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The Spine Blog

Friday, June 5, 2020

BMP meta-analysis: anything new to learn?

The controversy regarding the use of BMP-2 in lumbar fusion has died down to some degree, with surgeons tending to use it in situations with high risk for pseudarthrosis (i.e. long thoracolumbar fusions to the pelvis, revision fusion for pseudarthrosis, smokers) but not for routine one level fusions. A few meta-analyses comparing BMP to iliac crest bone graft (ICBG) have been published, with most concluding that BMP-2 increases fusion rate. These studies have focused less on other outcomes such as patient reported outcome measures (PROs), reoperation rate, and hospital length of stay. In an effort to add to the meta-analysis literature on the topic, Dr. Liu and colleagues from China performed a meta-analysis including 20 RCTs and over 2,000 patients comparing BMP to ICBG. Fourteen studies evaluated BMP-2 and 6 evaluated BMP-7. Six of the studies included ALIF procedures, 8 included PLIFs, and 6 included posterolateral fusions. They found that outcomes were different for BMP-2 and BMP-7, so subgroup analyses were performed for the two different BMPs. They found a significantly higher fusion rate for BMP-2, with an OR of 5.57. BMP-7 did not lead to higher fusion rate. Oswestry Disability Index score improvement was also significantly better for BMP-2, with a standardized mean difference of 1.9. There was no significant difference for the BMP-7 patients compared to ICBG. The BMP-2 group had a significantly lower reoperation rate, with an OR of 0.48. No significant difference was observed for the BMP-7 group on this outcome. The BMP-2 group also had a shorter operation time, with a standardized mean difference of -0.27. The difference for the BMP-7 group (0.13) was not significant. There were no differences in adverse events for either group. Overall, they graded the strength of the evidence as low to moderate.

The authors have performed a methodologically sound meta-analysis comparing BMP to ICBG. Their conclusions are in agreement with most of the literature on this topic and do not contain any surprises. Most spine surgeons have concluded that BMP-2 increases fusion rate, though it is an expensive product and may be associated with some complications related to increased post-operative inflammation (i.e. pain, wound drainage, seroma formation) and ectopic bone formation. This study also demonstrated that BMP-7 is no better than ICBG and probably should not be used in spine surgery, and this is consistent with current clinical practice. This study also showed significantly greater improvement on the ODI for patients treated with BMP-2, and a lower reoperation rate. The authors did not clearly define what they considered an adverse event and lumped all of them together, so it is difficult to draw any conclusions about this topic. They also did not report the absolute event rates and PRO scores (i.e. all data were presented as ORs and standardized mean differences), which makes it hard to interpret the clinical implications of the data. For example, they report an OR of 5.6 for fusion rate for BMP-2 relative to ICBG. This obviously does not translate into a fusion rate five times higher for the BMP-2 and demonstrates how ORs tend to magnify differences for common events. Looking at their raw data allows one to calculate a fusion rate of 96% for BMP-2 vs. 82% for ICBG. Similarly, ODI improvement was reported as a standard mean difference (i.e. the mean divided by the standard deviation), which is hard to convert to an actual difference in scores as the standard deviations were highly variable across studies. The main limitation of this and every meta-analysis is that the results are only as good as the data included, and many concerns have been raised about possible bias in these studies that were mostly industry-sponsored.1

Please read Dr. Liu's article in the June 15 issue. Does this change how you view BMP in lumbar fusion?

Adam Pearson, MD, MS

Associate Web Editor

REFERENCE

1.            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. The spine journal : official journal of the North American Spine Society 2011;11:471-91.