THE HEALING OF SEGMENTAL BONE DEFECTS, INDUCED BY RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN (RHBMP-2) - A RADIOGRAPHIC, HISTOLOGICAL, AND BIOMECHANICAL STUDY IN RATS

Subcutaneous implants of a recombinant human form of the bone-inducing protein rhBMP-2 (recombinant human bone morphogenetic protein-2) in rats have resulted in the local induction of endochondral bone formation. To test the osteoinductive activity of rhBMP-2 in an osseous location, we created five-millimeter segmental defects in the femora of forty-five adult male Sprague-Dawley rats. Two doses of lyophilized rhBMP-2 (1.4 or 11.0 micrograms) were implanted in each defect, together with guanidine-hydrochloride extracted demineralized rat-bone matrix as a carrier, and the results were compared with those in rats that had implantation of guanidine-hydrochloride extracted demineralized rat-bone matrix only. The formation and healing of bone were determined by radiographic, histological, and mechanical analysis. Both doses of rhBMP-2 induced formation of endochondral bone in the osseous defects in a dose-related manner. Implantation of 11.0 micrograms of rhBMP-2 yielded significant (p < 0.05) bone formation, resulting in radiographic, histological, and mechanical evidence of union. Despite new-bone formation in the defects that had received 1.4 micrograms of rhBMP-2, no instances of union were observed. CLINICAL RELEVANCE: RhBMP-2 is the first growth factor available in recombinant form to demonstrate osteoinductive activity leading to successful union in an orthotopic site. The results of this study support the potential application of rhBMP-2 as a bone-graft substitute of unlimited availability for clinical situations when local bone formation is needed.