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Scientific Articles   |    
Cancer Risk After Use of Recombinant Bone Morphogenetic Protein-2 for Spinal Arthrodesis
Eugene J. Carragee, MD1; Gilbert Chu, MD, PhD2; Rajat Rohatgi, MD, PhD2; Eric L. Hurwitz, DC, PhD3; Bradley K. Weiner, MD4; S. Tim Yoon, MD, PhD5; Garet Comer, MD1; Branko Kopjar, MD, MS, PhD6
1 Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Pavilion C, 4th Floor, Redwood City, CA 94063. E-mail address for E.J. Carragee: carragee@stanford.edu
2 Division of Oncology, Department of Medicine, Stanford University School of Medicine, CCSR 1145, Stanford University Medical Center, Stanford, CA 94305
3 Department of Public Health Sciences, John A. Burns School of Medicine, University of Hawaii, 1960 East-West Road, Biomedical Building, D-104H, Honolulu, HI 96822
4 Department of Orthopaedic Surgery, The Methodist Hospital and Research Institute, 6550 Fannin Street, Suite 2500, Houston, TX 77030
5 Department of Orthopaedic Surgery, Emory Orthopaedics & Spine Center, Emory University, 59 Executive Park South, Atlanta, GA 30329
6 Department of Health Services, University of Washington, 4333 Brooklyn Avenue N.E., Room 14-315, Seattle, WA 98195
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Investigation performed at Stanford University School of Medicine, Redwood City and Stanford, California; Emory University School of Medicine, Atlanta, Georgia; John A. Burns School of Medicine, Honolulu, Hawaii; The Methodist Hospital and Research Institute, Houston, Texas; and the University of Washington, Seattle, Washington



Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, one or more of the authors has had another relationship, or has engaged in another activity, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Sep 04;95(17):1537-1545. doi: 10.2106/JBJS.L.01483
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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.

Level of Evidence: 

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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