Morley John E
Division of Geriatric Medicine, Saint Louis University School of Medicine, 1402 S. Grand Blvd., M238, St. Louis, MO, 63104, USA.
Calcif Tissue Int. 2016 Apr;98(4):319-33. doi: 10.1007/s00223-015-0022-5. Epub 2015 Jun 23.
Sarcopenia is now clinically defined as a loss of muscle mass coupled with functional deterioration (either walking speed or distance or grip strength). Based on the FRAX studies suggesting that the questions without bone mineral density can be used to screen for osteoporosis, there is now a valid simple questionnaire to screen for sarcopenia, i.e., the SARC-F. Numerous factors have been implicated in the pathophysiology of sarcopenia. These include genetic factors, mitochondrial defects, decreased anabolic hormones (e.g., testosterone, vitamin D, growth hormone and insulin growth hormone-1), inflammatory cytokine excess, insulin resistance, decreased protein intake and activity, poor blood flow to muscle and deficiency of growth derived factor-11. Over the last decade, there has been a remarkable increase in our understanding of the molecular biology of muscle, resulting in a marked increase in potential future targets for the treatment of sarcopenia. At present, resistance exercise, protein supplementation, and vitamin D have been established as the basic treatment of sarcopenia. High-dose testosterone increases muscle power and function, but has a number of potentially limiting side effects. Other drugs in clinical development include selective androgen receptor molecules, ghrelin agonists, myostatin antibodies, activin IIR antagonists, angiotensin converting enzyme inhibitors, beta antagonists, and fast skeletal muscle troponin activators. As sarcopenia is a major predictor of frailty, hip fracture, disability, and mortality in older persons, the development of drugs to treat it is eagerly awaited.
肌肉减少症目前在临床上被定义为肌肉质量的丧失以及功能衰退(步行速度、距离或握力)。基于FRAX研究表明,不包含骨密度的问题可用于筛查骨质疏松症,现在有一种有效的简单问卷可用于筛查肌肉减少症,即SARC-F问卷。肌肉减少症的病理生理学涉及众多因素。这些因素包括遗传因素、线粒体缺陷、合成代谢激素减少(如睾酮、维生素D、生长激素和胰岛素样生长因子-1)、炎性细胞因子过多、胰岛素抵抗、蛋白质摄入和活动减少、肌肉血流量不足以及生长分化因子-11缺乏。在过去十年中,我们对肌肉分子生物学的理解有了显著增加,这导致未来治疗肌肉减少症的潜在靶点显著增加。目前,抗阻运动、补充蛋白质和维生素D已被确立为肌肉减少症的基本治疗方法。高剂量睾酮可增加肌肉力量和功能,但有许多潜在的限制副作用。正在临床开发的其他药物包括选择性雄激素受体分子、胃饥饿素激动剂、肌生成抑制素抗体、激活素II受体拮抗剂、血管紧张素转换酶抑制剂、β受体拮抗剂以及快肌肌钙蛋白激活剂。由于肌肉减少症是老年人衰弱、髋部骨折、残疾和死亡的主要预测因素,因此人们急切期待治疗该疾病的药物问世。