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Saturday, March 18, 2000

BMP to have major impact on orthopaedics this decade

Circa the Civil War, amputation was state-of-the-art orthopaedics. Today, it's implant arthroplasty and allograft transplants. But soon, regeneration of bone, cartilage and eventually entire joints will be commonplace tools in the therapeutic armamentarium, according to Thomas A. Einhorn, MD, pro-fessor and chairman of the Department of Orthopaedic Surgery, Boston University School of Medicine.

"In the 17th century, we were thinking about straightening out children as they grew," Dr. Einhorn said March 17, 2000 in an instructional course. "As we go into the 21st century, we have to think about how we are going to straighten things out with molecular models."

It may happen sooner than you think. In fact, by the end of this decade, bone morphogenic protein (BMP) should have already had a major impact on the practice of orthopaedic surgery, according to Dr. Einhorn.

BMP is a family of molecules known to have inductive properties. Dr. Einhorn defined osteoinduction as "a process which supports the mitogenesis of undifferentiated perivascular mesenchymal cells leading to the formation of osteoprogenitor cells with the capacity to form new bone."

Commercially-available demineralized bone matrix is a "first step" toward using osteoinduction in the surgical setting. But these materials may actually instead be osteoconductive, due to the fact that they contain not only BMPs but naturally-occurring extracellular matrix molecules, which are actually attachment sites for cells.

"You may not be so much stimulating undifferentiated mesenchymal cells," Dr. Einhorn explained. "But you may do something that's almost as good, which is to get cells resident in the tissues to attach to these sites, begin to differentiate, and express their own phenotype."

The concept of musculoskeletal regeneration is decades old. But research into this field was kick-started in the late 1980s, following the development of recombinant human BMP. Promising results have been seen in animal studies.

Dr. Einhorn described one such study he and colleagues have conducted involving the injection of a viscous formulation into the fracture site in a rat femoral defect model. The investigators noted a statistically significant increase in stiffness as early as 14 days after fracture and injection. In strength, there was a trend toward improvement at 3 weeks and statistical significance at 4 weeks.

Clinical applications of recombinant human BMP might include enhancing the healing of fresh fractures, enhancing healing of non-unions, and perhaps even spine fusions. Obviously, clinical trials will have to be completed first, but trials to ascertain safety and efficacy in humans are right around the corner.

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2000 Academy News March 18 Index B

Last modified 18/March/2000 by IS