Increased Bone Formation and Bone Mass Induced by Sclerostin Antibody Is Not Affected by Pretreatment or Cotreatment with Alendronate in Osteopenic, Ovariectomized Rats
Increased Bone Formation and Bone Mass Induced by Sclerostin Antibody Is Not Affected by Pretreatment or Cotreatment with Alendronate in Osteopenic, Ovariectomized Rats
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DOI：
10.1210/en.2011-0252
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发表时间：
2011-09-01
期刊：
影响因子：
4.8
通讯作者：
Ke, Hua Zhu
中科院分区：
文献类型：
--
作者：
Li, Xiaodong;Ominsky, Michael S.;Ke, Hua Zhu
临床研究表明，在用抗吸收剂阿仑膦酸钠（ALN）预治疗或联合治疗的情况下，甲状旁腺激素治疗对骨质疏松患者的骨合成代谢作用减弱。硬化蛋白单克隆抗体（Scl-Ab）作为一种新的治疗绝经后骨质疏松症的药物正在临床研究中。这些实验的目的是检查ALN预处理或联合处理对Scl-Ab在去卵巢（OVX）大鼠中骨合成代谢作用的影响。在Scl-Ab治疗开始之前，用ALN或赋形剂治疗10个月大的骨质疏松OVX大鼠6周。ALN预处理的OVX大鼠转换为单独的Scl-Ab或ALN和Scl-Ab的组合，再持续6周。将溶剂预处理的OVX大鼠转换为Scl-Ab或继续使用溶剂作为对照。Scl-Ab治疗增加面积骨矿物质密度，体积骨矿物质密度，骨小梁和皮质骨质量，骨强度与ALN或溶剂预处理的OVX大鼠相似。血清骨钙素和骨小梁，皮质内和骨膜表面的骨形成率反应类似于Scl-Ab在ALN或车辆预处理OVX大鼠。此外，与ALN的共同治疗没有显着影响骨形成的增加，骨质量，骨强度诱导Scl-Ab在OVX大鼠ALN预处理。这些结果表明，在骨质减少的OVX大鼠中，用Scl-Ab处理的骨形成、骨量和骨强度的增加不受ALN预处理或共处理的影响。（内分泌学152：3312-3322，2011）
Clinical studies have revealed a blunting of the bone anabolic effects of parathyroid hormone treatment in osteoporotic patients in the setting of pre- or cotreatment with the antiresorptive agent alendronate (ALN). Sclerostin monoclonal antibody (Scl-Ab) is currently under clinical investigation as a new potential anabolic therapy for postmenopausal osteoporosis. The purpose of these experiments was to examine the influence of pretreatment or cotreatment with ALN on the bone anabolic actions of Scl-Ab in ovariectomized (OVX) rats. Ten-month-old osteopenic OVX rats were treated with ALN or vehicle for 6 wk, before the start of Scl-Ab treatment. ALN-pretreated OVX rats were switched to Scl-Ab alone or to a combination of ALN and Scl-Ab for another 6 wk. Vehicle-pretreated OVX rats were switched to Scl-Ab or continued on vehicle to serve as controls. Scl-Ab treatment increased areal bone mineral density, volumetric bone mineral density, trabecular and cortical bone mass, and bone strength similarly in OVX rats pretreated with ALN or vehicle. Serum osteocalcin and bone formation rate on trabecular, endocortical, and periosteal surfaces responded similarly to Scl-Ab in ALN or vehicle-pretreated OVX rats. Furthermore, cotreatment with ALN did not have significant effects on the increased bone formation, bone mass, and bone strength induced by Scl-Ab in the OVX rats that were pretreated with ALN. These results indicate that the increases in bone formation, bone mass, and bone strength with Scl-Ab treatment were not affected by pre- or cotreatment with ALN in OVX rats with established osteopenia. (Endocrinology 152: 3312-3322, 2011)