雷奈酸锶:翻开了治疗骨质疏松的新篇章

Strontium ranelate:Novel paradigm in treatment of osteoporosis

雷奈酸锶是一个新型抗骨质疏松制剂,它和以前所用治疗骨质疏松的药物不同,其对骨代谢具有双重作用,即抑制骨吸收和促进骨的形成。尽管其机制尚不清楚,但在组织和细胞培养中,雷奈酸锶可以促进前成骨细胞的增生和分化,促进骨基质的合成。同时雷奈酸锶还可以抑制破骨细胞分化和破骨细胞活性并刺激破骨细胞凋亡。在体内,雷奈酸锶可使正常的大鼠和小鼠骨形成增强和骨吸收降低,并可改善骨的微细结构。在卵巢切除大鼠,雷奈酸锶在保持高水平骨形成的同时抑制骨吸收,增加骨量和骨的强度。在临床实验中,雷奈酸锶不仅可以增加血清碱性磷酸酶(骨的形成指标)的水平,并可降低血清C-交联端肽Ⅰ型胶原(骨的吸收指标)的水平。组织测量学研究显示,雷奈酸锶可以使成骨细胞的表面和骨的矿物质沉积率增加,而骨吸收的参数下降。雷奈酸锶可降低椎骨以及非椎骨新发骨折的危险性。这些前临床和临床实验结果显示雷奈酸锶是安全、有效的抗骨质疏松药物,其刺激骨形成和抑制骨吸收的双重作用使其有可能成为抗骨质疏松的理想药物。

Strontium ranelate is a novel antiosteoporotic agent. Differently with previous antiosteoporotic drugs, it has unique dual effects on bone metabolism, the effects of inhibition on bone resorption and stimulation on bone formation. Although the mechanism of action is still under rigorous research, strontium ranelate stimulates preosteoblast proliferation, differentiation and bone matrix synthesis in rat or mouse culture system. In contrast, it decreases osteoclastie cell differentiation and resorbing activity, and increases osteoelast apoptosis. In vivo, strontium ranelate can increase bone formation,reduce bone resorption and improve bone microstructure in normal mice or rats. In ovariectomized rats, strontium ranelate decreases bone resorption but maintains high bone formation, resulting in increased bone mass and strength. In clinical trial, strontium ranelate can increase the level of serum alkaline phosphatase （bone formation marker） and decrease the level of serum type I collagen C-telopeptide crosslink （bone resorption marker）. In histomorphometrie analysis, the osteoblast surface and mineral apposition rate increased whereas bone resorption parameters decreased in strontium ranelate treated patients. The treatment with strontium ranelate reduces the risk of new fracture in vertebral and non-vertebral. Those preclinical and clinical data indicate that strontium ranelate is safe and effective antiosteoporotic drug. Its dual effects on induction of bone formation and reduction of bone resorption may make strontium ranelate ideal candidate for antiosteoporosis.