Sex steroids and the construction and conservation of the adult skeleton
Sex steroids and the construction and conservation of the adult skeleton
复制标题
DOI：
10.1210/er.23.3.279
复制
发表时间：
2002-06-01
影响因子：
20.3
通讯作者：
Melton, LJ
中科院分区：
文献类型：
--
作者：
Riggs, BL;Khosla, S;Melton, LJ
在这里，我们回顾并扩展了一个新的关于退化性骨质疏松症病理生理学的统一模型，该模型将雌激素（E）确定为维持骨量的关键激素，而 E 缺乏是两性与年龄相关的骨质流失的主要原因。此外，E 和睾酮 (T) 都是骨骼生长和成熟的关键调节因子，E 与 GH 和 IGF-I 一起启动 3 至 4 岁的青春期生长突增，使骨骼质量加倍。虽然两性都需要 E 来达到最大峰值骨量，但 T 对刺激骨膜并置的额外作用导致成年男性骨骼尺寸较大且皮质较厚。老年女性会经历两个阶段的骨质流失，而老年男性只会经历一个阶段。在女性中，更年期会启动一个以松质骨为主的加速期，这种骨质流失会在 4-8 年内迅速下降，直至渐近，随后进入无限期持续的缓慢期。加速期是由于 E 对骨转换的直接抑制作用丧失所致，骨转换是由成骨细胞和成骨细胞中的 E 受体介导的作用。在随后的缓慢阶段，松质骨丢失率降低，但皮质骨丢失率不变或增加。该阶段主要由继发性甲状旁腺功能亢进介导。这是由于 E 对骨骼外钙代谢的作用丧失所致。由此产生的外部钙损失增加了维持骨骼平衡所需的膳食钙摄入量。由于 E 缺乏、衰老或两者兼有而导致的成骨细胞功能受损也会导致骨质流失的缓慢阶段。尽管老年男性的血清生物利用度 (Bio) E 和 Bio T 均下降，但 Bio E 是骨质流失的主要预测因子。因此，两种性类固醇对于形成峰值骨量都很重要，但 E 缺乏是两性与年龄相关的骨质流失的主要决定因素。
Here we review and extend a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) as the key hormone for maintaining bone mass and E deficiency as the major cause of age-related bone loss in both sexes. Also, both E and testosterone (T) are key regulators of skeletal growth and maturation, and E, together with GH and IGF-I, initiate a 3- to 4-yr pubertal growth spurt that doubles skeletal mass. Although E is required for the attainment of maximal peak bone mass in both sexes, the additional action of T on stimulating periosteal apposition accounts for the larger size and thicker cortices of the adult male skeleton. Aging women undergo two phases of bone loss, whereas aging men undergo only one. In women, the menopause initiates an accelerated phase of predominantly cancellous bone loss that declines rapidly over 4-8 yr to become asymptotic with a subsequent slow phase that continues indefinitely. The accelerated phase results from the loss of the direct restraining effects of E on bone turnover, an action mediated by E receptors in both osteoblasts and osteoblasts. In the ensuing slow phase, the rate of cancellous bone loss is reduced, but the rate of cortical bone loss is unchanged or increased. This phase is mediated largely by secondary hyperparathyroidism. that results from the loss of E actions on extraskeletal calcium metabolism. The resultant external calcium losses increase the level of dietary calcium intake that is required to maintain bone balance. Impaired osteoblast function due to E deficiency, aging, or both also contributes to the slow phase of bone loss. Although both serum bioavailable (Bio) E and Bio T decline in aging men, Bio E is the major predictor of their bone loss. Thus, both sex steroids are important for developing peak bone mass, but E deficiency is the major determinant of age-related bone loss in both sexes.