Effect of ED-71 on modeling of bone in distraction osteogenesis

We investigated the effect of 2-beta-(3-hydroxypropoxy)-1alpha,25-dihydroxyvitamin D3 (ED-71) on the modeling of bone in distraction osteogenesis. The tibiae of 30 rabbits were lengthened by 10 mm in 10 days. Following osteotomy, ED-71 (0.05 microg/kg) was administered subcutaneously twice a week to the ED-71 group until necropsy. The bone mineral content (BMC) of the lengthened callus was measured by dual-energy X-ray absorptiometry (DXA). Five rabbits per group were killed at 1, 3, and 8 weeks after completion of lengthening, and the lengthened callus was examined histologically and histomorphometrically. Bone volume of the lengthened callus was measured by peripheral quantitative computed tomography (pQCT) at 8 weeks after the completion of lengthening. At all timepoints the BMC in the ED-71 group was significantly higher than that in the untreated group. The mineral apposition rate and bone formation rate were higher in the ED-71 group than in the untreated group at 1 and 3 weeks after the completion of lengthening on the coronal section. In cross sections, the cortical area and width in the ED-71 group showed significantly higher values than in the untreated group at 8 weeks after the completion of lengthening. Both the endosteal osteoid surface and endosteal eroded surface showed no differences between groups. However, the endosteal mineral apposition rate and endosteal bone formation rate were significantly higher in the ED-71 group. At 8 weeks after completion of lengthening, the intracortical area and intracortical BMC were significantly greater in the ED-71 group than in the untreated group, but no significant difference was noted in intracortical BMD. These findings indicate that ED-71 increases callus volume during the early period after the completion of lengthening, resulting in thick cortical bone formation.