Intramuscular bone induction by the simultaneous administration of recombinant human bone morphogenetic protein 2 and bisphosphonate for autobone graft

An ideal substitute for bone graft is autobone tissue, of which there is an ample supply of the required form and with vascularity. Our strategy is to generate intramuscular autogenous bone by administering recombinant human bone morphogenetic protein 2 (rhBMP-2) with β-tricalcium phosphate (β-TCP) as a carrier, and to transplant this bone as a muscle-pedicled autograft. However, in a previous study (Jingushi et al., J. Orthop. Sci. 7, 490, 2002), bone resorption occurred early after bone induction. This study was conducted to determine whether rhBMP-2-induced bone tissue could be maintained by simultaneous administration of bisphosphonate, and to investigate whether the induced bone could be used for bone grafting. In this study, we first applied rhBMP-2 alone to a β-TCP disk and inoculated it into rat quadriceps muscle. Bone area and the number of tartrate-resistant acid phosphatase (TRAP)-positive cells in the induced bone disk peaked at 2 weeks, and induced bone resorption occurred later. Bisphosphonate and rhBMP-2 were then simultaneously applied to a β-TCP disk and inoculated as in the first experiment. The addition of bisphosphonate decreased the number of TRAP-positive cells and increased the bone area and compression strength at 4 weeks. In the last experiment, a rhBMP-2 applied β-TCP disk treated with or without bisphosphonate was free-grafted to parietal bone 4 weeks after inoculation. Both bone disks united similarly. We concluded that the concurrent use of bisphosphonate prevented bone absorption attributed to osteoclast activity after bone induction by rhBMP-2. The bisphosphonate application did not disturb the union of induced bone to host bone.