title: Alfacalcidol enhances collagen quality in ovariectomized rat bones.
abstract: The aim of this study was to investigate the effects of alfacalcidol (1α(OH)D3 : ALF) on bone collagen employing an ovariectomized rat model. Thirty-five 16-week-old female Sprague-Dawley rats were divided into five groups: SHAM (sham-operated + vehicle), OVX (ovariectomy + vehicle), and three ALF-treated groups, that is, ovariectomy + 0.022 µg/kg/day ALF, ovariectomy + 0.067 µg/kg/day ALF, and ovariectomy + 0.2 µg/kg/day ALF. After 12 weeks of treatment, tibiae were subjected to histological, biochemical and immunohistochemical analyses. Collagen matrices in OVX bone appeared as immature and poorly organized; however, with the ALF treatment, it was improved in a dose-dependent manner. Contents of collagen and pyridinoline cross-link were decreased in OVX compared with SHAM, but they increased to the level comparable to SHAM in ALF-treated groups. The total aldehyde, that is, a sum of free and those involved cross-links, in the highest dose of ALF was significantly higher than the rest of the groups (p < 0.05). In addition, the expression of lysyl oxidase was increased in the all ALF-treated groups compared with OVX (p < 0.05). In conclusion, ALF increases not only the amount of collagen but also enhances the maturation of collagen in ovariectomy-induced osteoporotic bones, which likely contributes to the improvement of bone quality.
authors.affiliation: NC Oral Health Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagaoka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Terajima
authors.forename: Shizuka
authors.initials: S
authors.lastname: Yamada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Azuma
authors.forename: Takayuki
authors.initials: T
authors.lastname: Chida
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Yamauchi
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000096:biosynthesis*; D005260:Female; D006887:Hydroxycholecalciferols / Q000008:administration & dosage*; D010024:Osteoporosis / Q000188:drug therapy; D010052:Ovariectomy / Q000009:adverse effects; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000378:metabolism
chemical_list: D006887:Hydroxycholecalciferols; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D002118:Calcium; C008088:alfacalcidol
keywords: alfacalcidol; collagen; collagen cross-link; ovariectomized rats; vitamin D