An independent group at Yale University has dealt another blow to a bioengineered protein that was once commonly used in spinal fusion surgery. The Yale University Open Data Access Project found that the human recombinant bone morphogenetic protein-2 (rhBMP-2) “provided little or no benefit compared to bone graft and may be associated with more harms, possibly including cancer.”
The findings, published in the June 18 issue of the Annals of Internal Medicine, confirm a 2011 review of the product by the editors of the Spine Journal, led by Eugene Carragee, MD, professor of orthopedics at Stanford.
What is most troubling, Carragee says, is that the Yale group found that surgeons who received millions of dollars from Medtronic Inc., the maker of the protein, misrepresented its efficacy and underreported complications. Carragee and his colleagues had previously reported in the Spine Journal that the product, marketed as Infuse, carried a range of side-effects, including male sterility, urinary problems, infection, nerve and bone injury and possible cancer risk. Carragee said in a statement released by the journal:
To put the YODA findings in perspective, one must understand the carnival-like promotion that preceded BMP-2’s fall from grace. Market boosters advised that the BMP-2 product went beyond all other medical innovations. Perhaps confusing Infuse with penicillin or the polio vaccine, one zealot proclaimed: ‘Infuse, the single most successful biologic product ever launched in orthopedics and possibly ever in medicine.’
In a triumph of understatement, the YODA group informs us that ten years after its development, ‘it is difficult to identify a clear indication for BMP-2 use in spinal fusion.’ Ten years after penicillin was developed, people were saying it had saved a quarter million lives in World War II. Ten years after the polio vaccine, braces had disappeared from grammar schools. Ten years after BMP-2’s introduction, the YODA group could not identify a single compelling indication for use – but we know it can kill you in the cervical spine and probably can promote cancer, which can then kill you.
In 2012, the U.S. Senate Finance Committee conducted an investigation into the marketing of the product, as well as into physician/industry relationships and the scientific publishing process. It named three surgeons who had particularly lucrative financial ties with Medtronic, ranging from $10 million to $35 million each. These physicians had authored some of the early studies on BMP-2 that framed it in a positive light and helped launch it into general use by orthopedic surgeons.
Carragee says it’s unfortunate that after years of this “self-congratulatory research,” physicians still have a poor understanding of the protein:
At present these ‘concerns’ regarding higher rates of cancer, sterility, wound problems and nerve injury remain poorly described. The suggested reason for this gap in our understanding, if true, is simply appalling: these complications were systemically ‘misrepresented,’ ‘underreported,’ or just “missing’ from the first decade of publications. The research to better understand those complications and risks is still before us.
To its credit, Medtronic financed the $2.5 million YODA project.
Previously: For the record: Carragee on Medtronic spine stories, Stanford-led study on Medtronic bone product dominates the headlines, Stanford orthopedist reveals problems with Medtronic spinal fusion product, and Stanford study links spine product to male infertility