry (pin2–

5 mm)16 16 6 month: %1.50(0.26) 6 month: %4.56(0.33)

Camargo 2000 Human Hard Re-entry (pin1–8 mm)

16 16 6 month: %1.00(2.25) 6 month: %3.06(2.41)

Iasella 2003 Human Soft+hard

Re-entry (stent) 12 12 6 month: B %0.9(1.6) 6 month: %2.6(2.3)L %0.4(1.0)M %1.0(0.8)D %0.8(0.8)

Iasella 2003 Human Soft Re-entry (stent) 12 12 6 month: B 0.4(0.6)L 0.5(1.5)(Soft tissue thickness change)

Serino 2003 Human Hard Re-entry (stent) 12 13 6 month: B %0.8(1.6)M %0.6(1.0)D %0.8(1.5)

Schropp 2003 Human Hard Radio 46 46 12 month: M %0.3D %0.3

Schropp 2003 Human Soft+hard

Cast 46 46 3 month: B %0.1 3 month: %3.8L %0.8 6 month: %5.16 month: B 0.1 12 month: %6.1L %0.912 month: B 0.4L %0.8

Fiorellini 2005 Human Hard CT scan 20 ? 4 month: %1.17(1.23)Saldanha 2006 Human Hard Radio 21 21 6 month: %1.0 to 1.5 6 month: %0.1 to 1.3Barone 2008 Human Hard Re-entry (stent) 20 20 7 month: B %3.6(1.5) 7 month: %4.5(0.8)

L %3.0(1.6)M %0.4(1.2)D %0.5(1.0)

Kerr 2008 Human Hard CBVT(ref plate)

12 12 1 month:B %1.01(0.39) 1 month: %0.16(0.96)L %0.62(0.28) %0.62(0.24)3 month:B %0.95(0.9) %0.26(0.17)L %1.12(0.28) %0.10(0.10)

3 month: %2.20(0.81)%1.30(0.24)%0.59(0.17)%0.28(0.10)

Aimettl 2009 Human Hard Re-entry (stent) 18 18 3 month: B%1.2(0.6)L %0.9(1.1)M %0.5(0.9)D %0.5(1.1)

Crespi 2009 Human Hard Radio 15 15 3 month: %3.75(0.63)Moya-Villaescusa2010

Human Hard Radio 100 100 3 month: %4.32(0.23)

Pelegrine 2010 Human Hard Re-entry (pin) 6 15 6 month: %1.17(0.26)Rasperini 2010 Human Hard Stent 3 3 3 month: %2.2

6 month: %5.7(4.2)Yilmaz 1998 Human Hard Cast 5 10 3 month: %0.1(0.52) 3 month: %0.1(0.23)

12 month: %0.5(0.76) 12 month: %0.4(0.48)Rodd 2007 Human Hard Cast 16 16 3 month: 15.7%

6 month: 25.3%9 month: 22%(Bone surface area)

Oghli 2010 Human Hard Cast 72 101 3 month: %0.3(0.5)



with a net loss of 0.8 mm at 12 months

(Fig. 10).

Horizontal linear combined hard and soft tissuealteration

Four studies (Carlsson & Persson 1967; Yil-

maz et al. 1998; Schropp et al. 2003; Oghli &

Steveling 2010) presented data on the com-

bined hard and soft tissue change in the hori-

zontal dimension following extraction.

The only study using radiographic methods

(Carlsson & Persson 1967) demonstrated a

reduction of the alveolar width in the magni-

tude of 2.2 mm at 2 months, which subse-

quently increased to 3.6 mm at 12 months;

this measurement was taken 3 mm from the

alveolar crest.

Study casts were used in some of the stud-

ies (Yilmaz et al. 1998; Schropp et al. 2003;

Oghli & Steveling 2010) to evaluate the

change in the horizontal dimension (Fig. 11).

Yilmaz et al. (1998) showed a 3- and 12-

month reduction in width of 0.1 ± 0.23 mm

and 0.4 ± 0.48 mm respectively, while Oghli

& Steveling (2010) reported a 3-month reduc-

tion of 0.3 ± 0.5 mm. Horizontal resorption

of the alveolar hard and soft tissue between 3

and 12 months was also reported by Schropp

et al. (2003); at 3 months the resorption was

3.8 mm, this increased to 5.1 mm at

6 months and culminated to a value of

6.1 mm at 12 months.

The latter three studies (Yilmaz et al.

1998; Schropp et al. 2003; Oghli & Steveling

2010) had quite many similarities and an

attempt to calculate the weighted means for

these three studies was launched. However,

the study by Schropp et al. (2003) failed to

provide any information on the standard

deviations in the study, so it was impossible

to utilize the inverse variance method to cal-

culate the weighted means.

Cross-sectional surface area alteration of combinedalveolar hard and soft tissues

A single study reported on change in alveolar

surface area of the hard and soft tissues com-

bined (Rodd et al. 2007); measurements were

obtained from study casts acquired prior to,

and at 3, 6 and 9 months following extrac-

tion of maxillary central incisors in children.

The reductions in surface area were presented

as a percentage of the surface area on the pre-

extraction cast, and were as follows: 15.7%

at 3 months, 25.3% at 6 months and 22% at

9 months.

Overall combined hard and soft tissue changes

With the aid of various assessment methods,

a longitudinal change of the combined hard

and soft tissues in the vertical dimension

was found to be anywhere between a loss of

4.0 mm to a gain of 0.4 mm over a period of

2–12 months.

Study casts and radiographs were employed

to assess the reduction of the combined hard

and soft tissues in the horizontal dimension.

This reduction was demonstrated to be

between 0.1 and 6.1 mm when the observa-

tion periods varied from 3 to 12 months, and

the measurements were taken at the alveolar

crest. When the measurements were taken

3 mm apical to the alveolar crest, the corre-

sponding horizontal reductions of the com-

bined hard and soft tissues were 2.2 mm at

2 months and 3.6 mm at 12 months. Reduc-

tions in cross-sectional surface area of the tis-

sues were up to 22% after 9 months.

Mimicking the changes of the alveolar hard

tissue, there is a similar pattern of resorption

when we look at the combined hard and

soft tissue entity; the horizontal alteration is

always more substantial than the vertical

change.

Discussion

The 20 included studies in this systematic

review were of different study designs and

measured dimensional change in various

ways.

Eleven randomized controlled clinical tri-

als, five controlled clinical trials and four

cohort studies were included in this review.

It is common knowledge that randomized

controlled clinical trials and the systematic

review of randomized controlled clinical tri-

als provide the highest level of evidence

related to intervention and therapy. However,

in the case of post-extractional dimensional

changes of the alveolar hard and soft tissues,

there are no randomized controlled clinical

trials where the control procedure is where

the tooth was left in situ and the test proce-

dure was extraction. Hence, the cohort stud-

ies where post-extraction alveolar hard and

soft tissues changes were monitored longitu-

dinally might provide better insight and be

the more appropriate study design.

The three main measuring methods uti-

lized were: (i) re-entry (ii) imaging and (iii)

study models. The re-entry method consti-

tuted of elevating a flap during extraction

and again at re-evaluation. All the studies

using the re-entry method measured the

parameters from a fixed reference, namely an

acrylic stent or a titanium pin or screw. The

imaging method included the utilization of

periapical radiographs, lateral cephalometric

radiography, or computer tomography. The

method where study models were utilized

required that study impressions be taken

before, or immediately after extraction, and

again at re-evaluation.

Re-entry studies evaluated hard tissue as

well as soft tissues as separate entities, while

imaging studies evaluated either hard tissue

dimension only, or the combined hard and

soft tissue changes. Study model studies

focused on combined hard and soft tissue

dimensional changes. During data analysis

process, we subdivided the data into different

groups, mainly according to measurement

methods and the tissues involved. The

groups include (i) hard tissue group, (ii) soft

tissue group, and (iii) combined hard and soft

tissue group.

Heterogeneity assessment

The 20 included studies had different obser-

vation time points, methodologies, and

Fig. 10. Vertical (linear) change of hard and soft tissues

combined.

Fig. 11. Horizontal (linear) change of hard and soft tis-

sues combined.



measurement methods. Heterogeneity assess-

ment was performed in six re-entry studies

(Lekovic et al. 1997, 1998; Camargo et al.

2000; Iasella et al. 2003; Serino et al. 2003

and Pelegrine et al. 2010) calculating mean

vertical hard tissue change, and five studies

(Lekovic et al. 1997, 1998; Camargo et al.

2000; Iasella et al. 2003 and Pelegrine et al.

2010,) calculating horizontal hard tissue

change. These studies had similarity in terms

of the method of measurements employed.

The studies all employed re-entry methods,

utilizing an acrylic stent or a titanium pin or

screw as a fixed reference from which to

measure the dimensional changes. The differ-

ences in sample sizes, different behaviours of

study populations, varied observation time

points and measurement parameters contrib-

uted to the heterogeneity. Although weighted

means were calculated, the resultant values

should really only be used for reference pur-

poses. The robustness and applicability of the

weighted means should be interpreted with

caution.

Hard tissue vertical dimensional change

Buccal/lingual vs. mesial/distal

Three studies (Iasella et al. 2003; Barone

et al. 2008; Aimetti et al. 2009) measured

vertical dimensional changes of all the buc-

cal, lingual, mesial and distal bone plates.

Two of the three studies, namely Barone

et al. (2008) and Aimetti et al. (2009), demon-

strated that buccal/lingual sites (0.9–3.6 mm

loss at 3–7 months) had more resorption than

mesial/distal sites (0.4–0.5 mm loss at 3–

7 months). Referring to the calculated values

of the respective weighted mean, buccal bone

plates (1.24 mm loss at 3–7 months) also had

a tendency to resorb more than mesial/distal

bone sites (0.8–0.84 mm at 3–7 months)

(Fig. 2). One possible explanation for this

trend is that the mesial and distal bone levels

are partially determined by the presence or

absence of neighbouring teeth; mesial/distal

bone levels are held stable by the presence of

adjacent teeth.

Buccal vs. lingual

Iasella et al. (2003), Barone et al. (2008) and

Aimetti et al. (2009) measured vertical

dimensional changes at both buccal and lin-

gual bone plates. All three studies showed

that the buccal plate resorption (0.9–3.6 mm

at 3–7 months) was of greater magnitude

than that of the lingual plate (0.4–3 mm at 3

–7 months). This finding was similar to pre-

vious studies in the canine model (Araujo &

Lindhe 2005; Araujo et al. 2005). This pattern

of resorption can be explained by the bundle

bone concept as proposed by Araujo & Lind-

he (2005). According to this theory, a larger

proportion of the buccal plate is made up of

bundle bone relative to the lingual plate; as

bundle bone is a tooth-dependent tissue, it is

quickly resorbed after tooth extraction and

with its resorption, a substantial portion of

the buccal plate is lost. In our review of the

literature, however, the relative height differ-

ence between the buccal and lingual bone

plates in humans was less marked compared

to the canine model by Araujo & Lindhe

(2005). The relative difference in height of

the buccal and lingual plate is estimated to

be around 0.3–0.6 mm over a period of 3 and

7 months, in our review. One possible expla-

nation for the observed differences between

human models and canine models is that the

buccal plate in humans is on average equally

prone to resorption as the lingual aspect of

the ridge (Van der Weijden et al. 2009).

Mesial vs. distal

Four studies (Iasella et al. 2003; Serino et al.

2003; Barone et al. 2008 and Aimetti et al.

2009) measured vertical dimensional changes

of both mesial and distal bone plates. All four

studies showed the extent of resorption to be

between 0.4 and 0.8 mm over an observation

period of 3–7 months.

Hard tissue vertical dimensional percentagechange

Lekovic et al. (1997, 1998), Camargo et al.

(2000), Pelegrine et al. (2010) reported base-

line data of the internal socket height imme-

diately post-extraction. Internal socket height

is a measurement from buccal bone crest to

the bottom of the extraction socket. The pro-

vision of baseline internal socket height

enabled us to calculate the percentage change

in height of the buccal bone wall relative to

the baseline height of the buccal bone wall

over time. The percentage change reflected

the amount of vertical resorption of the buc-

cal plate only; this was found to be between

11% and 22% six months post-extraction.

Percentage changes of lingual, mesial and

distal bony plates could not be calculated due

to lack of baseline data, but it is expected to

be less than 11–22%, as the amount of

resorption in these areas have been shown to

be of a comparatively lesser magnitude. Cor-

respondingly, from this this percentage, we

can interpret that there might be 78–89%

bone fill of the original socket height, calcu-

lated as percentage vertical bone fill equals

one minus vertical dimensional percentage

change.

Hard tissue horizontal dimensional change

Five re-entry studies (Lekovic et al. 1997,


Pelegrine et al. 2010) showed that there was

range of 2.46–4.56 mm horizontal bone loss

and weighted mean resorption of 3.79 mm at

6 months. However, theses studies only pro-

vided data for horizontal resorption at the

level of the alveolar crest, no data was avail-

able on magnitude of horizontal resorption a

distance away from the alveolar crest. Kerr

et al. (2008) demonstrated a relative decrease

in horizontal ridge reduction as the distance

from the alveolar crest increased. This find-

ing was similar to a dog study done by Ara-

ujo & Lindhe (2009), which observed more

resorption at coronal third and least resorp-

tion at apical third of the alveolar ridge.

Hence, it is expected that the amount of hor-

izontal resorption might be less than

weighted mean of 3.79 mm at 6 months

when the measurement is taken at a distance

from the alveolar crest.

Hard tissue horizontal dimensional percentagechange

There was 32% reduction at 3 months, and

29–63% reduction in horizontal dimension

at 6 months. This demonstrated that possi-

bly more than half of the ridge width could

be resorbed after 6 months in some patients.

However, a definite conclusion cannot be

drawn from these data, on whether the

resorption was from the buccal or lingual.

Studies by Pietrokovski & Massler (1967),

Schropp et al. (2003), Araujo & Lindhe

(2005) and Barone et al. (2008) all suggest

that tissue loss is more pronounced on the

buccal aspect than from the lingual or pala-

tal aspect.

Vertical hard tissue vs. horizontal hard tissuechange

The amount of horizontal dimensional

change was found to be greater than that of

the vertical dimension, in both absolute val-

ues and percentage change. Horizontal reduc-

tion (3.79 ± 0.23 mm) was more than vertical

reduction (1.24 ± 0.11 mm on buccal, 0.84 ±

0.62 mm on mesial and 0.80 ± 0.71 mm on

distal) at 6 months. Percentage vertical

change was 11–22% at 6 months while per-

centage horizontal change was 32% at

3 months, and 29–63% between 6 and

7 months.

Soft tissue changes

Only one study by Iasella et al. (2003) was

found to have measured soft tissue thickness

change after extraction. There was a 0.4–



0.5 mm gain in soft tissue thickness on buc-

cal and lingual sites at 6 months. Interest-

ingly, from this study, a difference was found

in the change of soft tissue thickness over a

natural healing socket, and sockets aug-

mented using bio-resorbable membranes and

grafts. There was net gain of soft tissue

thickness in the natural healing group and a

net loss in the augmented group. One possi-

ble explanation for this observation was that

the membrane or graft placed might have

interfered with the soft tissue vascularity in

the augmented group. We must remember

that the vascular supply to the soft tissue is

derived from the underlying bone, and the

placement of membranes or grafts might

interfere with re-vascularization of the soft

tissues. In contrast, there is no interposing

material between the bone and the overlying

soft tissues in the naturally healing sockets.

Although there was an observed gain in soft

tissue thickness over a naturally healing

socket, a robust conclusion cannot be drawn

from this single study.

In addition, this study also demonstrated a

trend where the lingual soft tissues were

thicker than that on the buccal; lingual soft

tissues were nearly twice as thick. The meth-

ods and materials in the study could explain

this difference; majority of teeth extracted

within the study were maxillary teeth where

palatal soft tissue is expected to be much

thicker than that of the buccal. Hence, this

finding may only be applicable to the maxil-

lary extraction sockets, but not mandibular

ones. Note that this study only had a sample

size of 12 non-molar extraction sockets,

hence we should be cautious when trying to

interpret the results of this study.

Vertical combined hard and soft tissue change

Two studies by Yilmaz et al. (1998) and Sch-

ropp et al. (2003) demonstrated very subtle

changes in the vertical dimension of the hard

and soft tissues combined, between 3 and

12 months post-extraction. The changes ran-

ged from a gain of 0.1 mm to a loss of

0.9 mm at 6 months and a gain of 0.4 mm to

a loss of 0.8 mm at 12 months. Schropp et al.

(2003) also observed a small increase buccally

and a reduction orally.

Horizontal combined hard and soft tissuechange

Three studies (Yilmaz et al. 1998; Schropp

et al. 2003 and Oghli & Steveling 2010)

reported data on horizontal hard and soft tis-

sue changes. The studies by Yilmaz et al.

(1998) and Schropp et al. (2003) had a follow-

up of up to 12 months; both studies exhib-

ited a trend where there was a rapid reduc-

tion in first 3 months and gradual change

from thereafter, up to 12 months. Weighted

mean reduction showed this change to be

1.3 mm at 3 months and 5.1 mm at

12 months.

Vertical vs. horizontal combined hard and softchange

Hard and soft tissue showed a combined hori-

zontal reduction of 0.1–3.8 mm and 5.1 mm

at 3 and 6 months respectively. Correspond-

ingly, in the vertical dimension, this change

was between 0.1 and 0.8 mm reduction at

3 months, and 0.1 mm gain to 0.9 mm

reduction at 6 months. Overall, the demon-

strated horizontal change was more substan-

tial than the vertical change.

Combined hard and soft tissue change vs. hardtissue change only

In the horizontal dimension, the combined

hard and soft tissue reduction was 5.1 mm at

6 months, while the corresponding hard

tissue reduction was between 2.46 and

4.56 mm, with a weighted mean reduction of

3.79 mm.

Hence, at 6 months post-extraction, the

combined hard and soft tissues demonstrated

a tendency towards a more substantial reduc-

tion than hard tissue only; this observation is

not corroborated in the vertical aspect.

In the vertical dimension, when consider-

ing only hard tissue change (loss of 0.4–

1.5 mm at 6 months), the magnitude of this

change was greater than that of the hard and

soft tissues combined (0.1 mm gain to

0.9 mm reduction at 6 months). A plausible

explanation might be that the increase in soft

tissue thickness (gain of 2.1 mm occlusally

vs. gain of only 0.4–0.5 mm on buccal/lin-

gual) compensated for the reduction in hard

tissue height.

Possible factors affecting dimensional changeafter tooth extraction

Flap vs. flapless

Using a canine model, Fickl et al. (2008a)

demonstrated that there was significant dif-

ference of the extent of bone resorption

between flap and flapless extractions. The

flapless group had lower extent of resorption

compared to the flap group. Blanco et al.

(2008) also showed similar trend in another

study, although the study was investigating

ridge alterations after immediate implants

with or without flap. However, Araujo &

Lindhe (2009) found that the differences

between the flap and flapless groups in their

study were negligible after 6 months. Hence,

raising a flap during extraction may only

affect the short-term dimensional alterations

of the alveolar ridge.

Overeruption of adjacent teeth

Mizutani & Ishihata (1976) found that the

over-eruption of teeth adjacent to the extrac-

tion socket affected the overall dimensional

change of ridge. The vertical alveolar ridge

height in this study decreased slightly ini-

tially, followed by a gradual increase later on,

which negated the previous reduction or even

surpassed the amount of resorption to result

in a net gain. The study speculated that the

over-eruption of teeth adjacent to extraction

sites might have affected the pattern of

dimensional change observed.

Smoking

Smoking may affect the extent of vertical

reduction of the alveolar ridge after extrac-

tion. Saldanha et al. (2006) showed that

there was a significant difference in dimen-

sional reduction between smoking and non-

smoking groups. There was vertical alveolar

ridge reduction of 1.5 mm in smokers and

1.0 mm in non-smokers, 6 months post-

extraction.

Single-rooted vs. multiple-rooted teeth

Moya-Villaescusa & Sanchez-Perez (2010)

study showed there was no significant differ-

ence in vertical dimensional change between

single-rooted (4.16 mm loss) and multi-rooted

teeth (4.48 mm loss), although there was a

tendency that multi-rooted teeth exhibited

greater resorption of the alveolar ridge.

Chlorhexidine

Rinsing with 15 ml of 0.12% chlorhexidine

digluconate mouthrinse twice daily for

1 month, starting 2 days after extraction may

have some effect on the observed vertical

change of the mesial and distal bone. Bragger

et al. (1994) showed that patients rinsing for

1 month with a placebo solution lost almost

1 mm of bone height over a 6-month period

after extraction, while in patients rinsing

with the chlorhexidine solution, the crestal

alveolar bone level was maintained.

Immediate denture

Carlsson & Persson (1967) showed that there

was no significant difference in alveolar

dimensional change between patients with

immediate or conventional dentures in the

long-term. Take note, however, that the

usage of immediate dentures had a tendency

to affect dimensional change in short-term,



but the effect would be negligible after

2 years post-extraction.

Bone resorption pattern after 12 months

Only one study (Carlsson & Persson 1967)

followed dimensional changes in human

alveolar ridge for up to 5 years. This study

displayed a similar pattern where there was a

relatively rapid reduction in the first

6 months in both vertical and horizontal

dimension, followed by a gradual reduction

thereafter; the reduction continued at a

steady rate for up to 5 years. This finding

could suggest that bone resorption will con-

tinue throughout life once the teeth are

extracted. Take note, however, that all the

patients in this study wore complete den-

tures; dentures were inserted 2 months after

extractions in the conventional group and

immediately after extractions in the immedi-

ate group. We can speculate that the usage of

removable complete dentures may also affect

the pattern of resorption of the alveolar tis-

sues.

Conclusions

In conclusion, the studies included in this

review demonstrated that horizontal bone

loss (29–63%, 2.46–4.56 mm, weighted mean

3.79 mm at 6 months) was more substantial

than vertical bone loss (11–22%, 0.8–1.5 mm,

weighted mean 1.24 mm at 6 months) after

tooth extraction. The buccal aspect generally

displayed more resorption than the lingual/

palatal aspect. There is an observed resorp-

tion pattern of rapid reduction in the first 3–

6 months, followed by gradual reduction

thereafter, throughout life.

Soft tissue on the buccal and lingual sur-

faces of the alveolar ridge has a tendency to

increase in thickness after extraction, as

reported in one study; the significance of this

finding is as yet unknown. The same study

also documented that 6 months post-extrac-

tion, a soft tissue cover of 2.1 mm in thick-

ness developed over the original socket; this

soft tissue thickness that develops post-

extraction may mask the real extent of hard

tissue resorption and impact on the overall

outcome of any reconstructive efforts, espe-

cially with regard to aesthetics. However,

more studies might be required to arrive at a

more definitive value of soft tissue changes

post-extraction, and clarify the influence of

this change.

Overall, dimensional alterations of the

alveolar hard and soft tissues can be quite

extensive, and an astute clinician will do

well to understand the pattern and sequelae

of these changes, to arrive at predictable

treatment outcomes

Acknowledgement: This study has

been made possible by an educational grant

of the Osteology Foundation, Lucerne,

Switzerland.

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Rodd, H.D., Malhotra, R., O’Brien, C.H., Elcock, C.,

Davidson, L.E. & North, S. (2007) Change in sup-

porting tissue following loss of a permanent max-

illary incisor in children. Dental Traumatology

23: 328–332.

Saldanha, J.B., Casati, M.Z., Neto, F.H., Sallum, E.

A. & Nociti, F.H. Jr (2006) Smoking may affect

the alveolar process dimensions and radiographic

bone density in maxillary extraction sites: a pro-

spective study in humans. Journal of Oral &

Maxillofacial Surgery 64: 1359–1365.



changes following single-tooth extraction: a clini-


International Journal of Periodontics & Restor-


Serino, G., Biancu, S., Iezzi, G. & Piattelli, A.

(2003) Ridge preservation following tooth extrac-

tion using a polylactide and polyglycolide sponge

as space filler: a clinical and histological study in

humans. Clinical Oral Implants Research 14:

651–658.

Tallgren, A. (1972) The continuing reduction of

the residual alveolar ridges in complete denture

wearers: a mixed-longitudinal study covering

25 years. Journal of Prosthetic Dentistry 27: 120

–132.

Van der Weijden, F., Dell’Acqua, F. & Slot, D.E.

(2009) Alveolar bone dimensional changes of

post-extraction sockets in humans: a systematic

review. Journal of Clinical Periodontology 36:

1048–1058.

Yilmaz, S., Efeoglu, E. & Kilic, A.R. (1998) Alveolar

ridge reconstruction and/or preservation using

root form bioglass cones. Journal of Clinical Peri-


List of included articles:








versus extraction alone for ridge preservation

after tooth removal: a clinical and histomorpho-

metric study. Journal of Periodontology 79: 1370–

1377.

Bragger, U., Schild, U. & Lang, N.P. (1994) Effect of

chlorhexidine (0.12%) rinses on periodontal tissue

healing after tooth extraction. (II). Radiographic

parameters. Journal of Clinical Periodontology

21: 422–430.



Nadic, M., Jancovic, S. & Orsini, M. (2000) Influ-


cess dimensions after exodontia. Oral Surgery

Oral Medicine Oral Pathology Oral Radiology &

Endodontology 90: 581–586.

Carlsson, G.E. & Persson, G. (1967) Morphologic

changes of the mandible after extraction and

wearing of dentures. A longitudinal, clinical, and

x-ray cephalometric study covering 5 years. Od-

ontologisk Revy 18: 27–54.

Crespi, R., Cappare, P. & Gherlone, E. (2009) Mag-





ogy 80: 210–218.















J., Nummikoski, P.V. & Mellonig, J.T. (2008) The

effect of ultrasound on bone dimensional changes

following extraction: a pilot study. Journal of


Lekovic, V., Camargo, P.M., Klokkevold, P.R., We-

inlaender, M., Kenney, E.B., Dimitrijevic, B. &

Nedic, M. (1998) Preservation of alveolar bone in

extraction sockets using bioabsorbable mem-

branes. Journal of Periodontology 69: 1044–1049.

Lekovic, V., Kenney, E.B., Weinlaender, M., Han, T.,

Klokkevold, P., Nedic, M. & Orsini, M. (1997) A

bone regenerative approach to alveolar ridge main-

tenance following tooth extraction. Report of 10

cases. Journal of Periodontology 68: 563–570.

Moya-Villaescusa, M.J. & Sanchez-Perez, A. (2010)

Measurement of ridge alterations following tooth

removal: a radiographic study in humans. Clini-

cal Oral Implants Research 21: 237–242.





Pelegrine, A.A., da Costa, C.E., Correa, M.E. &

Marques, J.F. Jr (2010) Clinical and histomorpho-

metric evaluation of extraction sockets treated

with an autologous bone marrow graft. Clinical


Rasperini, G., Canullo, L., Dellavia, C., Pellegrini,

G. & Simion, M. (2010) Socket grafting in the

posterior maxilla reduces the need for sinus aug-

mentation. International Journal of Periodontics

& Restorative Dentistry 30: 265–273.

Rodd, H.D., Malhotra, R., O’Brien, C.H., Elcock, C.,

Davidson, L.E. & North, S. (2007) Change in sup-

porting tissue following loss of a permanent max-

illary incisor in children. Dental Traumatology

23: 328–332.

Saldanha, J.B., Casati, M.Z., Neto, F.H., Sallum, E.

A. & Nociti, F.H. Jr (2006) Smoking may affect

the alveolar process dimensions and radiographic

bone density in maxillary extraction sites: a pro-

spective study in humans. Journal of Oral &






International Journal of Periodontics & Restor-







651–658.

Yilmaz, S., Efeoglu, E. & Kilic, A.R. (1998) Alveolar




List of excluded full text articles and the reason for exclusion:

Agbaje, J.O., Jacobs, R., Michiels, K., Abu-Ta’a, M.

& van Steenberghe, D. (2009) Bone healing after

dental extractions in irradiated patients: a pilot

study on a novel technique for volume assess-

ment of healing tooth sockets. Clinical Oral

Investigations 13: 257–261.

Exclusion criteria: reported parameters not

relevant or not useful.



Ahn, J.J. & Shin, H.I. (2008) Bone tissue formation

in extraction sockets from sites with advanced

periodontal disease: a histomorphometric study

in humans. The International Journal of Oral &

Maxillofacial Implants 23: 1133–1138.

Exclusion criteria: no measurements of

alveolar dimensional changes (eg. description

of healing process or bony shape change, or

histology only).Alissa, R., Esposito, M., Horner, K. & Oliver, R.

(2010) The influence of platelet-rich plasma on

the healing of extraction sockets: an explorative

randomised clinical trial. European Journal of

Oral Implantology 3: 121–134.


relevant or not useful.Altundal, H. & Guvener, O. (2004) The effect of

alendronate on resorption of the alveolar bone fol-

lowing tooth extraction. The International Jour-

nal of Oral & Maxillofacial Surgery 33: 286–293.


relevant or not useful.Alves-Rezende, M.C. & Okamoto, T. (1997) Effects

of fibrin adhesive material (tissucol) on alveolar

healing in rats under stress. Brazilian Dental

Journal 8: 13–19.




histology only).Amemori, H. (1966) An experimental study of

changes in the form of the mandible after extrac-

tion of lower posterior teeth. I. The areal change

of mandibular frontal sections.. Bulletin of Tokyo

Medical & Dental University 13: 59–74.

Exclusion criteria: study carried out on ani-

mals.Anitua, E. (1999) Plasma rich in growth factors: pre-

liminary results of use in the preparation of

future sites for implants. The International Jour-

nal of Oral & Maxillofacial Implants 14: 529–

535.




histology only).Araujo, M., Linder, E., Wennstrom, J. & Lindhe, J.

(2008) The influence of bio-oss collagen on heal-

ing of an extraction socket: an experimental

study in the dog. International Journal of Peri-

odontics & Restorative Dentistry 28: 123–135.


relevant or not useful.Araujo, M.G. & Lindhe, J. (2005) Dimensional ridge

alterations following tooth extraction. An experi-

mental study in the dog.. Journal of Clinical Peri-


Exclusion criteria: only measured relative

difference in height between buccal and lin-

gual plates of the alveolus.Araujo, M.G. & Lindhe, J. (2009a) Ridge alterations




Exclusion criteria: no baseline data avail-

able for comparison, thus unable to arrive at

an estimate of dimensional change over time.Araujo, M.G. & Lindhe, J. (2009b) Ridge preserva-

tion with the use of bio-oss collagen: a 6-month


Research 20: 433–440.

Exclusion criteria: sample did not include

untreated/undisturbed extraction sockets left

to heal spontaneously.Araujo, M.G., Sukekava, F., Wennstrom, J.L. &

Lindhe, J. (2005) Ridge alterations following

implant placement in fresh extraction sockets: an

experimental study in the dog. Journal of Clin




to heal spontaneously.Ashman, A. & Bruins, P. (1985) Prevention of alveo-

lar bone loss postextraction with htr grafting

material. Oral Surgery Oral Medicine & Oral

Pathology 60: 146–153.

Exclusion criteria: descriptive report on

procedure/technique; commentary.Ashman, A. & Bruins, P. (1987) Prevention of alveo-

lar bone loss postextraction with htr polymer

grafting material. Journal of Oral Implantology

13: 270–281.


procedure/technique; commentary.Bahat, O., Deeb, C., Golden, T. & Komarnyckij, O.

(1987) Preservation of ridges utilizing hydroxyapa-

tite. International Journal of Periodontics &

Restorative Dentistry 7: 34–41.



to heal spontaneously.Bergstedt, H., Wictorin, L. & Lundquist, G. (1973)

Transplantation of bone treated with ethylenedia-

mine into tooth sockets in immediate denture

patients. Sven Tandlak Tidskr 66: 39–48.

Exclusion criteria: study subjects had

immediate dentures after extraction, hence

they did not have undisturbed healing post-

extraction.Berkovitz, B.K. (1971) The healing process in the

incisor tooth socket of the rat following root

resection and exfoliation. Archives of Oral Biol-

ogy 16: 1045–1054.




histology only).Bianchi, J., Fiorellini, J.P., Howell, T.H., Sekler, J.,

Curtin, H., Nevins, M.L. & Friedland, B. (2004)

Measuring the efficacy of rhbmp-2 to regenerate

bone: a radiographic study using a commercially

available software program. International Journal

of Periodontics & Restorative Dentistry 24: 579–

587.


relevant or not useful.Boyes-Varley, J.G., Cleaton-Jones, P.E. & Lownie, J.

F. (1988) Effect of a topical drug combination on

the early healing of extraction sockets in the ver-

vet monkey. The International Journal of Oral &



alveolar dimensional changes (e.g. description


histology only).Boyne, P.J. (1995) Use of htr in tooth extraction

sockets to maintain alveolar ridge height and

increase concentration of alveolar bone matrix.

General Dentistry 43: 470–473.


relevant or not useful.Brandao, A.C., Brentegani, L.G., Novaes, A.B. Jr,

Grisi, M.F., Souza, S.L., Taba Junior, M. & Salata,

L.A. (2002) Histomorphometric analysis of rat

alveolar wound healing with hydroxyapatite alone

or associated to bmps. Brazilian Dental Journal

13: 147–154.


relevant or not useful.Cardaropoli, G., Araujo, M., Hayacibara, R., Sukek-

ava, F. & Lindhe, J. (2005) Healing of extraction

sockets and surgically produced – augmented and

non-augmented – defects in the alveolar ridge. An

experimental study in the dog.. Journal of Clini-

cal Periodontology 32: 435–440.




histology only).Carlsson, G.E., Thilander, H. & Hedegard, B. (1967)

Histologic changes in the upper alveolar process

after extractions with or without insertion of an

immediate full denture. Acta Odontolologica

Scandinavica 25: 21–43.




histology only).Carmagnola, D., Adriaens, P. & Berglundh, T.

(2003) Healing of human extraction sockets filled

with bio-oss. Clinical Oral Implants Research

14: 137–143.




histology only).Dayan, D., Bodner, L. & Horowitz, I. (1992) Effect

of salivary gland hypofunction on the healing of

extraction wounds: a histomorphometric study in

rats. Journal of Oral & Maxillofacial Surgery 50:

354–358.




histology only).Fickl, S., Zuhr, O., Wachtel, H., Bolz, W. & Huerz-

eler, M. (2008b) Tissue alterations after tooth





mals.Fickl, S., Zuhr, O., Wachtel, H., Stappert, C.F.,

Stein, J.M. & Hurzeler, M.B. (2008c) Dimensional



changes of the alveolar ridge contour after differ-

ent socket preservation techniques. Journal of



mals.Fickl, S., Zuhr, O., Wachtel, H., Bolz, W. & Huerz-

eler, M.B. (2008c) Hard tissue alterations after

socket preservation: an experimental study in the

beagle dog. Clinical Oral Implants Research 19:

1111–1118.



an estimate of dimensional change over time.Gauthier, O., Boix, D., Grimandi, G., Aguado, E.,

Bouler, J.M., Weiss, P. & Daculsi, G. (1999) A

new injectable calcium phosphate biomaterial for

immediate bone filling of extraction sockets: a

preliminary study in dogs. Journal of Periodontol-

ogy 70: 375–383.


relevant or not useful.Gorustovich, A., Veinsten, F., Costa, O.R. & Gug-

lielmotti, M.B. (2004) Histomorphometric evalua-

tion of the effect of bovine collagen granules on

bone healing. An experimental study in rats. Acta

Odontologica Latinoamericana 17: 9–13.


relevant or not useful.Green, L.J., Gong, J.K. & Neiders, M.E. (1969) Rela-

tionship between sr85 uptake and histological

changes during healing in dental extractionwounds

in rats.Archives of Oral Biology 14: 865–872.




histology only).Guglielmotti, M.B. & Cabrini, R.L. (1985) Alveolar

wound healing and ridge remodeling after tooth

extraction in the rat: a histologic, radiographic,

and histometric study. Journal of Oral & Maxil-

lofacial Surgery 43: 359–364.


relevant or not useful.Guglielmotti, M.B., Ubios, A.M. & Cabrini, R.L.

(1985) Alveolar wound healing alteration under

uranyl nitrate intoxication. Journal of Oral

Pathology 14: 565–572.


relevant or not useful.Guglielmotti, M.B., Ubios, A.M. & Cabrini, R.L.

(1986) Alveolar wound healing after x-irradiation:

a histologic, radiographic, and histometric study.

Journal of Oral & Maxillofacial Surgery 44: 972–

976.



an estimate of dimensional change over time.Hahn, E., Sonis, S., Gallagher, G. & Atwood, D.

(1988) Preservation of the alveolar ridge with

hydroxyapatite-collagen implants in rats. Journal

of Prosthetic Dentistry 60: 729–734.


mals.Hars, E. & Massler, M. (1972) Effects of fluorides,

cortico-steroids and tetracyclines on extraction

wound healing in rats. Acta Odontologica Scan-

dinavica 30: 511–522.




histology only).Horn, Y., Sela, M.N., Shlomi, B., Ulmansky, M. &

Sela, J. (1979) Effect of irradiation-timing on the

initial socket healing in rats. International Jour-

nal of Oral Surgery 8: 457–461.




histology only).Hsieh, Y.D., Devlin, H. & McCord, F. (1995) The

effect of ovariectomy on the healing tooth socket

of the rat. Archives of Oral Biology 40: 529–531.



an estimate of dimensional change over time.Huebsch, R.F. & Hansen, L.S. (1969) A histopatho-

logic study of extraction wounds in dogs. Oral

Surgery Oral Medicine & Oral Pathology 28: 187

–196.




histology only).Iino, G., Nishimura, K., Omura, K. & Kasugai, S.

(2008) Effects of prostaglandin e1 application on

rat incisal sockets. The International Journal of

Oral & Maxillofacial Implants 23: 835–840.


relevant or not useful.Iizuka, T., Miller, S.C. & Marks, S.C. Jr (1992)

Alveolar bone remodeling after tooth extraction

in normal and osteopetrotic (ia) rats. Journal of

Oral Pathology & Medicine 21: 150–155.



to heal spontaneously.Indovina, A. Jr & Block, M.S. (2002) Comparison of 3

bone substitutes in canine extraction sites. Journal

of Oral & Maxillofacial Surgery 60: 53–58.


relevant or not useful.Kangvonkit, P., Matukas, V.J. & Castleberry, D.J.

(1986) Clinical evaluation of durapatite sub-

merged-root implants for alveolar bone preserva-

tion. The International Journal of Oral &





extraction.Lavelle, C.L. (1985) Preliminary study of mandibu-

lar shape after tooth loss. Journal of Prosthetic





histology only).Librus, H., Pietrokovski, J., Ulmanski, M. & Geda-

lia, I. (1973) The effect of fluoride on molar

socket healing in the rat. Archives of Oral Biol-

ogy 18: 1283–1289.




histology only).Lindeboom, J.A., Tjiook, Y. & Kroon, F.H. (2006)

Immediate placement of implants in periapical

infected sites: a prospective randomized study in

50 patients. Oral Surgery Oral Medicine Oral

Pathology Oral Radiology & Endodontology 101:

705–710.



to heal spontaneously.Loo, W.D. (1968) Ridge preservation with immedi-

ate treatment dentures. Journal of Prosthetic



procedure/technique; commentary.Luvizuto, E.R., Queiroz, T.P., Dias, S.M., Okamoto,

T., Dornelles, R.C., Garcia, I.R. Jr & Okamoto, R.

(2010) Histomorphometric analysis and immunol-

ocalization of rankl and opg during the alveolar

healing process in female ovariectomized rats

treated with oestrogen or raloxifene. Archives of

Oral Biology 55: 52–59.




histology only).Magro Filho, O. & de Carvalho, A.C. (1990) Appli-

cation of propolis to dental sockets and skin

wounds. Journal of Nihon University School of





histology only).Magro-Ernica, N., Magro-Filho, O. & Rangel-Garcia,

I. (2003) Histologic study of use of microfibrillar

collagen hemostat in rat dental sockets. Brazilian

Dental Journal 14: 12–15.


relevant or not useful.Mathai, J.K., Chandra, S., Nair, K.V. & Nambiar, K.

K. (1989) Tricalcium phosphate ceramic as imme-

diate root implants for the maintenance of alveo-

lar bone in partially edentulous mandibular jaws.

A clinical study. Australian Dental Journal 34:

421–426.


relevant or not useful.Matsumoto, M. (1968) Changes in residual ridge of

the mandible after extraction and wearing exten-

sion saddle type of removable partial dentures. (a

longitudinal, clinical and roentgenographic inves-

tigation). Bulletin of Tokyo Medical & Dental

University 15: 67–89.

Exclusion criteria: length of observation

period not reported.Michael, C.G. & Barsoum, W.M. (1976) Comparing

ridge resorption with various surgical techniques

in immediate dentures. Journal of Prosthetic

Dentisty 35: 142–155.






extraction.Minsk, L. (2005) Extraction-site ridge preservation.

Compendium of Continuing Education in Den-

tistry 26: 272.


procedure/technique; commentary.Mizutani, H. & Ishihata, N. (1976) Decrease and

increase in residual ridges after extraction of

teeth in monkeys (part I). Bulletin of Tokyo Med-

ical & Dental University 23: 157–168.


mals.Nevins, M., Camelo, M., De Paoli, S., Friedland, B.,

Schenk, R.K., Parma-Benfenati, S., Simion, M.,

Tinti, C. & Wagenberg, B. (2006) A study of the

fate of the buccal wall of extraction sockets of

teeth with prominent roots. International Journal

of Periodontics & Restorative Dentistry 26: 19–

29.


relevant or not useful.Nevins, M.L., Camelo, M., Schupbach, P., Kim, D.

M., Camelo, J.M. & Nevins, M. (2009) Human his-

tologic evaluation of mineralized collagen bone

substitute and recombinant platelet-derived

growth factor-bb to create bone for implant place-

ment in extraction socket defects at 4 and

6 months: a case series. International Journal of

Periodontics & Restorative Dentistry 29: 129–139.



to heal spontaneously.Normando, A.D., Maia, F.A., Ursi, W.J. & Simone,

J.L. (2010) Dentoalveolar changes after unilateral

extractions of mandibular first molars and their

influence on third molar development and posi-

tion. World Journal of Orthodontics 11: 55–60.


relevant or not useful.Olson, H.M. & Hagen, A. (1982) Inhibition of post-

extraction alveolar ridge resorption in rats by di-

chloromethane diphosphonate. Journal of Peri-

odontal Research 17: 669–674.


mals.Olson, R.A., Roberts, D.L. & Osbon, D.B. (1982) A

comparative study of polylactic acid, gelfoam,

and surgicel in healing extraction sites. Oral Sur-

gery Oral Medicine & Oral Pathology 53: 441–

449.




histology only).Oltramari, P.V., Navarro Rde, L., Henriques, J.F.,

Taga, R., Cestari, T.M., Janson, G. & Granjeiro, J.

M. (2007) Evaluation of bone height and bone

density after tooth extraction: an experimental

study in minipigs. Oral Surgery Oral Medicine

Oral Pathology Oral Radiology & Endodontology

104: 9–16.


mals.Ortega, K.L., Rezende, N.P., Araujo, N.S. & Ma-

galhaes, M.H. (2007) Effect of a topical antimicro-

bial paste on healing after extraction of molars in

hiv positive patients: randomised controlled clini-

cal trial. British Journal of Oral & Maxillofacial

Surgery 45: 27–29.


relevant or not useful.Pessoa, R.S., Oliveira, S.R., Menezes, H.H. & de

Magalhaes, D. (2009) Effects of platelet-rich

plasma on healing of alveolar socket: split-mouth

histological and histometric evaluation in cebus

apella monkeys. Indian Journal of Dental

Research 20: 442–447.



an estimate of dimensional change over time.Pietrokovski, J. (1967) Healing of the socket

following tooth extraction. Alpha Omegan 60:

126–129.




histology only).Pietrokovski, J. & Massler, M. (1967a) Alveolar

ridge resorption following tooth extraction. Jour-

nal of Prosthetic Dentistry 17: 21–27.

Exclusion criteria: length of observation

period not reported.Pietrokovski, J. & Massler, M. (1967b) Ridge remod-

eling after tooth extraction in rats. Journal of

Dental Research 46: 222–231.




histology only).Pietrokovski, J. & Massler, M. (1971) Residual ridge

remodeling after tooth extraction in monkeys.

Journal of Prosthetic Dentistry 26: 119–129.




histology only).Pinto, J.R., Bosco, A.F., Okamoto, T., Guerra, J.B. &

Piza, I.G. (2002) Effects of nicotine on the healing

of extraction sockets in rats. A histological study.

Brazilian Dental Journal 13: 3–9.




histology only).Puia, S.A., Renou, S.J., Rey, E.A., Guglielmotti, M.

B. & Bozzini, C.E. (2009) Effect of bismuth sub-

gallate (a hemostatic agent) on bone repair; a his-

tologic, radiographic and histomorphometric

study in rats. The International Journal of Oral

& Maxillofacial Surgery 38: 785–789.


relevant or not useful.Quinn, J.H. & Kent, J.N. (1984) Alveolar ridge

maintenance with solid nonporous hydroxylapa-

tite root implants. Oral Surgery Oral Medicine &

Oral Pathology 58: 511–521.




histology only).Richardson, A. (1965) The pattern of alveolar bone

resorption following extraction of anterior teeth.

Dental Practitioner & Dental Record 16: 77–80.


relevant or not useful.Rothamel, D., Schwarz, F., Herten, M., Engelhardt,

E., Donath, K., Kuehn, P. & Becker, J. (2008)

Dimensional ridge alterations following socket

preservation using a nanocrystalline hydroxyapa-

tite paste: a histomorphometrical study in dogs.


cial Surgery 37: 741–747.



an estimate of dimensional change over time.Sattayasanskul, W., Brook, I.M. & Lamb, D.J. (1988)

Dense hydroxyapatite root replica implantation:

measurement of mandibular ridge preservation.






extraction.Scheer, P. & Boyne, P.J. (1987) Maintenance of alve-

olar bone through implantation of bone graft sub-

stitutes in tooth extraction sockets. Journal of

the American Dental Association 114: 594–597.


procedure/technique; commentary.Sclar, A.G. (1999) Preserving alveolar ridge anatomy

following tooth removal in conjunction with

immediate implant placement. The bio-col tech-

nique. Atlas of the Oral & Maxillofacial Surgery

Clinics of North America 7: 39–59.


procedure/technique; commentary.Serino, G., Rao, W., Iezzi, G. & Piattelli, A. (2008)

Polylactide and polyglycolide sponge used in

human extraction sockets: bone formation fol-

lowing 3 months after its application. Clinical





histology only).Sharan, A. & Madjar, D. (2008) Maxillary sinus

pneumatization following extractions: a radio-

graphic study. The International Journal of Oral

& Maxillofacial Implants 23: 48–56.




histology only).Shi, B., Zhou, Y., Wang, Y.N. & Cheng, X.R. (2007)

Alveolar ridge preservation prior to implant place-

ment with surgical-grade calcium sulfate and

platelet-rich plasma: a pilot study in a canine



model. The International Journal of Oral & Max-

illofacial Implants 22: 656–665.


mals.Smith, N. (1974) A comparative histological and

radiographic study of extraction socket healing in

the rat. Australian Dental Journal 19: 250–254.




histology only).Teofilo, J.M., Brentegani, L.G. & Carvalho, T.L.

(2001) A histometric study in rats of the effect of

the calcium antagonist amlodipine on bone heal-

ing after tooth extraction. Archives of Oral Biol-

ogy 46: 375–379.


relevant or not useful.

Teofilo, J.M., Leonel, D.V. & Lamano, T. (2010)

Cola beverage consumption delays alveolar bone

healing: a histometric study in rats. Brazilian

Oral Research 24: 177–181.




histology only).Thilander, H. & Astrand, P. (1973) The effect of tet-

racyclines on socket healing. Acta Odontologica

Scandinavica 31: 131–139.




histology only).Ubios, A.M., Jares Furno, G. & Guglielmotti, M.B.

(1991) Effect of calcitonin on alveolar wound

healing. Journal of Oral Pathology & Medicine

20: 322–324.


relevant or not useful.Wu, Z., Liu, C., Zang, G. & Sun, H. (2008) The

effect of simvastatin on remodelling of the alveo-

lar bone following tooth extraction. The Interna-

tional Journal of Oral & Maxillofacial Surgery

37: 170–176.



to heal spontaneously.Yugoshi, L.I., Sala, M.A., Brentegani, L.G. & Lama-

no Carvalho, T.L. (2002) Histometric study of

socket healing after tooth extraction in rats trea-

ted with diclofenac. Brazilian Dental Journal 13:

92–96.



to heal spontaneously.



Copyright of Clinical Oral Implants Research is the property of Wiley-Blackwell and its content may not becopied or emailed to multiple sites or posted to a listserv without the copyright holder's express writtenpermission. However, users may print, download, or email articles for individual use.

Osteology Consensus Report

Christoph H.F. HammerleMauricio G. AraujoMassimo SimionMauricio G. Araujo

Evidence-based knowledge on thebiology and treatment of extractionsockets

Authors’ affiliations:Christoph H.F. Hammerle, Center of DentalMedicine, Clinic of Fixed and RemovableProsthodontics and Dental Material Science,University of Zurich, Zurich, SwitzerlandMauricio G. Araujo, Department of Dentistry, StateUniversity of Maringa, Parana, BrazilMassimo Simion, Departmet of Periodontology,IRCCS Ca Granda Foundation – Ospedale MaggiorePoliclinico, Department of Reconstructive, Surgicaland Diagnostic Science, University of Milan,Department of Periodonology, College of Dentistry,King Saud University, Riyadh, Saudi ArabiaMauricio G. Araujo, Department of Dentistry, StateUniversity of Maringa, Parana, Brazil

Corresponding author:Mauricio G. AraujoDepartment of DentistryState University of MaringaParana, BrazilTel.: +41 44 634 32 51Fax: +41 44 634 43 05e-mail: [email protected]

Conflicts of interestThe authors declare no conflicts of interest.

Key words: bone regeneration, clinical research, clinical trials, guided tissue regeneration,

wound healing

Abstract

Objectives: The fresh extraction socket in the alveolar ridge represents a special challenge in

everyday clinical practice. Maintenance of the hard and soft tissue envelope and a stable ridge

volume were considered important aims to allow simplifying subsequent treatments and

optimizing their outcomes in particular, when implants are planned to be placed.

Material and Methods: : Prior to the consensus meeting four comprehensive systematic reviews

were written on two topics regarding ridge alteration and ridge preservation following tooth

extraction and implant placement following tooth extraction. During the conference these

manuscripts were discussed and accepted thereafter. Finally, consensus statements and

recommendations were formulated.

Results: : The systematic reviews demonstrated that the alveolar ridge undergoes a mean

horizontal reduction in width of 3.8 mm and a mean vertical reduction in height of 1.24 mm

within 6 months after tooth extraction. The techniques aimed at ridge preservation encompassed

two different approaches: i) maintaining the ridge profile, ii) enlarging the ridge profile.

Regarding timing of implant placement the literature showed that immediate implant placement

leads to high implant survival rates. This procedure is primarily recommended in premolar sites

with low esthetic importance and favorable anatomy. In the esthetic zone, however, a high risk for

mucosal recession was reported. Hence, it should only be used in stringently selected situations

with lower risks and only by experienced clinicians. In molar sites a high need for soft and hard

tissue augmentation was identified.

Conclusions: : Future research should clearly identify the clinical and patient benefits resulting

from ridge preservation compared with traditional procedures. In addition, future research should

also aim at better identifying parameters critical for positive treatment outcomes with immediate

implants. The result of this procedure should be compared to early and late implant placement.

The fresh extraction socket in the alveolar

ridge represents a special challenge in every-

day clinical practice. Regardless of the subse-

quent treatment maintenance of the ridge

contour will frequently facilitate all further

steps of therapy. This is particularly true for

treatments involving the placement and

reconstruction of dental implants. It has been

demonstrated in numerous animal and clini-

cal studies in humans that following tooth

extraction undisturbed wound healing will

lead to loss of ridge volume and change in

ridge shape.

The aim of the present consensus report

was to critically evaluate the scientific evi-

dence regarding ridge alterations following

tooth extraction and to assess the effects of

treatment strategies aiming at preservation of

the ridge following tooth extraction. Further-

more, this consensus analyzed the clinical

outcomes of implant placement into sockets

at different time spans following tooth

extraction.

Workshop discussion andconsensus

The group discussing the evidence and gener-

ating the consensus statements consisted of

individuals competent in different disciplines

of medical dentistry with a special emphasis

on implant therapy. Prior to the consensus

meeting, two groups of researchers wrote

comprehensive systematic reviews on two

topics each regarding ridge alterations and

*Osteology Consensus Group 2011: Mauricio G. Araujo,Maringa, Parana, Brazil; Dieter Bosshardt, Daniel Buser,Berne, Switzerland; William V. Giannobile, Ann Arbor,Michighan, USA; Reinhard Gruber, Vienna, Austria; Chr-istoph H.F. Hammerle, Ronald E. Jung, Zurich, Switzer-land; Niklaus P. Lang, Hong Kong SAR PRC; MyronNevins, Boston, Massachusetts, USA; Friedrich Neukam,Nuremberg, Germany; Mariano Sanz, Madrid, Spain;Massimo Simion, Milano, Italy; Georg Watzek, Vienna,Austria

Date:Accepted 8 October 2011

To cite this article:CHF Hammerle, Araujo MG, Simion M, On Behalf of theOsteology Consensus Group 2011. Evidence-based knowledgeon the biology and treatment of extraction sockets.Clin. Oral Impl. Res. 23(Suppl. 5), 2012, 80–82doi: 10.1111/j.1600-0501.2011.02370.x









ridge preservation following tooth extraction

and implant placement following tooth

extraction.

During the conference, the reviewers first

presented their manuscripts explaining how

the literature search was conducted, how the

data were extracted, analyzed, which results

were found and which conclusions could be

drawn. The entire group then discussed these

reports. Thereafter, all four manuscripts were

accepted. Another thorough discussion fol-

lowed on published data on lower levels of

evidence than the one included in the manu-

scripts and its impact on the conclusions to

be drawn. Finally, the group formulated con-

sensus statements and recommendations for

clinical practice and for future research.

Ridge preservation

Definition of terms

The group considered it important to define

terms regarding the various procedures,

which previously had been described in the

literature under the general term of “ridge

preservation.” It was obvious that a distinc-

tion needed to be made as described below.

Ridge preservation = preserving the ridge

volume within the envelope existing at the

time of extraction

Ridge augmentation = increasing the ridge

volume beyond the skeletal envelope existing

at the time of extraction

Consensus statements regarding ridgepreservation

The systematic review by Lang et al. (2012)

demonstrated that based on clinical studies

the alveolar ridge undergoes the following

dimensional changes within 6 months after

tooth extraction:

• Mean horizontal reduction in ridge width:

3.8 mm.

• Mean vertical reduction in ridge height:

1.24 mm.

Based on the systematic review by Vigno-

letti et al. (2012) the group concluded that

the reasons for ridge preservation included:

• Maintenance of the existing soft and hard

tissue envelope.

• Maintenance of a stable ridge volume for

optimizing functional and esthetic out-

comes.

• Simplification of treatment procedures

subsequent to the ridge preservation

(i) Generation of a good soft tissue volume

for the time of implant placement thus

simplifying implantation procedures at

earlier time points.

(ii) Generation of a good hard tissue volume

for the time of implant placement thus

simplifying implantation procedures at

later time points.

No high level evidence was found in the

literature regarding contraindications specific

for ridge preservation. Hence, the group made

the following consensus.

Contraindication for ridge preservation was

considered to encompass:

• General contraindication against oral sur-

gical interventions.

Furthermore:

• Infections at the site planned for ridge

preservation, which cannot be taken care

of during the ridge preservation surgery.

• Patients radiated in the area planned for

ridge preservation.

• Patients taking bisphosphonates.

Various techniques have been described in

the literature for so called ridge preserva-

tion. These techniques may be categorized

into two different groups: (i) techniques aim-

ing at maintaining the ridge profile (ridge

preservation), (ii) techniques aiming at

enlarging the ridge profile (ridge augmenta-

tion).

To enlarge the ridge profile flaps have

generally been raised and augmentation pro-

cedures using biomaterials for ridge contour-

ing with or without barrier membranes

have been performed. It appears that pri-

mary closure of the wound is beneficial

regarding the volume gained applying this

approach.

These indications were identified for ridge

preservation:

• Implant placement is planned at a time

point later than tooth extraction i.e.,

(i) When immediate or early implanta-

tion is not recommendable

(ii) When patients are not available for

the immediate or early implant

placement (pregnancy, holidays, …)

(iii) When primary stability of an

implant cannot be obtained

(iv) In adolescent people

• Contouring of the ridge for conventional

prosthetic treatment.

• Provided the cost/benefit ratio is positive.

• Reducing the need for elevation of the

sinus floor.

Regarding indication other than the ones

mentioned above, there is little or no evi-

dence.

Clinical recommendations regarding ridgepreservation

In general, the group made the following clin-

ical recommendations:

• Raising of a flap and placement of bioma-

terials (biomaterial for ridge contouring

and/or barrier membrane).

• Primary would closure.

• Materials with a low resorption and

replacement rate.

• Raising of flaps and placement of a

device/devices for contouring the ridge

profile.

Regarding the different materials applied in

clinical studies the systematic review did not

show significant differences between the var-

ious materials, (i.e., filler, membranes) except

for the collagen plug alone, which revealed

negative results.

Although primary wound closure was gen-

erally considered an important factor for suc-

cess, the literature did not allow a

meaningful comparison of different tech-

niques for primary wound closure (soft tissue

punch, connective tissue graft, barrier mem-

brane, soft tissue replacement matrix).

Future research regarding ridge preservation

Regarding future research the consensus sta-

ted the following:

• Focus on patient centered outcomes.

• Focus on clinical short-, medium-, and

long-term outcomes including biological,

technical, phonetic, and esthetic parame-

ters.

• Studies regarding possible benefits during

subsequent implant therapy encompass-

ing:

(i) Assessing the need for further hard and

soft tissue augmentation

(ii) Assessing the amount of further hard

and soft tissue augmentation.

(iii) Assessing esthetic outcomes.

• Conditions of the soft tissues, i.e., dis-

placement of the muco-gingival junction,

color of the ridge mucosa, amount of ker-

atinized mucosa.

• Techniques for soft tissue management, i.

e., raising of flaps yes/no.

• Method for soft tissue closure.

• Influence of the hard and soft tissue anat-

omy following tooth extraction: presence

or absence of bony socket walls, thick-

© 2011 John Wiley & Sons A/S 81 | Clin. Oral Impl. Res. 23(Suppl. 5), 2012/80–82

Hammerle et al !Evidence for treatment of extraction sockets










ness of the bony socket walls, soft tissue

area, volume, color, scars.

• Effect of various biomaterials applied for

ridge contouring.

• Effect of various biomaterials applied as

barrier membranes.

• Methodological studies on the optimal

type of measurements to assess the out-

come of treatment regarding soft tissue

and hard tissues.

• Development of consistent reference

points for 3D imaging technologies, when

studying changes in ridge morphology

regarding soft and/or hard tissues.

• Studies on the normal anatomy regarding

bone and soft tissue thickness and types

in different regions of the jaws.

• Studies on the effects of different extrac-

tion techniques on subsequent healing.

• Identify the most appropriate control

group for pre-clinical and clinical studies.

Timing for implant placement

Two systematic reviews were available (Lau

et al. 2012; Sanz et al. 2012) regarding timing

of implant placement into extraction sockets.

Both reviews focused on the highest level of

scientific evidence and were conducted with

reasonable and clearly defined inclusion and

exclusion criteria.

Consensus statements regarding timing forimplant placement

Limited to esthetic sites the systematic

reviews lead to following conclusions:

• Immediate implant placement leads to

high implant survival rates.

• Immediate implant placement is associ-

ated with a high risk for mucosal recession.

A wide range regarding the amount of

recessions is reported in the literature.

• Several risk factors for the development

of mucosal recession have been identified:

(i) Smoking

(ii) Presence of a thin buccal bone plate

(i.e., <1 mm thick)

(iii) Presence of a thin soft tissue biotype

(iv) Facial implant position

• Augmentation of soft and hard tissues is

frequently necessary.

• The procedure of immediate implant place-

ment into extraction sockets should be

used very restrictively in the esthetic area.

Limited to posterior sites the systematic

review by Lau et al. 2012 lead to the follow-

ing conclusions:

• For single tooth implants high survival

and low complication rates have been

reported.

• Molar sites present situations with lim-

ited indications due to anatomical rea-

sons.

• When immediate implants are placed in

molar sites, soft and hard tissue augmen-

tation is frequently necessary.

• Premolars represent the sites with the

most favorable indication due to the nor-

mally favorable anatomical situation and

the generally low esthetic demands.

The treatments of fully edentulous jaws

and of multiple extraction sites have not

been duly addressed in the literature.

Clinical recommendations regarding timing forimplant placement

As based on the literature the group con-

cluded that in situations, where no risk fac-

tors are present (situations rarely occurring),

this procedure may be recommended for

experienced clinicians.

Immediate implant placement is primarily

recommended in premolar sites with low

esthetic importance and favorable anatomy.

In areas of esthetic priority implant installa-

tion into the fresh extraction socket (Type I

placement) is not recommended.

Several published prospective case series

not included in the present systematic review

using the early implant placement protocol

have reported intermediate to long-term

excellent esthetic results (Belser et al. 2009;

Buser et al. 2011). These results lend addi-

tional support to the recommendation of type

II instead of type I implant placement follow-

ing tooth extraction in esthetic sites.

Future research regarding timing for implantplacement

These recommendations are valid for both

anterior and posterior sites.

• Reporting of frequency analyses of com-

plication should become standard.

• Studies addressing immediate implanta-

tion in the absence of risk factors.

• Comparison of surgical approaches with

and without the elevation of flaps.

• Comparison of surgical approaches with

and without filler materials in the gap

between the buccal aspect of the implant

and the buccal bone wall.

• Assess the influence of the distance of

the implant to the buccal bone wall on

bone formation.

• Comparison of different filler materials in

different clinical situations.

• Comparison of type 1 (immediate) and

type 2 (early) implant placement in low

risk situations.

• Comparison of type 2 (early) and type 3

(delayed) implant placement.

• Identify the ideal clinical protocols and

the best biomaterials for type 1, type 2,

and type 3 implant placement.

• Changes in the contours of the ridge over

extended periods of time.

References

Belser, U.C., Grutter, L., Vailati, F., Bornstein, M.

M., Weber, H.-P. & Buser, D. (2009) Outcome

evaluation of early placed maxillary anterior sin-

gle-tooth implants using objective esthetic crite-

ria: a cross-sectional, retrospective study in 45

patients with a 2- to 4-year follow-up using pink

and white esthetic scores. Journal of Periodontol-

ogy 80: 140–151.

Buser, D., Wittneben, J., Bornstein, M.M., Grutter,

L., Chappuis, V. & Belser, U.C. (2011) Stability of

contour augmentation and esthetic outcomes of

implant-supported single crowns in the esthetic

zone: 3-year results of a prospective study with

early implant placement postextraction. Journal


Lang, N.P., Pun, B.L., Lau, I.K.Y., Li, K.Y. & Wong,

M.C.M. (2012) A systematic review on survival

and success rates of implants placed immediately

into fresh extraction sockets after at least one

year. Clinical Oral Implants Research 23(Suppl.

5): 39–66.

Sanz, I., Garcia-Gargallo, M., Herrara, D., Martin,

C., Figuero, E. & Sanz, M. (2012) Surgical proto-

cols for early implant placement in post-extrac-

tion sockets. A systematic review. Clinical Oral

Implants Research 23(Suppl. 5): 67–79.

Tan, W.L., Wong, T.W.L., Wong, M.C.M. & Lang,

N.P. (2012) A systematic review of post-extract-

ional alveolar bone dimensional changes in

humans. Clinical Oral Implants Research 23

(Suppl. 5): 1–21.

Vignoletti, F., Matesanz, P., Rodrigo, D., Figuero,

E., Martin, C. & Sanz, M. (2012) Surgical proto-

cols for ridge preservation after tooth extraction.

A systematic review. Clinical Oral Implants

Research 23(Suppl. 5): 22–38.

82 | Clin. Oral Impl. Res. 23(Suppl. 5), 2012/80–82 © 2011 John Wiley & Sons A/S

Hammerle et al !Evidence for treatment of extraction sockets


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The International Journal of Periodontics & Restorative Dentistry

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Volume 33, Number 1, 2013

71

Tooth extraction may lead to dif-ferent patterns of bone resorption, apposition, and remodeling that make it dif!cult to predict the !-nal ridge contour and dimension. The clinician’s decision to augment extraction sockets is important be-cause ungrafted extraction sockets may undergo progressive bone resorption without intervention.1–3 Complete bone regeneration to the pre-extraction crestal bone level is not always possible, regard-less of grafting materials or the use of barrier membranes.2–4

Autogenous bone has been considered the gold standard for bone grafting, but the morbidity and complications associated with harvesting have provided a reason to consider alternatives. Alloplas-tic biomaterials such as hydroxy-apatite (HA) and !–tricalcium phosphate (!-TCP) are promising bone substitutes because of their unlimited supply, but a lack of evi-dence and inconsistent clinical re-ports have made clinicians weary of their use.5–8

A barrier membrane is com-monly used in conjunction with a bone graft to maintain space and foster selective osteogenic cells

1 Assistant Professor, Division of Periodontology, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.

2 Assistant Professor, University of Genoa, Genoa, Italy.3 Institute for Advanced Dental Studies, Belo Horizonte, Brazil.4 Assistant Clinical Professor, Division of Periodontology, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA.

5 Schupbach Ltd, Service and Research for Histology, Microscopy and Imaging, Horgen, Switzerland.6 Associate Clinical Professor, Division of Periodontology, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA. Correspondence to: Dr David M. Kim, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA 02115, USA; fax: 617-432-1897; email: [email protected]. ©2013 by Quintessence Publishing Co Inc.

David M. Kim, DDS, DMSc1/Nicola De Angelis, DDS2/Marcelo Camelo, DDS3 Marc L. Nevins, DMD, MMSc4/Peter Schupbach, PhD5/Myron Nevins, DDS6

The purpose of this study was to determine the clinical and histologic ef!cacy of the combination of alloplastic biphasic calcium phosphate composed of 30% hydroxyapatite and 70% !–tricalcium phosphate (Osteon II) and a cross-linked collagen membrane used to reconstruct an extraction socket with new bone formation. Twelve patients, from two private dental practices, requiring extraction of maxillary and mandibular nonmolar teeth (n = 30) received both Osteon II (0.5- to 1.0-mm particle size) and the collagen membrane. The primary healing intention group (group A, n = 12) received primary "ap closure over the membrane, while in the secondary healing intention group (group B, n = 18), the membrane was left exposed. Early wound healing seemed to be slower in group B when compared to group A, but the difference was not noticeable after 4 weeks. Clinical reentry revealed that the dimensions of the ridge appeared to be maintained in both groups, and internal socket bone !ll was evident. The grafted area appeared to be well vascularized, but clinically visible graft particles were noted in some cases. Light microscopic analysis revealed the formation of new bone directly apposing the surfaces of graft particles and bridging the space between them, indicating that the graft material behaved as an osteoconductive scaffold. The mean amount of vital bone in group A was 40.3% ± 7.8%, while the remaining graft was 6.0% ± 4.0%. The mean amount of vital bone in group B was 47.3% ± 11.3%, while the remaining graft was 18.0% ± 20.0%. The absence of primary "ap closure did not affect the percentage of vital bone formation or residual graft. (Int J Periodontics Restorative Dent 2013;33:71–78. doi: 10.11607/prd.1463)

Ridge Preservation With and Without Primary Wound Closure: A Case Series

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72

to populate the defect while ex-cluding epithelial cells and !bro-blasts.9 Resorbable membranes are accompanied by fewer adverse events than nonresorbable mem-branes when exposed because they degrade naturally.10,11 Ex-posed non–cross-linked collagen membranes may resorb too quickly to accommodate bone formation, while cross-linked collagen mem-branes may allow stabilization of the collagen !bers to maintain the membrane’s integrity.11,12

The purpose of this study was to determine the clinical and histo-logic ef!cacy of the combination of alloplastic biphasic calcium phos-phate composed of 30% HA and 70% !-TCP (Osteon II, Dentium) and a cross-linked collagen mem-brane (Collagen Membrane, Dentium) used to reconstruct an extraction socket with new bone formation. In addition, the safety and ef!cacy of soft and hard tis-sue regeneration in sites with in-

tentional exposure of the collagen membrane was investigated.

Method and materials

Twelve patients (2 men, 10 women; age range, 33 to 70 years), from two private dental practices, requiring extraction of maxillary and mandib-ular nonmolar teeth (n = 30) partici-pated in this outpatient study. They required removal of one or more teeth and expressed a desire for replacement with dental implants. Patients were systemically healthy with no surgical contraindications. Oral and written explanations of the study, including the risks, bene-!ts, and alternative therapies, were thoroughly discussed. All patients volunteered for the protocol and signed an informed consent form based on the Helsinki Declaration of 1975, as revised in 2000. Preop-erative assessments including intra-oral examination, and radiographic

evaluations (periapical radiographs and computed tomography [CT] scans) were performed.

The surgical procedure was performed under local anesthe-sia (2% xylocaine with 1:100,000 epinephrine). An intrasulcular inci-sion was extended along the study teeth followed by elevation of buc-cal and lingual full-thickness "aps (Fig 1). Atraumatic tooth extrac-tions were performed to minimize trauma to the socket walls, and careful investigation was done to identify possible bone dehiscences and fenestrations. Sockets with a thin or partially missing labial plate (< 50%) were selected to undergo the proposed ridge regeneration.

Thirty extraction sockets re-ceived both Osteon II (0.5- to 1.0-mm particle size) and Collagen membrane. The primary healing intention group (group A, n = 12) received primary "ap closure over the membrane, while in the sec-ondary healing intention group

Fig 1 The patient presented with a failed root canal treatment and recurrent caries beneath the crown margins on the maxillary left canine and second premolar. Implants were selected to replace the two teeth.

Fig 2 Atraumatic extraction was performed to preserve the buccal plate, and both sockets were grafted with Osteon II.

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73

(group B, n = 18), the membrane was left exposed. All extraction sites were incrementally graft-ed with Osteon II until the graft was level with the existing crestal bone, and a barrier membrane was trimmed and closely adapted to !t the contours of the grafted site (Figs 2 and 3). Simple inter-rupted sutures (Silk and Vicryl, Ethicon) were used to position the "ap over the augmented area (Fig 4). Both verbal and written postoperative instructions were given to patients, and appropri-ate antibiotics and analgesics were prescribed. Sutures were removed 7 to 10 days postsurgery, and pa-tients were seen at regular intervals during the 6 months of healing.

Postoperative periapical ra-diographs and a CT scan were obtained 6 months after the ridge regeneration procedure prior to the implant surgery. Soft and hard tissue biopsy specimens of the grafted areas were obtained using

either 3- or 4-mm trephine burs (Dentium) along the long axis of the treated sites prior to implant place-ment. Twenty-three cores were ob-tained (11 from group A, 12 from group B). The collected cores were kept in the trephine burs, placed in formalin, and shipped to a his-tologist. Tapered dental implants (SuperLine, Dentium) were placed into the biopsy sites, and primary stability was veri!ed in all cases.

Light microscopy

The bone cores were embedded following complete dehydration in ascending grades of ethanol in a light-curing one-component res-in (Technovit 7200 VLC, Heraeus Kulzer). Polymerized blocks were initially ground to bring the tissue

components closer to the cutting surface. A 100-µm-thick section was cut away from the block us-ing a bandsaw equipped with a

diamond-coated blade (Exakt). The !nal thickness of 40 μm was achieved by grinding and !nal pol-ishing steps with 1,200-, 2,400-, and 4,000-grit sandpaper. Sec-tions from each block were used for staining with Sanderson rapid bone stain (methylene blue and so-dium permanganate).

Backscatter scanning electron microscopy

Following the light microscopic evaluation, the ground sections were destained by polishing with 6-μm diamond paste. They were then washed and sputter-coated with a 6-nm-thick carbon layer and examined in the backscatter modus of a Supra 40VP scanning electron microscope (Zeiss). Back-scatter scanning electron micros-copy (BSEM) micrographs were produced from the same levels as those for light microcopy.

Fig 3 Collagen membrane placed to protect the underlying graft material.

Fig 4 Membrane intentionally exposed at both grafted sites.

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74

Results

Clinical and radiographic evaluations

All 12 patients completed the study without signi!cant adverse events or complications (Fig 5). Early wound healing seemed to be slower at the intentionally exposed sites (group B) when compared to primary "ap closure sites (group A), but the dif-ference was not noticeable after 4 weeks. Continuous maturation of the tissue covering the membrane was noted after 4 weeks in group B. No spontaneous membrane expo-sure was noted in group A.

Radiographic analysis revealed that mesial and distal crestal bone levels were maintained in both groups. Sockets in both groups un-derwent similar radiographic matu-ration (Figs 6a and 6b).

The soft tissue that formed over the exposed membrane ap-peared to be !rm in texture at the 6-month biopsy sampling. The re-sistance of the regenerated bone to trephine and osteotomy drills indicated that the regenerated bone was dense and !rm. Clinical reentry was performed after rais-ing a full-thickness "ap to assess the quality of regenerated bone. The dimensions of the ridge ap-peared to be maintained in both groups, and internal socket bone !ll was evident (Fig 7). The grafted area appeared to be well vascu-larized, but clinically visible graft particles were noted in some cas-es. The buccolingual dimensions of the augmented alveolar ridge allowed placement of dental im-plants that were at least 4.5 mm in width.

Light microscopy and BSEM analyses

Histologic evaluation of the bone cores from the augmented area provided an opportunity to ex-amine the quality and quantity of newly formed bone and remnants of grafting material (Figs 8 to 12). The connective tissue was devoid of in"ammatory cell in!ltrate but was characterized by the presence of a dense network of collagen !-bers with no membrane remnants (Figs 8b and 11b). Evidence of mature bone formation and resid-ual bone grafting material was ob-served to varying degrees (Figs 8b and 11b). Newly formed bone seemed to be directly apposed to the surfaces of graft particles and bridged the space between them, indicating that the graft material behaved as an osteoconductive

Fig 5 Excellent soft tissue healing was observed at the 15-week postoperative visit.

Figs 6a and 6b Six-month postoperative CT scans revealed preserved ridge dimensions of the sockets as well as radiographic maturation of bone grafts for the (a) canine and (b) second premolar.

a

b

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75

Fig 7 Clinical reentry with a full-thickness !ap revealed that the dimensions of the ridge were maintained, and internal socket bone "ll was evident.

Figs 8a and 8b (a) BSEM and (b) light microscopic micrograph from the same section through a core showing new bone formation (NB), marrow space (M), and graft particles (G) (group A).

500 μm

500 μm

NB M NB Ga

b

500 μm

500 μm

NB G G M NB G CT

a

b

Fig 9 Light microscopic micrograph showing newly formed bone (NB) and marrow space (M) (group A).

Fig 10 Ongoing bone formation was characterized by the pres-ence of osteoblasts and osteoid (group A). NB = new bone.

NB

M

NBNB

OsteoblastsOsteoid

50 μm500 μm

Figs 11a and 11b (a) BSEM and (b) light microscopic micrograph from the same section through a core showing new bone formation (NB), marrow space (M), and graft particles (G) (group B). CT = connec-tive tissue.

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76

scaffold (Fig 12). The presence of both osteoblasts and osteoclasts indicated active bone formation as well as bone remodeling.

BSEM evaluation of cores con!rmed the presence of newly formed bone surrounding the graft particles (Figs 8a and 11a). BSEM enabled the graft particles to be dis-tinguished from bone and nonmin-eralized tissue by their more dense and whiter appearance and shape.

Histomorphometric analysis

Histomorphometric analysis was performed on 10 selected speci-mens (5 from group A, 5 from group B). There were no signi!-cant differences between the two groups regarding the amount of vi-tal bone and residual graft (P > .05). The mean amount of vital bone in group A was 40.3% ± 7.8%, while the remaining graft was 6.0% ± 4.0%. The mean amount of vi-tal bone in group B was 47.3% ± 11.3%, while the remaining graft

was 18.0% ± 20.0%. Therefore, the absence of primary "ap closure did not affect the percentage of vital bone formation or residual graft.

Discussion

Ridge preservation immediately after tooth extraction has been ad-vocated to preserve the ridge and soft tissue dimension to allow ideal implant placement.3,13 Ideal bone substitutes should not only pre-serve the socket dimension but also encourage new bone ingrowth into the grafted area, thereby forming a living bridge between the existing bone, new bone, and remaining bone substitutes.14 With time, newly formed bone should penetrate and replace much of the graft through the bone remodeling process.14

This study investigated the role of an alloplastic biomaterial and collagen membrane in preserv-ing the ridge dimension after the extraction of teeth. The biocom-patibility and osteoconductivity of

the combination of HA and !-TCP have been previously reported.15–22 Osteon II is composed of 30% HA and 70% !-TCP (granules are 70% porous with interconnected pores of 250 μm). The reason to combine an insoluble HA with a resorbable !-TCP is that the slow-resorbing HA will maintain the volume while the faster-resorbing !-TCP will pro-mote bone regeneration.

This study provided a healing period of 6 months to induce incor-poration of the grafts with subse-quent maturation of newly formed bone tissue. A similar amount of bone regeneration as well as pres-ervation of alveolar ridge dimen-sions was observed in both primary and secondary healing intention groups. It was apparent that after a 6-month healing period, the graft-ed area was stable enough to en-sure successful implant placement.

Histologic analysis of obtained bone cores revealed intimate con-tact between mineralized bone tissue and graft particles, con!rm-ing the osteoconductive property

Fig 12 Graft particles (G) were seen partially embedded in newly formed bone (NB) (group B).

NB

NB

NBG

GG

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77

of the biomaterial. The percent-age of vital bone volume (40.3% for group A and 47.3% for group B) was equivalent to other studies of HA and !-TCP composite bone graft. For example, Froum et al16 reported a 28.35% mean vital bone volume when a mixture of 60% HA and 40% !-TCP was used as a sinus augmentation material. While the amount of vital bone formed after the augmentation may not corre-late to implant survival, it can be an accurate indicator to assess and compare the healing potential of the graft.16 Because of the higher !-TCP content in Osteon II (70%), a signi!cant amount of graft particles were resorbed histologically. Thus, it appeared as though new bone formation was occurring simultane-ously with material degradation.

A barrier membrane is used along with bone graft material to stabilize the blood clot, exclude epithelial and connective tissue, and enable osteogenic cells to pro-liferate and differentiate.9 Early or spontaneous membrane exposure may lead to bacterial colonization, infection, or membrane degrada-tion with a poor regenerative out-come because soft tissue growth progresses at the rate of 0.5 to 1.0 mm per day and can take 7 to 10 days to granulate.23–27 Cross-linked collagen membranes remain intact longer than non–cross-linked membranes, but the non– cross-linked or low–cross-linked collagen membranes may not pro-vide effective barrier function if ex-posed prematurely.27

Recent publications support the idea that the intentional ex-

posure of a resorbable membrane does not adversely affect the re-generative outcome.13,28 Primary "ap closure was not necessary to achieve bone augmentation when healing was marked by minimal in"ammation and rapid epithelial migration over the exposed mem-brane.28 The similarity between the treatments indicated that the ab-sence of primary closure did not affect the percentage of vital bone regeneration or the difference in graft stability or osseointegration.

Conclusions

The use of a composite alloplastic biomaterial in combination with a collagen membrane allowed postextraction ridge preservation as well as suf!cient bone qual-ity and quantity to place dental implants. Although intentional membrane exposure could have resulted in compromised barrier function to support regeneration, the sites that healed by second-ary intention revealed similar clini-cal, radiographic, and histologic !ndings as those that healed by primary intention. The use of this alloplastic biomaterial can be con-sidered as a viable alternative to the use of autogenous bone or other bone substitutes.

Acknowledgments

This study was funded by a grant from Dentium.

References

1. Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue contour changes following single-tooth extraction: A clinical and radiographic 12-month prospective study. Int J Peri-odontics Restorative Dent 2003;23: 313–323.

2. Fiorellini JP, Howell TH, Cochran D, et al. Randomized study evaluating re-combinant human bone morphogenetic protein-2 for extraction socket augmen-tation. J Periodontol 2005;76:605–613.

3. Nevins M, Camelo M, De Paoli S, et al. A study of the fate of the buccal wall of ex-traction sockets of teeth with prominent roots. Int J Periodontics Restorative Dent 2006;26:19–29.

4. Araújo M, Linder E, Wennström J, Lindhe J. The in"uence of Bio-Oss Collagen on healing of an extraction socket: An exper-imental study in the dog. Int J Periodon-tics Restorative Dent 2008;28:123–135.

5. Mellonig JT, Valderrama P, Cochran DL. Clinical and histologic evaluation of cal-cium-phosphate bone cement in inter-proximal osseous defects in humans: A report in four patients. Int J Periodontics Restorative Dent 2010;30:121–127.

6. Lupovici J. Regenerative strategies for anterior esthetic rehabilitation: A clini-cal and histologic case report. Compend Contin Educ Dent 2010;31:614–618, 620, 622–623.

7. Kim DM, Nevins M, Camelo M, et al. Hu-man histologic evaluation of the use of the dental putty for bone formation in the maxillary sinus: Case series. J Oral Implantol 2012;38:391–398.

8. De Coster P, Browaeys H, De Bruyn H. Healing of extraction sockets !lled with BoneCeramic prior to implant placement: Preliminary histological !ndings. Clin Im-plant Dent Relat Res 2011;13:34–45.

9. Melcher AH. On the repair potential of periodontal tissues. J Periodontol 1976; 47:256–260.

10. Fontana F, Maschera E, Rocchietta I, Simion M. Clinical classi!cation of com-plications in guided bone regeneration procedures by means of a nonresorb-able membrane. Int J Periodontics Re-storative Dent 2011;31:265–273.

11. Moses O, Pitaru S, Artzi Z, Nemcovsky CE. Healing of dehiscence-type defects in implants placed together with different barrier membranes: A comparative clini-cal study. Clin Oral Implants Res 2005;16: 210–219.

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12. Bornstein MM, Bosshardt D, Buser D. Effect of two different bioabsorbable collagen membranes on guided bone regeneration: A comparative histomor-phometric study in the dog mandible. J Periodontol 2007;78:1943–1953.

13. Cardaropoli D, Cardaropoli G. Preser-vation of the postextraction alveolar ridge: A clinical and histologic study. Int J Periodontics Restorative Dent 2008;28: 469–477.

14. Hing KA. Bioceramic bone graft substi-tutes: In!uence of porosity and chem-istry. Int J Appl Ceram Technol 2005;2: 184–199.

15. Cordaro L, Bosshardt DD, Palattella P, Rao W, Serino G, Chiapasco M. Maxillary sinus grafting with Bio-Oss or Straumann Bone Ceramic: Histomorphometric re-sults from a randomized controlled mul-ticenter clinical trial. Clin Oral Implants Res 2008;19:796–803.

16. Froum SJ, Wallace SS, Cho SC, Elian N, Tarnow DP. Histomorphometric com-parison of a biphasic bone ceramic to anorganic bovine bone for sinus aug-mentation: 6- to 8-month postsurgical assessment of vital bone formation. A pilot study. Int J Periodontics Restorative Dent 2008;28:273–281.

17. Kim YK, Yun PY, Lim SC, Kim SG, Lee HJ, Ong JL. Clinical evaluations of OS-TEON as a new alloplastic material in si-nus bone grafting and its effect on bone healing. J Biomed Mater Res B Appl Bio-mater 2008;86:270–277.

18. Kim YK, Yun PY, Kim SG, Lim SC. Analy-sis of the healing process in sinus bone grafting using various grafting materials. Oral Surg Oral Med Oral Pathol Oral Ra-diol Endod 2009;107:204–211.

19. Frenken JW, Bouwman WF, Braven-boer N, Zijderveld SA, Schulten EA, ten Bruggenkate CM. The use of Straumann Bone Ceramic in a maxillary sinus !oor elevation procedure: A clinical, radiologi-cal, histological and histomorphometric evaluation with a 6-month healing period. Clin Oral Implants Res 2010;21:201–208.

20. Mardas N, Chadha V, Donos N. Alveo-lar ridge preservation with guided bone regeneration and a synthetic bone sub-stitute or a bovine-derived xenograft: A randomized, controlled clinical trial. Clin Oral Implants Res 2010;21:688–698.

21. Mardas N, D’Aiuto F, Mezzomo L, Ar-zoumanidi M, Donos N. Radiographic alveolar bone changes following ridge preservation with two different bioma-terials. Clin Oral Implants Res 2011;22: 416–423.

22. Kim DM, Camelo M, Nevins M, Fateh A, Schupbach P, Nevins M. Alveolar ridge construction with a composite alloplastic biomaterial. Int J Periodontics Restor-ative Dent 2012;32:e204–e209.

23. Engler WO, Ramfjord SP, Hiniker JJ. Heal-ing following simple gingivectomy. A triti-ated thymidine radioautographic study. I. Epithelialization. J Periodontol 1966;37: 298–308.

24. Simion M, Baldoni M, Rossi P, Zaffe D. A comparative study of the effectiveness of e-PTFE membranes with and without ear-ly exposure during the healing period. Int J Periodontics Restorative Dent 1994;14: 166–180.

25. Simion M, Maglione M, Iamoni F, Scar-ano A, Piattelli A, Salvato A. Bacterial penetration through Resolut resorbable membrane in vitro. An histological and scanning electron microscopic study. Clin Oral Implants Res 1997;8:23–31.

26. Hämmerle CH, Jung RE. Bone augmen-tation by means of barrier membranes. Periodontol 2000 2003;33:36–53.

27. Oh TJ, Meraw SJ, Lee EJ, Giannobile WV, Wang HL. Comparative analysis of collagen membranes for the treatment of implant dehiscence defects. Clin Oral Implants Res 2003;14:80–90.

28. Kim DM, Nevins M, Camelo M, et al. The feasibility of demineralized bone matrix and cancellous bone chips in conjunc-tion with an extracellular matrix mem-brane for alveolar ridge preservation: A case series. Int J Periodontics Restor-ative Dent 2011;31:39–47.

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459

Socket Site Preservation Using Bovine Bone Mineral With and Without a Bioresorbable Collagen Membrane

Mally Perelman-Karmon, DMD, MS*/Avital Kozlovsky, DMD** Roman Lilov, DMD***/Zvi Artzi, DMD****

Tooth extraction leads to morpho-logic changes and resorption of the alveolar ridge as a result of a lack of biomechanical forces on the bone.1,2 In the immediate postextraction phase, the fresh extraction socket possesses a unique wound-healing cascade.3–5 Marked dimensional al-terations occur in the edentulous ridge after extraction.1,5,6

In the anterior maxilla, there is consistent bone resorption where the buccal plate is thin. Bone re-sorption leads to palatal/lingual and apical positioning of the alveo-lar crest, since resorption is more prominent in the buccal plate.1,5

Thus, preserving the alveolar ridge and achieving appropriate ridge dimensions are important7,8 when an implant-supported fixed partial denture is required.

The increasing demand for es-thetic implant dentistry challenges the clinician. The implant location should comply with the patient’s esthetic, functional, and phonetic needs. Guided tissue regeneration (GTR), a biologic principle based on a selective cell population, achieves sufficient volume of regenerated

The purpose of this study was to compare extraction sites augmented with bovine bone mineral (BBM) with and without resorbable membrane coverage. BBM particles were grafted in fresh human extraction sockets of 23 patients; in 12 of these patients, a guided tissue regeneration (GTR) membrane was applied. After 9 months of histomorphometric evaluation, cylindric hard tissue specimens were obtained. Percent bone area fractions (BAFs) of the crestal, middle, and apical sections from each specimen were calculated using the point-counting technique. Changes in values were compared. In sites augmented with BBM, the mean BAF ranged from 22.8% (coronal) to 36.3% (apical) compared to sites augmented with BBM and collagen membrane (35.2% [coronal] to 47% [apical]). Comparison between the different depths and the two groups showed a distinct increase in BAF from coronal to apical regions (P < .001). This pattern was observed in both groups (P < .001) and was significantly higher in the group augmented with BBM and collagen membrane (P < .05). In the immediate postextraction phase, BBM as a grafted biomaterial preserved the socket volume and enabled newly formed bone for future implant site preparation. The amount of the osseous fraction increased with GTR membrane. (Int J Periodontics Restorative Dent 2012;32:459–465.)

* Department of Oral Sciences, School of Dental Medicine, State University of New York, Buffalo, New York, USA; Formerly, Undergraduate Student, The Maurice and Gabriela Goldschleger Scool of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.

** Associate Professor, Department of Periodontology, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.

*** Private Practice, Netanya, Israel.**** Associate Professor and Director of Graduate Periodontics, Department of

Periodontology, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel. Correspondence to: Prof Zvi Artzi, School of Dental Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 61390, Israel; email: [email protected].



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bone.9 Different types of GTR mem-branes are used with and without a biomaterial scaffold10,11 to maintain space over a bony defect (extrac-tion socket void) and to prevent undesired cells from migrating into the defect. The membrane protects the blood clot formed in the socket. By protecting and secluding the socket from the adjacent interfer-ing connective tissue cells, the membrane enables and promotes osteogenic cell migration into the defect.9

After extraction, the defined area serves as a wound-healing site. The healing cascade of the socket is dominated by coagulum, which is gradually occupied by granula-tion tissue followed by a provision-al matrix (connective tissue).4 One week postextraction, the socket is characterized by granulation tissue consisting of a vascular network, im-mature connective tissue, osteoid formation in the apical portion, and epithelial coverage over the wound. At 1 month postextrac-tion, the socket is characterized by dense connective tissue overlying the residual sockets and filled with granulation tissue. A trabecular pattern of bone starts to emerge. Epithelium used for wound cover-age is complete following the se-quence of bone formation.3,4

In a periodontal deteriorating situation, when destruction of par-tial or complete socket walls is evi-dent, ingrowth of connective tissue into the extraction site is unavoid-able, leading to a deficient ridge. The use of bone substitute, such as bovine bone mineral (BBM), pre-

serves the alveolar ridge by stabiliz-ing the blood clot, thus maintaining the volume at the site and simulta-neously serving as an osteoconduc-tive guide rail to facilitate continual bone formation.12–17 BBM applied in conjunction with a bioresorbable membrane after a healing period of 9 months has shown complete hori-zontal bone augmentation.11

While the significant contri-bution of applying a selective se-cluded barrier in GTR or guided bone regeneration (GBR) proce-dures is evident, the application of membrane coverage at a fresh extraction socket while at the same time obtaining complete soft tis-sue closure is a challenge. Further-more, since bone tissue has been formed with and without the use of a membrane in animal and human studies,7,8,12,13,16–18 the indication of a GBR surgical modality in a unique healing site (ie, fresh extraction socket) should be interpreted.

The objective of this study was to compare the amount of bone area fraction in fresh extraction sites using BBM as the grafting biomaterial, protected or unpro-tected with a resorbable collagen membrane, and by using a rotating pedicle flap or coronally advanced flap to achieve complete soft tissue closure.

Method and materials

This study included 23 fresh single- root extraction sockets in 23 healthy patients (16 women, 7 men) with no systemic diseases. Patients

ranged from 26 to 68 years of age and were nonsmokers. The proce-dure was explained, and patients signed consent forms. The study was in accordance with the Helsinki Declaration.

Before extraction, clinical (probing) and radiographic param-eters were collected (Figs 1a and 1b). Sites exhibiting severe to com-plete socket wall destruction were excluded.

Extracted teeth included max-illary incisors (n = 10) and maxil-lary (n = 8) and mandibular (n = 5) single-root premolars. At least 50% of sockets were partially resorbed/destructed at one to two walls, but not circumferentially so that the inclusion criteria of containing the grafted particles and supporting the applied over-latticed resorb-able membrane could be met. Immediately following extraction, BBM particles (250 to 1,000 µm; Bio-Oss, Geistlich) were placed to fill the site completely (Fig 1c). The decision to use sites with or with-out the application of a resorbable membrane was determined ran-domly by flipping a coin before ex-traction. A double layer of collagen membrane (Bio-Gide, Geistlich) was applied in 11 sites (Fig 1d). The membrane covered the entire site and was secured labially and lin-gually under soft tissue flaps.

In the maxilla, complete soft tissue closure was obtained using a rotating pedicle flap from the pala-tal side. Advanced coronal, buccal, and lingual flaps ensured soft tissue closure in mandibular premolars. The distal superficial end of the



461

pedicle flap was de-epithelialized and sutured (4-0 Vicryl, Ethicon) to the inner layer of the buccal flap to obtain complete soft tissue clo-sure over the membrane-protected grafted site (Fig 1e). The same soft tissue management was performed in the unprotected group (n = 13) but without applying the GTR membrane. The exposed palatal area was left for secondary healing.

Patients were prescribed anal-gesics (naproxen 275 mg; Narocin, Teva Pharmaceutical) and instruct-ed to rinse with 0.2% chlorhexidine gluconate (Tarodent, Taro Pharma-ceutical) twice a day for 30 seconds for 2 weeks. Complete soft tissue healing was observed at 1 month postgrafting (Fig 1f). Computed to-mography scans were taken to plan the future implant prosthetic recon-struction (Fig 1g).

Since BBM is a slow biodegrad-able material,17 an extended heal-ing phase was allowed for possible interpretation between membrane-protected and unprotected healing sites. At 9 months, at implant place-ment, a midcrestal incision was made to expose the grafted site (Fig 1h). At this stage, instead of the usual sequence of step-up drill-ing for implant site preparation, a 2.5-mm–internal diameter trephine bur was applied to harvest a cylin-dric hard tissue core approximately 8 mm in length. The apical end of each specimen was marked for ori-entation to identify the peripheral versus deep ends.

Specimens (n = 23) were fixed in 10% neutral buffered formalin for 1 week and then decalcified

with 5% formic acid for 2 weeks. The decalcified cylindric speci-mens were embedded in paraffin and transversely cut into serial sec-tions 5-µm wide using a microtome (Leica RM 2245, Leica Microsys-tems). Each core was cut uniform-ly from the peripheral to deeper regions. Slides were stained with hematoxylin-eosin. From each tis-sue cylinder, six representative cuts undamaged during microtome cut-ting were selected for morphomet-ric analysis: two from the coronal portion (1 to 2 mm), two from the middle core, and two from the apical end (1 to 2 mm). Data from each pair were averaged and used as such.

Histomorphometry

In each section, bone area fraction at membrane-protected (m-BAF) and biomaterial-only (BAF) grafted sites was measured using an adap-tation of the point-counting proce-dure.12,17,19–22 Briefly, each section was examined in a projection mi-croscope (Visopan, Reichart, Leica) at 20× magnification. A 64-square (1.5 × 1.5 cm) graticule was su-perimposed on the screen for the point-counting calculation. Bone tissue was recorded whenever the graticule center (marked with “+”) hit the bone tissue.12,21,22 The sum (Pi) of the points overlying the bone tissue was calculated. Percentage of bone tissue was evaluated as a portion of the entire section area (Pi / Σi), where Σi represents the to-tal number of points superimposed on each section.



462

All measurements were taken by the same investigator. To de-termine the reproducibility of the

measurements and the coefficient of variation (CV) for each parameter, 10 randomly selected slides were

Fig 1a (left) Clinical appearance of a maxillary right central incisor. The marginal gingiva was inflamed, and the tooth had migrated slightly labially and mesially be-cause of the periodontal condition.

Fig 1b (right) Periapical radiograph of the maxillary central incisor. Severe periodontal destruction is evident.

Fig 1c Fresh extraction socket filled with BBM particles.

Fig 1d Bioresorbable membrane applied to cover the augmented socket.

Fig 1e Complete soft tissue closure was obtained using a pedicle palatal rotated flap.

Fig 1f At 1 month, soft tissue healing was evident.

Fig 1g Buccolingual computed tomogra-phy section of the grafted extraction site.

Fig 1h At reentry, a wide buccolingual os-seous table had been established.



463

measured 5 times, not consecu-tively, without reference to the pre-vious data. The mean CV of bone (2.2%), biomaterial particle (2%), and remaining concavity area fractions (1.8%) indicated that these measure-ments were highly reproducible.

During measurements, the in-vestigator was masked to the type of site with respect to whether the mea-surement was conducted on protect-ed or unprotected membrane sites; the same applied for its depth.

Repeated-measures analysis of variance was used. The within-subject factor was depth, and the between-subject factor was mem-brane coverage. Values were con-sidered significant at P < .05.

Results

All patients were observed fre-quently, and postoperative heal-ing was immaculate. Histologic examination revealed that all cores harbored an abundance of BBM particles surrounded by newly formed bone. In the membrane-protected group, total bone frac-tion ranged from 23% to 72% (mean, 40.8% ± 10.61%) (Figs 2a and 2b). m-BAF ranged from 24.0% to 52.5% (mean, 35.2% ± 9.18%), 24.5% to 59.5% (mean, 40.2% ± 10.74%), and 23.0% to 72.0% (mean, 46.95% ± 12.83%) at the crestal, middle, and apical regions, respectively. In the unprotected

group, total BAF ranged from 15% to 54% (mean, 29.7% ± 7.21%). BAF ranged from 15.0% to 33.0% (mean, 22.8% ± 5.11%), 16.5% to 47.5% (mean, 29.9% ± 8.98%), and 21.5% to 54.0% (mean, 36.3% ± 11.3%) at the crestal, middle, and apical regions, respectively.

Mean m-BAF was significantly greater than BAF at all respective depths (P < .05). In both groups (m-BAF and BAF), a gradual in-crease in bone area fraction was observed from the coronal to apical areas. Within each type, the bone area fraction in the apical region was statistically greater than that in the middle and crestal areas (P < .001) (Fig 3).

Fig 2a (left) Typical coronal decalcified section cut. An abundance of soft tissue (ST) and grafted particles (P) surrounded by newly formed bone (B) can be seen (hematoxylin-eosin, original magnification ×25).

Fig 2b (right) Apical section with a high percentage of bone area fraction (B) (hematoxylin-eosin, original magnification ×25).

0

10

20

30

40

50

60

70

Crestal Middle

**

††

††

**

***

Apical

Membrane-protected

Unproteced

Mea

n B

AF

(%)

Fig 3 Mean BAF at the crestal, middle, and apical regions of the membrane-protected and unprotected extraction sites augmented by BBM particles. **P < .05; ***P < .001, †P < .001 (within-subject data).

ST

ST

P PP

B

B

B

B

BB



464

Discussion

BBM, which has been used for over 20 years, has proven to be a suitable biomaterial in augmentation proce-dures. Clinical and histologic stud-ies have shown the efficacy of this osteoconductive material.11,18,23,24 A high osteoconductive property by BBM has also been shown in a recent comparative study in human extraction sockets.15

BBM particles have been shown to be well integrated with regenerated bone in extraction and alveolar ridge deficiency sites in animal16,23,25 and human clinical studies,11,18,24,26 as well as in mor-phometric studies.12,22 In a human study,27 excellent osseointegration and crestal bone level maintenance were shown when implant place-ment was combined with bone augmentation using BBM as the grafting biomaterial.

In the current study, all 23 con-secutive patients showed primary soft tissue closure and excellent healing whether GTR membrane coverage was applied or not. However, the point-counting his-tomorphometry disclosed a distin-guishable observation. Regardless of the depth of the examined his-tologic section, a membrane- protected grafted socket site showed greater newly formed bone when compared with unpro-tected grafted sites. It should be considered that a membrane-pro-tected site is advantageous since the GTR membrane confines the grafted particles during the first period of healing and stabilizes the

entire site, in addition to its bio-logic contributions. In unprotected sites, some particulate biomate-rial would be lost or reside in the overlying soft tissue. Nevertheless, in both sites, BBM particles were surrounded by newly formed bone, and all sites exhibited clinical hard tissue formation, which was suit-able for implant site preparation.

The slow resorption rate of BBM does not inhibit continuous bone formation. On the contrary, it enhances it progressively.17

In unprotected grafted human sockets,12,26 BAF increases when approaching the apical area. In-trabony defects healed with BBM alone or with BBM and a resorb-able membrane. It has been shown that the amount of bone regenera-tion is further enhanced with the latter.28

Caution should be taken when internalizing the morphometric data if the examined sites are nei-ther identical nor standardized before grafting. However, the re-peated outcomes at the 12 versus 11 consecutively examined sockets should strengthen the findings.

In this study, the least BAF was found in the crestal zone, regardless of whether the site was membrane-protected. This could be explained by the distance between the socket walls.12 In the extraction site, the distance between the socket walls is reduced toward the apical region. Thus, this is an amply nourished site.

The fact that a membrane-pro-tected socket site showed greater newly formed bone was anticipat-

ed. In a computed tomography– derived bone density study in dogs,29 similar findings were shown with regard to the contribution of the GTR modality. Moreover, wound site stability and undesired micromovement,30 which can occur in this region, might influence the remodeling process.

Conclusions

BBM, as a grafted biomaterial in fresh extraction sockets, preserved its volume and enabled newly formed bone for future implant site preparation. The application of GBR increased the osseous fraction.

Acknowledgments

The authors thank Mrs Ilana Gelerntner for the statistical analysis and Ms Rita Lazar for editorial assistance.



465

References

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2. Pietrokovski J, Massler M. Alveolar ridge resorption following tooth extraction. J Prosthet Dent 1967;17:21–27.

3. Amler MH, Johnson PL, Salman I. Histo-logical and histochemical investigation of human alveolar socket healing in un-disturbed extraction wounds. J Am Dent Assoc 1960;61:32–44.

4. Cardaropoli G, Araújo M, Lindhe J. Dynamics of bone tissue formation in tooth extraction sites. An experimental study in dogs. J Clin Periodontol 2003;30: 809–818.

5. Araújo MG, Lindhe J. Dimensional ridge alterations following tooth extraction. An experimental study in the dog. J Clin Periodontol 2005;32:212–218.

6. Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue con-tour changes following single tooth extrac-tion: A clinical and radiographic 12-month prospective study. Int J Periodontics Re-storative Dent 2003;23:313–323.

7. Nevins M, Camelo M, De Paoli S, et al. A study of the fate of the buccal wall of ex-traction sockets of teeth with prominent roots. Int J Periodontics Restorative Dent 2006;26:19–29.

8. Araújo MG, Lindhe J. Ridge preserva-tion with the use of Bio-Oss collagen: A 6-month study in the dog. Clin Oral Im-plants Res 2009;20:433–440.

9. Dahlin C, Linde A, Gottlow J, Nyman S. Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg 1988; 81:672–676.

10. Diès F, Etienne D, Abboud NB, Ouhay-oun JP. Bone regeneration in extraction sites after immediate placement of an e-PTFE membrane with or without a bioma-terial. A report on 12 consecutive cases. Clin Oral Implants Res 1996;7:277–285.

11. Hämmerle CH, Jung RE, Yaman D, Lang NP. Ridge augmentation by applying bioresorbable membranes and deprot-einized bovine bone mineral: A report of twelve consecutive cases. Clin Oral Im-plants Res 2008;19:19–25.

12. Artzi Z, Tal H, Dayan D. Porous bovine bone mineral in healing of human extraction sockets. Part 1: Histomorphometric eval-uation at 9 months. J Periodontol 2000; 71:1015–1023.

13. Artzi Z, Nemcovsky CE, Tal H. Efficacy of porous bovine bone mineral in vari-ous types of osseous deficiencies: Clini-cal observations and literature review. Int J Periodontics Restorative Dent 2001;21:395–405.

14. Cardaropoli G, Araújo M, Hayaci- bara R, Sukekava F, Lindhe J. Healing of extraction sockets and surgically pro-duced—augmented and non-augment-ed—defects in the alveolar ridge. An experimental study in the dog. J Clin Periodontol 2005;32:435–440.

15. Lee DW, Pi SH, Lee SK, Kim EC. Com-parative histomorphometric analysis of extraction sockets healing implanted with bovine xenografts, irradiated cancellous allografts, and solvent-dehydrated al-lografts in humans. Int J Oral Maxillofac Implants 2009;24:609–615.

16. Artzi Z, Givol N, Rohrer MD, Nemcovsky CE, Prasad HS, Tal H. Qualitative and quantitative expression of bovine bone mineral in experimental bone defects. Part 1: Description of a dog model and histo-logical observations. J Periodontol 2003; 74:1143–1152.

17. Artzi Z, Givol N, Rohrer MD, Nemcovsky CE, Prasad HS, Tal H. Qualitative and quantitative expression of bovine bone mineral in experimental bone defects. Part 2: Morphometric analysis. J Peri-odontol 2003;74:1153–1160.

18. Artzi Z, Nemcovsky CE. The application of deproteinized bovine bone mineral for ridge preservation prior to implantation. Clinical and histological observations in a case report. J Periodontol 1998;69: 1062–1067.

19. Chalkey HW. Method for quantitative morphologic analysis of tissues. Natl Can-cer Inst 1943;4:47–53.

20. Bellhouse DR. Area estimation by point counting techniques. Biometrics 1981;37: 303–312.

21. Artzi Z, Nemcovsky CE, Dayan D. Nonce-ramic hydroxyapatite bone derivative in sinus augmentation procedures: Clinical and histomorphometric observations in 10 consecutive cases. Int J Periodontics Restorative Dent 2003;23:381–389.

22. Artzi Z, Kozlovsky A, Nemcovsky CE, Weinreb M. The amount of newly formed bone in sinus grafting procedures de-pends on tissue depth as well as the type and residual amount of the grafted mate-rial. J Clin Periodontol 2005;32:193–199.

23. Berglundh T, Lindhe J. Healing around implants placed in bone defects treated with Bio-Oss. An experimental study in the dog. Clin Oral Implants Res 2007;8: 117–124.

24. Skoglund A, Hising P, Young C. A clinical and histologic examination in humans of the osseous response to implanted natu-ral bone mineral. Int J Oral Maxillofac Im-plants 1997;12:194–199.

25. Hockers T, Abensur D, Valentini P, Legrand R, Hämmerle CH. The combined use of bioresorbable membranes and xenografts or autografts in the treatment of bone de-fects around implants. A study in beagle dogs. Clin Oral Implants Res 1999;10: 487–498.

26. Artzi Z, Tal H, Dayan D. Porous bovine bone mineral in healing of human extrac-tion sockets: 2. Histochemical observa-tions at 9 months. J Periodontol 2001; 72:152–159.

27. Meijndert L, Raghoebar GM, Schüpbach P, Meijer HJ, Vissink A. Bone quality at the implant site after reconstruction of a local defect of the maxillary anterior ridge with chin bone or deproteinised cancellous bo-vine bone. Int J Oral Maxillofac Surg 2005; 34:877–884.

28. Camelo M, Nevins ML, Schenk RK, et al. Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Gide. Int J Periodontics Restorative Dent 1998;18: 321–331.

29. Kim M, Kim JH, Lee JY, et al. Effect of bone mineral with or without collagen mem-brane in ridge dehiscence defects follow-ing premolar extraction. In Vivo 2008;22: 231–236.

30. Haney JM, Nilvéus RE, McMillan PJ, Wikesjö UM. Periodontal repair in dogs: Expanded polytetrafluoroethylene barrier membranes support wound stabilization and enhance bone regeneration. J Peri-odontol 1993;64:883–890.


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Journal of Periodontology; Copyright 2013 DOI: 10.1902/jop.2013.120585

1

Ridge Preservation Comparing a Socket Allograft Alone to a Socket Allograft Plus a Facial Overlay Xenograft: A Clinical and Histologic Study in Humans

Evmenios Poulias, DDS, MS*, Henry Greenwell, DMD, MSD†, Margaret Hill, DMD‡, Dean Morton, DMD, MS§, Ricardo Vidal, DDS, MS‖, Brian Shumway, DMD, MS¶,

Thomas L. Peterson, DDS, MS#

Private Practice, Athens, Greece.

Professor, Director of Graduate Periodontics, University of Louisville, Louisville, KY.

Associate Professor, Assoc Dean Postdoctoral Education, University of Louisville, Louisville, KY.

Professor, Chair, Dept of Oral Health & Rehabilitation, University of Louisville, Louisville, KY.

Assistant Professor, Periodontics, University of Louisville, Louisville, KY.

Assistant Professor, Oral Pathology, University of Louisville, Louisville, KY.

Private Practice, Macon, Georgia. Background. Previous studies of ridge preservation showed a loss of about 18% or 1.5 mm of

crestal ridge width in spite of treatment. The primary aim of this randomized, controlled, blinded clinical trial was to compare a socket graft to the same treatment plus a buccal overlay graft, both with a polylactide membrane, to determine if loss of ridge width can be prevented by use of an overlay graft.

Methods. Twelve positive control patients received an intrasocket mineralized cancellous allograft (Socket group) while twelve test patients received the same socket graft plus buccal overlay cancellous xenograft (Overlay group). Horizontal ridge dimensions were measured with a digital caliper and vertical ridge changes were measured from a stent. Prior to implant placement at 4 months a trephine core was obtained for histologic analysis.

Results. The mean horizontal ridge width at the crest for the Socket group decreased from 8.7 ± 1.0 mm to 7.1 ± 1.5 mm for a mean loss of 1.6 ± 0.8 mm (p < 0.05) while the Overlay group decreased from 8.4 ± 1.4 mm to 8.1 ± 1.4 mm for a mean loss of 0.3 ± 0.9 mm (p > 0.05). The Overlay group was significantly different from the Socket group (p < 0.05). Histologic analysis revealed that the Socket group had 35 ± 16% vital bone while the Overlay group had 40 ± 16% (p > 0.05).

Conclusions. The Overlay treatment significantly prevented loss of ridge width and preserved or augmented the buccal contour. The Socket and Overlay groups healed with a high percentage of vital bone.

KEY WORDS: allograft; xenograft; grafting, bone; socket graft; bone regeneration.

Following extraction there is substantial resorption of the alveolar ridge resulting in compromised ridge dimensions. Araujo et al. have shown that bone resorption is most pronounced on the buccal.1-5 This is due to loss of bundle bone that results in the loss of a portion of the buccal plate. When human extraction alone studies are reviewed as a






2

group they show that, on average, approximately 3.7 mm or 45% of horizontal ridge width is lost within a 4 to 6 month period.6-14 Ridge height, on the other hand, is less affected and on average only about 1.6 mm is lost.6-14

In an effort to reduce post-extraction bone loss clinicians have performed what is known as a ridge preservation procedure. This treatment utilizes an osseous graft and/or a barrier membrane to manage the extraction socket. The goal of this procedure is to ensure that adequate ridge width is preserved to allow implant placement totally within bone and to avoid complications such as implant dehiscence and fenestration. In spite of these efforts, most studies of ridge preservation show that there is still some loss of horizontal ridge width that can lead to a concave buccal contour and may lead to a dehiscence or fenestration at the time of implant placement. Ridge preservation studies as a group show that, on average, about 1.5 mm or 18% of horizontal ridge width is lost.6-

9,11-32 Ridge height is minimally affected and, on average, less than about 0.5 mm of height is lost.6-15,17,18,20,21,23,24,27,29-33

Wang et al. have described a "sandwich" technique of layered osseous grafting that utilizes an outer layer that resists resorption and will remain in place for an extended or indefinite period.34 The inner layer, on the other hand, is resorbed and replaced more quickly by newly formed vital bone. These principles will be utilized in this study.

Bovine xenograft has been reported to resorb very slowly and become fibrous encapsulated while cancellous allograft is resorbed and replaced more quickly through a process known as creeping substitution.18,34-40 These two materials fulfill the principles proposed by Wang et al.34 Therefore the cancellous allograft was chosen as a rapidly resorbing socket graft while the bovine xenograft was chosen as a buccal overlay to resist resorption and preserve the buccal contour. The specific aim of this study was to determine if ridge preservation treatment can be performed in a manner that will prevent the loss of crestal ridge width thereby preserving the original buccal contour. Comparing a socket graft alone to a socket graft plus a facial overlay will provide a valid test of the hypothesis that loss of crestal ridge width can be prevented when a slowly resorbing facial overlay graft is utilized.

METHODS

Study Design A total of 24 patients participated in this 4-month randomized, controlled, blinded clinical study of ridge preservation in sequentially entered single extraction sites of nonmolar teeth to be replaced by a dental implant. Twelve positive control patients were randomly selected, using a coin toss, to receive ridge preservation treatment with an intrasocket, mineralized, cancellous, particulate allograft (500-800 µm, Socket group).* The twelve test patients received the same intrasocket allograft plus a facial overlay with a mineralized, cancellous, particulate bovine xenograft (250-1000 µm, Overlay group).† A bioresorbable polylactide membrane was used to cover the osseous graft in both groups.‡ Four months after the grafting procedure the implant placement surgery was performed and a trephine core was removed from the osteotomy site for histologic analysis. All surgical procedures were completed by one operator (EP) under the direction of one mentor (HG). The surgeon was trained in the procedures until considered proficient. All


3

blinded measurements were performed by one blinded examiner (TP), who was unaware of the treatment assignment at all time points. The mentor performed the coin toss after flap reflection and immediately prior to graft placement and verified the measurements taken by the blinded examiner. All patients signed an informed consent approved by the University of Louisville Institutional Review Board in August 2011, when this study 11.0352 was also approved. This study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000. The study was conducted between September 2011 and July 2012 in the Graduate Periodontics clinic at the University of Louisville.

Outcome Variables The primary outcome variable was crestal horizontal ridge width and the power analysis was based on this variable. Other variables evaluated included vertical ridge dimension change and histologic assessment of vital bone, non-vital bone and trabecular space.

Inclusion/Exclusion Criteria Subjects met the eligibility criteria if they were at least 18 years of age and had one nonmolar tooth requiring extraction that would be replaced by a dental implant. Extraction sites were bordered by at least one tooth. Exclusion criteria included: 1) debilitating systemic diseases, or diseases that have a clinically significant effect on the periodontium; 2) molar extraction sites; 3) presence of or history of osteonecrosis of the jaws; 4) history of IV bisphosphonate treatment; 5) history of oral bisphosphonate treatment for more than three years; 6) pregnancy or lactation; 7) known allergy to any material or medication used in the study; 8) required antibiotic prophylaxis; 9) previous head and neck radiation therapy; 10) history of chemotherapy in the last 12 months; 11) long term steroid or non-steroidal anti-inflammatory drug therapy; or 12) failure to sign an informed consent approved by the Human Studies Committee. Patients were excluded post-treatment if they developed infection or had an adverse reaction to any of the materials used in the study.

Clinical and Radiographic Parameters Each patient received a diagnostic work-up that included standardized periapical radiographs, study casts, clinical photographs, and a full periodontal examination. Radiographic and study cast data will not be presented or discussed. Customized occlusal stents were fabricated on the study casts to serve as fixed reference guides for the vertical measurements.9

Clinical parameters on adjacent teeth assessed at baseline and at the 4-month re-entry included Plaque Index, Gingival Index, bleeding on probing (dichotomous), keratinized tissue width, recession, probing depth, clinical attachment level, CEJ to alveolar crest distance, and tooth mobility.41,42 Horizontal ridge width was recorded with a modified digital caliper measuring to the nearest 10-2 at the mid-socket crestal level and 5 mm apically. Vertical distance from the acrylic stent to the alveolar crest was measured mesially, mid-socket and distally on all buccal, occlusal and lingual surfaces using a 15 mm North Carolina periodontal probe.9


4

Surgical Treatment Full thickness flaps were elevated to expose both the facial and the palatal/lingual aspects of the alveolar ridge. The flaps were extended one tooth mesial and distal to the preservation site on the buccal and vertical incisions were placed on the buccal and palatal. Papillae preservation incisions were used to keep the papilla intact.43 The teeth were extracted as atraumatically as possible using periotomes, elevators and forceps. After the extraction, the socket was carefully curetted to remove all soft tissue.

The allograft and xenograft materials were hydrated in a 50 mg/ml solution of tetracycline. The socket allograft was placed to the level of the alveolar crest and the facial overlay xenograft was placed over the buccal wall of the extraction socket from the alveolar crest to about 12 mm apical and was extended about half a tooth to the mesial and distal. The polylactide barrier membrane was trimmed to completely cover the socket and extended at least 3 mm past the alveolar crest and at least 3 mm past the lateral and apical borders of the facial xenograft. The membrane overlying the central portion of the socket was left exposed. Flaps were replaced or slightly coronally positioned. If needed, an apical periosteal split was performed to permit adequate flap release for tension-free closure. Flaps were sutured with a 4-0 polytetrafluoroethylene suture.§ Compression of the facial overlay graft was avoided by ensuring that flap closure was tension free. Patients were given a post-surgical regimen consisting of 375 mg naproxen (twice a day for one week), 50 mg doxycycline hyclate (once a day for two weeks) and narcotic analgesics as needed. Patients were seen every two weeks until soft tissue closure was complete and then monthly until the 4-month implant placement.

Implant Placement Full-thickness flaps were elevated on the buccal and palatal/lingual using a papilla preservation technique. All baseline clinical measurements were repeated and a standardized radiograph was taken. A 2.7 x 6.0 mm trephine was used with copious chilled saline irrigation to remove a core from the osteotomy site prior to implant placement.║ The core was subsequently placed in 10% buffered formalin for histologic processing. A dental implant was placed and flaps were replaced and sutured with 4-0 silk or the polytetrafluoroethylene sutures described previously.

Contour Data Pre- and post-treatment unlabelled occlusal clinical photographs were compared to determine the initial and final buccal contour. Each contour was subjectively categorized as a concave, flat or convex contour. Two blinded examiners (HG, EP) had to agree on each contour categorization. Since this was a subjective evaluation it was considered important to use two examiners. Subsequently the pre-and post-treatment categories were compared to determine if there was a loss, no change or a gain in terms of contour.

Tooth Type Data Data from previous studies of ridge preservation at this institution (this study, 2 publications, and 5 Master's theses) that were measured using the same technique as in this study were grouped according to tooth type to determine initial and final ridge


5

dimensions, the change and the percent change.9,18 Data for this analysis came from sites that received socket treatment alone without an overlay graft.

Histologic Analysis Trephine cores (2.7 X 6 mm) were decalcified and 12-15 step serial sections were taken from the center of each longitudinally sectioned core. The sections were stained with hematoxylin and eosin. Ten slides per patient were prepared, each containing at least 4 sections. Six randomly selected fields, 1 per section if possible, were used to obtain percent cellular bone, acellular bone, and trabecular space using an American Optics light microscope at 150x with a 10x objective and 15x reticle eyepieces.9

Statistical Methods Means and standard deviations were calculated for all parameters. A paired t-test was used to evaluate the statistical significance of the differences between initial and final data. An unpaired t-test was used to evaluate statistical differences between the test and control groups. The sample size of 11 per group gave 80% statistical power to detect a difference of 1 mm between groups for crestal ridge width. Power calculations were based on data from previous studies.9,18

RESULTS A total of 24 patients were entered in this study. For the Socket group 8 females and 4 males with a mean age of 52 ± 16, ranging from 26 to 77 years, were enrolled while 5 females and 7 males with a mean age of 58 ± 11, ranging from 38 to 71 years, were enrolled in the Overlay group. All sites were bordered by at least one tooth mesially or distally. The Socket group consisted of 1 maxillary incisor, 2 maxillary canines, 8 maxillary premolars, and 1 mandibular premolar. The Overlay group consisted of 5 maxillary incisors, 1 maxillary canine, and 6 maxillary premolars. There were 2 smokers enrolled in the Socket group and 2 in the Overlay group. The reason for extraction in the Socket group was 9 due to caries, 2 due to root fracture and 1 due to root resorption; in the Overlay group 6 were extracted due to caries, 5 due to root fracture and 1 due to root resorption. There were no adverse events that occurred due to this treatment.

All 24 patients completed the study, however, one patient in the Overlay group (1/12) was excluded following data analysis. This patient had a buccal wall missing at the time of extraction and the amount of ridge width gain was large. This represented an outlier value that skewed the data and did not represent what typically happens following a ridge preservation procedure.

Clinical Indices Plaque index, gingival index and bleeding on probing had low initial values for both groups, about 0.1 ± 0.1, and were virtually unchanged at the 4-month implant placement visit. There were no significant differences between initial and final values or between the test and the control groups (p > 0.05).


6

Horizontal Ridge Width Changes The Socket group had a statistically significant mean loss of crestal width of 1.6 ± 0.8 mm (p < 0.05) while the Overlay group had mean loss of only 0.3 ± 0.9 mm, which was not statistically significant (p > 0.05, Table 1). The difference between the 2 groups was statistically significant (p < 0.05). At 5 mm apical to the crest the Socket group had a significant mean loss of 0.8 ± 0.5 mm (p < 0.05) while the Overlay showed a statistically significant mean gain of 0.5 ± 0.6 mm (p < 0.05). The difference between the test and control groups was statistically significant (p < 0.05, Table 1).

Vertical Ridge Height Change On the mid-buccal the Socket group gained a mean of 0.5 ± 2.9 mm while the Overlay group gained 0.3 ± 2.6 mm, which was not statistically significant for either group (p > 0.05). The difference between the test and control groups was not statistically significant (p > 0.05, Table 2). Data and statistical significance for the mid-lingual, the mesial and the distal portion of the socket are shown in Table 2.

CEJ to Osseous Crest Changes Mesial CEJ to osseous crest distance for the Socket group showed a significant mean loss of 0.3 ± 0.3 mm (p < 0.05), while the Overlay group also had a significant mean loss of 0.5 ± 0.4 mm (p < 0.05). Distal CEJ to osseous crest distance for the Socket group showed a significant mean loss of 0.5 ± 0.7 mm (p < 0.05), while the Overlay group had a mean loss of 0.3 ± 0.5 mm, which was not statistically significant (p > 0.05). There were no statistically significant differences between groups for either mesial or distal sites.

Buccal Contour For the Socket group 5 sites ended with a concave contour while 7 were flat. For the Overlay group 4 sites ended with a flat contour while 7 were convex. In the Socket group this represented a loss of contour for 9 sites and no change for 3. For the Overlay group 4 sites had no change in contour while 7 showed a gain.

Histologic evaluation The Socket group healed with a mean of 35 ± 16% vital bone, 21 ± 13% non-vital bone and 44 ± 9% trabecular space, while the Overlay group healed with a mean of 40 ± 16% vital bone, 17 ± 11% non-vital bone, and 43 ± 12% trabecular space. There were no statistically significant differences between the Socket and Overlay groups for vital or non-vital bone or trabecular space (p > 0.05, Table 3).

DISCUSSION The primary aim of this 4-month randomized, controlled, blinded clinical study was to test the hypothesis that crestal ridge width could be preserved when a facial overlay xenograft that resists resorption was used. It was demonstrated that crestal ridge width can be almost entirely preserved when a slowly resorbing buccal overlay xenograft is used therfore the hypothesis should be accepted. This is in contrast to previous ridge


7

preservation studies where about 18% of crestal ridge width was lost.6-9,11-32 Furthermore at 5 mm apical to the crest there was a gain of 0.5 mm of ridge width. This supports the concept proposed by Wang et al. that a slowly resorbing outer layer of grafting material may resist resorption and have a beneficial effect on the final result.34 They also proposed that a rapidly resorbing inner graft layer is beneficial since it will be replaced by newly formed vital bone. In this study the socket graft was mineralized particulate cancellous allograft that healed with a high percentage of vital bone present. This means that at the site of implant placement, the previous socket area, there was a high percentage of vital bone present to promote osseointegration.

One question that needs to be considered is when an overlay graft is indicated. It adds time and expense to the ridge preservation procedure so there should be a compelling reason to complicate the grafting procedure by using an additional graft material. Data from ridge preservation sites from this study and other studies at the University of Louisville (2 publications and 5 Master's theses) indicate that maxillary sites tend to have more resorption than mandibular sites and that maxillary anterior sites tend to have the highest percentage of lost ridge width when compared to other sites (Table 4).9,18 Another consideration in maxillary anterior sites is that there is often a significant undercut or ridge concavity that extends corono-apically. This phenomenon can lead to a fenestration at the time of implant placement while narrow crestal ridge width may lead to dehiscence.

According to Woelfel's Dental Anatomy textbook maxillary incisors are about 6.0 mm in buccal-palatal width at the cervix, canines are about 7.5, premolars are about 8.1 and molars are about 10.7 mm.44 Mandibular dimensions are about 5.5 mm for incisors, 7.5 for canines, 7.1 for premolars and 8.9 mm for molars. This means that the smaller the initial ridge (socket) dimension the more likely that the site will need an overlay graft. Thus incisor, canine and premolar sites are the most likely candidates for an overlay graft, especially if a significant undercut is present. Mandibular incisor sites are the narrowest, however, the greatest percent resorption occurs in the maxilla (Table 4). Thus initial site width, likely percent resorption, and depth of the undercut are all factors that may influence the decision to use an overlay graft. Site analysis following tooth extraction utilizing these factors will lead to the best treatment decision.

Another advantage of the bovine xenograft is preservation of the original buccal contour in a mesio-distal direction. Without an overlay graft this contour is likely to become concave (Figure 1a) while use of the overlay most often results in a convex (Figure 1b) or at least a flat contour. In this study all pre- and post-op contour clinical photos were evaluated and scored for initial and final contour. This demonstrated that the overlay graft preserved or gained ridge contour, which is an esthetic advantage, while the Socket group lost contour at most sites.

If the goal of implant surgery is to place the implant totally within vital bone with no dehiscence or fenestration defects then the selection of a ridge preservation procedure can be an important decision. Development of an adequate ridge is also important if implant placement will be done using a flapless procedure, which may have esthetic advantages for the soft tissue and papillae. Another advantage of adequate ridge width is that following implant placement having 2 mm of bone buccal to the implant will help prevent soft tissue recession.45,46 Inadequate crestal ridge width, on the other hand, could


8

lead to implant dehiscence and potentially peri-implantitis. While additional grafting can be performed at the time of implant placement, the goal of the initial grafting procedure should be to establish adequate ridge dimensions so that no further grafting will be necessary at the time of implant placement. Therefore the overlay graft may be useful in successful development of adequate ridge width.

The most difficult aspect of the ridge preservation procedure is maintaining or gaining crestal ridge width. This means graft compression at the crest must be avoided and graft displacement either apically or laterally must be prevented. This was accomplished in this study by extending the flap one tooth mesial and distal to the extraction site. For the papilla preservation flap, the papillary incision was similar to that recommended by Bernimoulin et al. for a coronally positioned flap.43 Thus a new papilla tip was created about 3 mm apical to the existing papilla tip. The existing papilla was then de-epithelialized and the new papilla tip was positioned coronally to the tip of the existing papilla. An apical periosteal release gave adequate flap mobility to allow coronal positioning and to accommodate a thick layer of xenograft.

About 3 to 4 mm of xenograft thickness was placed as a buccal overlay, and perhaps more thickness was achieved apically. Also the graft was extended mesially and distally to the mid-root prominence of the adjacent teeth. This helped prevent apical and lateral displacement of the graft. Crestally the flap was closed with minimal tension to avoid graft compression. Another factor may have been the slight rigidity of the polylactide membrane, which also helped resist crestal compression.

Two previous studies tested the effect of an overlay graft.16,17 One showed a gain and one showed a slight loss of ridge width. Simon et al. showed a gain and the overlay graft was applied to the buccal, the crest and to the palatal/lingual.16 The gain was about 1.1 mm of ridge width, however, the measurement was at 3 mm apical to the crest rather than at the crest as was done in this study. Also different graft and membrane materials were used. Thus, although the data are not directly comparable, the present study confirms that the overlay graft approach can have a beneficial effect. Zubillaga et al. was performed in a similar fashion to Simon et al. but they used different graft materials, which resulted in a slight loss of about 0.5 mm of ridge width at 3 mm apical to the crest.17

Histologic analysis showed a high percentage of vital bone in the mid-socket area where the trephine core was harvested, which is where the cancellous allograft was placed (Table 3). This indicated that the goal of the Wang et al. layered graft had been achieved and that the implant would be placed in an area with a high percentage of vital bone.34 None of the histologic sections showed any signs of the xenograft. This indicates that it served to maintain and gain space and did not collapse into the socket area as the bundle bone and the allograft resorbed. The cancellous allograft used followed the healing pattern described by Burchardt et al. for cancellous autograft.37 Figure 2a-c demonstrates the vital bone, osteoblasts and appositional bone growth they reported as prominent features of cancellous graft healing.

A resorbable polylactide barrier membrane was used to contain the graft particles and to fulfill the objectives of guided bone regeneration. Thus the membrane was used to promote more rapid bone formation by preventing the ingrowth of connective tissue or


9

epithelium due to its barrier function. Since the primary objective of this study was to compare two grafting techniques the same membrane was used at all sites. The membrane was easy to use and all sites healed without any membrane associated complications. The portion of the membrane overlying the socket opening was left exposed and this resorbed by 6 to 8 weeks. Soft tissue had formed in this area by the time of membrane resorption and thus the graft was completely covered by either membrane or soft tissue at all times.

While there are many different ridge preservation procedures to choose from, the buccal overlay approach using a xenograft appears to be a viable option. When site analysis is used it can be determined whether the overlay or the intrasocket approach is the most appropriate treatment. The choice of graft materials to accomplish different purposes within the same graft as proposed by Wang et al. appears to be a valid and useful concept in implant site development surgery.34 Preservation of the original buccal contour is an esthetic advantage of this periodontal plastic surgery procedure.

Conflict of Interest Statement: This study was performed in Graduate Periodontics, University of Louisville without any grant funding. No commercial interests were involved and the authors report no conflict of interest. Dr. Greenwell has previously performed research for Sunstar Americas. Their membranes were used in this study but they supplied no funding or materials for this study.

Sources of support: This study received no support from outside sources. Drs. Poulias, Greenwell, Hill, Morton, Vidal, Shumway and Peterson report no financial relationships related to any products involved in this study. Dr. Greenwell performs research for Sunstar Americas, Chicago, IL.

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2. Araujo MG, Sukekava F, Wennstrom JL, Lindhe J. Ridge alterations following implant placement in fresh extraction sockets: an experimental study in the dog. J Clin Periodontol 2005;32:645-652.

3. Araújo M, Linder E, Wennström J, Lindhe J. The influence of Bio-Oss Collagen on healing of an extraction socket: an experimental study in the dog. Int J Periodontics Restorative Dent 2008;28:123-135.

4. Araújo MG, Lindhe J. Ridge alterations following tooth extraction with and without flap elevation: an experimental study in the dog. Clin Oral Implants Res 2009;20:545-549.

5. Araujo MG, Lindhe J. Socket grafting with the use of autologous bone: an experimental study in the dog. Clin Oral Implants Res 2011;22:9-13.

6. Lekovic V, Kenney EB, Weinlaender M, et al. A bone regenerative approach to alveolar ridge maintenance following tooth extraction. Report of 10 cases. J Periodontol 1997;68:563-570.

7. Lekovic V, Camargo PM, Klokkevold PR, et al. Preservation of alveolar bone in extraction sockets using bioabsorbable membranes. J Periodontol 1998;69:1044-1049.

8. Camargo PM, Lekovic V, Weinlaender M, et al. Influence of bioactive glass on changes in alveolar process dimensions after exodontia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:581-586.


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9. Iasella JM, Greenwell H, Miller RL, et al. Ridge preservation with freeze-dried bone allograft and a collagen membrane compared to extraction alone for implant site development: A clinical and histologic study in humans. J Periodontol 2003;74:990-999.

10. Serino G, Biancu S, Iezzi G, Piattelli A. Ridge preservation following tooth extraction using a polylactide and polyglycolide sponge as space filler: A clinical and histological study in humans. Clin Oral Implants Res 2003;14:651-658.

11. Barone A, Aldini NN, Fini M, Giardino R, Calvo-Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: A clinical and histomorphometric study. J Periodontol 2008;79:1370-1377.

12. Pelegrine AA, da Costa CE, Correa ME, Marques JF Jr. Clinical and histomorphometric evaluation of extraction sockets treated with an autologous bone marrow graft. Clin Oral Implants Res 2010;21:535-542.

13. Ahead of print. Festa VM, Addabbo F, Laino L, Femiano F, Rullo R. Porcine-derived xenograft combined with a soft cortical membrane versus extraction alone for implant site development: A clinical study in humans. [published online ahead of print November 14, 2011]. Clin Implant Dent Relat Res; doi 10.1111/j.1708-8208.2011.00398.

14. Brownfield LA, Weltman RL. Ridge preservation with or without an osteoinductive allograft: A clinical, radiographic, micro-computed tomography, and histologic study evaluating dimensional changes and new bone formation of the alveolar ridge. J Periodontol 2012;83:581-589.

15. Nemcovsky CE, Serfaty V. Alveolar ridge preservation following extraction of maxillary anterior teeth. Report on 23 consecutive cases. J Periodontol 1996;67:390-395.

16. Simon BI, Von Hagen S, Deasy MJ, Faldu M, Resnansky D. Changes in alveolar bone height and width following ridge augmentation using bone graft and membranes. J Periodontol 2000;71:1774-1791.

17. Zubillaga G, Von Hagen S, Simon BI, Deasy MJ. Changes in alveolar bone height and width following post-extraction ridge augmentation using a fixed bioabsorbable membrane and demineralized freeze-dried bone osteoinductive graft. J Periodontol 2003;74:965-975.

18. Vance GS, Greenwell H, Miller RL, Hill M, Johnston H, Scheetz JP. Comparison of an allograft in an experimental putty carrier and a bovine-derived xenograft used in ridge preservation: A clinical and histologic study in humans. Int J Oral Maxillofac Implants 2004;19:491-497.

19. Cardaropoli D, Cardaropoli G. Preservation of the post-extraction alveolar ridge: A clinical and histologic study. J Periodont Res 2008;28:469-477.

20. Neiva RF, Tsao YP, Eber R, Shotwell J, Billy E, Wang HL. Effects of a putty-form hydroxyapatite matrix combined with the synthetic cell-binding peptide P-15 on alveolar ridge preservation. J Periodontol 2008;79:291-299.

21. Beck TM, Mealey BL. Histologic analysis of healing after tooth extraction with ridge preservation using mineralized human bone allograft. J Periodontol 2010;81:1765-1772.

22. Mardas N, Chadha V, Donos N. Alveolar ridge preservation with guided bone regeneration and a synthetic bone substitute or a bovine-derived xenograft: A randomized, controlled clinical trial. Clin Oral Implants Res 2010;21:688-698.

23. Toloue SM, Chesnoiu-Matei I, Blanchard SB. A clinical and histomorphometric study of calcium sulfate compared with freeze-dried bone allograft for alveolar ridge preservation. J Periodontol 2012;83:847-855.

24. Fernandes PG, Novaes AB Jr, de Queiroz AC, et al. Ridge preservation with acellular dermal matrix and anorganic bone matrix cell-binding peptide P-15 after tooth extraction in humans. J Periodontol 2011;82:72-79.

25. Engler-Hamm D, Cheung WS, Yen A, Stark PC, Griffin T. Ridge preservation using a composite bone graft and a bioabsorbable membrane with and without primary wound closure: A comparative clinical trial. J Periodontol 2011;82:377-387.


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26. Gholami GA, Najafi B, Mashhadiabbas F, Goetz W, Najafi S. Clinical, histologic and histomorphometric evaluation of socket preservation using a synthetic nanocrystalline hydroxyapatite in comparison with a bovine xenograft: A randomized clinical trial. Clin Oral Implants Res 2012;23:1198-1204.

27. Nam HW, Park JB, Lee JY, et al. Enhanced ridge preservation by bone mineral bound with collagen-binding synthetic oligopeptide: A clinical and histologic study in humans. J Periodontol 2011;82:471-480.

28. Stimmelmayr M, Guth JF, Iglhaut G, Beuer F. Preservation of the ridge and sealing of the socket with a combination epithelialised and subepithelial connective tissue graft for management of defects in the buccal bone before insertion of implants: A case series. Br J Oral Maxillofac Surg 2012;50:550-555.

29. Brkovic BM, Prasad HS, Konandreas G, et al. Simple preservation of a maxillary extraction socket using beta-tricalcium phosphate with type I collagen: Preliminary clinical and histomorphometric observations. J Can Dent Assoc 2008;74:523-528.

30. Kutkut A, Andreana S, Kim HL, Monaco E Jr. Extraction socket preservation graft before implant placement with calcium sulfate hemihydrate and platelet-rich plasma: A clinical and histomorphometric study in humans. J Periodontol 2012;83:401-409.

31. Wood RA, Mealey BL. Histologic comparison of healing after tooth extraction with ridge preservation using mineralized versus demineralized freeze-dried bone allograft. J Periodontol 2012;83:329-336.

32. Hoang TN, Mealey BL. Histologic comparison of healing after ridge preservation using human demineralized bone matrix putty with one versus two different-sized bone particles. J Periodontol 2012;83:174-181.

33. Fotek PD, Neiva RF, Wang HL. Comparison of dermal matrix and polytetrafluoroethylene membrane for socket bone augmentation: A clinical and histologic study. J Periodontol 2009;80:776-785.

34. Wang HL, Misch C, Neiva RF. "Sandwich" bone augmentation technique: Rationale and report of pilot cases. Int J Periodontics Restorative Dent 2004;24:232-245.

35. Wallace SS, Froum SJ, Cho S-C, et al. Sinus augmentation utilizing anorganic bovine bone (Bio-Oss) with absorbable and nonabsorbable membranes placed over the lateral window: Histomorphometric and clinical analyses. Int J Periodontics Restorative Dent 2005;25:551-559.

36. Scarano A, Pecora G, Piattelli M, Piattelli A. Osseointegration in a sinus augmented with bovine porous bone mineral: Histological results in an implant retrieved 4 years after insertion. A case report. J Periodontol 2004;75:1161-1166.

37. Burchardt H. The biology of bone graft repair. Clin Orthop Relat Res 1983;174:28-42.

38. Goldberg VM, Stevenson S. The biology of bone grafts. Semin Arthroplasty 1993;4:58-63.

39. Sbordone C, Toti P, Guidetti F, Califano L, Santoro A, Sbordone L. Volume changes of iliac crest autogenous bone grafts after vertical and horizontal alveolar ridge augmentation of atrophic maxillas and mandibles: A 6-year computerized tomographic follow-up. J Oral Maxillofac Surg 2012;70:2559-2565.

40. Sbordone L, Levin L, Guidetti F, Sbordone C, Glickman A, Schwartz-Arad D. Apical and marginal bone alterations around implants in maxillary sinus augmentation grafted with autogenous bone or bovine bone material and simultaneous or delayed dental implant positioning. Clin Oral Implants Res 2011;22:485-491.

41. Silness J, Löe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 1964;22:121-135.

42. Löe H. The gingival index, the plaque index and the retention index systems. J Periodontol 1967;38(Suppl):610-616.

43. Bernimoulin JP, Luscher B, Mühlemann HR. Coronally repositioned periodontal flap. Clinical evaluation after one year. J Clin Periodontol 1975;2:1-13.


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44. Scheid RC, Weiss G. Woelfel's Dental Anatomy. Eighth Edition. Philadelphia: Lippincott Williams & Wilkins; 2012:65-162.

45. Spray JR, Black CG, Morris HF, Ochi S. The influence of bone thickness on facial marginal bone response: Stage 1 placement through stage 2 uncovering. Ann Periodontol 2000;5:119-128.

46. Buser D, Martin W, Belser UC. Optimizing esthetics for implant restorations in the anterior maxilla: Anatomic and surgical considerations. Int J Oral Maxillofac Implants 2004;19(Suppl):43-61.

Address correspondence and requests for reprints to Dr. Henry Greenwell, Graduate Periodontics, School of Dentistry, University of Louisville, Louisville, KY 40292

(address is complete); Phone 502 852-6928; Fax 502 852-1317; email [email protected]

Submitted September 26, 2012; accepted for publication December 12, 2012.

Figure 1a.

Concave ridge contour associated with intrasocket graft alone treatment at 4 months associated with the extraction of tooth #5.

Figure 1b.

Convex ridge contour associated with the overlay graft treatment at 4 months associated with the extraction of tooth #4.

Figure 2a.

Vital bone harvested from the cancellous allograft site, which contains osteocytes in the lacunae. 100X.

Figure 2b.

Osteoblasts lined up along the surface of vital bone. Arrows indicate osteoblasts. 200X.

Figure 2c.

Appositional bone growth with vital bone growing on non-vital residual graft particles. Arrows indicate vital bone that has formed on non-vital bone. 200X.

Table 1

Horizontal Ridge Width for Intrasocket and Overlay Sites Mean ± sd in mm Group Initial Final Change % Change Range

Intrasocket at Crest 8.7 ± 1.0 7.1 ± 1.5 -1.6 ± 0.8* -19 ± 11 -3.4 to - 0.5

Overlay at Crest 8.4 ± 1.4 8.1 ± 1.4 -0.3 ± 0.9† -3 ± 10 -2.0 to 0.9

Intrasocket at 5 mm 9.1 ± 0.9 8.4 ± 0.9 -0.8 ± 0.5* -8 ± 5 -1.8 to 0.0

Overlay at 5 mm 8.6 ± 1.9 9.1 ± 2.0 0.5 ± 0.6*† 7 ± 8 -0.8 to 1.5

* = p < 0.05 between initial and 4-month values

† = p < 0.05 between overlay and intrasocket groups


13

Table 2

Vertical Ridge Height Change for Intrasocket and Overlay Sites Mean ± sd in mm

Location Intrasocket Overlay Intrasocket Overlay

Mean Change ± sd in mm Range in mm

Mid-Buccal 0.5 ± 2.9 0.3 ± 2.6 -2.0 to 8.0 -3.0 to 5.0

Mid-Lingual -0.4 ± 0.6 -0.5 ± 0.7* -1.5 to 0.5 -1.5 to 0.5

Mesial -0.5 ± 0.4* -0.6 ± 0.4* -1.2 to 0.0 -1.1 to 0.0

Distal -0.8 ± 0.3* -0.4 ± 0.4*† -1.3 to -0.1 -1.0 to 0.0

* = p < 0.05 between initial and 4-month values

† = p < 0.05 between overlay and intrasocket groups

Table 3

Histologic Data at Implant Placement for Intrasocket and Overlay Sites Mean ± sd Group Time n % Vital % Non-vital % Trabecular

Intrasocket 4 month 12 35 ± 16 21 ± 13 44 ± 9

Overlay 4 month 11 40 ± 16 17 ± 11 43 ± 12

Table 4

Ridge Dimensions by Tooth Type Mean ± sd in mm Tooth Type n Initial Final Change % Change

Maxillary Incisor 38 7.7 ± 1.0 5.8 ± 1.4 -1.9 ± 1.2 -24 ± 15

Mandibular Incisor 2 5.9 ± 0.2 5.1 ± 0.0 -0.9 ± 0.2 -15 ± 3

Maxillary Canine 8 8.8 ± 0.7 6.4 ± 2.1 -2.4 ± 2.0 -28 ± 22

Mandibular Canine 3 7.8 ± 1.8 7.0 ± 2.5 -0.8 ± 1.7 -10 ± 23

Maxillary Premolar 99 9.4 ± 1.2 8.0 ± 1.3 -1.4 ± 1.1 -14 ± 11

Mandibular Premolar 24 7.8 ± 1.3 7.4 ± 1.3 -0.4 ± 1.0 -4 ± 13

* RegenerOssTM, BioMet 3i, Palm Beach Gardens, FL 33410 † Bio-Oss, Geistlich Pharma North America, Inc, Princeton, NJ 08540 ‡ Guidor®, Sunstar Americas, Inc, Chicago, IL 60630 § Cytoplast® PTFE Suture, Osteogenics Biomedical, Inc, Lubbock, TX 79424 ║ H & H Company, Ontario, CA 91761


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http://www.joponline.org/action/showImage?doi=10.1902/jop.2013.120585&iName=master.img-000.jpg&w=375&h=117


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http://www.joponline.org/action/showImage?doi=10.1902/jop.2013.120585&iName=master.img-001.jpg&w=199&h=449

Dimensional alterations ofextraction sites after differentalveolar ridge preservationtechniques – a volumetric studyThalmair T, Fickl S, Schneider D, Hinze M, Wachtel H. Dimensional alterations ofextraction sites after different alveolar ridge preservation techniques – a volumetricstudy. J Clin Periodontol 2013; doi: 10.1111/jcpe.12111.

AbstractObjectives: The aim of this randomized controlled clinical study was to assesssoft tissue contour changes after different alveolar ridge preservation procedures.Material and Methods: Following tooth extraction, 30 patients were randomlyassigned to the following treatments (Tx) - Tx 1: xenogenic bone substitute (pre-hydrated collagenated cortico-cancellous porcine bone) and free gingival graft; Tx2: free gingival graft alone; Tx 3: xenogenic bone substitute; Tx 4: no furthertreatment (control). Impressions were obtained before tooth extraction (baseline)and 4 months after surgery. Cast models were optically scanned, digitally super-imposed and horizontal measurements of the contour alterations between timepoints were performed using digital imaging analysis.Results: All groups displayed contour shrinkage at the buccal aspect rangingfrom a mean horizontal reduction of !0.8 " 0.5 mm (Tx 1) to !2.3 " 1.1 mm(control). Statistically significant differences were found between Tx 1 and Tx 4as well as Tx 2 and Tx 4. A significant positive influence of the free gingival grafton the maintenance of the ridge width was recorded (p < 0.001).Conclusion: In this study, alveolar ridge preservation techniques were not able toentirely compensate for alveolar ridge reduction. Covering the orifice of theextraction socket with a free gingival tissue graft seems to have the potential tolimit but not avoid the post-operative external contour shrinkage based on opticalscans.

Tobias Thalmair1, Stefan Fickl2,David Schneider4, Marc Hinze1 andHannes Wachtel1,3

1Private Institute for Periodontology andImplantology, Munich, Germany; 2Departmentof Periodontology, Julius-MaximiliansUniversity, Wurzburg, Germany; 3Departmentof Prosthodontics, Dental School, FreeUniversity of Berlin, Berlin, Germay; 4Clinic ofFixed and Removable Prosthodontics andDental Material Science, University of Zurich,Zurich, Switzerland

Key words: alveolar ridge preservation;dimensional alterations; extraction socket;soft tissue punch

Accepted for publication 28 March 2013

Marked morphological and dimen-sional alterations of the alveolarridge occur after tooth extraction(Cardaropoli et al. 2003, Schroppet al. 2003, Araujo and Lindhe,2005). Both horizontal and vertical

changes in dimensions are expectedin hard tissue as well as soft tissue(Van der Weijden et al. 2009). Theresulting dimensional changes havebeen evaluated by volumetric analy-sis in a clinical study (Schropp et al.2003). The loss of volume in the hor-izontal dimension amounts 5–7 mmwithin the first 12 months. This cor-responds with approximately 50% ofthe original width of the alveolarbone (Schropp et al. 2003). Theresorption of the ridge is morepronounced on the buccal than on

the lingual aspect of the extractionsocket (Araujo and Lindhe, 2005)and limited to the marginal one-third of the post-extraction site (Ara-ujo et al. 2008). It was suggestedthat the higher amount of resorptionat the buccal aspect is due to therelatively greater proportion of bun-dle or “tooth-derived” bone faciallythat loses its function after toothextraction and undergoes atrophy(Araujo and Lindhe, 2005). As thebuccal wall of the tooth socket isfrequently partially or completely

Conflict of interest and source offunding statement:

The authors declare that they have noconflicts of interest. This study wassupported in part by Tecnoss, Torino,Italy.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 1

J Clin Periodontol 2013; doi: 10.1111/jcpe.12111







resorbed (Araujo and Lindhe, 2005),consequently a collapse of thebuccal soft tissue leads to markedbucco-oral alterations (Schroppet al. 2003). In particular, in theanterior zone the mentioned altera-tions of the extraction socket canjeopardize the aesthetic outcome ofany dental treatment involving toothextraction.

To reduce volumetric changesoccurring after tooth extraction,different treatment modalities havebeen recommended. As implantinstallation was not able to alterbiological procedures (Ara!ujo et al.2005, Botticelli et al. 2004), it wassuggested that incorporation ofbiomaterials into a fresh extractionsocket could be a suitable techniquefor socket augmentation with theability to maintain the ridge dimen-sion to a certain extent (Nevins et al.2006, Cardaropoli et al. 2005). Sev-eral studies have proposed variousridge preservation techniques follow-ing tooth extraction including theplacement of graft materials and/orthe use of occlusive membranes(Camargnola et al. 2003, Lekovicet al. 1998, Lekovic et al. 1997,Cardaropoli et al. 2005) showingthat a significant reduction in alveo-lar bone resorption could beavoided. However, data obtainedfrom experimental studies showedthat incorporation of biomaterialsinto the extraction socket is not ableto diminish the biological process ofthe buccal bone plate (Fickl et al.2008a, Fickl et al. 2008b).

Techniques to achieve soft tissueclosure of extraction sites have beendeveloped, mainly related toimmediate implant placement. Junget al. (2004) introduced the soft tissuepunch technique, the extractionsocket was filled with a bone substi-tute and covered with an epithelial-ized free connective tissue graft. Itwas proposed that stabilizing the softtissue architecture with a free gingivalgraft has beneficial effects on mini-mizing the soft tissue shrinkage (Junget al. 2004). It was demonstrated thatplacing a deproteinized bovine bonematerial (DBBM) into the extractionsocket and closing the socket with afree gingival graft was beneficial inlimiting the volumetric shrinkage(Fickl et al. 2008b, Fickl et al. 2008a).

To date, it is still uncertain whichalveolar ridge preservation technique

is the most predictable. Therefore,the aim of this clinical investigationwas to evaluate, to which extent afiller or a soft tissue socket sealcontributes to ridge preservation.

Materials and Methods

The research protocol and the con-sent form of this clinical investiga-tion were approved by the ethicalcommittee of the Julius-MaximiliansUniversity, Wuerzburg, Germany(183/11).

Study population

Subjects selected for participating inthis prospective clinical study werecounselled and written informedconsent was obtained prior to thesurgical procedure (Helsinki Declara-tion of 1975 as revised in 2000). Thepatients were enrolled and treated ina period of time between January2011 and September 2011.

The study population consistedof 30 adult patients (mean age 46.2,range 24–72 years, 13 females)requiring treatment of tooth extrac-tion in the anterior zone ranging tothe second bicuspid. The reasons forextraction included root fractures,endodontic treatment failures andadvanced caries lesions.

The following exclusion criteriawere applied:(1) Age <18 years.(2) Smoking status of more than 10cigarettes/day.(3) Presence of relevant medical con-ditions: Patients with diabetes mell-itus, unstable or life-threateningconditions, or requiring antibioticprophylaxis. Patients with medica-tion of drugs influencing the bonemetabolism were also excluded.(4) Pregnant or lactating women.(5) History of malignancy, radiother-apy, or chemotherapy for malignancyin the past 5 years.(6) History of autoimmune disease.(7) Presence of acute periodontal orperiapical pathology.

Only teeth with an intact buccalbone plate were included in thestudy population. The condition ofthe buccal bone plate was evaluatedintra-surgically after tooth extrac-tion. All extraction sites presented aminimum width of 2 mm of kerati-nized gingival tissue.

All patients received instructionsin oral hygiene and underwent initialperiodontal evaluation includingprofessional tooth cleaning with scal-ing and polishing until full-mouthplaque score and full-mouth bleedingscore <20% were reached.

Inter-examiner accuracy control

All surgical procedures were per-formed by four operators (H.W.,T.T., S.F. and M.H.) in the sameclinic (Private Institute for Periodon-tology and Implantology, Munich,Germany).

To control the accuracy andrepeatability between surgeons, a cali-bration meeting was held in Munich(October 2010). Procedures wereexplained using digital images and sur-gical videos. Within the discussion atthe calibration meeting, it was decidedto make a variation to the originalapproved protocol (two-arm studywith Tx 1 and Tx 3) and to add twoadditional groups (Tx 2 and Tx 4).

Clinical procedure

Before surgery, impressions of thejaws were obtained in a one-step/two-viscosity technique with polye-ther impression materials (Perma-dyne Garant 2:1/Permadyne PentaH; 3M Espe, St. Paul, MN, USA).

Following the administration oflocal anaesthesia, an intra-sulcularincision was performed and the teethwere gently extracted withoutelevation of a mucoperiosteal flap orcompromising the marginal gingiva.Care was taken to produce as littletrauma as possible to the bonearound the alveolus. If necessary, theteeth were sectioned to allow atrau-matic extraction and, more impor-tantly, preservation of all bone walls.In case of deep fractured teeth, whenthe remaining supragingival toothstructure was insufficient for the useof a forceps, a specific root extractiondevice with intra-canalicular anchor-age (Benex-Extractor, Zepf Medizin-technik GmbH, Seitingen-Oberflacht,Germany) was used to avoid traumato the surrounding tissues. The extr-action sockets were carefully curettedto remove granulation tissue.

Patients were enrolled sequen-tially. A randomization list wasgenerated. Randomization envelopeswere supplied and numbered sequen-

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

2 Thalmair et al.

tially containing the treatmentallocation according to the randomi-zation list.

The extraction sites were ran-domly assigned to one of the follow-ing treatments:

Treatment 1 (Tx 1): The extrac-tion socket was treated using thesocket seal technique (Jung et al.2004). The internal marginal gingivaof the extraction socket was deepi-thelialized with a diamond bur untilbleeding was evident. The extractionsocket was filled with a xenogenicbone substitute (pre-hydrated colla-genated cortico-cancellous porcinebone; mp3 OsteoBiol, Tecnoss, Tor-ino, Italy) to the level of the bonecrest. A free gingival graft with athickness of 3 mm was harvestedfrom the palate/tuberosity andsutured to the marginal gingiva of theextraction socket with several inter-rupted sutures (Seralene 7–0, SeragWiesner, Naila, Germany) (Fig. 1).

Treatment 2 (Tx 2): The internalmarginal gingiva of the extractionsocket was deepithelialized with adiamond bur and a free gingivalgraft was sutured into the orifice ofthe extraction socket in the samemanner as in Tx 1, however, withoutthe use of a filler material.

Treatment 3 (Tx 3): The extrac-tion socket was filled with mp3(OsteoBiol, Tecnoss, Torino, Italy)and secured with a non-resorbablesuture material (Gore-Tex CV5,W.L. Gore & Associates, Putzbrunn,Germany) without the use of a gingi-val graft (Fig. 2).

Treatment 4 (Tx 4): The extrac-tion socket remained with its bloodclot only (control).

Consecutively, a pre-fabricatedresin-bonded bridge was fixed to theadjacent teeth without any contactof the pontics to the extractionsocket with an auto-polymerizingresin material (Clearfil Cores; Kura-ray, Tokyo, Japan).

Post-surgical protocol

The patients were instructed to rinsewith 0.2% chlorhexidine digluconatetwice a day for at least 2 weeks(Vaughan and Garnick, 1989). Toreduce swelling, Ibuprofen (600 mg)was prescribed (Pearlman et al.1997). Sutures were removed 7 daysafter surgery. Polyether impressions(Permadyne Garant 2:1/Permadyne

Penta H; 3M Espe) were obtained4 months after tooth extraction.

Evaluation of tissue contour changes

The analysis of the soft tissue contourchanges was performed at the Clinicof Fixed and Removable Prosthodon-tics and Dental Material Science,University of Zurich, according toprevious studies (Fickl et al. 2009,Thoma et al. 2010).

Master casts of each patient weremade with dental stone (CAM-Base,Dentona AG, Dortmund, Germany)utilizing the pre-extraction and fol-low-up impressions after 4 months.The cast models were opticallyscanned and digitized (Iscan D101,Imetric GmbH, Courgenay, Switzer-land) creating STL files (StandardTessellation Language). The STL filesof these digital models representingthe two treatment time points wereimported into a specific software(SMOP, Swissmeda, Zurich, Switzer-land) and were superimposed accord-ing to the buccal surface of theadjacent teeth using the best-fit algo-rithm. The same software was used tomeasure the dimensional changes inthe relevant buccal alveolar ridge areacomparing the contour before toothextraction and 4 months after ther-apy (Fig. 3). The area of measure-ment was defined by a line parallel tothe tooth axis in the middle of the

mesial and distal papilla, by themucogingival line and the most coro-nal contour line of the alveolar ridge.As the size of this area differed fromsite due to the difference in tooth/gapsize, the mean volume change perarea was calculated as a distance inbuccal direction (!d [mm] = !vol[mm3]/area [mm2]) to allow a directcomparison of dimensional changesbetween the sites.

Before the beginning of the evalua-tion, a calibration exercise was per-formed to obtain reproducibility forthe measurement of the relevant buccalarea. This analysis was conducted bytwo examiners (D.S. and T.T.), one ofthem was blinded (D.S.).

Statistical analysis

Sample size calculation was per-formed on the results of previousstudies (Fickl et al. 2009, Ficklet al. 2008b) and resulted in sevensubjects per group. For the primaryoutcome variable (mean dimensionalchange) it was assumed that thetrue difference between groupswould amount to 0.75 mm with aSD of 0.5. The Type I error proba-bility was set at 0.05, the statisticalpower at 80%.

Statistical analysis was performedusing a statistical software program(SPSS 20, IBM Corporation, Arm-onk, NY, USA) by a statistician (M.

(a) (b)

(c) (d)

Fig. 1. Treatment group 1. (a) after gentile extraction of tooth 21 the buccal wall isintact, (b) a xenogenic bone substitute is applied into the extraction socket, (c) a gingi-val autograft is sutured to the marginal soft tissue, (d) clinical situation 4 monthspost-surgically.


Different alveolar ridge preservation techniques 3

Roos) at the Division of Biostatistics,University of Zurich.

The primary outcome variable washorizontal soft tissue dimensionalchange at 4 months after toothextraction.

Descriptive statistics including boxplots were used to indicate the mean,median, minimum, maximum valuesand the standard deviation in eachtreatment group. Kolmogorov–Smir-nov Test was used to check the cor-

rectness of the normality assumption.Differences in mean distance changebetween groups were tested by apply-ing one-way analysis of variance(ANOVA) and post hoc Scheffe test.

Influence of bone filler materialand soft tissue seal and other variableslike age, gender, jaw or tooth typewere the secondary outcome variables.

Two-way ANOVA was used to iden-tify possible influence of the bonesubstitute filler and the soft tissue seal

on the mean distance change. Spear-man correlation was computed toindicate associations between themean distance change and variables(age, gender, jaw, jaw location andmethod of extraction). Fisher’s exacttest was applied to find associationsbetween two binary variables. Krus-kal–Wallis tested the influence of thesurgeons. The level of significancewas set at p < 0.05.

Results

All patients completed the study. Thirtypatients were included (13 females);eight were smokers. The mean age was46.2 years, ranging from 24 to 72 years(Table 1 and Appendix S1).

Qualitative assessment

Healing of all treatment groups wasuneventful. No intra-operative or post-operative complications occurred.Clinically, 1 week after insertion of thegingival graft, all areas were vascular-ized, some parts were covered withfibrin and responded by bleeding afterremoval of the fibrinoid surface.Necrotic parts or incomplete woundclosure were not observed.

After 4 months, all free gingivalgrafts of group Tx 1 and Tx 2 werefully integrated.

Quantitative assessment

The results of the dimensional evalua-tion are displayed in Tables 2 and 3and Appendix S1.

Horizontal contour shrinkage at thebuccal aspect during the 4 month heal-ing period was observed in all groupsand ranged from !0.8 " 0.5 mm (Tx1) to !2.3 " 1.1 mm (Tx 4/Control).

The following dimensional changesoccurred according to the treatmentoption (descriptive data betweenstages):

Treatment 1 (Tx 1): Meandimensional differences betweenbaseline and the 4 month scan were!0.79 " 0.5 mm (range: !0.13 to!1.33 mm) buccally.

Treatment 2 (Tx 2): Fourmonths after tooth extraction, thefollowing dimensional changes wererecorded for the buccal aspect:!0.85 " 0.6 mm (range: !0.15 to!1.60 mm).

Treatment 3 (Tx 3): The meandifferences between baseline and the

(a) (b)

(c) (d)

Fig. 2. Treatment group 3. (a) tooth 14 needs to be extracted, (b) a xenogenic bonesubstitute is applied into the extraction socket, (c) buccal view and (d) occlusal view at4 months post-surgically display the contour preservation.

(a) (b)

(c) (d)

Fig. 3. Measured area of tissue volume changes. (a) and (b) superimposed images dem-onstrating volumetric changes between baseline (yellow colour area) and 4 months(green colour area). (c) and (d) buccal and occlusal view of the measured area (regionof interest) in blue colour.


4 Thalmair et al.

4 month scans were !1.45 " 0.7 mm(range: !0.73 to !2.14 mm).

Treatment 4 (Tx 4): The meandifference of the dimensional con-tour changes was !2.29 " 1.1 mm(range: !1.23 to !3.34 mm).

The comparison of the groups byunpaired t-tests (one-way ANOVA)resulted in significant differences indimensional change between the testgroups Tx 1 and Tx 2 comparedwith control group Tx 4. No othersignificant differences were observedbetween groups (Fig. 4).

Two-way ANOVA showed a signifi-cant influence of the soft tissuesocket seal leading to a lower degreein shrinkage (B = 1.05; p < 0.001).The influence of the filler was esti-mated to be not significant(B = 0.42; p = 0.125).

The extraction procedure – sepa-ration of the root, extraction withforceps or with a mechanical device– had no influence on the buccalcontour changes.

There was no difference in thevolume alterations regarding thelocation of the tooth. No differencewas found between teeth located inmaxilla or mandibula.

Spearman correlation did notshow any significant associationbetween predictors (age, gender,smoking, jaw, jaw location andmethod of extraction) and the meandistance difference.

Kruskal–Wallis test revealed nostatistically significant differenceamong the different surgeons(p = 0.964).

Discussion

Indications for ridge preservationare maintaining a stable ridge vol-ume for optimizing functional andaesthetic outcome and simplifyingthe treatment procedures subsequentto ridge preservation.

This study evaluated differenttechniques for alveolar ridge preser-vation following tooth extraction,generating sufficient soft tissue vol-ume for the time of implant place-ment thus simplifying implantationprocedures at earlier time points.The use of xenogenic bone substi-tute, a free gingival graft and thecombination of both for alveolarridge preservation were assessed.Preserving the extraction socket by

the application of a free gingivalgraft with or without a xenogenicbone substitute reduced post-opera-tive tissue shrinkage to a certainextent. The outcome of this random-ized controlled clinical investigationdemonstrated that the different alve-olar ridge preservation techniquesresulted in less contour reductionfrom the buccal aspect when com-pared with unassisted socket healing.

The findings of this study can bewell compared to previous animalstudies using a similar volumetricdata analysis. The horizontal contourchanges on the buccal aspect, afterextraction the socket was filled withDBBM and covered with a free gin-gival graft, demonstrated !1.5 mm.It was concluded that the applicationof DBBM seemed to limit the tissueshrinkage (Fickl et al. 2008b).

A xenogenic porcine bone substi-tute was used in this clinical trial, itwas investigated as natural scaffold fornew bone formation. An almost com-plete incorporation of the cortico-can-cellous particles surrounded by vitalbone was observed (Barone et al.2008). Compared to ridge preservationwith a bovine bone substitute, thegrafted sites comprised connective tis-sue including the graft particles andsmall amounts of newly formed bone(Carmagnola et al. 2003).

The results of this study indicatethat the free gingival graft for cover-ing the extraction socket revealedstatistically significant superiorresults in minimizing the buccal con-tour shrinkage, irrespective of addi-tionally a xenogenic bone substitutewas applicated or not. The biologicalintegration of the free gingival graftwas successful as no complicationregarding graft necrosis could beobserved. It can be assumed that thesoft tissue cover at the extraction sitehas the potential to limit the post-operative contour alterations to acertain extent.

This is in accordance with theclinical study of Jung et al. (2004),who reported that 3 weeks after sur-gery, 99.7% of the soft tissue graftswere fully integrated (Jung et al.2004). Landsberg and Bichacho(1994) stated that due to primarywound closure and the additionalmechanical stability of the free auto-graft, the soft tissue collapse mightbe avoided to a certain extent. A sta-tistically significant effect of the

Table 1. Randomization of treatment options per extraction sites

Group Number Gender(M/F)

Smoker Maxilla(anter/premol)

Mandibula(premol)

Reason fortooth

extraction(endo/

fract/caries)

Tx 1 8 3/5 2 7 (4/3) 1 5/3/–Tx 2 8 7/1 1 7 (4/3) 1 4/2/2Tx 3 7 5/2 2 5 (2/3) 2 3/2/2Tx 4 7 3/4 2 5 (2/3) 2 3/2/2

endo, endodontic reason; fract, root fracture; caries, advanced caries lesion.

Table 3. Volumetric data describing the distribution according to mean dimensional change

Group <0.5 mm 0.5–1.0 mm 1.0–1.5 mm 1.5–2.0 mm >2.0 mm

Tx 1 3 2 3 – –Tx 2 2 3 2 1 –Tx 3 – 2 2 2 1Tx 4 – – 2 1 3

Table 2. Descriptive statistics with measured area (mm2/mm3) and volume changes (mean,minimum and maximum)

Group Area (mm2) ! Vol (mm3) Mean ! distance(mm)

Min/max ! distance(mm)

Tx 1 22.04 " 3.70 19.92 " 3.77 !0.79 " 0.5 !0.13 " 0.17/!1.33 " 0.21Tx 2 23.46 " 2.16 24.89 " 7.68 !0.85 " 0.6 !0.15 " 0.20/!1.60 " 0.19Tx 3 19.63 " 1.29 32.89 " 6.96 !1.45 " 0.7 !0.73 " 0.15/!2.14 " 0.35Tx 4 19.72 " 3.35 41.41 " 15.96 !2.29 " 1.1 !1.23 " 0.26/!3.34 " 0.54



gingival autograft with respect to themaintenance of the tissue contoursat the buccal aspect was found(Landsberg and Bichacho, 1994).

Within the limits of this studyevaluating the soft tissue contour vol-ume, primary wound closure bymeans of a free gingival graft to sealthe orifice of the extraction socketmight be more beneficial compared tohealing by secondary intention. Thisis contrary to several clinical trialsreporting successful treatment out-comes with secondary wound healing(Camargnola et al. 2003, Serino et al.2003, Serino et al. 2008).

Ridge preservation by simplyusing a xenogenic bone substituteseemed to be more effective thanhealing by clot alone, but this differ-ence was statistically not significantin the present investigation. Thislack of evidence may be due to thesmall number of subjects. This find-ing would be in accordance with sev-eral clinical trials indicating a strongevidence that ridge preservation withgrafting materials is more effective(Barone et al. 2008, Cardaropoli andCardaropoli, 2008). However, it wasdemonstrated that in marginal por-tions of some sockets bone substituteparticles surrounded by granulationtissue occurred (Araujo et al. 2010,Araujo and Lindhe, 2009).

According to previous studiesshowing that the resorption of thealveolar ridge is more pronouncedon the buccal than on the lingualaspect of the extraction socket (Ara-ujo and Lindhe, 2005, Schropp et al.2003), only the buccal soft tissue

compartment of the experimentalsites was analysed. This is a limita-tion of the study. Because measure-ments were based on master models,no statements can be made as towhether the documented horizontalvolume resorption was caused byloss of soft tissue or underlyingbone. However, no complete preser-vation of the outline of the alveolarcrest could be assessed in particularat the buccal aspect.

The applied technique showed ahigh reproducibility and an excellentaccuracy for measuring volumechanges with a measurement errorbelow 10 mm (Mehl et al. 1997,Windisch et al. 2007). This methodoffers advantages including its non-invasive character, absence of radia-tion and the fact that it can easily beapplied. Currently, there is oneshortcoming of the techniquebecause optical scans were per-formed on study casts in this study.The accuracy of the method is highlyinfluenced by the accuracy of theimpressions and the casts.

Another limitation of the study isthe small number of patients in eachgroup. Further clinical investigationshould be conducted to recruit alarger patient collective to increasethe statistical power of clinical inves-tigations.

It is generally assumed that theanterior segment of the dentitionresponded differently than premolarsites to horizontal ridge reduction.This may indicate that anterior sitesare more susceptible to ridge altera-tions than premolar sites. The results

of this clinical trial did not show adifference in location and type oftooth.

The most important clinicalimpact of alveolar ridge preservationtechniques on patient-related out-come should be to optimize implantplacement in the correct position andto avoid additional augmentationprocedure. However, a statistical sig-nificance favouring one alveolar ridgepreservation technique does not nec-essarily lead to a clinical benefit forthe patient, unless the whole treat-ment is simplified or made more suc-cessful. There is still a lack ofsufficient evidence on implant-relatedoutcome. Only few studies reportedon a possible influence of alveolarridge preservation on placingimplants and need of further augmen-tation therapies (Serino et al. 2008,Fiorellini et al. 2005). Therefore, thepositive influence of alveolar ridgepreservation techniques on patient-related outcome may be attributedmore to achieving enhanced restor-ative and aesthetic outcomes, as wellas better maintenance of healthy peri-implant soft tissues (Vignoletti et al.2012).

In conclusion, the present clinicalstudy demonstrates that the investi-gated alveolar ridge preservationtechniques were not able to preventsoft tissue contour alterations entirelyafter tooth extraction. It appears thatcomplete ridge preservation is notpossible with the alveolar ridge pres-ervation techniques evaluated. Theuse of a free gingival graft coveringthe extraction socket was beneficialfor maintaining soft tissue volume.More studies including a higher num-ber of patients or sites are needed tofurther investigate these findings.

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Supporting Information

Additional Supporting Informationmay be found in the online versionof this article:

Appendix S1. Individual data of the30 patients. The table reports base-line patient characteristics, treatmentassignement, surgeon and outcomevariables for each patient. The volu-metric changes from baseline to 4months postoperative are expressedin mean, minimum and maximumchange distance.

Address:Tobias ThalmairPraxis Dr. ThalmairKammergasse 1085354 FreisingGermanyE-mail: [email protected]

Clinical Relevance

Scientific rational for the study:Effective ridge preservation tech-niques could reduce the need forridge augmentation proceduresassociated with the subsequentimplant treatment.Principal findings: Ridge preserva-tion procedures using an

autogenous free connective tissuegraft as a socket seal are able toreduce horizontal ridge alterations inpost-extraction sites.Practical implications: In clinicalcases where significant ridge resorp-tion is expected after tooth extrac-tion, the use of a free gingival graft– with or without the application of

a bone substitute – could provide arelatively simple and inexpensivetreatment to limit the contourshrinkage, eventually eliminatinglater augmentation procedures.



Fabio VignolettiPaula MatesanzDaniel RodrigoElena FigueroConchita MartinMariano Sanz

Surgical protocols for ridgepreservation after tooth extraction.A systematic review

Authors’ affiliations:Fabio Vignoletti, Paula Matesanz, Daniel Rodrigo,Elena Figuero, Conchita Martin, Mariano Sanz,ETEP Research Group, University Complutense,Madrid, Spain

Corresponding author:Prof. Mariano SanzFacultad de OdontologıaUniversidad Complutense de MadridPlaza Ramon y Cajal, 28040 Madrid, SpainTel.: +34 913 941 901Fax: +34 913 941 910e-mail: [email protected]

Key words: bone grafts, bone regeneration, bone substitutes, dental implants, ridge preserva-

tion, systematic review, tooth extraction

Abstract

Objective: This systematic review aims to evaluate the scientific evidence on the efficacy in the

surgical protocols designed for preserving the alveolar ridge after tooth extraction and to evaluate

how these techniques affect the placement of dental implants and the final implant supported

restoration.

Material and methods: A thorough search in MEDLINE-PubMed, Embase and the Cochrane Central

Register of controlled trials (CENTRAL) was conducted up to February 2011. Randomized clinical

trials and prospective cohort studies with a follow-up of at least 3 months reporting changes on

both the hard and soft tissues (height and/or width) of the alveolar process (mm or %) after tooth

extraction were considered for inclusion.

Results: The screening of titles and abstracts resulted in 14 publications meeting the eligibility

criteria. Data from nine of these 14 studies could be grouped in the meta-analyses. Results from

the meta-analyses showed a statistically significant greater ridge reduction in bone height for

control groups as compared to test groups (weighted mean differences, WMD = !1.47 mm; 95% CI

[!1.982, !0.953]; P < 0.001; heterogeneity: I2 = 13.1%; v2 P-value = 0.314) and a significant greater

reduction in bone width for control groups compared to the test groups (WMD = !1.830 mm; 95%

CI [!2.947, !0.732]; P = 0.001; heterogeneity: I2 = 0%; v2 P-value = 0.837). Subgroup analysis was

based on the surgical protocol used for the socket preservation (flapless/flapped, barrier

membrane/no membrane, primary intention healing/no primary healing) and on the measurement

method utilized to evaluate morphological changes. Meta-regression analyses demonstrated a

statistically significant difference favoring the flapped subgroup in terms of bone width (meta-

regression; slope = 2.26; 95% IC [1.01; 3.51]; P = 0.003).

Conclusions: The potential benefit of socket preservation therapies was demonstrated resulting in

significantly less vertical and horizontal contraction of the alveolar bone crest. The scientific

evidence does not provide clear guidelines in regards to the type of biomaterial, or surgical

procedure, although a significant positive effect of the flapped surgery was observed. There are no

data available to draw conclusions on the consequences of such benefits on the long-term

outcomes of implant therapy.

The alveolar processes in the jaws are tooth-

dependent structures that will undergo signif-

icant structural changes whenever the teeth

are lost. The dynamics and magnitude of

these changes have been investigated in the

dog model (Kuboki et al. 1988; Devlin et al.

1997; Cardaropoli et al. 2003; Araujo & Lind-

he 2005; van Kesteren et al. 2010) as well as

in humans (Amler et al. 1960; Evian et al.

1982; Devlin & Sloan 2002; Trombelli et al.

2008). These investigations have identified

the key processes of tissue modelling and

remodelling after tooth extraction that even-

tually lead to a reduction on the overall ridge

dimensions with significant changes in both

the buccal and lingual bone crests.

The amount of vertical and horizontal

resorption of the socket walls has been inves-

tigated with different methods, ranging from

studying and measuring cast models (Pietro-

kovski & Massler 1967; Johnson 1969;

Schropp et al. 2003), to radiographic analysis

Date:Accepted 26 August 2011

To cite this article:Vignoletti F, Matesanz P, Rodrigo D, Figuero E, Martin C,Sanz M. Surgical protocols for ridge preservation after toothextraction. A systematic review.Clin. Oral Impl. Res. 23(Suppl. 5), 2012, 22–38doi: 10.1111/j.1600-0501.2011.02331.x


(Schropp et al. 2003), clinical assessment

with individually pre-fabricated acrylic stents

during re-entry surgeries (Lekovic et al. 1998;

Camargo et al. 2000) and histological studies

in experimental animal models (Cardaropoli

et al. 2003; Araujo & Lindhe 2005). These

studies have evidenced that most of the

resorption occurs during the first 3 months

of healing, although dimensional changes can

be observed up to 1 year after tooth extrac-

tion, resulting in approximately 50% reduc-

tion of the bucco-lingual dimension of the

alveolar ridge (Schropp et al. 2003), mainly

due to the resorption of the buccal bone plate

(Araujo & Lindhe 2005).

The clinical consequences of these physio-

logical hard and soft tissue changes may

affect the outcome of the ensuing therapies

aimed to restore the lost dentition, either by

limiting the bone availability for ideal

implant placement or by compromising the

aesthetic result of the prosthetic restorations.

To counteract these early tissue changes after

tooth extraction, different socket preservation

therapies have been proposed, ranging from a

careful flapless tooth extraction aiming for an

undisturbed socket healing (Fickl et al.

2008a, 2008b), to the immediate placement

of dental implants (Paolantonio et al. 2001),

to filling the resulting alveolar socket with

different grafting materials, with and without

barrier membranes (Fickl et al. 2008a, 2008b).

The possible beneficial effect of a flapless

surgery during tooth extraction for limiting

the resorptive process of the alveolar crest

has been investigated in pre-clinical models

by comparing the outcomes with a flapped

conventional surgery. Although some studies

have shown slightly less pronounced bone

remodelling of the alveolar ridge after flapless

tooth extraction (Fickl et al. 2008a, 2008b),

other studies have failed to encounter signifi-

cant differences between flapped and flapless

tooth extractions (Araujo & Lindhe 2009).

Similarly, the possible beneficial effect of

using grafting procedures or guided bone

regeneration (GBR) to preserve the ridge after

tooth extraction has been tested in both ani-

mal and human studies. Using the dog experi-

mental model (Araujo & Lindhe 2009; Araujo

et al. 2008) filled the socket immediately after

tooth extraction with bovine-derived hydroxy-

apatite or with an autogenous bone graft (Ara-

ujo & Lindhe 2011). While the placement of

the xenograft counteracted the ridge contrac-

tion in the buco-lingual dimension, grafting

with autogenous bone did not significantly

alter the ridge resorptive process. In humans,

the application of regenerative bio-materials,

such as bone autografts, allografts, guided tis-

sue regeneration procedures, xenografts and

most recently, growth factors, has also been

evaluated with varying degrees of success to

maintain the anatomical dimensions of the

alveolar ridge after tooth extraction. A recent

systematic review (Ten Heggeler et al. 2010)

evaluated the efficacy of these therapies in

non-molar alveolar regions suggesting that

these techniques may not prevent the physio-

logical resorptive bone processes after tooth

extraction, although they may aid in reducing

the resulting bone dimensional changes. This

investigation, however, could not draw firm

conclusions due to the limitations in the

existing clinical research.

In terms of histological outcomes in

humans (Becker et al. 1999), used different

biomaterials, such as demineralized freeze-

dried bone, autologous bone, human morpho-

genetic proteins in a carrier to graft human

extraction sockets, reporting that the graft

materials were, 3–7 months later, mainly

surrounded by connective tissue. In contrast

(Artzi et al. 2000), using the same xenogeneic

graft material found the graft particles in

direct contact with bone, although in a simi-

lar study, using the same grafting material

(Carmagnola et al. 2003) found the graft par-

ticles remained within the socket more than

6 months after the extraction and only 40%

of the particles were in direct contact with

bone. It is, therefore, uncertain whether these

socket preservation therapies improve the

outcomes of the different rehabilitation

approaches after tooth loss.

The objective of the present study was to

systematically review all the scientific evi-

dence regarding these therapeutic interven-

tions for socket preservation after tooth

extraction and to assess systematically

the potential benefit of such techniques/

materials when compared with what occurs

when the socket is left to heal spontane-

ously.

The specific objectives were: (1) to describe

the surgical techniques and biomaterials

most commonly used to preserve the socket

architecture after tooth extraction; (2) to eval-

uate their expected outcome on the alveolar

ridge dimension and (3) to assess their impact

on the bone availability for ideal implant

placement or on the resulting prosthetic res-

toration.


Development of a protocol

A protocol covering all aspects of the system-

atic review methodology was developed

before the start of the review, including the

following definitions (Needleman 2002):

• Focused question.

• Study population.

• Types of intervention.

• Types of comparisons.

• Search strategy.

• Eligibility criteria for study inclusion.

• Outcome measures.

• Screening methods and data extraction.

• Quality assessment and data synthesis.

• Assessment of heterogeneity and drawing

of conclusions.

Focused question

“Which are the effects of the different socket

preservation approaches used immediately

after tooth extraction, compared to the spon-

taneous healing of the socket, in terms of the

alveolar ridge hard and soft tissue dimen-

sional changes and in terms of providing suf-

ficient bone availability for implant

placement and/or a restorative final success-

ful outcome?”

Population of study, type of intervention and type ofcomparison

The population of interest for this review

was represented by humans with at least one

tooth to be extracted, older than 18 years and

in good general health. A minimum sample

size (10 subjects per group) was established

in an attempt to minimize the publication

bias. The definition used for extraction

socket preservation therapy was: “Any thera-

peutic approach carried out immediately after

tooth extraction aimed to preserve the alveo-

lar socket architecture and to provide the

maximum bone availability for implant

placement.”

The specific therapeutic interventions eval-

uated in this study were:

• filling the socket with autologous bone

grafts or bone substitutes (allogenic, xeno-

genic and synthetic grafts);

• isolating the socket with the use of bar-

rier membranes, soft tissue autografts or

soft tissue substitutes (allogenic and oth-

ers) and,

• promoting the healing process of the

socket by the addition of growth factors

or bone morphogenetic proteins.

These interventions were compared to the

spontaneous healing of the socket.

Search strategy

Three electronic databases were used as

sources in the search for studies satisfying the


Vignoletti et al "Ridge preservation after tooth extraction

inclusion criteria: (1) The National Library of

Medicine (MEDLINE via Pubmed); (2) Embase

and (3) Cochrane Central Register of Con-

trolled Trials. These databases were searched

for studies published until February 2011.

The search was limited to human subjects.

The following search terms were used:

Population

(<[text words] Tooth> OR <[MeSH terms/

all subheadings] “Tooth”>) AND

([text words] Extraction)

OR

(<[Text words] Tooth extraction OR Extrac-

tion socket* OR Alveolar socket* OR dental

extraction* OR tooth removal OR socket*

OR ridge-socket* OR post-extraction socket*

OR fresh extraction socket* OR alveolar

crest> OR <[MeSH terms/all subheadings]

“Tooth Extraction*” OR “Tooth socket*”>)

Intervention

[text words] Socket*preservation OR Ridge

preservation OR bone preservation OR socket*

seal OR Site* preservation OR Bone filler* OR

Autologous bone graft* OR autologous bone

OR autogenous bone graft* OR Autogenous

bone OR bone substitute* OR growth factor*

OR rhBMP OR bone morphogenetic protein*

OR allogenic graft* or Allograft* OR xenogen-

ic graft* OR OR xenogeneic graft* OR xeno-

graft* OR synthetic graft* OR Barrier

membrane* OR membrane* OR resorbable

membrane* or non-resorbable membrane OR

guided bone regeneration OR GBR OR freeze

dried bone allograft* OR demineralized freeze

dried bone allograft* OR DFDBA OR FDBA

OR Bio-Oss OR Bio-Oss Collagen OR Allo-

plast* OR tricalciumphosphate OR cerasorb

OR Bioglass OR polymeric OR collagen sponge

OR Collagen OR collagen fleece OR collagen

plug* OR Bioguide OR Ossix OR Gore tex OR

ePTFE OR soft tissue* autograft* OR connec-

tive tissue graft* OR punch OR free gingival

graft*OR soft tissue* substitute*OR allogenic

soft tissue* OR alloderm OR acellular dermal

matrix OR collagen matrix.

There were no language restrictions. All

reference lists of the selected studies were

checked for cross-references. The following

journals were hand-searched: Journal of Clin-

ical Periodontology, Journal of Periodontol-

ogy, Journal of Periodontal Research;

Clinical Oral Implants Research, Interna-

tional Journal of Oral & Maxillofacial

Implants and Clinical Implant Dentistry and

Related Research.

Eligibility criteria for study inclusion

Randomized clinical trials (RCT) or prospec-

tive cohort studies with a follow-up of at

least 3 months after tooth extraction were

considered for inclusion in this review.

Outcome measures

The primary outcome variable chosen was the

bone dimensional changes occurring in the

socket wall after the tooth extraction and

the socket preservation therapy, measured as

the changes in the height and width of the

alveolar process (mm or %).

As secondary outcome variables, we con-

sidered the soft tissue dimensional changes

(in mm or %), the presence and amount of

keratinized tissue at time of implant place-

ment (yes/no or mm), the changes in clinical

attachment levels (CAL) evaluated at the

mesial and distal adjacent teeth, the avail-

ability of bone for implant placement (yes or

no), the need for soft and/or hard tissue aug-

mentation techniques at the time of implant

placement (number and type), the outcome of

the final implant supported restoration evalu-

ated in terms of the prosthetic and/or aes-

thetic result and assessed by the dentist or

the patient using different parameters or

indexes (Jemt index, VAS scale, etc.), and the

peri-implant health status evaluated radio-

graphically or clinically by means of probing

pocket depths, CAL, bleeding on probing and

the plaque index.

Screening methods and data extraction

First, two reviewers (PM and DR) screened

independently the titles and abstracts and did

the primary search. Subsequently, the studies

appearing to meet the inclusion criteria, or

those with insufficient data in the title and

abstract to make a clear decision, were

selected for evaluation of the full manuscript,

which was carried out independently by the

same two reviewers who determined their

eligibility. Any disagreement was resolved by

discussion with a third reviewer (FV). To pre-

vent selection bias, the reviewers were blind

to the name of the authors, institutions and

journal titles. All studies that met the inclu-

sion criteria underwent a validity assess-

ment. The reasons for rejecting studies at

this or at subsequent stages were recorded.

Special attention was paid to duplicate publi-

cations to avoid a likely bigger impact of the

same data on the overall result.

Data extraction

Two reviewers (PM and DR) independently

extracted the data using specially designed

data extraction forms. Any disagreement was

discussed and a third reviewer (EF or FV) was

consulted when necessary. The inter-

reviewer reliability of the data extraction was

calculated by determining the percentage of

agreement and the correlation coefficients

with Kappa analysis. Authors of studies were

contacted for clarification when data were

incomplete or missing. Data were excluded

until further clarification could be available

if agreement could not be reached. When the

results of a study were published more than

once or if the results were presented in a

number of publications, the most complete

dataset was included only once.

Quality assessment

The quality assessment of the included stud-

ies was undertaken independently and in

duplicate by one reviewer (PM) who was blind

to the name of the authors, institutions and

journal titles. This assessment was based on

the study design utilized according to the fol-

lowing criteria for Randomized controlled tri-

als: Quality assessment was carried out

following the recommendations by Cochrane

for assessing risk of bias (Higgins et al. 2009)

and also based on criteria proposed by Ten

Heggeler et al. (2010), which are based on the

RCT-checklist of the Dutch Cochrane Center

(2009), the CONSORT-statements (Schulz

et al. 2010), MOOSE-statement (Stroup et al.

2000), STROBE statements (von Elm et al.

2007) and the recommendations by Needle-

man (2002) and Esposito et al. (2001). Studies

were defined as low risk of bias if these six

criteria were clearly met in the study: random

allocation, definition of inclusion/exclusion

criteria for selecting the population, measures

to blind the patient and examiner, selection

of a representative population group, use of

identical treatment between groups except for

the intervention and detailed reporting of the

follow-up. When missing one of these criteria,

the study was classified as moderate potential

risk of bias. Missing two or more of these cri-

teria resulted in a high potential risk of bias

(Ten Heggeler et al. 2010).

The statistical heterogeneity among studies

was assessed using the Q test according to

Dersimonian and Laird, as well as the I2

index (Higgins et al. 2003) to know the per-

centage of variation in the global estimate

that was attributable to heterogeneity (I2 =

25%: low; I2 = 50%: moderate; I2 = 75%:

high heterogeneity). When the heterogeneity

values were high, a subgroup analysis was

carried out using the following explanatory

variables: (1) use of membrane (Yes/No); (2)

surgical technique (flap Yes/No); (3) primary

wound closure and (4) measurement tool

used to assess the morphological changes.

This subgroup analysis was performed using

meta-regression.



Data analysis

To summarize and to compare the selected

studies, the data on the primary outcome

(mean bone dimensional changes) were pooled

and analysed using means and 95% confi-

dence intervals. The data on secondary out-

comes were analysed depending on the type of

variable. For dichotomous variables (e.g. suc-

cessful implant placement), the estimates of

the effect were expressed as risk ratio and

95% confidence intervals. For continuous

variables (bone level changes, soft tissue

changes), weighted mean differences (WMD)

and 95% confidence intervals were used.

The study-specific estimates were pooled

using both the fixed effect model (Mantel-

Haenzel-Peto test) and the random effect

model (Dersimonian-Laird test). If a signifi-

cant heterogeneity was found, the random

effect model results were presented.

A Forest Plot was created to illustrate the

effects on the meta-analysis of the different

studies and the global estimation. The publi-

cation bias was evaluated using a Funnel

plot and the Egger’s linear regression

method. A sensitivity analysis of the meta-

analysis results was also performed (Tobias

1999). STATA® (StataCorp LP, Lakeway

Drive, College Station, TX, USA) inter-

cooled software was used to perform all

analyses. Statistical significance was defined

as a P-value <0.05.

Results

Screening

The search strategy resulted in 296 articles.

After an initial phase of screening (agreement

between reviewers of 89.53%; kappa = 0.46),

17 potentially relevant articles were identi-

fied. After reading the complete manuscripts,

three studies were excluded due to inade-

quate study design (Block & Jackson 2006);

inadequate control group (Yilmaz et al. 1998)

and due to only reporting secondary out-

comes (Norton et al. 2003). Hand-search or

cross-reference did not result in any addi-

tional article. Therefore, 14 studies were

finally included (Fig. 1).

Study design and study population

Twelve studies were RCTs with two to five

study groups and with a follow-up period

between 3 and 7 months (Hoad-Reddick et al.

1994; Lekovic et al. 1997; Lekovic et al.

1998; Bolouri et al. 2001; Froum et al. 2002;

Iasella et al. 2003; Fiorellini et al. 2005; Ba-

rone et al. 2008; Aimetti et al. 2009; Crespi

et al. 2009; Casado et al. 2010; Oghli & Ste-

veling 2010) (Table 1). Two studies were con-

trolled clinical studies, one with two study

groups and a 6-month follow-up period (Seri-

no et al. 2003) and the other with three study

groups and a 3-month follow-up (Serino et al.

2008). Six studies presented a split-mouth

design, whereas eight studies presented a par-

allel design.

The study population ranged from 10 indi-

viduals to 125. Smoking habit was reported

in four studies (Hoad-Reddick et al. 1994; Le-

kovic et al. 1997; Lekovic et al. 1998; Bolouri

et al. 2001; Froum et al. 2002; Iasella et al.

2003; Fiorellini et al. 2005; Barone et al.

2008; Aimetti et al. 2009; Crespi et al. 2009;

Casado et al. 2010; Oghli & Steveling 2010)

ranging from 0% to 12%. The periodontal

status of the extracted teeth was defined in

three studies (Serino et al. 2003; Serino et al.

2008). The localization of extracted teeth in

the mouth was reported in nine studies

(Hoad-Reddick et al. 1994; Lekovic et al.

1997; Lekovic et al. 1998; Bolouri et al. 2001;

Froum et al. 2002; Iasella et al. 2003; Fiorel-

lini et al. 2005; Barone et al. 2008; Aimetti

et al. 2009; Crespi et al. 2009; Casado et al.

2010; Oghli & Steveling 2010) in which

most, studied non-molar sites (Hoad-Reddick

et al. 1994; Lekovic et al. 1997; Lekovic et al.





veling 2010), although some were very spe-

cific to mandibular (Hoad-Reddick et al.

1994) or maxillary anterior teeth (Aimetti

et al. 2009), whereas others included any

teeth (Bolouri et al. 2001; Crespi et al. 2009).

Type of intervention and type of biomaterials

Most of the studies (Hoad-Reddick et al.

1994; Lekovic et al. 1997; Lekovic et al.



Studies included in quantitative synthesis

(meta-analysis)

(n = 9)

Records excluded

(n = 279)

Records screened

(n = 296)

Records after duplicates removed

(n = 296)

Identification

Eligibility

Inclusion

Screening

Additional records identified through other sources

(n = 0)

Records identified through database searching

(n = 296)

Full-text articles excluded, with reasons

(n = 3)

Did not fulfill the inclusion criteriaStudies included in

qualitative synthesis

(n = 14)

Full-text articles assessed for eligibility

(n = 17)

Fig. 1. Flow diagram (PRISMA format) of the screening and selection process.



UNCO

RREC

TEDPR

OOF

Table

1.Methods,

participants,interventions,

outcomes,

site

andfundingoftheselectedstudies

Study(#)

Method

Participants

Surgicalco

nsiderations

Intervention

Measurementmethod

Outcome

Site

andfunding

Hoad-Reddick

etal.

(1994)

(1)

RCTTwo

study

groups

Parallel

groups

6months

follow-up

18individuals

(-na)

Aged

54.4

years

Smokinghabit:

na

Periodontal

status:

na

Flapless

Primary

closure:na

Typ

eofsocket:

na

Test:Hyd

roxyapatite

granules

Control:Nosocketfilling

Lateral

cephalographs

anddental

pantomograms

Hard

tissue

dim

ensions:

defect

height(m

m)

Not

exp

lained

Not

ava

ilable

Lekovic

etal.

(1997)

(2)

RCTTwo

study

groups

Split

mouth

6months

follow-up

10individuals

(-3)

Aged

49.8

years

Smokinghabit:

na

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

na

Test:ePTFE

®membrane

Control:

Nosocketfilling

Reentrysurgery

Hard

tissue

dim

ensions:

defect

height(m

m),defect

width

(mm)

Yugoslavia

Not

ava

ilable

Lekovic

etal.

(1998)

(3)

RCTTwo

study

groups

Split

mouth

6months

follow-up

16individuals

(-0)

Aged

52.6

years

Smokinghabit:

na

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

na

Test:membraneofglyco

lide

andlactidepolimers

Control:

Nosocketfilling

Reentrysurgery

Hard

tissue

dim

ensions:

defect

height(m

m),defect

width

(mm)

Yugoslavia

Not

ava

ilable

Bolouri

etal.

(2001)

(4)

RCTTwo

study

groups

Split

mouth

24months

follow-up

18individuals

(-14)

Aged

54.4

years

Smokinghabit:

na

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

na

Test:BioplantHTR®

Control:

Nosocketfilling

Hard

tissue

dim

ensions:

optical

density

USA

BioplantInc.

South

Norw

alk,

CT

Froum

etal.

(2002)

(5)

RCTThree

study

groups

Split

mouth

6–8

months

follow-up

19individuals

(-na)

Aged

na

Smoking

habit:0%

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

4-w

all

Test

1:Bioactiveglass

Test

2:

DFD

BA

Control:Nosocket

filling

Histological

analysis

Histologicalanalysis

USA

Orthovita

Serino

etal.

(2003)

(6)

CTTwo

study

groups

Parallel

groups

6month

follow-up

45individuals

(-na)

Aged

na

Smoking

habit:na

Periodontal

status:

periodontitis

Flap

Primary

closure:YES

Typ

eofsocket:

na

Test:Sp

ongeofpolylactide-

polyglyco

lideacid

Control:No

socketfilling

Reentry

surgery

+stent

Hard

tissue

dim

ensions:

defect

height(m

m)


Italy

Not

ava

ilable

Iasella

etal.

(2003)

(7)

RCTTwo

study

groups

Parallel

groups

4–6

months

follow-up

24individuals

(-na)

Aged

51.5

Smoking

habit:na

Periodontal

status:

periodontitis

Flap

Primary

closure:NO

Typ

eofsocket:

na

Test:FD

BA

+tetracycline+

collagen

\mombrane

Control:

Nosocketfilling

Clinical+stent

Hard

tissue

dim

ensions:

defect

height(m

m),defect

width

(mm)

Soft

tissuedim

ensions


USA

Not

ava

ilable

Fiorellini

etal.

(2005)

(8)

RCTFive

study

groups

Parallel

groups

6months

follow-up

80individuals

(-0)

Aged

47.4

Smoking

habit:na

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

3-w

all(nobuccal

wall)

Test

1:0.75mg/m

lrhBMP/ACS

Test

2:1.50mg/m

lrhBMP/ACS

Control1:Nosocketfilling

Control2:placebo

CTscan

Defect

heightand

width

(mm

CTscan)

Needfor

augmentation

tech

nique


USA

Wye

th/Genetics

Institute,

Cambridge,MA

Barone

etal.

(2008)

(9)

RCTTwo

study

groups

Parallel

groups

7months

follow-up

40individuals

(-0)

Aged:na

Smokinghabit:

12.5%

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

4-w

all

Test:Corticocancellousporcine

bone+co

llagenmembrane


Reentry+stent

Hard

tissue

dim

ensions:

defect

height(m

m),defect

width

(mm)


Italy

Not

ava

ilable



Table

1.(continued)

Study(#)

Method

Participants

Surgicalco

nsiderations

Intervention

Measurementmethod

Outcome

Site

andfunding

Serino

etal.

(2008)

(10)

CTTwo

study

groups

Parallel

groups

3months

follow-up

20individuals

(-0)

Aged:

na

Smoking

habit:na

Periodontal

status:

Periodontitis

Flap

Primary

closure:NO

Typ

eofsocket:

na

Test:Sp

ongeof

polylactide-polyglyco

lide

acid

Control:No

socketfilling

Histological

analysis

Histological

analysis

Italy

Not

ava

ilable

Aim

etti

etal.

(2009)

(11)

RCTTwo

study

groups

Parallel

groups

3months

follow-up

40individuals

(na)

Aged:

51.27

Smoking

habit:0%

Periodontal

status:

na

Flapless

Primary

closure:NO

Typ

eofsocket:

na

Test:Medical-gradecalcium

sulphate

hemihyd

rate

Control:

Nosocketfilling

Reentry+stent

Dim

ensions

changes:

defect

height(m

m),

defect

width

(mm)

Histological

analysis

Italy

Not

ava

ilable

Crespi

etal.

(2009)

(12)

RCTThree

study

groups

Splitmouth

3months

follow-up

15individuals

(na)

Aged:

51.3

Smoking

habit:0%

Periodontal

status:

na

Flapless

Primary

closure:YES

(tissuegraft)

Typ

eofsocket:

3-w

all

(nobuccalwall)

Test

1:Magnesium-enrich

ed

hyd

roxyapatite

Test

2:Calcium

sulphate

Control:Nosocket

filling

PeriapicalXrays

Dim

ensions

changes:

defect

height(m

m).

Radiological

outcomes

Histological

analysis

Italy

Not

ava

ilable

Casado

etal.

(2010)

(13)

RCTFo

ur

study

groups

Split

mouth

4months

follow-up

19individuals

(na)

Aged:

na

Smoking

habit:na

Periodontal

status:

na

Flap

Primary

closure:YES

Typ

eofsocket:

na

Test

1:bovineBMP+bOM

Test

2:bovineBMP+bOM

+absorbable

membrane

Test

3:

absorbable

membrane

Control:

Nosocketfilling

Clinical+stent

Dim

ensions:

defect

width

(mm)

Histological

analysis

Brazil

Not

ava

ilable

Oghli&

Steve

ling

(2010)

(14)

RCTThree

study

groups

Parallel

groups

3months

follow-up

125individuals

(-14)

Aged:na

Smokinghabit:

na

Periodontal

status:

na

Flapless

Primary

closure:YES(soft

tissuegraft)

Typ

eofsocket:

na

Test

1:Autogenoussoft

tissue

graft

+co

llagenplug2

Test

2:

Autogenoussoft

tissuegraft

+co

llagenmatrix

with

gentamicin

Control:Nosocket

filling

Cast

Dim

ensions

changes:

defect

height(m

m)

Saudi

Arabia

+Germ

any

Not

ava

ilable

Abbreviationsoftheinterventions:

NA,data

notava

ilable;RCT,randomized

clinicaltrial;ACS,

absorbable

collagensponge;e-PTFE

,exp

anded

polytetrafluoroethylene;BMP,bonemorphogeneticpro-

tein;bOM,bovineorganic

matrix;CTscan,co

mputerize

dtomographyscanner;

RhBMP,reco

mbinanthuman

BMP-2;FD

BA,freeze

-dried

boneallograft;DFD

BA,demineralize

dfreeze

-dried

boneallo-

graft.





veling 2010) elevated buccal and lingual mu-

coperiosteal flaps to perform the tooth

extraction and achieved primary closure,

except two studies that did not aim for pri-

mary closure (Iasella et al. 2003; Serino et al.

2003; Serino et al. 2008) (Table 1). Flapless

extraction of the teeth was performed in four

studies (Hoad-Reddick et al. 1994; Aimetti

et al. 2009; Crespi et al. 2009; Oghli & Ste-

veling 2010) with two studies aiming to pri-

mary closure through a soft tissue autograft

(Crespi et al. 2009; Oghli & Steveling 2010).

Four studies reported on the socket status

after the extraction, with two studies report-

ing full integrity of the socket walls (Barone

et al. 2008) or minimum buccal bone loss

(Froum et al. 2002) (<2 mm), whereas two

studies (Fiorellini et al. 2005; Crespi et al.

2009) reported the absence of the buccal bone

wall.

Different biomaterials were used in the

test groups of the studies included in the

review. Test treatment could be either graft

alone (Hoad-Reddick et al. 1994; Lekovic

et al. 1997; Lekovic et al. 1998; Bolouri et al.

2001; Froum et al. 2002; Iasella et al. 2003;

Fiorellini et al. 2005; Barone et al. 2008; Ai-

metti et al. 2009; Crespi et al. 2009; Casado

et al. 2010; Oghli & Steveling 2010) or mem-

brane alone (Lekovic et al. 1997; Lekovic

et al. 1998; Casado et al. 2010), a combina-

tion of both (Iasella et al. 2003; Barone et al.

2008; Casado et al. 2010) or a combination of

graft and autogenous soft tissue graft (Crespi

et al. 2009 and Oghli & Steveling 2010).

Methods of measurement

The changes in the primary outcomes were

assessed by clinical and radiographical

examinations, as well as, by evaluation of

cast models. Hoad-Reddick et al. (1994), Fio-

rellini et al. (2005) and Crespi et al. (2009)

used radiographs (orto-pantomography, CT

scans, and periapical X-rays respectively).

Lekovic et al. (1998), Lekovic et al. (1997),

Serino et al. (2003), Barone et al. (2008), Se-

rino et al. (2008) and Aimetti et al. (2009)

assessed directly the bone changes at a re-

entry surgery. Within this group, four stud-

ies (Serino et al. 2003; Serino et al. 2008;

Barone et al. 2008; Aimetti et al. 2009) used

an acrylic stent to allow for reproducible

measurements, whereas two studies (Leko-

vic et al. 1997; Lekovic et al. 1998) utilized

titanium pins (Table 1). Two studies used

clinical measurements combined with

acrylic stents (Iasella et al. 2003; Casado

et al. 2010), whereas other two (Lekovic

et al. 1997; Oghli & Steveling 2010)

used cast models to evaluate the

dimensional changes between baseline and

the end of the investigation. The most fre-

quent method was the mid-buccal measure-

ment.

Quality assessment

Data from the quality assessment are

reported in Table 2. All studies except one

randomized controlled trial (Barone et al.

2008) and two controlled trials (Serino et al.

2003; Serino et al. 2008) were considered to

have a high risk of bias.

Study outcomes. Descriptive analyses of thechanges in the hard tissue dimensions

Table 3a depicts the differences in the bone

crest height between baseline and the end of

the investigations reported for test and con-

trol groups. Eleven of 14 studies evaluated

the changes in the height of the bone crest

comparing the socket preservation therapy

with sockets left to heal spontaneously

(Hoad-Reddick et al. 1994; Lekovic et al.

1997; Lekovic et al. 1998; Iasella et al. 2003;

Barone et al. 2008; Aimetti et al. 2009; Cres-

pi et al. 2009). Overall, the control groups

demonstrated a mean vertical bone loss that

ranged from !0.3 to !3.75 mm, whereas in

the test groups, results were more heteroge-

neous demonstrating mean vertical bone

changes ranging from !2.48 to 1.3 mm.

Differences between test and control

groups, as reported by the authors, were

statistically significant in four studies

included in the systematic review (Lekovic

et al. 1997; Lekovic et al. 1998; Iasella et al.

2003; Fiorellini et al. 2005). Lekovic et al.

(1997) evaluated the ridge bone dimensional

changes at re-entry using titanium pins

after GBR with e-PTFE membranes covering

the socket walls in submerged healing or

an untreated socket control. The same

research group used a similar experimental

design to assess GBR with a biabsorbable

membrane (Lekovic et al. 1998). Results

from both studies demonstrated statistically

significant differences (P < 0.0005) in favour

of the GBR approach demonstrating a

greater vertical resorption in the control

group.

Table 2. Quality assessment of the articles included

Quality criteria

# Author (year)

Adequatesequencegeneration?

Allocationconcealment? Blinding?

Incompleteoutcome dataaddressed?

Free ofselectivereporting?

Free ofotherbias?

Risk ofbias

1 Hoad-Reddick et al. (1994) c c 0 c a a High2 Lekovic et al. (1997) c c 0 a a a High3 Lekovic et al. (1998) a c 1 a a a High4 Bolouri et al. (2001) b c 1 c a a High5 Froum et al. (2002) c a 1 c a a High6 Serino et al. (2003) b b b a a a Moderate7 Iasella et al. (2003) b c 0 c a a High8 Fiorellini et al. (2005) b b 2 a a a High9 Barone et al. (2008) a c 1 a a a Moderate10 Serino et al. (2008) b b b a a a Moderate11 Aimetti et al. (2009) b c 1 c a a High12 Crespi et al. (2009) b c 1 c a a High13 Casado et al. (2010) c c 0 c a a High14 Oghli & Steveling (2010) b c 0 a a a High

Abbreviations of the interventions: a: adequate explanation in the text; b: inadequate explanation in the text; c: not listed; 0: not blinded; 1: single-blinded;2: double-blinded.



Iasella et al. (2003) with a similar design,

although evaluating the bone dimensional

changes at re-entry using an acrylic stent,

assessed the efficacy of filling the sockets

with freeze-dried bone allografts + tetracy-

cline and a collagen membrane in semi-sub-

merged healing. Differences with the

untreated control group were statistically

significant for the mid-buccal as well as

mesial and distal locations (P < 0.05), but not

for the mid-lingual locations.

Fiorellini et al. (2005) evaluated the ridge

height changes after therapy by computed

tomography reporting statistically significant

differences (P = 0.007) when comparing the

use of an absorbable collagen sponge (ACS)

soaked with 1.50 mg/ml rhBMP-2 with the

untreated control group.

Table 3b depicts the differences in the

width of the bone crest between baseline

and the end of the evaluation period

reported for test and control groups in eight

of the 14 studies (Lekovic et al. 1997; Leko-

vic et al. 1998; Iasella et al. 2003; Fiorellini

et al. 2005; Barone et al. 2008; Aimetti et al.

2009; Casado et al. 2010; Oghli & Steveling

2010). Overall, the control groups demon-

strated a mean horizontal bone loss that

ranged from !0.16 to !4.50 mm, whereas in

the test groups, results were more homoge-

neous demonstrating mean horizontal bone

changes ranging from 3.25 to !2.50 mm.

The differences between test and control

groups were statistically significant in five

studies.

Changes in soft tissue dimensions

Mean dimensional changes of soft tissues are

presented in Table 4. Two studies evaluated

the dimensional changes of the overall alveo-

lar ridge contour combining the changes of

hard and soft tissues (Lekovic et al. 1997; Og-

hli & Steveling 2010). Whereas Iasella et al.

(2003) evaluated the changes in gingival

thickness at different locations of the crest,

Lekovic et al. (1997) measured these changes

on cast models, both reporting significantly

less vertical and horizontal resorption in the

test group (P = 0.001). Oghli & Steveling

(2010), however, could not demonstrate dif-

ferences between using a collagen sponge

with/without gentamicine plus a circular soft

tissue graft to protect the wound, with the

untreated control socket (P = 0.07). Iasella

et al. (2003) also evaluated the gingival thick-

ness with an ultrasonic device at buccal and

lingual/palatal locations. Differences between

the ridge preservation therapy and the

untreated control were only statistically sig-

nificant for buccal sites.

Implant-related outcomes

Table 5 shows the studies with reported out-

comes on implant placement after tooth

extraction (Hoad-Reddick et al. 1994; Bolouri

et al. 2001; Froum et al. 2002; Iasella et al.

2003; Serino et al. 2003; Fiorellini et al. 2005;

Serino et al. 2008; Crespi et al. 2009; Aimetti

et al. 2009; Casado et al. 2010). Two studies

(Barone et al. 2008; Aimetti et al. 2009)

reported the placement of implants after 3

and >7 months without providing any details

on further soft or hard tissues augmentation

procedures. Two studies (Serino et al. 2003;

Serino et al. 2008) reported the placement of

dental implants after 6 and 3 months of heal-

ing respectively, specifying that all implants

achieved good primary stability in both test

and control groups. In one study (Fiorellini

et al. 2005), implants were inserted after

4 months of healing and statistically signifi-

cant differences were reported in favour of

the test group 1 (ACS+ 1.50 mg/ml rhBMP-2)

when compared to test group 2 (ACS+

0.75 mg/ml rhBMP-2) and the control treat-

ment, in regards to the number of secondary

augmentation surgeries needed, although no

further details were provided in regards to

the number and type of these procedures. In

the test 1 sites, 56.25% demonstrated ade-

quate bone volume for implant placement,

whereas the corresponding figures in test 2

and control groups were 25% and 12.5%

respectively.

Histological outcomes

Nine studies evaluated histologically, the

type of bone healing after 3 to >7 months

from the tooth extraction. Biopsies were

taken using a trephine before the osteotomy

preparation for implants insertion. Serial

decalcified sections were analysed under light

microscopy for qualitative and quantitative

histo-morphometrical analysis. Fiorellini

et al. (2005) and Casado et al. (2010) provided

descriptive histological observations, whereas

Froum et al. (2002), Barone et al. (2008), Seri-

no et al. (2008), Aimetti et al. (2009) and

Crespi et al. (2009) calculated fractions of

bone mineral, connective tissue and residual

graft material at different apico-coronal levels

of the socket. Serino et al. (2003) described

the fraction of bone mineral, whereas Iasella

et al. (2003) evaluated fractions of cellular/

acellular and trabecular bone.

Meta-analysis

Nine of the 14 included studies reported sim-

ilar comparisons and could be grouped in the

meta-analyses (Figs 2 and 3). The primary

outcome variables, defined as bone dimen-

sional changes (height and width of alveolar

process) were analysed and compared

between the test (socket preservation ther-

apy) and control group (spontaneous socket

healing). None of the other secondary out-

come variables could be grouped in meta-

analysis.

Seven studies were grouped in the meta-

analysis for bone height as the outcome vari-

able (Fig. 2). Two studies Fiorellini et al.

(2005), Crespi et al. (2009) evaluated two dif-

ferent preservation procedures, consequently,

each test socket preservation procedure vs.

the control group was considered as an inde-

pendent study in the meta-analysis. As there

was a high heterogeneity among the studies

(I2 = 95.2%; Tau2 = 0.639; v2 P-value <0.001),

we selected the random effect model for the

statistical evaluation. A statistically signifi-

cant greater reduction in bone height for con-

trol groups was demonstrated when

compared to the test groups (WMD =

!1.47 mm; 95% CI [!1.982, !0.953]; P

< 0.001; heterogeneity: I2 = 13.1%; v2 P-

value = 0.314). Due to this high heterogene-

ity, several subgroup analyses were performed

based on the surgical protocol used for the

socket preservation (flapless/flapped, barrier

membrane/no membrane, primary intention

healing/no primary healing) and on the mea-

surement method utilized to evaluate the

morphological changes.

None of the subgroup analyses achieved a

non-significant heterogeneity value. A ten-

dency towards greater weighted mean differ-

ences in favour of the test groups was

observed with flapless surgical protocol, no

membrane, primary intention healing and

with use of X-rays as measurement method

(Table 6). The meta-regression analysis failed

to encounter statistically significant differ-

ences among subgroups (data not shown).

Seven studies were grouped in the meta-

analysis on bone width as outcome variable

(Fig. 3). In two studies, more than one test

group were evaluated in comparison with the

control, and therefore they were considered

as independent (Serino et al. 2008; Oghli &

Steveling 2010). Also one study presented

data measured with two different outcome

measurements (cast models and re-entry sur-

gery) and they were also included indepen-

dently in the analyses (Lekovic et al. 1997).

As there was a high heterogeneity detected

among studies (I2 = 99.0%; Tau2 = 2.997; v2

P-value <0.001), the random effect model was

selected for the analysis. The results showed

a statistically significant greater reduction in

bone width for control groups when

compared to the socket preservation thera-



Table

3a.Outcomevariables:

changesin

boneheight,

expressedasmean(m

m)

Publication(#)

Verticalch

angesofthealveolarcrest

Interventions/groups

Measurement

method

Surgicalco

nsiderations

Control

Test

Diff.

P-value

Hoad-Reddick

etal.(1994)(1)

Test:Hyd

roxyapatite

granules

Control:No

socketfilling

Lateral

cephalographsand

dental

pantomograms

Flapless

Primary

closure:NO

Typ

eofsocket:

NA

2.42

0.65

ND:1.77

NA

Lekovicetal.

(1997);_1

(2)

Test:ePTFE

®membrane

Control:No

socketfilling

Reentrysurgery

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!1.2

!0.5

Mb:!0.7

0.001

Lekovicetal.

(1998)(3)


lideandlactide

polimers


Reentrysurgery

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!1.5

!0.38

Mb:!1.12

<0.0005

Serinoetal.(2003)(6)

Test:Sp

ongeofpolylactide–p

olyglyco

lide

acid


Reentrysurgery

+stent

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!0.8

1.3

Mb:!2.1

NA

Iasellaetal.(2003)(7)

Test:FD

BA

+tetracycline+co

llagen

mombrane


Clinical+stent

Flap

Primary

closure:NO

Typ

eof

socket:

NA

!0.9

1.3

Mb:!2.2

<0.05

Fiorellinietal.

(2005)_1(8)

Test

1:0.75mg/m

lrhBMP/ACS

Control:

Nosocketfilling

CTscan

Flap

Primary

closure:YES

Typ

eof

socket:

3-w

all(nobuccalwall)

!1.17

!0.62

ND:!0.55

NS

Fiorellinietal.

(2005)_2(8)

Test

2:1.50mg/m

lrhBMP/ACS

Control:

Nosocketfilling

CTscan

Flap

Primary

closure:YES

Typ

eof

socket:

3-w

all(nobuccalwall)

!1.17

!0.02

ND:!1.15

0.007

Baroneetal.(2008)

(9)

Test:Corticocancellousporcinebone+

collagenmembrane

Control:Nosocket

filling

Reentry+stent

Flap

Primary

closure:YES

Typ

eof

socket:

4-w

all

!3.6

!0.7

Mb:!2.9

NA

Baroneetal.(2008)

(9)


collagenmembrane

Control:Nosocket

filling

Reentry+stent

Flap

Primary

closure:YES

Typ

eof

socket:

4-w

all

!3.6

!0.7

Mb:!2.9

NA

Aim

ettietal.(2009)

(11)


sulphate

hemihyd

rate


Reentry+stent

Flapless

Primary

closure:NO

Typ

eofsocket:

NA

!1.2

!0.5

Mb:!0.7

NA

Crespietal.(2009)_1

(12)

Test

1:Magnesium-enrich

ed

hyd

roxyapatite


PeriapicalX-rays

Flapless

Primary

closure:YES

(tissuegraft)

Typ

eofsocket:

3-w

all(nobuccalwall)

!3.75

!0.48

ND:!3.27

NA

Crespietal.(2009)_2

(12)

Test

2:Calcium

sulphate

Control:No

socketfilling

PeriapicalX-rays

Flapless

Primary

closure:YES

(tissuegraft)

Typ

eofsocket:

3-w

all(nobuccalwall)

!3.75

!2.48

ND:!1.27

NA


P-valuesofthestatisticalanalysisoftheintergroupdifferencesin

thech

angesbetw

eenbaselineandendofthestudy.

SDofthemeansoftheintergroupdifferences

inthech

angesbetw


NS,

notstatisticallysignificant;

NA,data

notava

ilable;Mb,midbuccal;ND,notdefinedsite;ACS,

absorbable

collagensponge;RhBMP,reco

mbi-

nanthumanBMP-2;e-PTFE

,exp

andedpolytetrafluoroethylene;FD

BA,freeze

-driedboneallograft.



Table

3b.Outcomevariables:

changesin

bonewidth,expressedasmean(m

m)

Publication(#)

Horizo

ntalch

angesofthealveolarcrest


Measurement

method

Surgicalco

nsiderations

Control

Test

Diff.

P-value

Lekovicetal.(1997)_2

(2)

Test:ePTFE

®membrane

Control:No

socketfilling

Reentrysurgery

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!4.4

!1.8

!2.6

0.002

Lekovicetal.(1998)

(3)


lideandlactide

polimers


Reentrysurgery

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!4.56

!1.31

!3.25

<0.00001


Test:FD

BA

+tetracycline+co

llagen

mombrane


Clinical+stent

Flap

Primary

closure:NO

Typ

eof

socket:

NA

!2.6

!1.2

!1.4

<0.05

Fiorellinietal.

(2005)_1(8)

Test

1:0.75mg/m

lrhBMP/ACS

Control:

Nosocketfilling

CTscan

Flap

Primary

closure:YES

Typ

eof

socket:

3-w

all(nobuccalwall)

0.57

1.76

!1.19

NS

Fiorellinietal.

(2005)_2(8)

Test

2:1.50mg/m

lrhBMP/ACS

Control:

Nosocketfilling

CTscan

Flap

Primary

closure:YES

Typ

eof

socket:

3-w

all(nobuccalwall)

0.57

3.27

!2.7

0.000

Baroneetal.(2008)

(9)


collagenmembrane

Control:Nosocket

filling

Reentry+stent

Flap

Primary

closure:YES

Typ

eof

socket:

4-w

all

!4.5

!2.5

!2

NA

Aim

ettietal.(2009)

(11)


sulphate

hemihyd

rate


Reentry+stent

Flapless

Primary

closure:NO

Typ

eofsocket:

NA

!3.2

!2

!1.2

NA

Casadoetal.(2010)_1

(13)

Test

1:bovineBMP+bOM

Control:No

socketfilling

Clinical+stent

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!0.16

3.05

!3.21

NA

Casadoetal.(2010)_2

(13)

Test

2:bovineBMP+b

OM+resorbable

membrane


Clinical+stent

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!0.16

2.42

!2.58

NA

Casadoetal.(2010)_3

(13)

Test

3:resorbable

membrane

Control:No

socketfilling

Clinical+stent

Flap

Primary

closure:YES

Typ

eof

socket:

NA

!0.16

2.9

!3.06

NA

Oghli&

Steve

ling

(2010)_1(14)

Test

1:Autogenoussoft

tissuegraft

+co

llagenplug2


Cast

Flapless

Primary

closure:YES

(soft

tissuegraft)

Typ

eofsocket:

NA

!0.3

!0.8

0.5

0.001

Oghli&

Steve

ling

(2010)_2(14)

Test

2:Autogenoussoft

tissuegraft

+co

llagenmatrix

withgentamicin

Control:

Nosocketfilling

Cast

Flapless

Primary

closure:YES

(soft

tissuegraft)

Typ

eofsocket:

NA

!0.3

!0.1

!0.2

0.07


P-valuesofthestatisticalanalysisoftheintergroup

differencesin

thech

angesbetw


NS,

notstatisticallysignificant;

NA,data

not

ava

ilable;bOM,bovineorganic

matrix.



pies (WMD = !1.830 mm; 95% CI [!2.947,

!0.732]; P = 0.001; heterogeneity: I2 = 0%; v2

P-value = 0.837). Due to the high heterogene-

ity initially detected among the studies, sev-

eral subgroup analyses were performed. None

of the subgroup analyses achieved a non-sig-

nificant heterogeneity value for all groups. A

tendency towards greater weighted mean dif-

ferences in favour of test groups was observed

with the use of membranes, a flapped surgi-

cal protocol, primary intention healing and

with CT as outcome measurement (Table 7).

The meta-regression analyses demonstrated a

statistically significant difference only in the

flapless/flapped subgroup (meta-regression;

slope = 2.26; 95% CI [1.01; 3.51]; P = 0.003).

Publication bias and sensitivity analyses

No publication bias was detected for changes

in bone height (P = 0.352; Egger’s test), nor in

bone width (P = 0.357; Egger’s test). The sen-

sitivity analysis to assess the effect of indi-

vidual studies on the summary estimates of

the meta-analysis showed that the exclusion

of single studies did not substantially alter

any estimates. In terms of bone height

changes, the greater change in WMD could

be attributed to Crespi et al. (2009)

(!23.25%) (Table 8). In regards to bone

width, the sensitivity analyses identified

three potential studies as responsible for

most of the heterogeneity (Fiorellini et al.

[2005] [!10.49%], Lekovic et al. [1998]

[!11.46%] and Oghli & Steveling [2010]

[15.15% and 10.79%]) (Table 9).

Discussion

Socket preservation therapies have been pro-

posed with the aim of maintaining the hard

and soft tissue dimensions of the alveolar

ridge that are partially lost after tooth extrac-

tion as part of the natural physiological heal-

ing process. This objective is particularly

pursued in preparation for dental implant

installation to have the best bone avail-

ability for successful implant prosthesis

(Tarnow & Eskow 1996). Unfortunately,

there are very few well-designed clinical

studies evaluating the efficacy of these thera-

peutic procedures and the potential benefit of

the different techniques/materials used is

still debatable.

The present systematic review seeks to

provide scientific evidence on the existing

RCTs and CTs evaluating different surgical

protocols aimed for preserving the bone of

the alveolar ridge after tooth extraction. The

primary outcome variables selected were the

vertical and horizontal hard and soft tissue

dimensional changes of the bone crest at

least 3 months after the tooth extraction.

Overall, the results from the meta-analysis

demonstrated statistically significant higher

alveolar bone crest preservation in both

height and width in the test groups (interven-

tions for ridge preservation) when compared

with the healing of the untreated control

socket. In regards to the changes in bone

height, the overall WMD difference between

test and control groups amounted to

1.47 mm. Hence, the results from the meta-

analysis suggest that the use of socket preser-

vation therapies limits the dimensional

changes (vertical and horizontal) of the alveo-

lar ridge after tooth extraction. These data

are in agreement with a recent similar sys-

tematic review also assessing the influence

and potential benefit of socket preservation

procedures after tooth extraction in non-

molar regions of the mouth (Ten Heggeler

et al. 2010). These authors concluded, how-

ever, that although a benefit of such tech-

niques could be observed, vertical and

horizontal bone loss can be expected.

These results must be evaluated with cau-

tion as the quality assessment of the selected

studies demonstrated that all but two studies

(Barone et al. 2008; Serino et al. 2008) had a

high potential risk of bias. Furthermore, the

use of different biomaterials and surgical

techniques has been combined in this meta-

analysis, as well as the use of different types

of sockets (single/multiple, position in the

mouth and number of residual bony walls),

different reason of tooth extraction and differ-

ent methods of evaluation. This lack of con-

Table 4. Outcome variables. Soft tissue changes

Publication (#)

Soft tissue changes

Interventions/groupsMeasurementmethod Surgical considerations Control Test Diff. P-value

Lekovic et al.(1997)_1 (2)

Test: ePTFE®

membrane Control:No socket filling

Cast Flap; primary closure: YES Type ofsocket: NA Verticalmeasurements

!1 !0.2 Mb: !0.8 0.001

Flap; Primary closure: YES Type ofsocket: NA Horizontalmeasurements

!4.2 !1.8 !2.4 0.001

Iasella et al.(2003) (7)

Test: FDBA+ tetracycline+ collagenmombrane Control:No socket filling

Ultrasonic metre Flap Primary closure: NO Type ofsocket: NA

0.4 !0.1 0.5 <0.05

Oghli & Steveling(2010)_1 (14)

Test 1: Autogenoussoft tissue graft +collagen plug2Control: No socketfilling

Cast Flapless Primary closure: YES(soft tissue graft) Type of socket:NA Horizontal measurements

!0.3 !0.8 0.5 0.001

Oghli & Steveling(2010)_2 (14)

Test 2: Autogenoussoft tissue graft +

collagen matrix withgentamicin

Control: No socketfilling

Cast Flapless Primary closure: YES(soft tissue graft) Type of socket:NA Horizontal measurements

!0.3 !0.1 !0.2 0.07

P-values of the statistical analysis of the intergroup differences in the changes between baseline and end of the study.



Table

5.Im

plant-relatedoutcomes

Publication

Implant-relatedoutcomes


Implant

placement

Tim

eafter

extraction

Control

Test

Seco

ndary

augmentation

surgery

Histology

Restoration

Hoad-Reddicketal.

(1994)(1)

Test:Hyd

roxyapatite

granules

Control:No

socketfilling

No

––

––

No

NA

Bolouri

etal.(2001)

(4)

Test:BioplantHTR

Control:Nosocket

filling

No

––

––

No

NA

Froum

etal.(2002)(5)

Test

1:Bioactiveglass

Test

2:DFD

BA


No

––

––

Yes

NA

Serinoetal.(2003)(6)

Test:Sp


olyglyco

lide

acid


Yes

6months

Allsites

Allsites

NA

Yes

NA


Test:FD

BA

+tetracycline+co

llagen

mombrane


Yes

4–6

months

––

–Yes

NA

Fiorellinietal.(2005)

_1(8)

Test

1:0.75mg/m

lrhBMP/ACS

Control:

Nosocketfilling

Yes

4months

Yes

12.5%

adequate

bonevo

lume

Yes

25%

adequate

bonevo

lume

10

Yes

NA

Fiorellinietal.(2005)

_2(8)

Test

2:1.50mg/m

lrhBMP/ACS

Control:

Nosocketfilling

Yes

4months

Yes

12.5%

adequate

bonevo

lume

Yes56.25%

adequate

bone

volume

3P<0.05

test

1vs.test

2andco

ntrol(11)

NA

Baroneetal.(2008)

(9)


collagenmembrane

Control:Nosocket

filling

Yes

>7months

NA

NA

NA

Yes

NA

Serinoetal.(2008)

(10)

Test:Sp


olyglyco

lide

acid


Yes

3months

Allsites

Allsites

NA

Yes

NA

Aim

ettietal.(2009)

(11)


sulphate

hemihyd

rate


Yes

3months

NA

NA

NA

Yes

NA

Crespietal.(2009)

(12)

Test

1:Magnesium-enrich

ed

hyd

roxyapatite

Test

2:Calcium

sulphate


Yes

3months

––

Yes

NA

Casadoetal.(2010)

(13)

Test

1:bovineBMP+bOM

Test

2:

bovineBMP+bOM

+resorbable

membrane

Test

3:resorbable

membrane


No

––

––

Yes

NA


NA,data

notava

ilable;RCT,randomized

clinicaltrial;ACS,

absorbable

collagensponge;e-PTFE

,exp

anded

polytetrafluoroethylene;BMP,bonemorphogeneticpro-

tein;bOM,bovineorganic

matrix;CTscan,co

mputerize

dtomographyscanner;

RhBMP,reco

mbinanthuman

BMP-2;FD

BA,freeze

-dried

boneallograft;DFD

BA,demineralize

dfreeze

-dried

boneallo-

graft.



sistency and standardization, in spite of the

lack of publication bias, may have contrib-

uted to the high heterogeneity of the results.

In fact, in terms of vertical bone height

changes, 23.25% of this effect was attributed

to the study by Crespi et al. (2009) utilizing

magnesium-enriched hydroxyapatite com-

bined with the closing of the socket with a

soft tissue autograft. This individual study,

Fig. 2. Meta-analysis: changes in bone height.

Fig. 3. Meta-analysis: changes in bone width.



reporting mean differences between test and

control groups of 3.27 mm, however, only

selected sockets without full integrity of

their bone walls, usually lacking the buccal

cortical bone. This negative prognostic factor

for bone regeneration during undisturbed

socket healing may in part, have contributed

to the bigger effect of the socket preservation

therapy, compared with the other studies

included in the meta-analysis. Likewise, in

regards to the changes in bone width, three

studies provided the bigger heterogeneity in

the meta-analysis, contributing to 15.15%,

11.46% and 10.49% of the overall change

respectively (Lekovic et al. 1998; Fiorellini

et al. 2005; Oghli & Steveling 2010). In par-

ticular, on the negative effect side, Oghli &

Steveling (2010) that utilized a collagen

sponge as socket filler reported a higher bone

horizontal resorption in the test group. Apart

from the null efficacy of the filler used, the

fact that cast models were used to measure

these horizontal changes may have prevented

an accurate evaluation of the true dimen-

sions of the alveolar crest. In contrast, Fiorel-

lini et al. (2005) observed a difference of

3.85 mm in bone width when comparing the

use of 1.50 mg/ml rhBMP/ACS vs. the con-

trol socket.

The factors that may have contributed to

the obtained outcomes may be categorized

as: (1) the clinical conditions of the socket

site, i.e. integrity/non-integrity of the socket

bone walls, dimension and presence/absence

of adjacent teeth; (2) the surgical protocol uti-

lized, i.e. flapped/flapless surgery or primary

flap closure/secondary intention healing; (3)

the biomaterial used, i.e. membrane/no

membrane, type of graft material and (4) the

type of evaluation method utilized. In an

attempt to assess the influence of each of

these factors, a subgroup analysis was per-

formed, as well as meta-regression. The sub-

group analysis of flapped/flapless surgery

demonstrated a minor influence in the verti-

cal resorption process, although it showed a

significant difference in favour of the flapped

group in regards to the ridge horizontal

dimensional changes. When comparing the

relative efficacy of using barrier membranes

and/or grafts, while the use of membranes

alone reported more vertical bone change

than the use of grafts alone, membranes

obtained better results than grafts (either

alone or the combination of membrane and

graft) in terms of horizontal bone changes.

The subgroup analysis to assess the influence

of flap closure demonstrated a slight ten-

dency towards less bone loss in the horizon-

tal direction when the sockets healed by

Table 6. Meta-analyses by subgroups for changes in bone height

WMD 95% CI P-value I-squared

Membrane(a) No !1.511 !2.583; !0.440 0.006 95.2%(b) Yes !1.192 !1.589; !0.834 0.000 87.9%Flap(a) No !1.756 !3.400; !0.112 0.036 97.6%(b)Yes !1.179 !1.516; !0.842 0.000 81.7%Primary closure(a) No !1.293 !2.730; 0.145 0.078 72.4%*

(b) Yes !1.506 !2.077; !0.935 0.000 96.1%Outcome variable(a) Reentry + stent !1.861 !3.606; !0.386 0.013 89.3%(b) X-rays !2.276 !4.236; !0.316 0.023 97.9%(c) CT !0.866 !1.453; !0.279 0.004 14.5%(d) Clinical (stent) !2.200 !3.649; !0.751 0.003 NA(e) Cast !0.800 !1.039; !0.561 0.000 NA(f) Reentry surgery !0.912 !1.324; !0.501 0.000 90.6

NA, not applicable, as only one study was included in the subgroup.*Non-statistically significant differences.

Table 7. Meta-analyses by subgroups for changes in bone width

WMD 95% CI P-value I-squared

Membrane(a) No !0.982 !1.738; !0.227 0.011 93.3%(b) Yes !2.465 !3.074; !1.856 0.000 86.6%Flap(a) No !0.148 !0.788; 0.492 0.650 92.6%(b)Yes !2.563 !3.101; !2.795 0.000 81.2%Primary closure(a) No !1.263 !2.049; !0.478 0.002 0%(b) Yes !1.968 !3.217; !0.732 0.002 99.2%Outcome variable(a) Reentry + stent !1.682 !2.449; !0.914 0.000 47.0%*

(b) CT !3.026 !4.501; !1.551 0.000 52.3%*

(c) Clinical (stent) !1.400 !2.797; !0.003 0.050 NA(d) Cast !0.682 !1.841; 0.476 0.248 98.4%(e) Reentry surgery !2.986 !3.612; !2.361 0.000 76.2%

CT, computerized tomography; NA, not applicable, as only one study was included in the subgroup.*Non-statistically significant differences.

Table 8. Sensitivity analyses of the outcome variable bone heigth changes made with randomeffect model

Random estimation

WMD change (%)

Heterogeneity

Study omitted WMD 95% CI I-squared (%) P-value

Aimetti (2009) !1.55 !2.10; !1.00 5.70 12.44 0.328Barone (2008) !1.34 !1.86; !0.82 !8.70 4.85 0.396Crespi_1 (2009) !1.13 !1.41; !0.84 !23.25 49.25 0.038Crespi_2 (2009) !1.49 !2.05; !0.93 1.69 16.14 0.295Fiorellini_1 (2005) !1.55 !2.10; !1.01 5.93 12.6 0.327Fiorellini_2 (2005) !1.50 !2.05; !0.95 2.18 19.07 0.268Iasella (2003) !1.42 !1.95; !0.89 !3.07 18.87 0.269Lekovic_1 (1997) !1.55 !2.15; !0.96 5.83 0 0.447Lekovic_2 (1997) !1.57 !2.17; !0.96 6.69 0 0.465Lekovic (1998) !1.52 !2.19; !0.86 3.89 0 0.561Serino (2003) !1.42 !1.95; !0.89 !3.27 19.07 0.268None !1.47 !1.98; !0.95 0 13.71 0.314

Crespi_1: Magnesium-enriched hydroxyapatite vs. no socket filling.Crespi_2: Calcium sulphate vs. no socket filling.Fiorellini_1: 0.75 mg/ml rhBMP/ACS vs. no socket filling.Fiorellini_2: 1.5 mg/ml rhBMP/ACS vs. no socket filling.Lekovic_1: outcome measured in cast model.Lekovic_2: outcome measured in reentry surgery.



primary intention. In terms of the evaluation

methods used, only the radiographic evalua-

tion demonstrated significant vertical (X-

ray) and horizontal (CT) changes when com-

paring test and control groups. The use of

cast models and re-entry procedures was not

able to demonstrate such significant differ-

ences.

The results of the meta-regression analysis

showed that the surgical procedure (flapped/

flapless) was the most important factor influ-

encing the results. Flapped surgical proce-

dures demonstrated a significantly lesser

horizontal resorption of the socket, when

compared to flapless surgeries (meta-regres-

sion; slope = 2.26; 95% CI [1.01; 3.51];

P = 0.003). These results may be due to the

importance of achieving full closure and first

intention healing, mainly when the socket is

filled with a biomaterial or covered with a

barrier membrane. The effect of raising a flap

on the healing process of the socket after

tooth extraction is still controversial with

results from experimental models reporting

less pronounced bone remodelling of the

alveolar ridge after tooth extraction with a

flapless approach (Fickl et al. 2008a, 2008b)

or when using socket preservation procedures

(Fickl et al. 2008a, 2008b; Blanco et al. 2010)

and when placing implants immediately after

the tooth extraction (Blanco et al. 2010).

Other studies with a similar experimental

design, however, have failed to encounter sig-

nificant bone dimensional differences

between flapped and flapless tooth extrac-

tions (Araujo & Lindhe 2009).

The changes in the horizontal dimension

have been the ones benefited most by the

socket preservation techniques evaluated in

this systematic review. Precisely bone loss in

a horizontal dimension is the most important

consequence of tooth extraction during the

first 3–6 months of healing (Schropp et al.

2003). In this meta-analysis, the bone hori-

zontal changes in the control group were het-

erogeneous, ranging from !0.16 to

!4.50 mm. These differences may be due to

different factors, such as the socket location

and the thickness of the socket walls. Recent

studies in humans have shown the influence

of the location and the thickness of the

socket walls in the ensuing modelling and

remodelling processes after tooth extraction

(Ferrus et al. 2010; Januario et al. 2011).

One major limitation of this systematic

review is that no meta-analyses could be per-

formed on implant-related outcomes, due to

the lack of sufficient data. This fact is impor-

tant as there is no clear evidence that the

occurrence of bone resorption after tooth

extraction may significantly limit the place-

ment of dental implants. In fact, one study

(Serino et al. 2008) reported that implants

could be placed in all patients independently

of the group of treatment. The positive influ-

ence of the socket preservation therapy may

be attributed more to achieving enhanced

restorative and aesthetic outcomes, as well

as better maintenance of healthy peri-

implant soft tissues. These possible influ-

ences were not evaluated in the reviewed

studies. Only one study assessed the possible

influence of the socket preservation therapy

on the need of further augmentation thera-

pies and in fact, the test group reported

reduced needs of bone augmentation (Fiorel-

lini et al. 2005).

In conclusion, the results from this sys-

tematic review and meta-analysis have

shown that although some degree of bone

modelling and remodelling will occur after

tooth extraction, different ridge preservation

procedures resulted in significantly less verti-

cal and horizontal contraction of the alveolar

bone crest. The obtained results, however,

could not indicate which is the type of surgi-

cal procedure or biomaterial most suitable

for this clinical indication, although the use

of barrier membranes, a flap surgical proce-

dure and full flap closure demonstrated bet-

ter results. There are limited data, however,

on the possible influence of these therapies

on the long-term outcomes of implant ther-

apy.

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I Workshop BQDC Octubre 2013

Protocolo de Preservación del Alveolo José Nart e Ignacio Sanz

El proceso alveolar es una estructura dependiente de los dientes que se

desarrolla durante la erupción dental. El volumen y la forma del proceso

alveolar están determinados por la forma del diente, su eje de erupción

e inclinación (Schroeder et al. 1986).

La pérdida dental conlleva una pérdida de volumen en sentido

horizontal y vertical resultando en un reborde alveolar más estrecho y

más corto. Debido a que la cicatrización natural está asociada a una

pérdida de volumen de hasta el 50% durante el primer año, las técnicas

de preservación alveolar tienen como objetivo minimizar los cambios

volumétricos que se producen en los procesos alveolares con la

utilización de materiales de relleno óseo (van der Weijden et al. 2009).

El objetivo de esta revisión es conocer los resultados clínicos de la

técnica de preservación alveolar, las distintas variantes de la técnica

quirúrgica, los materiales de relleno óseo que podemos utilizar y crear un

árbol de decisiones que nos facilite la toma decisiones en la clínica para

conseguir los mejores resultados para nuestros pacientes en función de

la literatura disponible.

CICATRIZACIÓN ALVEOLAR

El primer paso cuando aparece una técnica es conocer las mejoras que

puede aportar al protocolo que se considera estándar. Es por ello que

debemos conocer los cambios dimensionales que se producen cuando

extraemos un diente y dejamos cicatrizar el alveolo por si mismo.

• Cambios en sentido vertical: Los estudios con reentrada en

humanos han mostrado que se produce una pérdida vertical del

11 al 22% a los 6 meses de la extracción de un diente. Si lo

miramos en valores absolutos, esta pérdida es de 1,24 mm de


media.

• Cambios en sentido horizontal: Los estudios con reentrada en

humanos han mostrado que se produce una pérdida horizontal

del 29 al 63%. En valores absolutos, la pérdida media es de 3.8

mm.

Si tenemos en cuenta que la mayor pérdida se produce en los primeros

3 meses y ésta continúa hasta los 6 meses, es importante conocer si

disponemos de alguna terapia que pueda contrarrestar estos cambios

volumétricos o, a lo sumo, limitarlos.

PRESERVACION ALVEOLAR La técnica de preservación del alveolo consiste en rellenar el alveolo

que queda tras la extracción de un diente con algún tipo de injerto

óseo, tratando de disminuir la pérdida del hueso alveolar. Al tratarse de

una técnica que se sale de lo que podríamos considerar como el

estándar, es importante revisar los siguientes puntos: eficacia clínica en

cuanto reducción de la pérdida tridimensional del hueso, indicaciones y

contraindicaciones, variantes de la técnica, resultados histológicos y

beneficios que pueden obtener nuestros pacientes.

1. Preservación de alveolo Vs. Extracción convencional

La reabsorción de la cresta que se produce al extraer un diente puede

limitarse con la técnica de preservación alveolar, pero no se puede

prevenir al 100%.

De 7 estudios, 5 han demostrado una menor reabsorción

estadísticamente significativa en sentido horizontal y 6 de 8 estudios lo

han demostrado estos resultados positivos para la reabsorción en

sentido vertical.

Para valorar el beneficio clínico en términos absolutos, disponemos de

varias revisiones sistemáticas que han evaluado a nivel global en cuánto

podemos reducir la pérdida ósea que se produce tras la extracción al

preserval el alveolo. En los meta-ánalisis de la revisión sistemática de

Vignoletti et al. 2012, la preservación de alveolo reduce de manera


significativa los cambios en los volúmenes óseos en sentido horizontal

(1.83 mm) y en sentido vertical (1.47 mm) en comparación a no realizar

la preservación tras la extracción. En otra revisión sistemática más

reciente (Orgeas et al. 2013) se mostró como la técnica de preservación

de alveolo es efectiva en reducir la reabsorción de hueso en sentido

horizontal (2.9mm) y vertical (0.9mm).

De estas revisiones podemos sacar además otras conclusiones, cómo

que la pérdida de hueso no sólo va a depender de la técnica

quirúrgica, sino también de la anatomía del alveolo. De este modo, se

ha demostrado que si las paredes óseas del alveolo son gruesas, se

reducen los cambios tridimensionales tras la extracción, sobre todo a

nivel de la tabla vestibular. Si tenemos en cuenta que la mayor parte de

las tablas vestibulares van a ser menores a 1 mm (Ferrus et al. 2010),

puede ser importante aplicar esta técnica en sectores estéticos para

limitar los cambios de volumen y, con ello, los problemas estéticos que

pueden acontecer tras la extracción.

2. Indicaciones y contraindicaciones

Indicaciones:

(i) Cuando los implantes inmediatos o tempranos no están

recomendados.

(ii) Cuando los pacientes no están disponibles para recibir un implante

inmediato o temprano (embarazo, vacaciones,…).

(iii) Cuando no se puede conseguir estabilidad primaria del implante

inmediato.

(iv) En pacientes adolescentes.

(v) Contorneado de la cresta para el tratamiento protésico

convencional.

(vi) El ratio coste/beneficio es positivo.

(vii) Reducción de la necesidad de realizar elevación del seno maxilar.


Contraindicación:

(i) Infecciones intralveolares que no se pueden controlar/eliminar.

(ii) Cuando el coste-beneficion para el paciente no sea justificable.

3. Técnica quirúrgica

Se ha demostrado que el uso de implantes dentales tras la extracción

de un diente no previene la reabsorción tridimensional de la cresta que

se produce cuando tras la exodoncia. Es por ello que hay que valorar

muy bien las indicaciones de los implantes inmediatos a la extracción.

Debido a esto, la preservación de la cresta alveolar puede suponer una

opción terapéutica alternativa a los implantes inmediatos en pacientes

con un alto riesgo de problemas estéticos.

Se han propuesto distintas modalidades quirúrgicas y distintos materiales

para rellenar el alveolo, entre las que destacan las siguientes:

(i) Cirugía sin elevación de colgajo, relleno del alveolo con algún

injerto óseo (hueso autólogo, hidroxiapatita enriquecida con

magnesio, matriz de hueso humano

desmineralizado/mineralizado y el mineral de hueso bovino

desproteinizado) y cierre del alveolo con injerto de tejido

blando autólogo (injerto libre de encía tipo punch o injerto de

tejido conectivo en sobre) o xenoinjerto (matriz de colágeno).

La indicación principal de esta técnica es para alveolos

íntegros que mantienen la totalidad de la tabla vestibular.

(ii) Cirugía sin elevación de colgajo, relleno del alveolo con algún

injerto óseo (hueso autólogo, hidroxiapatita enriquecida con

magnesio, matriz de hueso humano


desproteinizado) y cierre del alveolo con una membrana

reabsorbible o no reabsorbibles. A esta técnica se le podría

añadir un injerto de tejido blando para proteger los materiales

de regeneración. De nuevo, la indicación principal de esta

técnica es para alveolos con una tabla vestibular íntegra.


(iii) Cirugía con elevación de colgajo, relleno del alveolo con

algún injerto óseo (hueso autólogo, hidroxiapatita enriquecida

con magnesio, matriz de hueso humano


desproteinizado), membrana barrera reabsorbibles o no

reabsorbibles para proteger al injerto y cierre con colgajos

desplazados o con un injerto de tejido blando adicional. La

indicación principal de esta técnica es alveolos que han

perdido parcialmente alguna de las tablas vestibular o

palatina.

En cuanto a la revisión de la literatura, el uso de sustitutos óseos

(hidroxiapatita enriquecida con magnesio, la matriz de hueso humano


desproteinizado) junto a una membrana de colágeno ha mostrado ser

efectivo en minimizar los cambios volumétricos de la cresta que se

producen al extraer un diente y el uso únicamente de membranas

barrera mejora la cicatrización del alveolo.

Por otro lado se ha demostrado que obtenemos una mayor ganancia

ósea significativa en sentido horizontal cuando elevamos un colgajo y

colocamos una membrana barrera, lo que supone un mayor trauma

quirúrgico para el paciente y un mayor gasto económico, por lo que

hay que valorar muy bien el coste-beneficio de esta técnica.

Y en cuanto al papel del cierre por primera intención del alveolo, se ha

mostrado que el cubrir por completo el alveolo y el material de injerto

tienen un efecto limitado en la reducción de la reabsorción

tridimensional del hueso. Además, los injertos de tejido blando junto al

material de injerto no han mostrado ser factores claves para mejorar los

resultados de la técnica de preservación de alveolo.

Hoy por hoy, con la evidencia científica disponible, no podemos afirmar

que un injerto óseo en particular o una técnica quirúrgica concreta


sean superiores, por lo que resulta difícil establecer guías clínicas

concretas para la preservación de alveolo. No obstante, en un

apartado posterior proponemos un árbol de toma de decisiones que

nos puede ayudar a optimizar los resultados de la preservación y a

elegir las mejores indicaciones posibles.

4. Histología

A nivel histológico se han mostrado distintos grados de formación de

hueso. Lo más característico es que con algunos injertos se interfieren en

la cicatrización del alveolo y del hueso, retardándolas.

De 8 estudios analizados, 6 han demostrado que en el grupo de

preservación de alveolo hay mayor formación de hueso trabecular,

aunque con técnica, no siempre se promueve la formación de nuevo

hueso.

Además, el uso de xenoinjertos solo sirven como un andamio

(osteoconducción) y no estimulan la formación de nuevo hueso.

5. Beneficios

Cuando nosotros realizamos una técnica adicional al tratamiento

convencional (implante en cresta cicatrizada), lo que esperamos es no

sólo que se facilite la colocación del implante y que necesitemos una

menor regeneración ósea, si no que los resultados a largo plazo sean

mejores. Sin embargo, no disponemos de literatura que demuestre que

la preservación del alveolo mejore los resultados a largo plazo de los

implantes en comparación a los implantes inmediatos o a los colocados

en cresta cicatrizada.

Cabe destacar que de 4 estudios, 3 han demostrado que en el grupo

de preservación de alveolo se ha necesitado menos aumento óseo en

el momento de colocar los implantes.


Workshop BQDC Octubre 2013


PROTOCOLO QUIRÚRGICO

INSTRUCCIONES POST-OPERATORIAS Farmacoterapia: Hoy en día no tenemos evidencia de que los antibióticos sistémicos sean necesarios en la técnica de preservación de alveolo. En función del tipo de biomateriales que empleemos, podemos considerar dar las siguientes pautas:

- Amoxicilina 500mg. 1 comprimido/8 horas. 8 días. - Ibuprofeno 600 mg. 1 comprimido / 6-8 horas. 3-4 primeros días.

Alérgicos - Azitromicina 500 mg. 1compr / 24h. 3 días - Paracetamol 500mg. 1 compr/6-8 horas. 3-4 primeros días.

Instrucciones de higiene oral:

- Colutorio clorhexidina 0,2% o 0,12% durante 30 seg. 2 veces/día 14 días post-tratamiento.

- No cepillado en la zona durante 14 días. Tras dicho periodo, el cepillado será suave y progresivamente el paciente realizará su higiene con normalidad.

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