Zhiguang Chen1, Gen Ba, Tao Shen, Qin Fu. 1. Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, No. 36, Sanhao Street, Heping District, Shenyang 110004, People's Republic of China.
Abstract
BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) as a substitute for iliac crest bone graft (ICBG) has been increasingly widely used in lumbar fusion. It has been proven non-inferior in fusion success and clinical outcomes when compared with ICBG. However, increasingly, some potentially uncommon and serious complications associated with the use of rhBMP-2 have been of great concern to surgeons. The purpose of this study was to determine whether rhBMP-2 could be considered an effective and, more importantly, a relatively safe substitute for ICBG in lumbar fusion. METHODS: Randomized controlled trials that compared rhBMP-2 with ICBG for lumbar fusion were identified by computer and manual searching. The risk of bias and clinical relevance of the included studies were assessed. Publication bias was explored using funnel plot and statistical tests (Egger's test and Begg's test). Meta-analyses were performed using the Cochrane systematic review methods. RESULTS: Ten randomized controlled trials (1,342 patients) met the inclusion criteria. Compared with ICBG, the use of rhBMP-2 significantly decreased the risk of fusion failure at all time intervals (6 months: p < 0.0001, RR = 0.55, 95 % CI = 0.42-0.72; 12 months: p = 0.0003, RR = 0.53, 95 % CI = 0.37-0.75; 24 months: p < 0.00001, RR = 0.31, 95 % CI = 0.21-0.46) and the rate of reoperation (p = 0.0001, RR = 0.52, 95 % CI = 0.37-0.72). There was no statistical difference in clinical improvement on the Oswestry Disability Index, although a favorable trend in the rhBMP-2 group was found (p = 0.12, RR = 0.73, 95 % CI = 0.49-1.08). Subgroup analyses stratified by the type of surgical procedure yielded similar results. Owing to the different data formats, meta-analysis on adverse events was not performed. CONCLUSION: RhBMP-2 was superior to the ICBG for achieving fusion success and avoiding reoperation. However, evidence from the Food and Drug Administration document and subsequent independent studies has demonstrated that original, industry-sponsored trials underestimated rhBMP-2-related adverse events. There are still security risks in the use of rhBMP-2.
BACKGROUND: Recombinant humanbone morphogenetic protein-2 (rhBMP-2) as a substitute for iliac crest bone graft (ICBG) has been increasingly widely used in lumbar fusion. It has been proven non-inferior in fusion success and clinical outcomes when compared with ICBG. However, increasingly, some potentially uncommon and serious complications associated with the use of rhBMP-2 have been of great concern to surgeons. The purpose of this study was to determine whether rhBMP-2 could be considered an effective and, more importantly, a relatively safe substitute for ICBG in lumbar fusion. METHODS: Randomized controlled trials that compared rhBMP-2 with ICBG for lumbar fusion were identified by computer and manual searching. The risk of bias and clinical relevance of the included studies were assessed. Publication bias was explored using funnel plot and statistical tests (Egger's test and Begg's test). Meta-analyses were performed using the Cochrane systematic review methods. RESULTS: Ten randomized controlled trials (1,342 patients) met the inclusion criteria. Compared with ICBG, the use of rhBMP-2 significantly decreased the risk of fusion failure at all time intervals (6 months: p < 0.0001, RR = 0.55, 95 % CI = 0.42-0.72; 12 months: p = 0.0003, RR = 0.53, 95 % CI = 0.37-0.75; 24 months: p < 0.00001, RR = 0.31, 95 % CI = 0.21-0.46) and the rate of reoperation (p = 0.0001, RR = 0.52, 95 % CI = 0.37-0.72). There was no statistical difference in clinical improvement on the Oswestry Disability Index, although a favorable trend in the rhBMP-2 group was found (p = 0.12, RR = 0.73, 95 % CI = 0.49-1.08). Subgroup analyses stratified by the type of surgical procedure yielded similar results. Owing to the different data formats, meta-analysis on adverse events was not performed. CONCLUSION:RhBMP-2 was superior to the ICBG for achieving fusion success and avoiding reoperation. However, evidence from the Food and Drug Administration document and subsequent independent studies has demonstrated that original, industry-sponsored trials underestimated rhBMP-2-related adverse events. There are still security risks in the use of rhBMP-2.