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

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.

Cancer Risk from Bone Morphogenetic Protein Exposure in Spinal Arthrodesis

“…A recent systematic review of BMP and cancer suggests a possible dose-dependent relationship 10 . In clinical use, it is uncertain how much rhBMP-2 was given, as multiple kits may have been used.…”

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“…Enhancement in osteogenic differentiation and osteoinductivity of bioactive glass have also been achieved by incorporation of BMP-2. 37 It is still not clear the safety of BMP clinical application due to possible risk of cancer induce that reported by Poynton et al 38 Some researchers suggest dose depends of BMP to cancer risk 39 but optimal amount of this protein is not clear. Dynamic mechanical loading is other strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone mesenchymal stem cells and increasing the bone-forming activity of osteoblasts.…”

Bone Morphogenetic Proteins

“…Two products consisting of recombinant BMP-2 and BMP-7 loaded into absorbable collagen sponges are available; however, off-label applications increased complications, including the risk of tumors, have been reported in the literature (Carragee, Hurwitz, & Weiner, 2011;Devine, Dettori, France, Brodt, & McGuire, 2012;Einhorn & Gerstenfeld, 2015). This problem is probably due to an inadequate BMP dosage in the lesion site.…”