Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.

BACKGROUND

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote fusion in spinal surgery, but its safety has been questioned.

PURPOSE

To evaluate the effectiveness and safety of rhBMP-2.

DATA SOURCES

Individual-participant data obtained from the sponsor or investigators and data extracted from study publications identified by systematic bibliographic searches through June 2012.

STUDY SELECTION

Randomized, controlled trials of rhBMP-2 versus iliac crest bone graft (ICBG) in spinal fusion surgery for degenerative disc disease and related conditions and observational studies in similar populations for investigation of adverse events.

DATA EXTRACTION

Individual-participant data from 11 eligible of 17 provided trials sponsored by Medtronic (Minneapolis, Minnesota) (n = 1302) and 1 of 2 other eligible trials (n = 106) were included. Additional aggregate adverse event data were extracted from 35 published observational studies.

DATA SYNTHESIS

Primary outcomes were pain (assessed with the Oswestry Disability Index [ODI] or Short Form-36), fusion, and adverse events. At 24 months, ODI scores were 3.5% lower (better) with rhBMP-2 than with ICBG (95% CI, 0.5% to 6.5%) and radiographic fusion was 12% higher (CI, 2% to 23%). At or shortly after surgery, pain was more common with rhBMP-2 (odds ratio, 1.78 [CI, 1.06 to 2.95]). Cancer was more common after rhBMP-2 (relative risk, 1.98 [CI, 0.86 to 4.54]), but the small number of events precluded definite conclusions.

LIMITATION

The observational studies were diverse and at risk of bias.

CONCLUSION

At 24 months, rhBMP-2 increases fusion rates, reduces pain by a clinically insignificant amount, and increases early postsurgical pain compared with ICBG. Evidence of increased cancer incidence is inconclusive.

PRIMARY FUNDING SOURCE

Yale University Open Data Access Project.