The bone-muscle-adipose tissue axis: mechanisms and clinical implications

The prevalence of obesity, osteoporosis, and sarcopenia has increased dramatically over recent decades, contributing to frailty, disability, and reduced quality of life, particularly in aging populations. While excess body weight was traditionally considered protective for skeletal health due to increased mechanical loading, accumulating evidence indicates that adiposity, especially when centrally distributed and associated with metabolic dysfunction, may adversely affect bone quality and increase fracture risk despite normal or elevated bone mineral density. Bone, skeletal muscle, and adipose tissue are now recognized as components of an integrated biological system that communicates through endocrine, paracrine, and inflammatory pathways and shares common progenitor cells. Adipokines, myokines, and osteokines regulate tissue remodeling, energy metabolism, and insulin sensitivity, linking alterations in body composition to musculoskeletal and metabolic disorders. Aging amplifies these interactions through progressive muscle loss, visceral fat accumulation, hormonal changes, and chronic low-grade inflammation, giving rise to emerging clinical phenotypes like osteosarcopenic obesity. This review summarizes current clinical and biological evidence on the interactions among obesity, skeletal muscle, and bone, and discusses the implications of these relationships for integrated lifestyle-based interventions aimed at preserving musculoskeletal integrity and metabolic health across the lifespan. KEY WORDS: Excess adiposity, body composition, body mass index, bone mineral density, skeletal muscle, sarcopenia, osteosarcopenic obesity.