Ammann Patrick, Shen Victor, Robin Bruno, Mauras Yves, Bonjour Jean-Philippe, Rizzoli Rene
Service of Bone Diseases, World Health Organization Collaborating Center for Osteoporosis Prevention, Geneva 14 CH-1211, Switzerland.
J Bone Miner Res. 2004 Dec;19(12):2012-20. doi: 10.1359/JBMR.040906. Epub 2004 Sep 13.
Strontium ranelate given to intact rats at doses up to 900 mg/kg/day increases bone resistance, cortical and trabecular bone volume, micro-architecture, bone mass, and total ALP activity, thus indicating a bone-forming activity and an improvement of overall bone tissue quality.
Various anti-osteoporotic agents are available for clinical use; however, there is still a need for drugs able to positively influence the coupling between bone formation and bone resorption to increase bone mass and bone strength. Strontium ranelate (PROTELOS), a new chemical entity containing stable strontium (Sr), was tested for its capacity to influence bone quality and quantity.
The long-term effects of strontium ranelate on bone were investigated in intact female rats treated with various doses of strontium ranelate (0, 225, 450, and 900 mg/kg/day) for 2 years. In a second series of experiments, the effects of 625 mg/kg/day were evaluated in intact male and female rats for the same period of time. Bone mineral mass and mechanical properties were evaluated at various skeletal sites (vertebra and femur), and bone tissue micro-architecture was evaluated by static histomorphometry at the tibio-fibular junction (cortical bone) and at the tibia metaphysis (trabecular bone). Plasma total alkaline phosphatase (ALP) activity and serum levels of insulin-like growth factor-I (IGF-I) were also assessed.
In female rats treated with strontium ranelate over 2 years, dose-dependent increases of bone strength and bone mass of the vertebral body (containing a large proportion of trabecular bone) and of the midshaft femur (containing mainly cortical bone) were detected without change in bone stiffness. Similar effects were observed in males at the level of the vertebra. This increase in mechanical properties was associated with improvements of the micro-architecture as assessed by increases of trabecular and cortical bone volumes and trabecular number and thickness. Finally, plasma total ALP activity and IGF-I were also increased in treated animals, compatible with a bone-forming activity of strontium ranelate.
A long-term treatment with strontium ranelate in intact rats is very safe for bone and improves bone resistance by increasing bone mass and improving architecture while maintaining bone stiffness.
给完整大鼠每日给予高达900毫克/千克的雷奈酸锶，可增加骨抗力、皮质骨和小梁骨体积、微结构、骨量以及总碱性磷酸酶活性，从而表明其具有成骨活性并能改善整体骨组织质量。
有多种抗骨质疏松药物可供临床使用；然而，仍需要能够积极影响骨形成与骨吸收之间耦合以增加骨量和骨强度的药物。雷奈酸锶（普乐可复）是一种含稳定锶（Sr）的新化学实体，对其影响骨质量和骨量的能力进行了测试。
在完整雌性大鼠中研究了雷奈酸锶对骨的长期影响，这些大鼠分别用不同剂量（0、225、450和900毫克/千克/天）的雷奈酸锶处理2年。在第二组实验中，在完整雄性和雌性大鼠中评估了625毫克/千克/天剂量在相同时间段内的效果。在多个骨骼部位（椎骨和股骨）评估骨矿物质质量和力学性能，并通过静态组织形态计量学在胫腓关节（皮质骨）和胫骨干骺端（小梁骨）评估骨组织微结构。还评估了血浆总碱性磷酸酶（ALP）活性和胰岛素样生长因子-I（IGF-I）的血清水平。
在接受雷奈酸锶治疗2年的雌性大鼠中，检测到椎体（含大量小梁骨）和股骨干中段（主要含皮质骨）的骨强度和骨量呈剂量依赖性增加，而骨硬度无变化。在雄性大鼠的椎骨水平也观察到类似效果。力学性能的这种增加与微结构的改善相关，这通过小梁骨和皮质骨体积以及小梁数量和厚度的增加来评估。最后，治疗动物的血浆总ALP活性和IGF-I也增加，这与雷奈酸锶的成骨活性相符。
在完整大鼠中用雷奈酸锶进行长期治疗对骨非常安全，通过增加骨量和改善结构同时保持骨硬度来提高骨抗力。
