Department of Medicine (RMH/WH), The University of Melbourne, Western Hospital, Footscray, Victoria, Australia.
Curr Opin Endocrinol Diabetes Obes. 2010 Jun;17(3):284-92. doi: 10.1097/MED.0b013e328339658c.
The review is timely given recent advances regarding mechanisms of androgen action on bone cells and in humans. Osteoporosis in men is an important public health problem. An improved understanding of the role of androgens in the pathophysiology of bone loss will lead to new treatments.
Androgen receptors are present in most bone cells. Testosterone acts on bone both directly via the androgen receptor and indirectly, following aromatization, via the oestrogen receptor. During skeletal modelling, ERalpha is critical for longitudinal bone growth. For periosteal growth and bone expansion, androgen receptor activation has a positive effect, whereas ERalpha activation is inhibitory. During skeletal remodelling, both receptor pathways generate similar and additive effects on bone.Androgen deficiency is a common secondary cause of osteoporosis in men and should be treated with testosterone, particularly in symptomatic men. However, lack of efficacy data for testosterone in osteoporosis means it is less useful as a first-line treatment in men with age-related declines in testosterone and osteoporosis, when other agents such as bisphosphonates and parathyroid hormone are effective.
Randomized, placebo-controlled trials of testosterone therapy in men with age-related declines in testosterone and osteoporosis are needed, and should carefully evaluate potential risks, as well as its efficacy in reducing fractures and other health benefits.
鉴于雄激素作用于骨细胞和人体的机制方面的最新进展,本综述非常及时。男性骨质疏松症是一个重要的公共卫生问题。对雄激素在骨丢失病理生理学中的作用有了更好的理解,将导致新的治疗方法。
雄激素受体存在于大多数骨细胞中。睾酮对骨骼有直接作用,通过雄激素受体,也有间接作用,通过芳香化作用,通过雌激素受体。在骨骼形成过程中,ERalpha 对纵向骨生长至关重要。对于骨膜生长和骨扩张,雄激素受体的激活有积极的影响,而 ERalpha 的激活则具有抑制作用。在骨骼重塑过程中,两种受体途径对骨骼产生相似且相加的效应。雄激素缺乏是男性骨质疏松症的常见继发性原因,应使用睾酮治疗,特别是在有症状的男性中。然而,由于缺乏睾酮治疗骨质疏松症的疗效数据,当其他药物如双膦酸盐和甲状旁腺激素有效时,睾酮在年龄相关性睾酮下降和骨质疏松症的男性中作为一线治疗的用途就较小。
需要在年龄相关性睾酮下降和骨质疏松症的男性中进行睾酮治疗的随机、安慰剂对照试验,并应仔细评估潜在风险及其在减少骨折和其他健康益处方面的疗效。