Optimal increase in bone mass by continuous local infusion of alendronate during distraction osteogenesis in rabbits.

Several methods have been used to increase bone mass in distraction osteogenesis. Since bone resorption as well as regeneration is stimulated in the distracted segment, bisphosphonate can be a beneficial agent for distraction osteogenesis. Here, we examined the effects of bisphosphonate injected continuously into the regenerate on bone volume, and architectural and mechanical properties of distraction osteogenesis. The left tibia of Japanese White rabbits (n=66) was subjected to slow distraction using an external fixator. At the beginning of the consolidation phase, alendronate (7 microg/kg/day) was infused directly into the lengthened segment for 14 days using an osmotic pump. Control rabbits were infused with phosphate buffered saline (PBS). The tibiae were monitored weekly by soft X-ray and dual-energy X-ray absorptiometry (DXA). The animals were sacrificed at 4, 6, and 8 weeks after operation to examine bone mineral density (BMD) and cortical bone thickness (CBT) by peripheral quantitative computerized tomography (pQCT), while the mechanical property of the lengthened tibia was measured by three-point bending test. In PBS-infused control animals, bone mineral content around the lengthened segment began to decrease after the first week of consolidation phase, forming a tubular bone structure with thin cortex. Infusion of alendronate increased peak bone mineral content around the lengthened segment. At the end of the experiment, volumetric BMD, CBT and mechanical strength of the lengthened segment of the treatment group were approximately twice those of the control animals. Alendronate infused in this manner significantly prevented the osteopenia that critically began early in the consolidation phase, though the dose used in this study was relatively low and no adverse events were noted.