Influence of bone osteocalcin levels on bone loss induced by ovariectomy in rats.
To investigate the role of osteocalcin (OC) in bones, bone parameters in warfarin (WF)-treated rats after ovariectomy (OVX) were compared with those in intact rats. Rats were divided into an intact group and WF-treated group. Warfarin was orally given to rats for 16 weeks, and then OVX was performed and rats in the WF-treated groups continued receiving WF. Twelve weeks after OVX, bone properties were observed. The diaphysial bone OC level in the WF group was 10%-14% of the normal level at the preoperative point and 12 weeks after surgery. On comparison of the intact and WF groups before surgery, no significant differences were noted in bone mass parameters or mechanical properties, but 12 weeks after surgery, the diaphysial bone mineral content (BMC), bone area, and cortical thickness (Cth) were significantly higher in the WF-sham group than in the intact-sham group. Ovariectomy significantly decreased the diaphysial BMC, bone mineral density (BMD), Cth, and maximum load, and increased the endosteal perimeter in the WF group. In the intact group, no such OVX-induced changes were noted, and the metaphysial bone area and the endosteal and periosteal perimeters were increased by OVX. The CO(3)/PO(4) ratio in the femur measured by Fourier-transform infrared imaging using reflection preparations was higher in the WF-sham group than the intact-sham group, and higher in the intact-OVX group than the intact-sham group, but no significant difference was noted between the WF-sham and WF-OVX groups. It has been reported that CO(3)(-) is contained in new bone and decreases with mineral maturation. These data suggest that long-term reduction in bone OC levels may induce the formation of immature bone, which is easily resorbed with changes in bone metabolism such as OVX, and that OC may be one of the factors affecting bone turnover.
Hara
Kuniko
K
Pharmacological Evaluation, Applied Drug Research Department, Clinical Research Center, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan. k-hara@hhc.eisai.co.jp
Kobayashi
Masatoshi
M
Akiyama
Yasuhiro
Y
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D002254:Carbonates / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D018483:Diaphyses / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism*; D016011:Normal Distribution; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism*; D010052:Ovariectomy; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017550:Spectroscopy, Fourier Transform Infrared; D014057:Tomography, X-Ray Computed; D014859:Warfarin / Q000494:pharmacology
D002254:Carbonates; D010710:Phosphates; D015675:Osteocalcin; D014859:Warfarin; D003094:Collagen