Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May;3(2):35-41.
doi: 10.1055/s-0031-1298616.

The use of rhBMP in spine surgery: is there a cancer risk?

John G Devine  1 , Joseph R Dettori, John C France, Erika Brodt, Robert A McGuire
Affiliations

The use of rhBMP in spine surgery: is there a cancer risk?

John G Devine et al. Evid Based Spine Care J. 2012 May.

Abstract

Study design: Systematic review.

Study rationale: Some have noted several safety issues associated with the use of bone morphogenetic proteins (BMPs), including cancer risk, stating both BMP and their receptors had been isolated from human tumors. In addition, data presented to the US Food and Drug Administration (FDA) on the product AMPLIFY™ (rhBMP-2, 40 mg) revealed a higher number of cancers in the investigational group compared with the control.

Objective: To independently review the cancer risk of rhBMP-2 use in spine fusion as published in the peer-reviewed literature and in the publicly available FDA data summaries.

Methods: A systematic review of the literature was undertaken for articles published through January 2012. Pubmed, Cochrane, National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Two independent reviewers revised articles. Inclusion and exclusion criteria were set and each article was subjected to a predefined quality-rating scheme.

Results: Five published peer-reviewed studies and two FDA safety summaries reported the occurrence of cancer in patients treated with spinal fusion using rhBMP-2 or rhBMP-7. Cancer data for on-label use of rhBMP-2 (InFUSE™) were reported in the FDA data summary but not in one published pivotal study. The risk of cancer was same in both the rhBMP-2 and control groups, 0.7% after 24 months. Off-label use of rhBMP for posterolateral fusion (PLF) was associated with a slightly higher risk of cancer compared with controls in three randomized controlled trials and one poorly conducted retrospective cohort study at various follow-ups. In PLF the risk of cancer was 3.8% using 40 mg of BMP-2 compared with 0.9% in the control group. Two RCTs evaluating rhBMP-7 reported a cancer risk of 12.5% and 5.6% in the rhBMP-7 group compared with 8.3% and 0% in the control groups, respectively. The differences in these studies were not statistically significant; however, the sample sizes for these studies were small.

Conclusions: Cancer risk with BMP-2 may be dose dependent, illustrating the need to continue to study this technology and obtain longer follow-up on patients currently enrolled in the FDA trials. Additionally, refined guidelines regarding the routine use of BMPs should be developed, taking into account the FDA summary data that is not routinely scrutinized by the practicing surgeon.

PubMed Disclaimer

Conflict of interest statement

The authors declare no financial conflict of interest.

Figures

Fig. 1
Fig. 1
Results of literature search.
Fig. 2
Fig. 2
AP image intensifier showing the moment when the dye is injected into a L4-L5 disc discography.
See this image and copyright information in PMC

References

    1. Poynton A R, Lane J M. Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976) 2002;27 16:S40–48. - PubMed
    1. Carragee E J, Hurwitz E L, Weiner B K. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 2011;11(6):471–491. - PubMed
    1. Food and Drug Administration (FDA) Summary of Safety and Effectiveness Data (SSED) for P050036 Medtronic’s AMPLIFY™ rhBMP-2 Matrix. Orthopaedic and Rehabilitation Devices Advisory Panel Available at: http://www.fda.gov/​downloads/​advisorycommittees/​committeesmeetingmate...
    1. Delawi D, Dhert W J, Rillardon L. et al.A prospective, randomized, controlled, multicenter study of osteogenic protein-1 in instrumented posterolateral fusions: report on safety and feasibility. Spine (Phila Pa 1976) 2010;2010;35(12):1185–1191. - PubMed
    1. Vaccaro A R, Anderson D G, Patel T. et al.Comparison of OP-1 Putty (rhBMP-7) to iliac crest autograft for posterolateral lumbar arthrodesis: a minimum 2-year follow-up pilot study. Spine (Phila Pa 1976) 2005;30(24):2709–2716. - PubMed
Reference Editorial Perspective
    1. Carragee E J, Hurwitz E L, Weiner B K. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 2011;11(6):471–491. - PubMed