title: Cancer risk from bone morphogenetic protein exposure in spinal arthrodesis.
abstract: BACKGROUND
  The U.S. Food and Drug Administration reported a higher incidence of cancer in patients who had spinal arthrodesis and were exposed to a high dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) compared with the control group in a randomized controlled trial. The purpose of this study was to determine the risk of cancer after spinal arthrodesis with BMP.
  
  
  METHODS
  We retrospectively analyzed the incidence of cancer in 467,916 Medicare patients undergoing spinal arthrodesis from 2005 to 2010. Patients with a preexisting diagnosis of cancer were excluded. The average follow-up duration was 2.85 years for the BMP group and 2.94 years for the control group. The main outcome measure was the relative risk of developing new malignant lesions after spinal arthrodesis with or without exposure to BMP.
  
  
  RESULTS
  The relative risk of developing cancer after BMP exposure was 0.938 (95% confidence interval [95% CI]: 0.913 to 0.964), which was significant. In the BMP group, 5.9% of the patients developed an invasive cancer compared with 6.5% of the patients in the control group. The relative risk of developing cancer after BMP exposure was 0.98 in males (95% CI: 0.94 to 1.02) and 0.93 (95% CI: 0.90 to 0.97) in females. The control group showed a higher incidence of each type of cancer except pancreatic cancer.
  
  
  CONCLUSIONS
  Recent clinical use of BMP was not associated with a detectable increase in the risk of cancer within a mean 2.9-year time window.
  
  
  METHODS
  Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin School of Medicine and Public Health, UWMF Centennial Building, 1685 Highland Avenue, 6th Floor, Madison, WI 53705-2281. E-mail address for M.P. Kelly: Mpkelly3@wisc.edu. E-mail address for P.A. Anderson: Anderson@ortho.wisc.edu.
authors.forename: Mick P
authors.initials: MP
authors.lastname: Kelly
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, NMH/Arkes Family Pavilion 13th Floor, 676 North Saint Clair, Chicago, IL 60611. E-mail address for J.W. Savage: jsavage@nmff.org. E-mail address for W.K. Hsu: whsu@nmff.org.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Savage
authors.affiliation: Departments of Human Oncology, Medical Physics, and Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, K4/314 Clinical Sciences Center, 600 Highland Avenue, Madison, WI 53792-4675. E-mail address: Bentzen@humonc.wisc.edu.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, NMH/Arkes Family Pavilion 13th Floor, 676 North Saint Clair, Chicago, IL 60611. E-mail address for J.W. Savage: jsavage@nmff.org. E-mail address for W.K. Hsu: whsu@nmff.org.
authors.forename: Wellington K
authors.initials: WK
authors.lastname: Hsu
authors.affiliation: PearlDiver Technologies, Inc., P.O. Box 1765, Warsaw, IN 46581. E-mail address: scott@pearldiverinc.com.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Ellison
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin School of Medicine and Public Health, UWMF Centennial Building, 1685 Highland Avenue, 6th Floor, Madison, WI 53705-2281. E-mail address for M.P. Kelly: Mpkelly3@wisc.edu. E-mail address for P.A. Anderson: Anderson@ortho.wisc.edu.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Anderson
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D055396:Bone Morphogenetic Protein 2 / Q000009:adverse effects / Q000627:therapeutic use; D019485:Bone Morphogenetic Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D006278:Medicare / Q000706:statistics & numerical data; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D018426:SEER Program; D017678:Sex Distribution; D013122:Spinal Diseases / Q000188:drug therapy* / Q000601:surgery; D013123:Spinal Fusion / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2