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 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 17beta-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. 17beta-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 17beta-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.
Shiraishi
A
A
Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Company, Shizuoka, Japan.
Takeda
S
S
Masaki
T
T
Higuchi
Y
Y
Uchiyama
Y
Y
Kubodera
N
N
Sato
K
K
Ikeda
K
K
Nakamura
T
T
Matsumoto
T
T
Ogata
E
E
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000503:physiopathology*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D010024:Osteoporosis / Q000503:physiopathology*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar
D006887:Hydroxycholecalciferols; D004958:Estradiol; C008088:alfacalcidol