Autogeneic iliac crest graft versus bone morphogenetic protein 2 in lumbar fusion: a Meta-analysis

doi:10.3969/j.issn.2095-4344.2016.43.020

Abstract

Abstract:

BACKGROUND: As a substitute for autogeneic iliac crest, bone morphogenetic protein 2 has been widely used in lumbar fusion and relative trials.
OBJECTIVE: To assess the effectiveness and safety of bone morphogenetic protein 2 in lumbar fusion.
METHODS: CBM, Medline, Embase and the Cochrane Central Register of Controlled Trial databases were retrieved for relevant randomized controlled trials of bone morphogenetic protein 2 versus autogenous iliac crest graft in lumbar fusion published before September 2015. A Meta-analysis was performed utilizing the Cochrane system.
RESULTS AND CONCLUSION: Totally 14 randomized controlled trials met the inclusion criteria, including 1 613 patients. Meta-analysis results showed that the reoperation rate and operation time in bone morphogenetic protein 2 group were significantly less than those in the autogenous iliac crest graft group (P ≤ 0.01), and the fusion rate was significantly higher than that in the autologous iliac crest graft group (P ≤ 0.01). There were no significant differences in the clinical outcomes, complications, intraoperative blood loss, hospitalization time, patient satisfaction and work status after surgery between two groups. Based on the limited evidence, bone morphogenetic protein 2 for lumbar degenerative disease exerts no significant superiority to the autologous iliac crest graft. Moreover, more high-quality randomized controlled trials with long-term follow-up are needed to further assess the effectiveness and safety of bone morphogenetic protein 2 in lumbar fusion.

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

Key words: Bone Morphogenetic Proteins, Spinal Fusion, Randomized Controlled Trial, Tissue Engineeering

CLC Number:

R318

Zhang Hai-fei, Zhang Zhi-yu, Cui Yan, Wang Feng, Ma Cheng-bin, Zhang Wei.

Autogeneic iliac crest graft versus bone morphogenetic protein 2 in lumbar fusion: a Meta-analysis

[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(43): 6521-6529.

Figures/Tables 11

2.4 定量数据的Meta分析 13项研究比较了两组术后融合率(实验组599例患者，对照组439例)[12-13，15-25]，组间差异显著[RR=1.19，95%CI(1.08-1.31)，P=0.000 3]，但研究间存在明显异质性(Ⅰ2=72%)，见图2。6项研究提供了关于临床总体疗效的数据(实验组219例，对照组184例)[12-15，17，23]，Meta分析发现两组间无显著差异[RR=1.08，95%CI(0.94-1.23)，P=0.27]，且各组没有异质性(Ⅰ2=13%)，见图3。关于并发症，合并了6项研究的数据，包括实验组457例及对照组433例患者，结果显示两组并没有显著差异[RR=1.05，95%CI=0.79-1.41，P=0.74]，且各组没有异质性(Ⅰ2=25%)，见图4。13项研究比较了两组的再次手术率[13-25]，共包括实验组835例及对照组768例患者，结果显示，实验组患者再次手术率显著低于对照组[RR=0.63，95%CI(0.44-0.91)，P=0.01]，且各组没有异质性(Ⅰ2=25%)，见图5。8项研究比较了两组手术时间[12-13，18，21-25]，结果显示，实验组手术时间短于对照组[MD=-0.33，95%CI(-0.58，-0.08)，P=0.009]，但各研究间异质性较大(Ⅰ2 = 81%)。而且这8项研究也比较了两组术中出血量，但结果表明在术中出血量上两组并没有显著差别[MD=-54.96，95%CI(119.05，9.13)，P=0.09], 各组异质性依然较大(Ⅰ2=76%)。6项研究比较了两组平均住院日[12-13，21-23，25]，结果无差异[MD=-0.64，95%CI(-1.12，-0.06)，P =0.03]，但各组间异质性较大(Ⅰ2 =76%)。4项研究比较了两组术后患者满意度[13-15，17]，分析结果显示无统计学差异[RR=1.06，95%CI(0.86，1.32)，P=0.58]，各组间存在轻度异质性(Ⅰ2 =44%)。7项研究比较了两组术后24个月时患者的工作状态[12，14-15，17，20，22-23]，结果显示两组无统计学差异(RR=1.05，95%CI(0.85，1.30)，P =0.63)。组间存在轻度异质性(Ⅰ2=38%)。"

References

[1]Arrington ED,Smith WJ,Chambers HG,et al. Complications of iliac crest bone graft harvesting.Clin Orthop Relat Res.1996;329:300-309.
[2]Urist MR.Bone Formation by autoinduction. Science. 1965;150:893-899.
[3]Celeste AJ,Iannazzi JA,Taylor RC,et al.Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone.Proc Natl Acad Sci USA. 1990;87: 9843-9847.
[4]Furlan AD,Pennick V,Bombardier C,et al.2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group.Spine (Phila Pa 1976). 2009;34:1929-1941.
[5]Higgins JPT,Green S.Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011].The Cochrane Collaboration.2011.
[6]DerSimonian R,Laird N. Meta-analysis in clinical trials. Control Clin Trials.1986;7:177-188.
[7]Egger M,Smith GD,Schneider M,et al.Bias in meta-analysis detected by a simple, graphical test. BMJ.1997;315(7109):629-634.
[8]Begg CB,Mazumdar M.Operating characteristics of a rank correlation test for publication bias.Biometrics. 1994;50(4):1088-1101.
[9]Egger M,Smith GD.Bias in location and selection of studies.BMJ.1998;316:61-66.
[10]Duval S,Tweedie R.Trim and fill: a simple funnel-plot based method of testing and adjusting for publication bias in meta-analysis.Biometrics. 2000;56(2): 455-463.
[11]Sutton AJ,Duval SJ,Tweedie RL,et al.Empirical assessment of effect of publication bias on meta-analyses.BMJ.2000;320(7249):1574-1577.
[12]Boden SD,Zdeblick TA,Sandhu HS,et al.The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report. Spine(Phila Pa 1976).2000;25(3):376-381.
[13]Boden SD,Kang J,Sandhu H,et al.Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial:2002 Volvo Award in clinical studies.Spine(Phila Pa 1976). 2002; 27(23):2662-2673.
[14]Burkus JK,Gornet MF,Dickman CA,et al.Anterior lumbar interbody fusion using rhBMP-2 with tapered interbody cages.J Spinal Disord Tech. 2002;15:337-349.
[15]Burkus JK,Transfeldt EE,Kitchel SH,et al.Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2.Spine(Phila Pa 1976). 2002;27:2396-2408.
[16]Burkus JK,Dorchak JD,Sanders DL.Radiographic assessment of interbody fusion using recombinant human bone morphogenetic protein type 2.Spine(Phila Pa 1976).2003;28:372-377.
[17]Haid RW Jr,Branch CL Jr,Alexander JT,et al.Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages.Spine J.2004;4(5):527-538.
[18]Glassman SD,Dimar JR,Carreon LY,et al.Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion.Spine(Phila Pa 1976).2005;30(15):1694-1698.
[19]Burkus JK,Sandhu HS,Gornet MF,et al.Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery.J Bone Joint Surg Am. 2006;87(6):1205-1212.
[20]Dimar JR,Glassman SD,Burkus KJ,et al.Clinical outcomes and fusion success at 2 years of single-level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft.Spine (Phila Pa 1976).2006;31(22):2534-2539.
[21]Glassman SD,Carreon LY,Djurasovic M,et al. RhBMP-2 versus iliac crest bone graft for lumbar spine fusion: a randomized, controlled trial in patients over 60 years of age.Spine(Phila Pa 1976). 2008;33(26):2843-2849.
[22]Dimar JR 2nd,Glassman SD,Burkus JK,et al.Clinical and radiographic analysis of an optimized rhBMP-2 formulation as an autograft replacement in posterolateral lumbar spine arthrodesis.J Bone Joint Surg Am.2009;91(6):1377-1386.
[23]Dawson E,Bae HW,Burkus JK,et al.Recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge with an osteoconductive bulking agent in posterolateral arthrodesis with instrumentation.A prospective randomized trial.J Bone Joint Surg Am.2009;91(7):1604-1613.
[24]Michielsen J,Sys J,Rigaux A,et al.The effect of recombinant human bone morphogenetic protein-2 in single-level posteriorlumbar interbody arthrodesis.J Bone Joint Surg Am.2013;95(10):873-880.
[25]Hurlbert RJ,Alexander D,Bailey S,et al.rhBMP-2 for posterolateral instrumented lumbar fusion: a multicenter prospective randomized controlled trial. Spine(Phila Pa 1976).2013;38:2139-2148.
[26]An H,Boden SD,Kang J,et al.Summary statement: emerging techniques for treatment of degenerative lumbar disc disease. Spine(Phila Pa 1976).2003;28(15 Suppl):S24-S25.
[27]Poynton AR,Lane JM.Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976).2002;27:S40-48.
[28]Benglis D,Wang MY,Levi AD.A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery.Neurosurgery.2008;62(5 Suppl 2): ONS423-431.
[29]Carragee EJ,Hurwitz EL,Weiner BK.A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned.Spine J.2011;11(6):471-491.
[30]Mussano F,Ciccone G,Ceccarelli M,et al.Bone morphogenetic proteins and bone defects: a systematic review.Spine(Phila Pa 1976). 2007;32:824-830.
[31]Papakostidis C,Kontakis G,Bhandari M,et al.Efficacy of autologous iliac crest bone graft and bone morphogenetic proteins for posterolateral fusion of lumbar spine: a meta-analysis of the results. Spine(Phila Pa 1976). 2008;33(19):E680-692.
[32]Agarwal R,Williams K,Umscheid CA,et al. Osteoinductive bone graft substitutes for lumbar fusion: a systematic review.J Neurosurg Spine.2009; 11(11): 729-740.
[33]Donell S,Garrison K,Shemilt I,et al.Bone Morphogenetic Protein-2 for Spinal Fusion: Meta-analysis of Randomised Controlled Trials.UEA Website. Available：http://www.uea.ac.uk/~wo158 /BMP-2%20for%20SF%20-%20Meta-analysis%20of%20RCTs.pdf. Accessed Dec 12,2013.
[34]Blumenthal SL,Gill K.Can lumbar spine radiographs accurately determine fusion in postoperative patients? Correlation of routine radiographs with a second surgical look at lumbar fusions.Spine(Phila Pa 1976). 1993;18(9):1186-1189.
[35]Mroz TE,Wang JC,Hashimoto R,et al.Complications related to osteobiologics use in spine surgery: a systematic review.Spine(Phila Pa 1976). 2010;35(20): S86-104.
[36]Fu R,Selph S,McDonagh M,et al.Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis.Ann Intern Med.2013;158(12):890-902.
[37]Simmonds MC,Brown JV,Heirs MK,et al.Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.Ann Intern Med.2013;158(12):877-889.
[38]Carragee EJ,Hurwitz EL,Weiner BK.A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned.Spine J.2011;11: 471-491.
[39]Yale School of Medicine. Available: http://medicine.yale.edu/core/projects/yodap/datasharing/ medtronic/463_158787_YorkrhBMP2FinalReport. pdf.Accessed Dec 12,2013.