title: Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.
abstract: BACKGROUND
  Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote fusion in spinal surgery, but its safety has been questioned.
  
  
  OBJECTIVE
  To evaluate the effectiveness and safety of rhBMP-2.
  
  
  METHODS
  Individual-participant data obtained from the sponsor or investigators and data extracted from study publications identified by systematic bibliographic searches through June 2012.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The observational studies were diverse and at risk of bias.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Yale University Open Data Access Project.
authors.affiliation: Centre for Reviews and Dissemination, University of York, York, United Kingdom.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Simmonds
authors.forename: Jennifer V E
authors.initials: JV
authors.lastname: Brown
authors.forename: Morag K
authors.initials: MK
authors.lastname: Heirs
authors.forename: Julian P T
authors.initials: JP
authors.lastname: Higgins
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Mannion
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rodgers
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Stewart
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects* / Q000627:therapeutic use*; D004185:Disability Evaluation; D006801:Humans; D007085:Ilium / Q000637:transplantation; D015994:Incidence; D055959:Intervertebral Disc Degeneration / Q000601:surgery*; D009369:Neoplasms / Q000453:epidemiology; D010149:Postoperative Pain / Q000517:prevention & control; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013123:Spinal Fusion / Q000379:methods; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2