Exercise-responsive crosstalk within local muscle-bone units in osteosarcopenia: from mechanotransduction to secretome signalling.

Osteosarcopenia is a geriatric syndrome characterized by the overlapping features of osteoporosis and sarcopenia. Its core pathology extends beyond parallel declines in bone and muscle mass. It also involves coordinated disturbances in muscle contractile capacity, skeletal mechanosensitivity, bone marrow cell-lineage commitment, and muscle- and bone-derived secretory signalling. Exercise represents a key non-pharmacological intervention that simultaneously targets skeletal muscle and bone. However, previous studies have mainly focused on changes in systemic bone mineral density, muscle mass, or circulating endocrine factors, whereas the site-specific adaptive relationship between particular muscle groups and adjacent skeletal sites has not been sufficiently integrated. This review aims to address the mechanisms underlying exercise-responsive crosstalk within local muscle-bone units in osteosarcopenia. We focus on the lumbar paraspinal muscle-vertebral body unit and the hip periarticular muscle-proximal femur unit, integrating evidence from imaging studies, animal experiments, exercise interventions, and endocrine mechanisms of muscle-bone communication. Current evidence suggests that exercise promotes adaptive remodeling of local muscle-bone units through site-specific mechanical loading and modulation of the local secretome. This includes both the paraspinal muscle-vertebral body unit and the hip periarticular muscle-proximal femur unit. The concept of exercise-responsive local muscle-bone units provides a translational framework for understanding site-specific degeneration in osteosarcopenia and for developing more precise exercise-based interventions.