RCT of PLF

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 A Prospective Randomized Study of Posterolateral Lumbar Fusion (printer-friendly)  www.medscape. com Authors and Disclosures Chi-Chien Niu, MD, Tsung-Ting Tsai, MD, Tsai-Sheng Fu, MD, Po-Liang Lai, MD, Lih-Huei Chen, MD, and Wen- Jer Chen, MD Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chang Gung Institute of Technology, Taoyuan, Taiwan. Address correspondence and reprint requests to  Wen-Jer Chen, MD, Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing St, Kweishan, Taoyuan 333, Taiwan; E-mail: [email protected]  From Spine   A Com parison of Posterolateral Lum bar Fusion Comparing  Autograft, Autogenous Lamin ectomy Bone w ith Bone Marrow Aspira te, and Calc ium Sulphate with Bone Marrow  Aspirate: A P rospective Randomized Study BMA and Autograft, Autogenous Laminectomy Bone or Calcium Sulphate Chi-Chien Niu, MD; Tsung-Ting Tsai, MD; Tsai-Sheng Fu, MD; Po-Liang Lai, MD; Lih-Huei Chen, MD; Wen-Jer Chen, MD Posted: 03/09/2010; Spine. 2009;34(25):271 5-9. © 2009 Lippincott Williams & Wilkins Abstract and Introduction Abstract Study Design. A prospective clinical study. Objective. To evaluate whether the fusion rate of autogenous laminectomy bone chips and calcium sulfate pellets could be augmented by bone marrow aspirate (BMA) in one-level lumbar posterolateral fusion. Summary of Background Data. An in vivo animal study has indicated that BMA augments spinal arthrodesis. Methods. Forty-three patients undergoing surgery for instrumented one-level fusion with decompression were divided into 2 groups. Autologous iliac crest bone graft (ICBG) was placed in 1 posterolateral gutter (control), while on the other side (test), an equal quantity of laminectomy bone chips mixed with BMA while harvesting the iliac bone graft (group 1) or an equal quantity of calcium sulfate pellets soaked in BMA (group 2) was placed. Radiographic assessment was performed every 3 months (3  12 months) and then annually. The statuses of fusion on either side of the vertebra were http://www.medscape.com/viewarticle/715691_print (1 of 12) [1/12/2011 1:45:53 PM]

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Prospective Randomized Study of Posterolateral Lumbar Fusion (printer-friendly)

www.meds

uthors and Disclosures

hi-Chien Niu, MD, Tsung-Ting Tsai, MD, Tsai-Sheng Fu, MD, Po-Liang Lai, MD, Lih-Huei Chen, MD, and We

r Chen, MD 

epartment of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine

hang Gung Institute of Technology, Taoyuan, Taiwan.

ddress correspondence and reprint requests to 

en-Jer Chen, MD, Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing St, Kweisha

oyuan 333, Taiwan; E-mail: [email protected] 

rom Spine 

A Comparison of Posterolateral Lumbar Fusion ComparingAutograft, Autogenous Laminectomy Bone w ith BoneMarrow Aspirate, and Calcium Sulphate with Bone MarrowAspirate: A P rospective Random ized StudyMA and Autograft, Autogenous Laminectomy Bone or Calcium Sulphate

hi-Chien Niu, MD; Tsung-Ting Tsai, MD; Tsai-Sheng Fu, MD; Po-Liang Lai, MD; Lih-Huei Chen, MD; Wen-Jer Chen, M

osted: 03/09/2010; Spine. 2009;34(25):2715-9. © 2009 Lippincott Williams & Wilkins

bstract and Introduction

bstract

udy Design. A prospective clinical study.

bjective. To evaluate whether the fusion rate of autogenous laminectomy bone chips and calcium sulfate pellets

uld be augmented by bone marrow aspirate (BMA) in one-level lumbar posterolateral fusion.

ummary of Background Data. An in vivo animal study has indicated that BMA augments spinal arthrodesis.

ethods. Forty-three patients undergoing surgery for instrumented one-level fusion with decompression were divi

o 2 groups. Autologous iliac crest bone graft (ICBG) was placed in 1 posterolateral gutter (control), while on the

de (test), an equal quantity of laminectomy bone chips mixed with BMA while harvesting the iliac bone graft (grou

an equal quantity of calcium sulfate pellets soaked in BMA (group 2) was placed. Radiographic assessment was

rformed every 3 months (3 –12 months) and then annually. The statuses of fusion on either side of the vertebra w

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Prospective Randomized Study of Posterolateral Lumbar Fusion (printer-friendly)

aterials and Methods

e study was carried out with the approval of the Institutional Review Board of our hospital. From August 2003 to

04, 43 consecutive patients with lumbar spinal stenosis and one-level low-grade degenerative or spondylolytic

ondylolisthesis (grade I or II) or segmental instability prospectively underwent decompression and pedicle screw

strumented posterolateral fusions. The exclusion criteria for all patients included a history of previous lumbar spin

rgery, spinal infection, systemic autoimmune inflammatory disease, end-stage renal disease, and high-grade

ondylolisthesis. The patients were divided into 2 groups: the first 21 patients were group I and the subsequent 22

tients were group II. For both groups, 10 mL of autogenous iliac cancellous bone graft was placed in 1 side of

sterolateral gutter as the control side. On the other side as the test side, an equivalent amount (10 mL) of ALB c

ere soaked in BMA for group I, whereas Osteoset pellets were mixed with BMA in group II.

urgical Techniques

ecompressive laminectomy was performed to remove the spinal process and lamina in the region of spinal canal

enosis. The ALB chips that were extracted during laminectomy were morselized and were collected by meticulou

moving the covering soft tissue; this morselized bone chips was used as a graft on the test side in group I.

tologous cancellous bone (10 mL) was harvested from the posterior iliac crest by opening an approximately 3 ×

m window at the outer cortex, and this was grafted on the control side for both groups. While harvesting, 10 mL of

ne marrow was aspirated with a syringe from the ilium. The BMA was then mixed with the morselized laminecto

LB chips or CS (Osteoset) pellets for group 1 and 2, respectively. After placing the transpedicular screw/rod

strumentation at the target levels, the autologous iliac cancellous bone graft was placed on the control side (left s

this study). Then, on the test side (right side), laminectomy ALB chips (group I) and CS pellets (group II) that mix

th BMA were placed.

utcomes

nly fusion status was evaluated and recorded in this study. After surgery, fusion was radiographically assessed e

months during the first year and subsequently on an annual basis; computerized tomography scans were perform

least 1 year after the surgery. The radiographic analysis of the fusion status was performed by 2 independent sp

rgeons who were blinded to the test and control sides of the patients. A successful fusion was determined when

rgeons found radiographic evidences of fusion, and a solid fusion was defined as continuous intertransverse bon

dging at the target level on the follow-up radiographs (Figure 1) and/or computerized tomography scans (Figure

e fusion results of both sides were recorded separately for intergroup comparison; the data were compared

atistically using McNemar's χ2 test with a P value of <0.05 was considered statistically significant.

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Figure 1. A 27-year-old man received the posterolateral fusion and instrumentation at L5 –S1 for spondylolytic

spondylolisthesis. The immediately postoperative anteroposterior (AP) view (A) showed a mixture of local bone

chips and bone marrow aspirate (BMA) was used at the patients right side and the autologous iliac bone graft

was used at the left side. B, Significant bone bridging between transverse processes on bilateral sides was

showed in the 3-month AP view.

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Figure 2. The computer-tomogram reconstruction scan of lumbosacral spine was checked 1 or 2 years after

operation for the better identification of successful fusion between the transverse processes.

esults

oup I comprised 21 patients (7 males and 14 females) with an average age of 58 years (range, 27 –75 years). Th

tients with degenerative spondylolisthesis, spondylolytic spondylolisthesis, and segmental instability were numbe

, 5, and 1, respectively. Within group I, there is 1 patient with fusion level at L3 –L4, 16 patients with fusion level

–L5, and 4 patients with fusion level at L4 –L5. Group II comprised 22 patients (9 males and 13 females) with an

erage age of 59 years (range, 41 –72 years). The patients with degenerative spondylolisthesis, spondylolytic

ondylolisthesis, and segmental instability were numbered 17, 4, and 1, respectively. There is 1 patient with fusio

vel at L3-L4, 18 patients with fusion level at L4 –L5 and 3 patients with fusion level at L4 –L5. Smokers were equa

stributed in both groups (4/21 in group I and 5/22 in group II). The overall demographic data of both groups were

milar. All patients in group I and II had follow-up after surgery with an average of 24.6 months (range, 24 –29 mon

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d 24.1 month (range, 24 –27 months), respectively.

group I, 19 of 21 (90.5%) patients were observed to achieve solid bone fusion on the control side and 18 of 21

5.7%) patients achieved it on the test side (Figure 1), which indicates that there was no statistical difference in fu

es between both sides (P = 0.56).

group II, 20 of 22 (90.9%) patients were observed to achieve solid bone fusion on the control side, but only 10 o

0.5%) patient achieved it on the test side (Figure 3). As a result, there was a statistically significant difference in

sion rates between the control and test sides (P = 0.0016).

Figure 3. A 46-year-old woman received the posterolateral fusion and pedicle screw fixation at L4 –L5 for

degenerative spondylolisthesis. The immediately postoperative AP view (A) showed the mixture of Osteoset an

BMA was used at the patients right side and the autologous iliac bone graft was used at the patients left side.

The postoperative 1-year AP view (B) showed a significant bone bridging on the patients left side but no bone

bridging on the patients right side.

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scussion

e ideal bone graft substitute for spinal fusion should possess both osteoconductivity and osteoinductivity; moreo

e presence of osteogenetic cells is an added advantage of achieving a superior fusion rate that is equivalent to th

c bone graft. The grafts that primarily offer the property of osteoconductive are ceramic products such as

droxyapatite, calcium phosphate or sulfate, and freeze-dried allografts, which provide scaffolding that facilitate

teogenesis. In addition, the rhBMP and demineralized bone matrix products are the graft substitutes or expandeth osteoinductive character that also facilitate osteogenesis. That is to say, autologous iliac cancellous bone graf

ntains 3 critical elements of enhanced osteogenesis: trabeculae of bone which is acted as osteoconductive scaff

atrix of BMPs as osteoinductive factors, and osteoblasts as osteogenetic cells. Since it possesses all the

aracteristics required for an ideal bone graft, it is termed as the gold standard for grafts. However, bone graft

rvesting at the donor site can easily lead to significant morbidity[21 –24] and the material is relatively limited in

ailability.

onnolly et al  [25] clinically found the osteopromotive effects of whole bone marrow when autologous marrow was

ected into a tibial defect site. Although both blood and bone marrow could be immediately harvested and used a

tologous materials for osteopromotion, an in vivo animal study[19] proved that BMA has a higher osteogenic pote

an blood when it is impregnated through β-tricalcium phosphate (β-TCP), an osteoconductive scaffold. The reaso

this difference could be the presence of osteoprogenitor cells or bone marrow stem cells in BMA. Furthermore,

me study showed that the osteopromotive effect of BMA was also higher than concentrated mononuclear cells. T

ck of fibrin clot in which the cells can attach and migrate in the concentrated cell suspension may be the reason f

other adjuvant factor could be the osteoinductive factors that were presented in BMA, were absented in the

ncentrated cell group.

an adjuvant to porous calcium phosphate, TCP, and hydroxyapatite ceramics (osteoconductive grafts), marrow

ve been proved to be successful in enhancing osteogenesis in rats and sheep.[19,26,27] Even the beneficial effec

teogenesis of xenograft bone with autologous red marrow implanted in paravertebral muscle, an open system, h

so evidenced in a rat study.[28] These studies suggested that autologous bone marrow greatly facilitates

teopromotion in combination with grafts that are strongly osteoconductive or weakly osteoinductive in nature. Thesence of osteoprogenitor cells and osteoinductive factors in BMA is the critical reason for such enhanced effect

ese key factors are also present in the iliac crest autograft—the gold standard of bone grafting and play the

portant role of facilitating osteogenesis.

cording to the study by Muschler et al ,[18] enriched cancellous bone matrix plus bone marrow clot composite gra

at contain increased amount of marrow-derived osteogenic cells showed improvement in bone grafting. Despite l

ncentration of osteogenic cells in BMA, bone marrow clot could still provide a stabilized environment by serving

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affold in which the cells and factors could attach and migrate along with some osteotropic cytokines, growth facto

d additional angiogenic factors from the fibriolytic activity that occurred during the first several days within a clot.

ese characteristics of the adjuvant BMA play an important role in the process of successful bone healing.

hough bone marrow facilitates osteogenesis, only 43% of cases achieved successful bone formation when only

arrow autograft was transplanted into Wistar rats.[29] The explanation of this low success rate could be the absen

a proper scaffold which cause the soft marrow from the squeezing action of the muscles and poor maintenance

e marrow cells at the implantation site to reduce protection. Consequently, bone marrow graft is superior when it

ade as a composite graft due to the presence of osteoinductive factors in the marrow and the scaffold support

ovided by some solid osteoconductive grafts. Porous or trabecular scaffolding grafts are considered to be of a

perior quality.

e bone chips extracted during laminectomy are mainly cortical in nature. Trabecular bone and unmineralized ma

e main components of the marrow cavity, only comprise a small percentage of the posterior elements in the spina

ucture, including lamina, facet joints and spinal processes, which are the components that are resected during

minectomy. If these bone chips are used as a graft substitute for intertransverse fusion of the lumbar spine, the re

ay be theoretically inferior to the gold standard, posterior iliac cancellous bone graft, due to reduced osteoinducti

tivity. In this study, the osteoinductivity was augmented by impregnating the bone chips with BMA; additionally, t

od scaffolding of marrow was provided by the potential space presented in these bone chips, and fibrin clot from

MA could also provide an additional holding effect for all the chips, cells and matrix. Thus, in group I, the fusion ra

s graft was equivalent to that seen on the contralateral side (P > 0.05).

e ceramic bone graft substitute—Osteoset—is a composite of CS. According to an in vivo animal study,[30] CS

owed rapid resorption of CS pellet within 1 and 3 weeks, followed by major bone apposition at 3 and 6 weeks. In

udy, bony repair was still in progress up to week 12; however, the quality and quantity of the newly formed bone

gnificantly influenced by the occupied avascular fibrous tissue. Because of its early resorption, the scaffolding of

arrow as a discrete mass would be lost and left empty at the early stage. This interference might be more signific

ntertransverse fusion of the lumbar spine because it is an open system. The inferior osteogenetic result of CS w

ne marrow in this group was presumed to be due to the fact that early resorption had caused the loss of the

teoconductive property of Osteoset at the early stage and the osteoinductive effect offered by the BMA could no

aintained in an open system. Furthermore, Osteoset pellets are cylindrical and smooth-surfaced, and the effect o

alloping to keep marrow is certainly worse than the porous ceramics or the bone chips from laminectomy. Porou

d granular formed ceramics, such as calcium phosphate products, have longer survival time and ought to

gnificantly improve fusion when they are mixed with BMA; this will be the topic of a subsequent study.

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he manuscript submitted does not contain information about medical device(s)/drug(s).

o funds were received in support of this work. No benefits in any form have been or will be received from a commercial party relatedrectly or indirectly to the subject of this manuscript.

pine. 2009;34(25):2715-9. © 2009 Lippincott Williams & Wilkins