选择性雄激素受体调节剂在男性骨质疏松中的作用及机制

Role and mechanism of selective androgen receptor modulators in male osteoporosis

老年男性骨质疏松及骨折还没有引起足够的重视。性激素在原发性骨质疏松症及骨折发生发展中起着重要作用。睾酮是维持男性骨骼和肌肉质量的必需激素,雄激素能够促进肌肉骨骼合成代谢并改善骨质疏松,然而临床上男性老年雄激素替代治疗所引起的心血管事件和前列腺癌等风险增加限制了其常规使用。选择性雄激素受体调节剂通过与雄激素受体结合在不同组织细胞内诱导特异性的信号通路以及与5-α还原酶和芳香酶的局部相互作用实现组织选择性,从而减少雄激素替代治疗的常见不良反应。选择性雄激素受体调节剂目前已在多个动物实验中被证实能够促进骨合成、改善骨质疏松,但是相关的临床研究较少。本文对选择性雄激素受体调节剂在骨质疏松中的研究及机制进行讨论。

Osteoporosis and fractures in older men have not received sufficient attention.Sex hormones play an important role in the development of primary osteoporosis and osteoporotic fractures.Testosterone is an essential hormone for the maintenance of bone and muscle mass in men,which can exert musculoskeletal-anabolic actions and ameliorate osteoporosis.However,the increased risk of cardiovascular events and prostate cancer associated with androgen replacement therapy in elderly men limits its use.Selective androgen receptor modulators reduce the side effects of androgen replacement therapy by binding to the androgen receptor and inducing specific signaling pathways in different tissues.Also,selective androgen receptor modulators interactor with 5-alpha reductase to achieve tissue selectivity.Selective androgen receptor modulators have now been shown to promote bone formation and ameliorate osteoporosis in several animal studies,but there are fewer clinical studies.This review will discuss the role and mechanisms of selective androgen receptor modulators in male osteoporosis.