title: Comparison of incadronate and alfacalcidol on increased bone turnover caused by ovariectomy in rats.
abstract: Mineral density of trabecular bone at the metaphyses of right tibiae was measured by peripheral quantitative computed tomography (pQCT) in ovariectomized rats. Bone mineral density (BMD) decreased dramatically in the 4 weeks following ovariectomy, suggesting that the method is sensitive enough to detect decreased bone mineral density within a short period. Orally administered incadronate dose dependently inhibited the decrease in trabecular bone mineral density induced by ovariectomy, as assessed 4 weeks after surgery. Significant inhibition was observed at doses of more than 0.3 mg/kg/day. Moreover, incadronate at doses of 1 mg/kg or more inhibited the increase in urinary deoxypyridinoline levels induced by ovariectomy, and although slightly increased serum intact parathyroid hormone (PTH) levels were observed, no significant alteration in serum calcium ion levels or urinary calcium excretion occurred. In contrast, while alfacalcidol inhibited the decrease in bone mineral density and the increase in urinary deoxypyridinoline levels at a dose of 300 ng/kg, it significantly lowered serum intact PTH levels and elevated serum free calcium levels as well as urinary calcium excretion. These results suggest that incadronate exerts its pharmacological effect (inhibition of bone resorption and increase in bone mass) by a mechanism different from that of alfacacidol.
authors.affiliation: Clinical Pharmacology Research Laboratories, Pharmacology Department, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 1-8, Azusawa 1-chome, Itabashi, Tokyo 174-8511, Japan. teramurk@yamanouchi.co.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Teramura
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nozaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokubo
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002118:Calcium / Q000097:blood / Q000652:urine; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D004164:Diphosphonates; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; C071542:cimadronate; D002118:Calcium; C008088:alfacalcidol