As the INFUSE debate escalates, TSB thought it would be of interest to our bloggers to revisit a 2003 Letter to the The Spine Journal Editor by Edgar Dawson, M.D.. Dr. Dawson contributions to spine surgery was immense. An academician, Dr. Dawson's love of medicine was something to envy. In 2003, Dr. Dawson's letter addressed many of the concerns that have surrounded the recent INFUSE debate.
Dr. Dawson believed that the FDA approval of Bone Morphogenic Proteins was an important milestone in orthopaedic science, yet, he warned that it was time to pause and examine unresolved issues so as not to misuse a clinical treatment modality in "its infancy" despite over three decades of research. Contrary to some peoples opinions, Zdeblick, Burkus and Haid were not the founding founders of BMP , Dr. Mashall Urist, M.D., pioneered studies on bone induction and the identification of bone morphogenic proteins. He revolutionized the field of orthopaedic growth factors. A little history will educate some of our younger bloggers. But back to Dr. Dawson.
In the Letter to the Editor, Dr. Dawson warned that clinical results had not been as conclusive as pre-clinical results. The key to his observations were that carefully designed and well controlled trials yielded much different results than an uncontrolled environment. The preclinical and clinical studies of BMP's may not be as simple as differences in the healing potential of young healthy lab animals compared with human subjects. The key to Dawson's then letter was that "no dosing data was available from an actual clinical study." If ever there was a prophetic observation, Dawson warned that, "different indications will require not only different doses of proteins but potentially different carrier materials to obtain clinical efficacy." The argument can be made by those in the surgical community that it has been proven that the use of BMP-2 in posterolateral fusions has been efficacious, and rightfully so, but the question remains, how many post-op issues have never been reported or addressed? Just eight years ago, prior to his death, Dawson warned that "the use of BMP's are not without potential significant complications." The Marshall Urist's and Edgar Dawson's of the world were not only pioneers, they envisioned the potential side effects of a powerful therapeutic agent. They discussed the importance of containment at the site from their experience with exuberant bone formation in the soft tissues in animal studies.
One of the unknown risks that Dawson discussed was the role of antibodies that develop to BMP's in some patients post-op. Though the occurrence rate was higher for BMP-7, anti-body formation was reported to a lesser degree in patients that receive BMP-2. In 1985 Urist, Hudak, Huo, and Rasmussen published a paper entitled, "Osteoporosis: A Bone Morphogenic Protein Auto-Immune Disorder," citing increased levels of antibodies to BMP's in patients with osteoporosis, speculating that osteoporosis may be a BMP auto-immune disorder. In addition, BMP was contraindicated for pregnant women, and women were advised to use contraception for at least one year after implantation of BMP. Finally, as Dawson writes, BMP's have been isolated and identified in osteosarcomas.
Since the time of Dawson's death, the medical community has learned much more about the effects of dosing and containment, yet the cost effectiveness, the limitations, and potential complications must continue to be explored and documented in a transparent way for the safety of the patient first, and profits second. Sometimes people get those two things mixed up. But as Dawson points out, surgeons should never forget the basic principles of bone healing and biology, or as many of our bloggers know, it comes down to carpentry and craftsmanship and therein may lie the problem. The use of BMP was never intended for convenience, or as another short cut to getting great results. It all comes down to process, which includes meticulous graft site preparation and understanding how to deliver/dose this product. Too many people fail to understand process because all they care about is results. In closing, Dawson's prophecy is still with us whether we like it or not, the question is have we learned anything?