THE ADVANTAGE OF ALFACALCIDOL OVER VITAMIN D IN THE TREATMENT OF OSTEOPOROSIS

Shiraishi A., Higashi S., Ohkawa H., Kubodera N., Hirasawa T., Ezawa I., Ikeda K., Ogata E.

Summary. Although alfacalcidol is widely used in the treatment of osteoporosis, its mechanism of action in bone is not fully understood. Alfacalcidol stimulates intestinal calcium (Ca) absorption, increases urinary Ca excretion and serum Ca levels, and suppresses parathyroid hormone (PTH) secretion. It remains to be clarified, especially under vitamin D-replete conditions, whether alfacal-cidol exerts skeletal effects solely via these Ca-re-lated effects, whether the resultant suppression of PTH is a prerequisite for the skeletal actions of alfacalcidol, and, by inference, whether alfa-calcidol has an advantage over vitamin D in the treatment of osteoporosis. To address these issues, we: 1) compared the effects of alfacalcidol p.o. (0.025- 0.1 ig/kg body weight) vis-a-vis vitamin D₃ (50-400 ug/kg body weight) on bone loss in B-month-old, ovariectomized (OVX) rats as a function of their Ca-related effects; 2) examined whether the skeletal effects of alfacalcidol occur independently of suppression of PTH, using parathyroidectomized (PTX) rats continuously infused with hPTH (1-З4). The results indicate that: 1) in OVX rats, alfacalcidol increases bone mineral Density (BMD) and bone strength more effectively than vitamin D₃ at given urinary and serum Ca levels: larger Doses of vitamin D₃ are required to produce a similar BMD-increasing effect, in the face of hypercalcemia and compromised bone quality; 2) at Doses that maintain serum Ca below 10 mg/dl, alfacalcidol suppresses urinary Deoxypyridinoline excretion more effectively than vitamin D₃; 3) alfacalcidol is capable of increasing bone mass in PTX rats with continuous infusion of PTH, and therefore acts independently of PTH levels. It is suggested that alfacalcidol exerts bone-protective effects independently of its Ca-related effects, and is in this respect superior to vitamin D₃, and that the skeletal actions of alfacalcidol take place, at least in part, independently of suppression of PTH. Together, these results provide a rationale for the clinical utility of al-facalcidol and its advantage over vitamin D₃ in the treatment of osteoporosis.