THE EFFECTS OF RISEDRONATE ON CANINE CANCELLOUS BONE REMODELING - 3-DIMENSIONAL KINETIC RECONSTRUCTION OF THE REMODELING SITE

To investigate the dose-dependent effects of risedronate on cancellous bone remodeling, adult female beagle dogs were treated with either pl acebo, 0.1, 0.5, or 2.5 mg/kg/day of risedronate orally in an intermit tent cyclic regimen (7 days on 21 days off), repeated three times. Ili ac cancellous bone samples were subjected to histomorphometric analysi s and three-dimensional (3-D) kinetic reconstruction of the remodeling site was performed. In the 0.1 mg/kg dose group, resorption and activ ation indices were no different from the placebo group. However, wall thickness was increased resulting in a positive bone balance at the le vel of the remodeling unit. In the 0.5 and 2.5 mg/kg dose groups, a do se-dependent reduction in activation frequency and tissue level bone f ormation was observed. Resorption rates were also significantly decrea sed, 60% and 80% for the 0.5- and 2.5-mg/kg groups, respectively. An a pproximate 25% reduction in final erosion depth was noted in both thes e groups. Analyses of the growth curves of the bone packet confirmed t hat the kinetics of the growth of a completed packet were different in the 0.5- and 2.5-mg/kg dose groups compared with placebo. These chang es were associated with a significant increase in the final wall thick ness in both groups indicating no net impairment of osteoblast functio n. These increases in wall thickness in combination with the reduction s in final erosion depth in the 0.5 and 2.5 mg/kg groups resulted in a significant dose-dependent positive bone balance. This pharmacologica l profile suggests that risedronate may be of therapeutic utility in t he treatment of metabolic bone diseases where reductions in activation frequency and resorptive cell activity at the level of the remodeling unit are a therapeutic goal.