Girgis Christian M
Westmead Millennium Institute for Medical Research, 176 Hawkesbury Rd, Westmead, NSW, Australia,
Calcif Tissue Int. 2015 Mar;96(3):243-55. doi: 10.1007/s00223-015-9956-x. Epub 2015 Jan 31.
Sarcopenia and osteoporosis are two sides of the same coin. They represent different aspects of the same age-related process of musculoskeletal atrophy and together culminate in falls, fractures, deconditioning, and increased mortality in older individuals. However, the current therapeutic approach to the prevention of minimal trauma fracture is unilateral and focuses solely on bone. In theory, an integrated approach that recognizes the interaction between muscle and bone could break the vicious cycle of their combined involution and more effectively minimize falls/fractures. In this review, signaling pathways and cross-talk mechanisms that integrate bone/muscle, and the emergence of novel therapies that exploit these pathways to target osteoporosis/sarcopenia will be discussed. In broad terms, these agents act on nuclear receptors (e.g., VDR, AR) or transmembrane receptors (e.g., activins, GH/IGF-1) expressed in muscle and bone, and seek to alter biologic responses to musculoskeletal aging, loading, and injury. Challenges in the development of these dual bone-muscle therapies, early clinical trials examining their safety/efficacy, and novel targets that hold promise in the reversal of musculoskeletal aging will be discussed.
肌肉减少症和骨质疏松症是同一枚硬币的两面。它们代表了与年龄相关的肌肉骨骼萎缩过程的不同方面，共同导致老年人跌倒、骨折、身体机能下降和死亡率增加。然而，目前预防轻微创伤性骨折的治疗方法是片面的，仅侧重于骨骼。理论上，一种认识到肌肉与骨骼之间相互作用的综合方法可能会打破它们共同退化的恶性循环，并更有效地减少跌倒/骨折。在这篇综述中，将讨论整合骨骼/肌肉的信号通路和相互作用机制，以及利用这些通路针对骨质疏松症/肌肉减少症的新型疗法的出现。广义而言，这些药物作用于肌肉和骨骼中表达的核受体（如维生素D受体、雄激素受体）或跨膜受体（如激活素、生长激素/胰岛素样生长因子-1），并试图改变对肌肉骨骼衰老、负荷和损伤的生物学反应。将讨论这些双肌肉骨骼疗法开发中的挑战、检验其安全性/有效性的早期临床试验，以及在逆转肌肉骨骼衰老方面具有潜力的新靶点。
