Prolonged inactivity and disuse conditions, such as those experienced during spaceflight and prolonged
bedrest, are frequently accompanied by detrimental effects on the motor system, including skeletal muscle
atrophy and bone loss, which greatly increase the risk of
osteoporosis and fractures. Moreover, the decrease in
glucose and
lipid utilization in skeletal muscles, a consequence of
muscle atrophy, also contributes to the development of
metabolic syndrome. Clarifying the mechanisms involved in disuse-induced musculoskeletal deterioration is important, providing therapeutic targets and a scientific foundation for the treatment of musculoskeletal disorders under disuse conditions. Skeletal muscle, as a powerful endocrine organ, participates in the regulation of physiological and biochemical functions of local or distal tissues and organs, including itself, in endocrine, autocrine, or paracrine manners. As a motor organ adjacent to muscle, bone tissue exhibits a relative lag in degenerative changes compared to skeletal muscle under disuse conditions. Based on this phenomenon, roles and mechanisms involved in the communication between skeletal muscle and bone, especially from muscle to bone, under disuse conditions have attracted widespread attention. In this review, we summarize the roles and regulatory mechanisms of muscle-derived
myokines and extracellular vesicles (EVs) in the occurrence of
muscle atrophy and bone loss under disuse conditions, as well as discuss future perspectives based on existing research.