title: Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis.
abstract: BACKGROUND
  Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor known to have in vitro effects on the growth and invasiveness of cancer. It has been approved by the U.S. Food and Drug Administration in limited doses for single-level anterior spinal arthrodesis, but it is commonly used off-label and at high doses. The effect of rhBMP-2 on the risk of cancer has been a concern. We sought to evaluate the risk of new cancers in patients receiving high-dose rhBMP-2.
  
  
  METHODS
  We used publicly available data from a pivotal, multicenter, randomized controlled trial of patients with degenerative lumbar spine conditions who underwent a single-level instrumented posterolateral arthrodesis with either high-dose rhBMP-2 in a compression-resistant matrix (CRM) (rhBMP-2/CRM; n = 239) or autogenous bone graft (control group; n = 224). We compared the risks of new cancers in the rhBMP-2/CRM and control groups at two and five years after surgery.
  
  
  RESULTS
  At two years, with 86% follow-up, there were fifteen new cancer events in eleven patients in the rhBMP-2/CRM group compared with two new cancer events in two patients in the control group treated with autogenous bone graft. The incidence rate of new cancer events per 100 person-years was 3.37 (95% confidence interval [CI], 1.89 to 5.56) in the rhBMP-2/CRM group at two years compared with 0.50 (95% CI, 0.06 to 1.80) in the control group. The incidence rate ratio was 6.75 (95% CI, 1.57 to 60.83; p = 0.0026) at two years. Calculated in terms of the number of patients with one or more cancer events two years after the surgery, the incidence rate per 100 person-years was 2.54 (95% CI, 1.27 to 4.54) in the rhBMP-2/CRM group compared with 0.50 (95% CI, 0.06 to 1.82) in the control group at two years; the incidence rate ratio was 5.04 (95% CI, 1.10 to 46.82; p = 0.0194). At five years, there was a 37% loss of follow-up, but a significantly greater incidence of cancer events was still observed in the rhBMP-2/CRM group.
  
  
  CONCLUSIONS
  A high dose of 40 mg of rhBMP-2/CRM in lumbar spinal arthrodesis was associated with an increased risk of new cancer.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Pavilion C, 4th Floor, Redwood City, CA 94063, USA. carragee@stanford.edu
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Carragee
authors.forename: Gilbert
authors.initials: G
authors.lastname: Chu
authors.forename: Rajat
authors.initials: R
authors.lastname: Rohatgi
authors.forename: Eric L
authors.initials: EL
authors.lastname: Hurwitz
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Weiner
authors.forename: S Tim
authors.initials: ST
authors.lastname: Yoon
authors.forename: Garet
authors.initials: G
authors.lastname: Comer
authors.forename: Branko
authors.initials: B
authors.lastname: Kopjar
mesh_terms: D000328:Adult; D000368:Aged; D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects* / Q000627:therapeutic use; D016025:Bone Transplantation / Q000009:adverse effects* / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D013122:Spinal Diseases / Q000601:surgery; D013123:Spinal Fusion / Q000009:adverse effects* / Q000379:methods
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins