Dong Qinzuo, Li Danyang, Zhang Ke, Shi Hua, Cai Ming, Li Yangdi, Zhao Rong, Qin Dongdong
First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, China.
Second Clinical Medical College, Yunnan University of Chinese Medicine, Kunming, China.
J Endocrinol. 2025 Sep 16;266(3). doi: 10.1530/JOE-25-0234. Print 2025 Sep 1.
Osteosarcopenia (OS) is a syndrome defined by the concurrent presence of sarcopenia and osteoporosis in the elderly population, which markedly elevates the risk of falls, fractures, and mortality. Recent studies demonstrate that disruption of muscle-bone biochemical crosstalk emerges as a key driver of OS pathogenesis, and that targeting pivotal mediators and pathways can concurrently restore musculoskeletal homeostasis. However, the precise molecular mechanisms and targeted therapeutic strategies remain inadequately explored. This review systematically summarizes the epidemiological risk factors and pathophysiological mechanisms underpinning OS, with emphasis on the interplay within musculoskeletal metabolism among myokines (e.g., fibroblast growth factors 21, FGF21, and irisin), osteokines (e.g., osteocalcin, OCN, receptor activator of nuclear factor-κB ligand, RANKL, and sclerostin, SOST), adipokines, and shared signaling pathways such as mitochondria-associated axes, Wnt/β-catenin, and nuclear factor-κB (NF-κB), as well as discusses the potential efficacy of direct and indirect interventions targeting these factors and biochemical signals, which provides innovative strategies and prospective research directions for developing precision-targeted therapies against OS and other degenerative musculoskeletal disorders. In addition, we propose that precise modulation of muscle-bone signaling constitutes a promising approach to treat OS. Future efforts should prioritize standardizing diagnostic criteria and advancing the development of therapies targeting critical muscle-bone biochemical interaction nodes to optimize the management of musculoskeletal comorbidities in the aging population.
骨少肌少症（OS）是一种在老年人群中由肌少症和骨质疏松症同时存在所定义的综合征，它显著增加了跌倒、骨折和死亡的风险。最近的研究表明，肌肉与骨骼生化信号传导的破坏是OS发病机制的关键驱动因素，靶向关键介质和信号通路可以同时恢复肌肉骨骼的稳态。然而，精确的分子机制和靶向治疗策略仍未得到充分探索。本综述系统地总结了OS的流行病学危险因素和病理生理机制，重点关注肌动蛋白（如成纤维细胞生长因子21，FGF21，和鸢尾素）、骨动蛋白（如骨钙素，OCN，核因子-κB受体激活剂配体，RANKL，和硬化蛋白，SOST）、脂肪因子以及线粒体相关轴、Wnt/β-连环蛋白和核因子-κB（NF-κB）等共享信号通路在肌肉骨骼代谢中的相互作用，并讨论了针对这些因素和生化信号的直接和间接干预的潜在疗效，这为开发针对OS和其他退行性肌肉骨骼疾病的精准靶向治疗提供了创新策略和前瞻性研究方向。此外，我们提出精确调节肌肉与骨骼的信号传导是治疗OS的一种有前景的方法。未来的努力应优先标准化诊断标准，并推进针对关键肌肉与骨骼生化相互作用节点的治疗方法的开发，以优化老年人群肌肉骨骼合并症的管理。
