Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: Distinct actions from estrogen

Although alfacalcidol has been widely used for the treatment of osteoporosi s in certain countries, its mechanism of action in bone, especially in the vitamin D-replete state, remains unclear. Here we provide histomorphometric as well as biochemical evidence that alfacalcidol suppresses osteoclastic bone resorption In an ovariectomized rat model of osteoporosis. Furthermore , when compared with 17 beta-estradiol, a representative antiresorptive dru g, it is evident that alfacalcidol causes a dose-dependent suppression of b one resorption, and yet maintains or even stimulates bone formation, as ref lected in increases in serum osteocalcin levels and bone formation rate at both trabecular and cortical sites. 17 beta-Estradiol, which suppresses bon e resorption to the same extent as alfacalcidol, causes a parallel reductio n in the biochemical and histomorphometric markers of bone formation. As a final outcome, treatment with alfacalcidol increases bone mineral density a nd improves mechanical strength more effectively than 17 beta-estradiol, wi th a more pronounced difference in cortical bone. We conclude that estrogen s depress bone turnover primarily by suppressing bone resorption and, as a consequence, bone formation as well, whereas alfacalcidol "'supercouples" t hese processes, in that it suppresses bone resorption while maintaining or stimulating bone formation.