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Friday, December 13, 2013
The Latest BMP-2 Trial—Anything New?

The use of BMP-2 in spine surgery remains controversial, and the indications for its use are unclear. Recent meta-analysis of the industry sponsored trials demonstrated higher fusion rates but no improvements in clinical outcomes across many different applications.1 In the December 1 issue, Dr. Hurlbert and his colleagues from Canada reported the results of their industry-sponsored RCT comparing BMP-2 to iliac crest bone graft (ICBG) in one- or two-level instrumented posterolateral lumbar fusion. They randomized approximately 200 patients, with 98% follow-up through two years. An additional 41 patients in each group were followed out to four years. Similar to the other BMP-2 trials, they reported a significantly higher fusion rate (97% vs. 70%) at two years, but no improvement in clinical outcome measures (Oswestry Disability Index, SF-36, and VAS back and leg pain scores) at any time point. The ICBG group experienced a low rate of graft related complications, none of which required a return trip to the OR. The BMP-2 group had significantly more complaints of headache and non-spine related pain in early follow-up. The infection rate was approximately twice as high in the BMP-2 group compared to the ICBG group (10% vs. 5%), though this difference was not statistically significant (p=0.12). Two patients in each group had to return to the OR for revision surgery related to pseudarthrosis. Contrary to expectations, the use of BMP-2 did not decrease blood loss or operative time. Overall, the results were similar to prior industry sponsored RCTs that have demonstrated higher fusion rates, similar clinical outcomes, and trends towards increased complications associated with BMP-2.

 

Given that the results of this trial are similar to previously published BMP-2 trials, most readers will not find much surprising about the current results. The apparent lack of an association between solid fusion and clinical outcomes for one-level instrumented lumbar fusions for degenerative disease has been reported in the past.2 Longer-term data has suggested that pseudarthrosis leads to worse outcomes in uninstrumented fusions, though no such finding has been reported for instrumented cases.3 As such, it remains unclear if obtaining a stable fibrous union with instrumentation is sufficient for a good outcome or if these patients will do worse in the long-term. It seems that the definition for fusion in the current study—including bilateral bridging bone between the transverse processes—sets the bar for fusion very high, and solid unilateral bridging bone may have similar outcomes to a solid bilateral fusion. The results of the current and prior studies make it very hard to justify the use of BMP-2 in one- or two-level posterolateral lumbar fusions for degenerative disease. BMP-2 does not seem to lead to any improvement in clinical outcome measures, may be associated with complications, and is very expensive.4 While this study and all prior industry sponsored trials have been underpowered to detect differences in rare complications such as infection, the fact that the infection rate was twice as high in the BMP-2 group is concerning. BMP-2 likely has a role in spine surgery, and a recent study has demonstrated both a higher fusion rate and better clinical outcomes in adult deformity patients treated with long thoracolumbar fusions to the sacrum.5 Instead of focusing on the more prevalent one- and two-level degenerative conditions where BMP-2 is probably not indicated, future RCTs should evaluate the use of BMP-2 in adult deformity surgery, where its use may be justified.

 

Please read Dr. Hurlbert’s article in the December 1 issue. Does this article change your approach to the use of BMP-2 in posterolateral lumbar fusion? Let us know by leaving a comment on The Spine Blog.

 

Adam Pearson, MD, MS

Associate Web Editor

 

REFERENCES

1.            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. Annals of internal medicine 2013;158:877-89.

2.            Fischgrund JS, Mackay M, Herkowitz HN, Brower R, Montgomery DM, Kurz LT. 1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation. Spine 1997;22:2807-12.

3.            Kornblum MB, Fischgrund JS, Herkowitz HN, Abraham DA, Berkower DL, Ditkoff JS. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective long-term study comparing fusion and pseudarthrosis. Spine 2004;29:726-33; discussion 33-4.

4.            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.

5.            Kim HJ, Buchowski JM, Zebala LP, Dickson DD, Koester L, Bridwell KH. RhBMP-2 is superior to iliac crest bone graft for long fusions to the sacrum in adult spinal deformity: 4- to 14-year follow-up. Spine 2013;38:1209-15.

 

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Spine Journal
This Blog provides a forum for discussion about high impact articles published in Spine, including the bi-annual publication of "Evidenced-Based Recommendations for Spine Surgery." Website users can use this forum to discuss how the articles have affected their practice and query the authors about their findings and recommendations.