title: Recombinant human bone morphogenetic protein-2: adverse events reported to the Manufacturer and User Facility Device Experience database.
abstract: BACKGROUND
  Adverse effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal surgery have previously been observed. However, because of its size, scope, and nature, the US Food and Drug Administration's database of postmarketing reports is useful for detecting new and unexpected safety concerns.
  
  
  OBJECTIVE
  To characterize adverse events reported to the FDA; to characterize off-label use of rhBMP-2.
  
  
  METHODS
  Review of adverse events reported to the FDA after the use of rhBMP-2 (INFUSE Bone Graft) in spinal surgery.
  
  
  METHODS
  The Manufacturer and User Facility Device Experience database was searched for the brand name "infuse bone graft," for reports received from July 2, 2002, through August 31, 2011. Adverse events were reviewed, summarized, and classified by an MD. For each report, the most important clinical entity was identified as the principal adverse event. Off-label uses were summarized.
  
  
  RESULTS
  Of 834 reports, four (0.5%) described procedures in which rhBMP-2 was used in accordance with the approved indication. Nearly half of all the reports, 370 (44.4%), stated that the patient required revision surgery or other invasive interventions to address the reported adverse event. Swelling, fluid collections, osteolysis, pain/radiculopathy, heterotopic bone, pseudarthrosis, surgical site infections and other wound complications, thromboembolic events, respiratory distress, cancer, and other events were reported.
  
  
  CONCLUSIONS
  Because of their duration, scope, and expense, prospective studies designed to estimate the risk of rare adverse events may be impractical. Despite its imperfections, postmarketing surveillance helps to narrow the focus by revealing patterns and prioritizing topics for further research. One should not extrapolate from these results to the rhBMP-2 experience as a whole; the findings reported here might not be representative. This analysis indicates that serious adverse events can occur after the use of rhBMP-2 in spinal surgery and raises many points that surgeons may wish to consider when deciding when and how to use this product in their patients.
authors.affiliation: US Food and Drug Administration, HFM-222, 1401 Rockville Pike, Rockville, MD 20852, USA. jane.woo@fda.hhs.gov
authors.forename: Emily Jane
authors.initials: EJ
authors.lastname: Woo
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects*; D000075202:Contraindications; D016208:Databases, Factual / Q000706:statistics & numerical data*; D016903:Drug Monitoring / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D056687:Off-Label Use; D009985:Orthopedics / Q000379:methods / Q000706:statistics & numerical data; D011247:Pregnancy; D011994:Recombinant Proteins / Q000009:adverse effects; D012086:Reoperation; D016212:Transforming Growth Factor beta / Q000009:adverse effects*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2