Session VII - Tibia

*The Effect of Human Recombinant Bone Morphogenic Protein (RHBMP-7) on the Healing of Open Tibial Shaft Fractures: Results of a Multi-Center, Prospective, Randomized Clinical Trial

Michael D. McKee, MD, FRCS(C); Emil H. Schemitsch, MD, FRCS(C); James P. Waddell, MD, FRCS(C); Hans J. Kreder, MD, FRCS(C); David J. G. Stephen, MD, FRCS(C); Ross K. Leighton, MD, FRCS(C); Richard E. Buckley, MD, FRCS(C); James N. Powell, MD, FRCS(C); Lisa M. Wild, BScN; Piotr A. Blachut, MD, FRCS(C); Peter J. O'Brien, MD, FRCS(C); S. Pirani, MD, FRCS(C); Robert G. McCormack, MD; and the Canadian Orthopaedic Trauma Society St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (a-Stryker Biotech, Inc.)

Purpose: Bone morphogenic protein has been shown to enhance bone formation and fracture healing in a number of experimental models. It remains unclear whether this material has a similar degree of efficacy in the human clinical situation. We sought to examine the effect of rhBMP-7 on healing of open tibial shaft fractures in a multicenter prospective, randomized clinical trial.

Methods: The trial was a prospective, randomized study involving seven university-affiliated trauma centers. Patients who had an open tibial shaft fracture amenable to intramedullary (IM) nailing were eligible for inclusion in the study. All patients received initial irrigation, debridement, and statically locked IM nailing. At the time of definitive wound closure (<7 days after injury) patients were randomized to standard wound closure or the addition of rhBMP-7 to the fracture site and standard wound closure. A total of 124 tibiae were included in the study (62 controls and 62 with rhBMP-7). Patients were evaluated clinically, radiographically, and serologically, including both standard and patient-based outcome measures (SF-36, MFAI, WOMAC). Primary endpoint evaluation at 6 months included radiographic evidence of fracture healing and the rate of secondary intervention.

Results: We detected no rhBMP-7-related adverse events clinically. The number of secondary interventions required for delayed and nonunion was lower in the rhBMP-7 group (17 compared with 8, P = 0.02). There was a trend toward improved functional outcome in the rhBMP-7 group (no pain with activity, 80% compared with 56%, P = 0.04; full weight bearing 95% compared with 84%, P = 0.11). The use of the material was clinically straightforward.

Conclusions: The application of rhBMP-7 to open tibial shaft fractures was technically feasible and not associated with any increase in adverse events. The addition of rhBMP-7 decreased the rate of secondary intervention. This material is useful in the treatment of human fractures.

· The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an "off label" use)