Molecular mechanisms of glucocorticoid-induced osteoporosis
Molecular mechanisms of glucocorticoid-induced osteoporosis
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DOI：
10.1016/s8756-3282(01)00610-x
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发表时间：
2001-12-01
期刊：
影响因子：
4.1
通讯作者：
Buttgereit, F
中科院分区：
文献类型：
--
作者：
Patschan, D;Loddenkemper, K;Buttgereit, F
长期使用糖皮质激素治疗导致的骨丢失是一种常见且临床相关的疾病。许多不同的糖皮质激素介导的效应导致骨密度降低：(I)糖皮质激素诱导的成骨细胞、骨细胞和破骨细胞功能的直接损害导致骨重建减少和骨微损伤修复减少；(Ii)甲状旁腺激素(PTH)的作用可能在糖皮质激素存在时更明显，而维生素D在类固醇诱导的骨质疏松症的发病机制中作用较小；(Iii)糖皮质激素拮抗性腺功能和抑制性类固醇的骨代谢作用，以及(Iv)钙的清除增加和肠道钙吸收减少导致肾脏钙负平衡，这被认为是促进继发性甲状旁腺功能亢进的原因。从机械论的观点来看，所有上述效应长期以来都被认为是在分子水平上完全由基因组作用介导的。然而，现在有越来越多的证据表明，存在与这种经典作用模式不相容的快速糖皮质激素效应。这些快速效应被称为非基因组效应，通过糖皮质激素与生物膜的相互作用，或者通过与膜受体的结合，或者通过物理化学相互作用来介导。这些效应在糖皮质激素性骨质疏松症的发病机制中发挥作用是可能的，但已被证明。(C)2001年，爱思唯尔科学公司。保留所有权利。
Bone loss resulting from long-term glucocorticoid therapy is common and clinically relevant. A number of different glucocorticoid-mediated effects are responsible for the reduction in bone density: (i) glucocorticoid-induced direct impairment of osteoblast, osteocyte, and osteoclast function leads to reduced bone remodeling and diminished repair of microdamage in bone; (ii) the effects of parathyroid hormone (PTH) might be more pronounced in the presence of glucocorticoids, whereas vitamin D plays a lesser role in the pathogenesis of steroid-induced osteoporosis; (iii) glucocorticoids antagonize gonadal function and inhibit the osteoanabolic action of sex steroids, and (iv) increased renal elimination and reduced intestinal absorption of calcium lead to a negative calcium balance that has been suggested to promote secondary hyperparathyroidism. From a mechanistic point of view, all of the aforementioned effects have long been considered to be mediated at the molecular level exclusively by genomic actions. However, there is now increasing evidence for the existence of rapid glucocorticoid effects that are incompatible with this classical mode of action. These rapid effects, termed nongenomic effects, are mediated by glucocorticoid interactions with biological membranes, either through binding to membrane receptors or by physicochemical interactions. It is possible, but has et to be shown, that these effects play a role in the pathogenesis of glucocorticoid-induced osteoporosis. (C) 2001 by Elsevier Science Inc. All rights reserved.