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GL Borromeo,* CE Tsao,* IB Darby,* PR Ebeling

Australian Dental Journal 2011; 56: 29

A REVIEW OF THE CLINICAL IMPLICATIONSOF BISPHOSPHONATES IN DENTISTRY

Review2011/10/11

Instructor: Dr.

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Introduction

Orofacial conditions with similar presentations to ONJ1. Osteoradionecrosis

2. Conditions affecting bone turnover

Bisphosphonates in different clinical settings1. Implants

2. Periodontics

3. Orthodontics

4. Endodontics

Management of ONJ1. Prevention

2. Treatment

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BISPHOSPHONATES(BPS)

BPs are drugs used to suppress bone turnover, primarily

through effects on osteoclasts.

Nitrogen-Containing Bisphosphonates (NBPs)

More Potent Less Potent

Zoledronic acid , Pamidronate Alendronate , Risedronate

Intravenously used Orally used

Prevent skeletal related events

(SREs) associated withmalignancy

Severe forms of osteogenesis

imperfecta

Osteoporosis

Pagets disease of bone

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POST-MENOPAUSAL OSTEOPOROSIS (PMO)

Alendronate , risedronate reducing vertebral, non-vertebral and hip fractures by 16 ~ 45%.

Annual IV zoledronic acid

reducing vertebral fractures(70%), non-vertebral fractures(25%)and hip fractures(41%)

Very low risk of jaw osteonecrosis of 1:3862

The benefitrisk ratio greatly favors tx with BPs inosteoporosis.

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BISPHOSPHONATE ASSOCIATED JAW

OSTEONECROSIS (ONJ)

An area of exposed bone in the maxillofacial region that

did not heal within eight weeks after identification by a

healthcare provider, in a patient who was receiving or had

been exposed to a bisphosphonate, and had not hadradiation therapy to the craniofacial region.

The American Society for Bone and Mineral Research (ASBMR) ,2007

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WHY THE CONDITION LOCALIZES TO THE JAWS ?

Bone turnover is higher in jaws than in general skeleton

BP accumulates in jaw at higher level

Oversuppresing turnover

Compromising jaw healing

both to Injury (e.g. tooth extraction)Normal microdamage from occlusion

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PATHOPHYSIOLOGY may be multifactorial

Oversuppression of bone turnover

Oversuppression of angiogenesis

Altered functioning of oral mucosal cells

Microbial flora

Anti-inflammatory effect

Genetic predisposition.

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AAOMS ONJ STAGING SYSTEM

American Association of Oral and Maxillofacial Surgeons

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SIGNIFICANT RISK FACTORS

1. Duration of BP exposure

2. Number of infusions

3. Zoledronic acid

4. Dental extraction5. Advanced age

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Australian Population-Based Survey, 2007

IV BP for malignancy

ONJ risk 0.88~1.15%

After a dental extraction 6.79.1%

Oral BP for osteoporosis

ONJ risk 0.010.04%

After a dental extraction 0.090.34 %

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Introduction

Orofacial conditions with similar presentations to ONJ

1. Osteoradionecrosis

2. Conditions affecting bone turnover

Bisphosphonates in different clinical settings

1. Implants2. Periodontics

3. Orthodontics

4. Endodontics

Management of ONJ1. Prevention

2. Treatment

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OSTEORADIONECROSIS (ORN)

ORN is caused by radiotherapy to the orofacial structures

creating hypoxic, hypocellular and hypovascular tissue.

Both ONJ and ORN

1. Necrosis of jaw bones

2. Susceptible to secondary infection.

Hyperbaric oxygen therapy (HBO)

For ORN: beneficial

For ONJ inconclusive

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CONDITIONS AFFECTING BONE TURNOVER

Osteopetrosis , pyknodysostosis

Genetic disorders in which osteoclast function is impaired.

Jaw osteomyelitis develops rarely

Denosumab for bone metastasis

Anti-RANKL antibody

(RANKL:receptor activator of nuclear factor-B ligand )

Comparable numbers of ONJ similar to zoledronic acid

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Phossy Jaw

Individuals exposed to white (yellow) phosphorous in match

stick production

White phosphorous is converted to a compound similar tomodern NBPs.

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Introduction

Orofacial conditions with similar presentations to ONJ1. Osteoradionecrosis

2. Conditions affecting bone turnover

Bisphosphonates in different clinical settings

1. Implants

2. Periodontics3. Orthodontics4. Endodontics

Management of ONJ1. Prevention

2. Treatment

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IMPLANTS

Implants in 50, 115, 101, 61 and 11 subjects with an oral BP

exposure hx found no cases of ONJ

A recent South Australian study ,2009

Receiving oral BPs implant failure risk 0.88%

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Topical BP Application

In animal models

May enhance osseointegration of dental implants

For humans

Toxic effects on the oral mucosa ONJ risk

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PERIODONTICS

Periodontal Disease A precipitant of ONJ

May necessitate invasive periodontal procedures or dental

extraction, and hence increase the risk of ONJ

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Administration of Systemic Bisphosphonates

Reducing alveolar bone loss The majority of animal models : yes

Controlled clinical trials in humans

Four trials : yes (alendronate )

One tirals: the effect was only noted in a subgroup with

low mandibular bone density.

One trials: no efficacy

Improving clinical parameters

Three trials : yes

Two trials : no efficacy

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ORTHODONTICS

BPs

Inhibition of orthodontic tooth movement,

rather than ONJ

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Topical BPs in ortho. tx for rats

1. inhibiting undesirable movement of anchor teeth

2. inhibiting post-tx relapse

For humans ? caution in light of ONJ risk

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Caution is advised with

1. Miniscrew skeletal anchorage devices

2. Mucosal trauma from retainers

3. Orthognathic surgery

4. Tooth extraction

Discontinue BPs prior to ortho. tx ? require further

investigation

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ENDODONTICS

Endodontic tx. is the preferred treatment over extraction to

minimize ONJ risk.

If ext. direct closure of the socket by suturing

antibiotic prophylaxis considered

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Introduction

Orofacial conditions with similar presentations to ONJ1. Osteoradionecrosis

2. Conditions affecting bone turnover

Bisphosphonates in different clinical settings

1. Implants2. Periodontics

3. Orthodontics

4. Endodontics

Management of ONJ

1. Prevention2. Treatment

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PREVENTION

ONJ is often refractory to tx BPs: terminal half-life of approximately 10 years.

Before BP therapy

A comprehensive oral evaluation

Invasive dental procedures and subsequent healing are

best completed

Under BP therapy

Biannual f/u to ensure oral health

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Under or after BP therapy

Pt using BP for osteoporosis managed in general dental practices

but invasive tx like periodontal bone contouring should

be modest

Pt using NBPs for malignancy

management should be under the care of a dental

specialist and the oncology team.

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Guidelines for Cessation

of Routine Oral and IV

BPs prior to InvasiveDental Procedures

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Before Invasive Dental Procedures

The guidelines are not consistent.

Oral BPs

Advising cessation 3M only when

1. BP exposure > 3Y

2. < 3Y but with glucocorticoid hx.

AAOMS,2009

IV BPs

Best ceased at least 1M , and not recommenced until

healing is achieved

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Beta-CTX-1A marker for bone resorption

(carboxyl-terminal cross-linked telopeptide of type I collagen )

used to predict ONJ risk prior to invasive dental tx

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TREATMENT

Conservative approach

If there is evidence of infection chlorhexidine 0.12%

rinse and systemic antibiotics

The ASBMR guidelines

Surgical tx for debridement should be conservative or

delayed

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No empirical evidence to cease BP therapy on ONJ

development.

Ceasing BP therapy for 3M on ONJ development

MFA,2009

Recommencement of BPs is best delayed until ONJ

resolution, with either oral non-NBPs or a reduced

frequency of IV NBPs, clinical condition permitting.

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CONCLUSIONS

1. BPs have revolutionized osteoporosis tx and confer considerableanti-fracture benefits that outweigh the small risk of ONJ.

2. In the context of substantial uncertainty, the implications of

bisphosphonate use in the dental clinical setting are still being

determined.

3. Invasive dental procedures are certainly to be avoided wherever

possible in patients with a hx of BP use, especially IV BPs for cancer.

4. Cessation of oral and IV BPs is advised, both prior to invasive

dental procedures and on development of ONJ.

5. Limited surgical debridement together with systemic and local

antibiotics is the favoured management of ONJ, however, healing is

not assured.

6. More controlled clinical studies are recommended to justify the use

of serum beta-CTX-1 in assessing ONJ risk.

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THANKS FOR YOUR ATTENTION!