THE EFFECT OF OSTEOGENIN (A BONE MORPHOGENETIC PROTEIN) ON THE FORMATION OF BONE IN ORTHOTOPIC SEGMENTAL DEFECTS IN RATS

We studied the effects of partially purified, natural osteogenin, a bone morphogenetic protein, on the formation of bone in rats. An osteoperiosteal segmental defect, eight millimeters wide, in the middle of the femoral diaphysis was created bilaterally in thirty-six adult male Fischer rats and stabilized with a polyacetyl plate and threaded Kirschner wires. One defect was filled with a cylinder of 60 per cent hydroxyapatite and 40 per cent tricalcium phosphate ceramic (pore diameter, 250 to 400 micrometers) containing 100 micrograms of partially purified bovine osteogenin, and the contralateral defect was filled with a hydroxyapatite-tricalcium ceramic cylinder without osteogenin. Eighteen animals (six animals each at one, two, and four months after the operation) were studied histologically and histomorphometrically. The implants from eighteen additional animals (six animals each at one, two, and four months after the operation) were subjected to biomechanical testing. Histomorphometry revealed that the total area of bone, the area of bone outside of the implant, and the amount of bone within the pores of the implant were all significantly (p less than or equal to 0.05) greater in the femora that had an implant with osteogenin than in those that had an implant without osteogenin at most time-periods. The presence of osteogenin had no significant effect on the biomechanical parameters measured in this study. CLINICAL RELEVANCE: Bone loss due to trauma, excision of a tumor, or loosening and subsidence of a joint prosthesis is a major clinical problem. Although bone has a remarkable potential for regeneration, predictable augmentation of the natural repair process would be useful in certain orthopaedic situations. Particularly attractive would be the augmentation of bone repair without the need for a cancellous autogenous bone graft, which necessitates a second operative procedure. In this study, an osteogenin-containing ceramic cylinder significantly (p less than or equal to 0.005) enhanced the formation of bone in and around a large segmental defect. This enhanced repair occurred without the addition of cancellous autogenous bone graft or marrow cells and suggests that osteogenin may be useful in the repair of skeletal defects and that this ceramic configuration may be a useful carrier of osteogenin.