Marie P J
INSERM U349 affiliated CNRS, Lariboisière Hospital, 2 rue Ambroise Pare, 75475, Paris cedex 10, France.
Osteoporos Int. 2003;14 Suppl 3:S9-12. doi: 10.1007/s00198-002-1344-5. Epub 2003 Mar 18.
Strontium ranelate (SR) is currently being developed for the treatment of osteoporosis. Pharmacologic studies in animal models have shown that its efficacy on bone mass is based on its original mode of action on bone formation and bone resorption. In normal mice, SR increased bone formation and vertebral bone mass. In normal rats, SR increased bone mass and the mechanical properties of vertebral, humeral and femoral bones, associated with increased femoral shaft diameter. Vertebral bone mineral density and bone strength were also increased by SR, whereas stiffness was not altered, underlining that the improvement in bone strength occurs without inducing defective bone mineralization. In normal adult monkey alveolar bone, SR decreased bone resorption and increased bone. In ovariectomized (OVX) rats, SR limited the reduction in bone mineral content and the decrease in trabecular bone volume induced by estrogen deficiency, by inhibiting bone resorption while maintaining bone formation. Curative treatment with SR also partially restored bone mass in OVX rats. In the model of hind limb immobilization in rats, SR reduced bone resorption and partially limited long bone loss, as assessed by bone mineral content, bone volume, and histomorphometric and biochemical indices of bone resorption. The unique mode of action of SR on bone formation and resorption is also supported by in vitro studies. In calvaria culture systems and osteoblastic cell cultures, SR enhanced the replication of preosteoblastic cells and consequently increased collagen synthesis. Moreover, SR inhibited the bone-resorbing activity of isolated mouse osteoclasts and devreased osteoclast differentiation markers in chicken bone marrow cultures. Altogether, these pharmacologic results suggest that SR optimizes bone metabolism by decreasing bone resorption and promoting bone formation, which may be of potential value in the treatment of osteoporosis.
雷奈酸锶（SR）目前正被开发用于治疗骨质疏松症。在动物模型中的药理学研究表明，其对骨量的疗效基于其对骨形成和骨吸收的原始作用模式。在正常小鼠中，SR增加骨形成和椎骨骨量。在正常大鼠中，SR增加骨量以及椎骨、肱骨和股骨的力学性能，同时股骨干直径增加。SR还增加了椎骨骨矿物质密度和骨强度，而硬度未改变，这表明骨强度的改善是在不诱导骨矿化缺陷的情况下发生的。在正常成年猴牙槽骨中，SR减少骨吸收并增加骨量。在去卵巢（OVX）大鼠中，SR通过抑制骨吸收同时维持骨形成，限制了雌激素缺乏引起的骨矿物质含量减少和小梁骨体积减小。用SR进行的治疗性处理也部分恢复了OVX大鼠的骨量。在大鼠后肢固定模型中，通过骨矿物质含量、骨体积以及骨吸收的组织形态计量学和生化指标评估，SR减少骨吸收并部分限制长骨丢失。SR对骨形成和吸收的独特作用模式也得到了体外研究的支持。在颅骨培养系统和成骨细胞培养中，SR增强了前成骨细胞的复制，从而增加了胶原蛋白的合成。此外，SR抑制了分离的小鼠破骨细胞的骨吸收活性，并降低了鸡骨髓培养中破骨细胞分化标志物的水平。总之，这些药理学结果表明，SR通过减少骨吸收和促进骨形成来优化骨代谢，这在骨质疏松症的治疗中可能具有潜在价值。
