Sato Amy Y, Peacock Munro, Bellido Teresita
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana, 46202.
Clin Rev Bone Miner Metab. 2018 Mar;16(1):33-47. doi: 10.1007/s12018-018-9242-3. Epub 2018 Feb 5.
Glucocorticoids (GC), produced and released by the adrenal glands, regulate numerous physiological processes in a wide range of tissues. Because of their profound immunosuppressive and anti-inflammatory actions, GC are extensively used for the treatment of immune and inflammatory conditions, the management of organ transplantation, and as a component of chemotherapy regimens for cancers. However, both pathologic endogenous elevation and long-term use of exogenous GC are associated with severe adverse effects. In particular, excess GC has devastating effects on the musculoskeletal system. GC increase bone resorption and decrease formation leading to bone loss, microarchitectural deterioration and fracture. GC also induce loss of muscle mass and strength leading to an increased incidence of falls. The combined effects on bone and muscle account for the increased fracture risk with GC. This review summarizes the advance in knowledge in the last two decades about the mechanisms of action of GC in bone and muscle and the attempts to interfere with the damaging actions of GC in these tissues with the goal of developing more effective therapeutic strategies.
糖皮质激素(GC)由肾上腺产生并释放,可调节多种组织中的众多生理过程。由于其具有强大的免疫抑制和抗炎作用,GC被广泛用于治疗免疫和炎症性疾病、器官移植管理以及作为癌症化疗方案的组成部分。然而,内源性病理性升高和长期使用外源性GC均与严重不良反应相关。特别是,过量的GC对肌肉骨骼系统具有毁灭性影响。GC增加骨吸收并减少骨形成,导致骨质流失、微结构恶化和骨折。GC还会导致肌肉质量和力量丧失,从而增加跌倒的发生率。对骨骼和肌肉的综合影响导致使用GC时骨折风险增加。本综述总结了过去二十年中关于GC在骨骼和肌肉中的作用机制以及试图干扰GC在这些组织中的破坏作用以开发更有效治疗策略的知识进展。