BMP-2 may lead to Cancer


Cancer Risk After Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis


Eugene J. Carragee, MD1; Gilbert Chu, ; Rajat Rohatgi, Eric L. Hurwitz, DC, Bradley K. Weiner, S. Tim Yoon, Garet Comer,  Branko Kopjar,

Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Pavilion C, 4th Floor, Redwood City, CA 94063.

J Bone Joint Surg Am, 2013 Sep 04;95(17):1537-1545. doi: 10.2106/JBJS.L.01483JBJS A

Level of Evidence: Therapeutic Level-2


  • rh-BMP2 has been approved by US FDA to be used in limited doses for single-level anterior spinal fusion . The effect of rhBMP-2 on the risk of cancer has been a concern.
  • Eugene Caragee, the Editor of Spine journal had earlier identified the risk of retrograde ejaculation and male infertility in male patients who underwent spinal fusion.
  • Caragee and colleagues evaluated the risk of new cancers in patients receiving high-dose rhBMP- in this new study
  • There has been extensive off label use of rhBMP-2, as in 2006, 25% of patients who underwent spinal fusion received BMP-2

Materials and Methods:

  • Data were evaluated from a pivotal, multicenter, randomized controlled trial of patients with degenerative lumbar spine conditions who underwent a single-level instrumented posterolateral spinal fusion 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).
  • They compared the risks of new cancers in the rhBMP-2/CRM and control groups at two and five years after surgery.


  •  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 follow up at 2 years was 86%
  • The incidence rate of new cancer events per 100 person-years was 3.37 in the rhBMP-2/CRM group at two years compared with 0.50 (95% CI, 0.06 to 1.80) in the control group.
  • There was a 37% loss of follow-up at five years, but a significantly greater incidence of cancer events was still observed in the rhBMP-2 administered patients
  • Also these adverse events have been noted in individuals with an inherently low cancer risk, the incidence of adverse effects could be higher in patients with increased risk of cancer.
  • Endogenous BMP-2 normally exists in extremely small quantities (0.1 ng/mL).The concentration of rhBMP-2 used in the trials is one to twenty million times ambient concentrations. BMP-2 probably exerts its effects via TGF-Beta by activation of ras proto-oncogene or inhibition of p53, the tumour suppressor gene, often called the “molecular policeman”


  • A high dose of 40 mg of rhBMP-2/CRM in lumbar spinal fusion was associated with an increased risk of new cancer events.

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