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Alfacalcidol Inhibits Bone Resorption and Stimulates Formation in an Ovariectomized Rat Model of Osteoporosis: Distinct Actions from Estrogen
Author(s) -
Shiraishi Ayako,
Takeda Satoshi,
Masaki Toshimi,
Higuchi Yoshinobu,
Uchiyama Yasushi,
Kubodera Noboru,
Sato Katsuhiko,
Ikeda Kyoji,
Nakamura Toshitaka,
Matsumoto Toshio,
Ogata Etsuro
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.4.770
Subject(s) - alfacalcidol , endocrinology , bone resorption , medicine , osteoporosis , ovariectomized rat , bone remodeling , resorption , cortical bone , bone mineral , estrogen , chemistry , anatomy
Abstract Although alfacalcidol has been widely used for the treatment of osteoporosis 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 17β‐estradiol, a representative antiresorptive drug, it is evident that alfacalcidol causes a dose‐dependent suppression of bone resorption, and yet maintains or even stimulates bone formation, as reflected in increases in serum osteocalcin levels and bone formation rate at both trabecular and cortical sites. 17β‐Estradiol, which suppresses bone resorption to the same extent as alfacalcidol, causes a parallel reduction in the biochemical and histomorphometric markers of bone formation. As a final outcome, treatment with alfacalcidol increases bone mineral density and improves mechanical strength more effectively than 17β‐estradiol, with a more pronounced difference in cortical bone. We conclude that estrogens depress bone turnover primarily by suppressing bone resorption and, as a consequence, bone formation as well, whereas alfacalcidol “supercouples” these processes, in that it suppresses bone resorption while maintaining or stimulating bone formation.