Curative Effect of Combined Treatment With Alendronate and 1α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

We investigated the combined effects of alendronate and 1α-hydroxyvitamin D3 (1α(OH)D3) on the bone mass and strength in aged ovariectomized rats and compared them with those of single treatments. Forty-week-old female rats underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats were daily administered vehicle alone, alendronate (0.2 or 1.0 mg/kg, p.o.), 1α(OH)D3 (0.02 μg/kg, p.o.), or the combinations of 0.2 or 1.0 mg/kg of alendronate and 1α(OH)D3. After 12 weeks, the groups receiving combined treatments had significantly increased bone density and mechanical strength of the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated group, and the effects were almost equal to or slightly less than the addition of those of the respective single treatments. The increase in mechanical strength was proportional to that in bone mineral density, suggesting that the stimulatory effects of these treatments on bone strength are ascribable primarily to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the strong effect of the combined treatment on trabecular bone in particular, which was associated with increased trabecular number and decreased bone turnover. We propose that the combination of daily alendronate and 1α(OH)D3 is clinically promising as a curative treatment of established postmenopausal osteoporosis.