The July 6, 2016, edition of The Journal of Bone & Joint Surgery features a large case-cohort study that may help older patients and clinicians decide whether to use bone morphogenetic protein (BMP) as an adjunct to lumbar arthrodesis. Among Medicare patients aged 65 years and older, Beachler et al. found that BMP use was not associated with the following:
- Overall cancer risk
- Increased risk of individual cancer types
- Increased risk of cancer in people who had cancer prior to undergoing lumbar arthrodesis
- Increased mortality after a cancer diagnosis
BMP was used in 30.7% of >3,600 lumbar-arthrodesis patients analyzed, and the lack of association between BMP use and cancer held whether patients received the growth factor as part of an FDA-approved anterior lumbar interbody fusion or as an off-label application.
In an accompanying commentary, Singh et al. laud the authors for designing a study that was not only well-powered but also analyzed risk among those with a medical history of cancer. The commentators emphasize, however, that the median follow-up in this study was 2.4 years, leading them to wonder “whether this time frame is sufficient to evaluate the impact of BMPs on carcinogenesis.”
Until a large, prospective, randomized trial on this subject is conducted, Singh et al. say, “the decision to use BMPs should be made on the basis of sound clinical judgment by the treating physician after a full disclosure of the potential risks to the patient.”
In diligent efforts to improve osseous bridges when performing spinal fusion surgery, orthopaedists have been using harvested allograft bone for more than a century and bone morphogenetic protein (BMP) for nearly a half century. Now, a European multicenter, randomized trial by Delawi et al., in the March 16, 2016 Journal of Bone & Joint Surgery, has compared overall success (defined as a combination of CT-determined fusion rates and clinical results at 12 months) between the two approaches among 113 patients.
This was a non-inferiority trial, and the BMP formulation used (Osigraft BMP-7, known commonly as OP-1 and available in the US in a similar formulation known as OP-1 Putty) was not non-inferior to iliac crest autograft. To clarify the potentially confusing double negative: OP-1 was less successful than autograft, due primarily to lower fusion rates. There were no significant between-group differences in clinical outcomes as measured by scores on the Oswestry Disability Index, although the authors added that “our follow-up period of one year may have been too short to show differences in clinical results.”
Delawi et al. conclude that, based on their findings, “use of OP-1 in place of autologous iliac crest bone graft in instrumented posterolateral lumbar fusions cannot be recommended.” That conclusion is echoed by commentator Jeffrey Coe, MD, who sees these findings as “another bit of evidence against the use of rhBMP-7 as a substitute for [iliac crest bone grafts] in posterolateral spinal fusion.”
It’s a known fact that zebra fish have innate abilities to regenerate lost appendages and organs, but will researchers be able to crack the code that would make the same thing possible for humans? A recent paper published in Cell Reports shows how the two molecular pathways—the Wnt signaling pathway and the bone morphogenetic protein (BMP) pathway– work together in zebra fish to regenerate fins when they are amputated. University of Oregon (UO) researchers believe that understanding these signaling mechanisms in zebra fish could support the design of regenerative therapies that direct human cells to behave similarly.
According to a UO press release, “The researchers found that cell-to-cell signaling mediated by the Wnt pathway helps existing mature bone cells become progenitor cells after fin amputation.” Then the BMP pathway directs the newly formed cells to develop into functional bone cells. Humans have these same pathways, and defects in them are linked to human bone diseases. Lead author Scott Stewart, PhD, said, “As we discover the cellular and molecular roles of the signals in zebra fish and pinpoint the missing network connections in mammals, maybe we could coax human bones to repair themselves equally as well.”