Ammann Patrick
Division of Bone Diseases, WHO Collaborating Center for Osteoporosis and Bone Disease, Department of Rehabilitation and Geriatrics, University Hospital of Geneva, CH-1211 Geneva 14, Switzerland.
Bone. 2006 Feb;38(2 Suppl 1):15-8. doi: 10.1016/j.bone.2005.09.023.
In vitro studies have suggested that strontium ranelate enhances osteoblastic cell replication leading to an increase in bone-forming activity. Simultaneously, strontium ranelate dose dependently decreases osteoclastic activity. In vivo studies indicate that strontium ranelate decreases bone resorption and maintains a high bone formation and prevents bone loss. This positive uncoupling between bone formation and bone resorption results in bone gain and improvement in bone geometry and microarchitecture in growing animals. In intact female rats, a 2-year period of exposure to strontium ranelate significantly increased bone mechanical properties of vertebrae and midshaft femur. All the determinants of bone strength were positively influenced by the treatment like bone mass, dimension, microarchitecture, and intrinsic bone tissue quality. The increment in bone mechanical properties was characterized by an increase in maximal load but also by a dramatic improvement in energy to failure, which was essentially due to an increment in plastic energy. Such modifications observed with strontium ranelate treatment are in good agreement with the improvement in intrinsic bone quality. These results strongly suggest that new bone formed following strontium ranelate treatment is able to withstand greater deformation before fracture. Furthermore, treatment with strontium ranelate prevents the deleterious effect of ovariectomy on bone strength. In this model, a 1-year period of exposure to strontium ranelate significantly prevents alteration of bone mechanical properties of vertebrae in association with a partial preservation of the trabecular microarchitecture: a dose-dependent effect on the bone volume/trabecular volume ratio and trabecular number and thickness.
体外研究表明，雷奈酸锶可增强成骨细胞的复制，从而增加骨形成活性。同时，雷奈酸锶剂量依赖性地降低破骨细胞活性。体内研究表明，雷奈酸锶可减少骨吸收，维持较高的骨形成，并预防骨质流失。骨形成与骨吸收之间这种积极的解偶联作用可使生长中的动物骨量增加，骨几何形状和微结构得到改善。在完整的雌性大鼠中，为期2年的雷奈酸锶暴露显著提高了椎骨和股骨干中部的骨力学性能。骨强度的所有决定因素都受到该治疗的积极影响，如骨量、尺寸、微结构和骨组织内在质量。骨力学性能的提高表现为最大负荷增加，同时能量至破坏也显著改善，这主要归因于塑性能的增加。雷奈酸锶治疗所观察到的这些变化与骨内在质量的改善高度一致。这些结果有力地表明，雷奈酸锶治疗后形成的新骨在骨折前能够承受更大的变形。此外，雷奈酸锶治疗可预防卵巢切除对骨强度的有害影响。在该模型中，为期1年的雷奈酸锶暴露可显著预防椎骨骨力学性能的改变，并部分保留小梁微结构：对骨体积/小梁体积比、小梁数量和厚度有剂量依赖性影响。
