Bone consolidation is enhanced by rhBMP-2 in a rabbit model of distraction osteogenesis

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a differentiation factor which has been shown to induce bone formation and heal bony defects in a variety of animal models. A possible application of rhBMP-2 is to accelerate bone regeneration during distraction osteogenesis, which clinically is a long procedure, often involving significant complications. In this study we tested the ability of rhBMP-2 to accelerate the consolidation phase of distraction osteogenesis in a rabbit model of leg lengthening. Tibiae were lengthened 2 cm over a period of ten days, rhBMP-2 was administered at the end of the lengthening phase. Two modes of rhBMP-2 application were tested: surgical implantation of rhBMP-2/ACS (absorbable collagen sponge) into the regenerate (50 mul of 1.5 mg/ml rhBMP-2, total dose = 75 mug rhBMP-2), and percutaneous injection of rhBMP-2/buffer (0.1 ml of 0.75 mg/ml rhBMP-2, total dose = 75 mug rhBMP-2) into three sites within the regenerate. Also, there were three groups of control animals: (1) no surgical intervention, (2) surgical implantation of buffer/ACS and (3) percutaneous injection of buffer. Rabbits were sacrificed at 5, 14 and 28 days after the interventions. Radiographic evaluation indicated a significant increase in bony union of the distraction regenerate in the rhBMP-2 treated groups compared with the untreated groups at 5 and 14 days. At 28 days, formation of a cortex and reestablishment of the medullary canal was evident only in the rhBMP-2 treated groups. The bone mineral content (BMC) of the regenerate was significantly higher in the rhBMP-2 treated groups at 4 and 14 days. However, at 28 days, BMC of the regenerate was similar in all groups. The average volumetric density of the regenerate was significantly higher in the rhBMP-2 injection group at day 14. In summary, both injection of rhBMP-2/buffer and implantation of rhBMP-2/ACS enhanced the consolidation stage of distraction osteogenesis in this rabbit model. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.