性激素在老年男性骨质疏松发病及治疗中作用的研究进展

Research progress of the role gonadal steroid hormones play in the pathogenesis and treatment of osteoporosis in elderly men

骨质疏松(osteoporosis, OP)与年龄增长密切相关,在老年人群中患病率显著高于中青年人群,严重危害老年人群的健康。性激素在男性骨骼代谢中发挥重要作用,其中,雌激素和雄激素都能够促进骨形成,对抗骨量丢失,而孕激素则可能对男性骨量的维持起到负性调节作用。老年男性体内雌激素、雄激素的缺乏与其骨密度降低、OP患病率增加都有着密切的关系,性激素及其受体调节剂为OP的治疗提供了新的思路。雌激素是目前女性绝经后骨质疏松(postmenopausal osteoporosis, PMOP)治疗的常用药物,并不被推荐用于治疗男性OP;雄激素替代治疗可使老年男性骨密度得到增加,但在前列腺和心血管安全性上存疑,因而并不推荐常规使用;选择性雌激素受体调节剂(selective estrogen receptor modulator, SERM)能提升血清睾酮水平,有助于增加腰椎和髋关节骨密度,降低骨折风险,但尚未被正式批准用于治疗男性OP,其疗效及安全性有待更多的临床试验来验证;选择性雄激素受体调节剂(selective androgen receptor modulator, SARM)应用于OP的相关研究尚处于起步阶段,目前仅在动物模型中被证实能够增加雄性大鼠的骨骼强度。本文就性激素在老年男性OP发病及治疗中的作用进行回顾和总结,以期为临床医师的工作提供一定参考。

Osteoporosis(OP) is closely related to aging, with higher prevalence in the elderly than in the young and middle-aged, which seriously endangers the health of the elderly. Gonadal steroid hormones play an important role in the male bone metabolism. Estrogen and androgen can promote bone formation and reduce bone loss, while progesterone may play a negative role in the maintenance of male bone mass. The deficiency of estrogen and androgen in the elderly men leads to the decrease of bone mineral density and increases their OP incidence rate. Gonadal steroid hormones and their receptor modulators provide new ideas for the treatment of OP. Estrogen is commonly used for the treatment of postmenopausal osteoporosis(PMOP), while not recommended for male OP. Androgen replacement therapy can increase bone mineral density in elderly men. However, there are doubts about prostate and cardiovascular safety, so routine use is not recommended. Selective estrogen receptor modulator(SERM) can increase the serum testosterone level, increase bone mineral density of lumbar spine and hip joint, and reduce the risk of fracture. But it has also not been officially approved for the treatment of male OP, and its efficacy and safety need to be verified by more clinical trials. Researches on the application of selective androgen receptor modulator(SARM) in OP are still at the initial stage. At present, SARM has only been proved to increase the bone strength of male mice in animal models. This paper reviews and summarizes the role of gonadal steroid hormones in the pathogenesis and treatment of OP in elderly men, aiming to provide some references for the clinical work of doctors.