Comparative Clinical Effectiveness And Safety Of Recombinant Human Bone Morphogenetic Protein Versus Iliac Crest Bone Graft For Lumbar Fusion: A Meta-analysis

Objective: Over the past few decades,lumbar fusion with autogenous iliac crest bone graft(ICBG)has become standard surgery for the treatment of lumbar degenerative diseases,such as lumbar spondylolisthesis and lumbar spinal stenosis,among others.However,harvesting the graft has been associated with donor site morbidity,such as persistent pain,iliac fracture,vascular and nerve injury,infection and so on.As a result,various bone graft substitutes have been developed.In recent years,recombinant human bone morphogenetic protein(rh BMP)has been widely used as a substitute in lumbar fusion due to high fusion success rate.Nevertheless,a degree of uncertainty remains concerning efficacy and safety of rh BMP in lumbar fusion.Thus,the objective of this study was to perform a meta-analysis,evaluating the clinical efficacy and safety of rh BMP and ICBG in lumbar fusion.Methods: Studies were searched from Pub Med,EMBASE,Cochrane Central Register of Controlled Trails and CNKI database and Wanfang database by using Medical Subject Headings terms “bone morphogenetic protein,” “bone transplantation,” and “spinal fusion.” Two independent researchers screened articles published as of January 31,2020 according to the inclusion criteria,assessed the bias of original articles,extracted data including fusion rate,improvement on Oswestry disability index(ODI),improvement on short Form-36(SF-36),improvement on numerical rating scale(NRS)of back pain and leg pain,complications and reoperation.Subgroup analysis based on protein type was performed.In addition,The Grading of Recommendations Assessment,Development,and Evaluation(GRADE)system was used to rate the overall body of evidence for each outcome.The meta-analysis was performed by Rev Man 5.3.Results: A total of 20 randomized controlled trials(2185 patients)met the inclusion criteria.There were higher fusion success rate(OR=3.79,95% CI,1.88-7.63,P=0.0002),better improvement on ODI(MD=1.54,95% CI,0.18-2.89,P=0.03),and lower reoperation(OR=0.59,95% CI,0.43-0.80,P=0.0007).A subgroup analysis,based on protein type(rh BMP-2 or rh BMP-7),was performed,which suggested that only rh BMP-2 had higher fusion success rate than ICBG(OR=5.57;95% CI2.95-10.52;P<0.00001),and rh BMP-7 had no significant advantage(OR=0.94,95%CI 0.49-1.81,P=0.86).Similarly,compared with ICBG,rh BMP-2 had lower risk of reoperation(OR=0.48,95% CI 0.33-0.68,P<0.0001),and better improvement on NRS of leg pain(MD=-0.84,95% CI,0.02-1.65,P=0.04).There was no significant difference in reoperation between rh BMP-7 and ICBG(OR=1.18,95% CI 0.62-2.23,P=0.62).There was no significant difference in the incidence of complications between rh BMP and ICBG(OR=0.91,95% CI 0.70-1.18,P=0.47).Conclusion: Compared with ICBG,rh BMP-2 exhibited a higher fusion success rate and reduced the risk of reoperation.There was no difference in the incidence of complications between rh BMP-2 or rh BMP-7 and ICBG.We believe that rh BMP,especially rh BMP-2,is a suitable substitute for ICBG in lumbar fusion.