Compston Juliet
University of Cambridge School of Clinical Medicine, Department of Medicine, Addenbrooke's Hospital, Hills Road, Cambridge UK CB2 0QQ.
Bone. 2015 Nov;80:150-156. doi: 10.1016/j.bone.2015.04.013.
Loss of muscle or bone mass occurs with ageing, immobility and in association with a variety of systemic diseases. The interaction of these two processes is most evident in the major contribution of falls to the risk of fractures in the elderly population. Exercise and nutrition are key common physiological variables that allow for preservation or formation of greater muscle or bone mass. However, although several pharmacological approaches have the potential to benefit both muscle and bone health, for example vitamin D, selective androgen receptor modulators and ghrelin mimetics, clinical trials with appropriate primary outcomes are lacking. Conventional approaches to address muscle loss are being extended to include stem cell biology and conserved molecular mechanisms of atrophy/hypertrophy. Pharmacological interventions to reduce fracture risk are exploring new mechanisms of action, in particular the uncoupling of bone resorption and formation. Emerging key issues for clinical trial design include adequate phenotyping of patients (personalised medicine), optimisation of the physiological background (multimodal approach) and the use of meaningful and robust outcomes relevant to daily clinical practice. At present, effective treatments that combine beneficial effects on both muscle and bone are lacking, although this is an important target for the future. This review therefore considers current and developing strategies to improve muscle function and bone strength in separate sections.
肌肉或骨量的流失会随着年龄增长、缺乏活动以及与多种全身性疾病相关联而发生。这两个过程的相互作用在跌倒对老年人群骨折风险的主要影响中最为明显。运动和营养是有助于维持或形成更多肌肉或骨量的关键常见生理变量。然而,尽管有几种药物治疗方法有可能对肌肉和骨骼健康都有益处,例如维生素D、选择性雄激素受体调节剂和胃饥饿素类似物,但缺乏具有适当主要结局的临床试验。解决肌肉流失的传统方法正在扩展到包括干细胞生物学和萎缩/肥大的保守分子机制。降低骨折风险的药物干预正在探索新的作用机制,特别是骨吸收与骨形成的解偶联。临床试验设计中出现的关键问题包括患者的充分表型分析(个性化医疗)、生理背景的优化(多模式方法)以及使用与日常临床实践相关的有意义且可靠的结局。目前,虽然这是未来的一个重要目标,但缺乏对肌肉和骨骼都具有有益作用的有效治疗方法。因此,本综述在不同章节中考虑了当前和正在发展的改善肌肉功能和骨骼强度的策略。