The advantage of alfacalcidol over vitamin D in the treatment of osteoporosis

Although alfacalcidol is widely used in the treatment of osteoporosis, its mechanism of action in bone is not fully understood. Alfacalcidol stimulate s intestinal calcium (Ca) absorption, increases urinary Ca excretion and se rum Ca levels, and suppresses parathyroid hormone (PTH) secretion. It remai ns to be clarified, especially under vitamin D-replete conditions, whether alfacalcidol exerts skeletal effects solely via these Ca-related effects, w hether the resultant suppression of PTH is a prerequisite for the skeletal actions of alfacalcidol, and, by inference, whether alfacalcidol has an adv antage over vitamin D in the treatment of osteoporosis. To address these is sues, we (1) compared the effects of alfacalcidol p.o. (0.025-0.1 mu g/kg B W) vis-a-vis vitamin D-3 (50-400 mu g/kg BW) on bone loss in 8-month-old, o variectomized (OVX) rats as a function of their Ca-related effects, and (2) examined whether the skeletal effects of alfacalcidol occur independently of suppression of PTH, using parathyroidectomized (PTX) rats continuously i nfused with hPTH(1-34). The results indicate that (1) in OVX rats, alfacalc idol increases BMD and bone strength more effectively than vitamin D-3 at g iven urinary and serum Ca levels: larger doses of vitamin D-3 are required to produce a similar BMD-increasing effect, in the face of hypercalcemia an d compromised bone quality; (2) at doses that maintain serum Ca below 10 mg /dl, alfacalcidol suppresses urinary deoxypyridinoline excretion more effec tively than vitamin D-3; and (3) alfacalcidol is capable of increasing bone mass in PTX rats with continuous infusion of PTH, and therefore acts indep endently of PTH levels. It is suggested that alfacalcidol exerts bone-prote ctive effects independently of its Ca-related effects, and is in this respe ct superior to vitamin D-3, and that the skeletal actions of alfacalcidol t ake place, at least in part, independently of suppression of PTH. Together, these results provide a rationale for the clinical utility of alfacalcidol and its advantage over vitamin D-3 in the treatment of osteoporosis.