Intramarrow Bone Morphogenetic Protein 4 Gene Delivery Improves Local Bone Quality in Femurs of Ovariectomized Rabbits

Background: Poor bone quality at implant recipient site is a major risk factor for implant failure. The purpose of this study is to examine the potential of intramarrow bone morphogenetic protein 4 (BMP4) gene delivery for local bone quality improvement. Methods: Adenoviral vector encoding human BMP4 (Ad-BMP4) was constructed. Adenovirus encoding p-galactosidase (Ad-LacZ) was used as a control virus. Ad-BMP4 and Ad-LacZ were injected into femurs of ovariectomized rabbits. The temporal changes in bone mineral density at injected areas were determined by repeated measurements by dual-energy x-ray absorptiometry at 0, 1, 2, 4, and 8 weeks after injection. The effects of gene delivery on cortical bone and cancellous bone were evaluated by microcomputed tomography analysis and histologic examination at 8 weeks. Results: The bone mineral density of the BMP4 group was significantly higher than the LacZ group at 4 and 8 weeks by 61% and 35%, respectively. Results from microcomputed tomography analysis and histologic examination at 8 weeks indicated thicker cortical bone and denser cancellous bone in the BMP4 group compared to the LacZ group. Conclusions: Intramarrow gene delivery of BMP4 effectively improved local bone quality for at least 8 weeks. The sustained delivery of osteogenic factors via local gene therapy approach may reduce implant failures associated with poor local bone quality. J Periodontol 2011;82:854-862.