Hara Kuniko, Kobayashi Masatoshi, Akiyama Yasuhiro
Pharmacological Evaluation, Applied Drug Research Department, Clinical Research Center, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan.
J Bone Miner Metab. 2007;25(6):345-53. doi: 10.1007/s00774-007-0781-9. Epub 2007 Oct 25.
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.
为研究骨钙素(OC)在骨骼中的作用,将卵巢切除(OVX)后接受华法林(WF)治疗的大鼠的骨参数与完整大鼠的骨参数进行比较。大鼠分为完整组和WF治疗组。给大鼠口服华法林16周,然后进行OVX,WF治疗组的大鼠继续接受WF治疗。OVX后12周,观察骨特性。WF组骨干骨OC水平在术前和术后12周为正常水平的10%-14%。术前比较完整组和WF组,骨量参数或力学性能无显著差异,但术后12周,WF假手术组的骨干骨矿物质含量(BMC)、骨面积和皮质厚度(Cth)显著高于完整假手术组。卵巢切除术显著降低了WF组的骨干BMC、骨矿物质密度(BMD)、Cth和最大负荷,并增加了骨内膜周长。在完整组中,未观察到OVX诱导的此类变化,而OVX增加了干骺端骨面积以及骨内膜和骨膜周长。使用反射制剂通过傅里叶变换红外成像测量的股骨中CO(3)/PO(4)比值,WF假手术组高于完整假手术组,完整OVX组高于完整假手术组,但WF假手术组和WF-OVX组之间未观察到显著差异。据报道,新骨中含有CO(3)(-),其随矿物质成熟而降低。这些数据表明,长期降低骨OC水平可能诱导未成熟骨的形成,这种骨在诸如OVX等骨代谢变化时容易被吸收,并且OC可能是影响骨转换的因素之一。