CO-ADMINISTRATION OF SYSTEMIC ZOLEDRONATE PROMOTES OSTEOGENESIS INDUCED BY A LOCAL CO-DELIVERY OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 AND β-TRICALCIUM PHOSPHATE IN THE BONE MARROW OF THE RABBIT FEMUR

Purpose: Bone morphogenetic proteins (BMPs) strongly induce osteogenesis. However, BMPs also directly or indirectly stimulate catabolic osteoclast activity, leading to strong bone resorption, especially in the bone marrow. The aim of this study was to investigate whether the combination of a local recombinant human BMP-2 (rh-BMP-2)/beta-tricalcium phosphate (β-TCP) composite with systemically administrated bisphosphonate, zoledronate (ZOL) could promote osteogenesis in a rabbit model. Methods: β-TCP columns, with or without rh-BMP-2 (30 μg/column), were implanted into the left femur canal of 20 rabbits. The animals were injected with 0.4mg of ZOL or saline 1 week after implantation. The implants were evaluated by micro-computed tomography (μ-CT) and histology 6 weeks after implantation. Results: μ-CT data revealed that the bone volume/tissue volume ratio of bone nodules inside β-TCP columns in combination with rh-BMP-2 and ZOL was significantly higher than that of β-TCP columns treated with rh-BMP-2, ZOL, or neither. Histological evaluation also revealed that significantly more new bone formed inside β-TCP columns treated with rh-BMP-2 and ZOL than inside β-TCP columns treated with rh-BMP-2, ZOL, or neither. Conclusion: This combination therapy contributed to the maintenance of the newly formed BMP-2-induced bone structure in the bone marrow.

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