Calcified Tissue International

, Volume 65, Issue 4, pp 311–316

The Advantage of Alfacalcidol Over Vitamin D in the Treatment of Osteoporosis

Authors

  • A.  Shiraishi
    • Product Research Lab, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo 171-8545, Japan
  • S.  Higashi
    • Product Research Lab, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo 171-8545, Japan
  • H.  Ohkawa
    • Product Research Lab, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo 171-8545, Japan
  • N.  Kubodera
    • Product Research Lab, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo 171-8545, Japan
  • T.  Hirasawa
    • Department of Food and Nutrition, Japan Women's University, Tokyo 112-8681, Japan
  • I.  Ezawa
    • Department of Food and Nutrition, Japan Women's University, Tokyo 112-8681, Japan
  • K.  Ikeda
    • Department of Geriatric Research, National Institute for Longevity Sciences, Aichi 474-8522, Japan
  • E.  Ogata
    • Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 170-8455, Japan
Article

DOI: 10.1007/s002239900704

Cite this article as:
Shiraishi, A., Higashi, S., Ohkawa, H. et al. Calcif Tissue Int (1999) 65: 311. doi:10.1007/s002239900704

Abstract.

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 alfacalcidol exerts skeletal effects solely via these Ca-related effects, whether the resultant suppression of PTH is a prerequisite for the skeletal actions of alfacalcidol, and, by inference, whether alfacalcidol 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 μg/kg BW) vis-à-vis vitamin D3 (50–400 μg/kg BW) on bone loss in 8-month-old, ovariectomized (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 infused with hPTH(1–34). The results indicate that (1) in OVX rats, alfacalcidol increases 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; and (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 alfacalcidol and its advantage over vitamin D3 in the treatment of osteoporosis.

Key words: Alfacalcidol — Vitamin D — Osteoporosis — Ovariectomized rats — Parathyroid hormone.
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Copyright information

© Springer-Verlag New York Inc. 1999