Exercise-Induced Regulation of Bone Remodeling via Mitophagy: A Review of Current Evidence.

Bone remodeling imbalance represents the fundamental pathological basis of osteoporosis. Exercise is broadly regarded as a valuable non-pharmacological strategy for preventing and managing osteoporosis; however, the precise molecular mechanisms through which exercise modulates bone metabolism remain incompletely understood. Mitophagy has recently been recognized as an important mediator linking exercise to the regulation of bone remodeling. This review centers on the "exercise-mitophagy-bone remodeling" axis, systematically outlining the biological processes and regulatory determinants of mitophagy within the bone microenvironment. Evidence suggests that mitophagy facilitates bone formation by preserving mitochondrial quality, attenuating oxidative stress, and optimizing cellular energy metabolism. Moreover, it exerts stage-specific inhibitory effects on bone resorption during osteoclast differentiation. Particular emphasis is placed on the mechanisms by which exercise activates mitophagy-related signaling pathways via metabolic, mechanical, and hypoxic stimuli. In addition, exercise may enhance the efficiency of this regulatory axis by maintaining vitamin D and calcium homeostasis and modulating estrogen signaling pathways. The differential effects of exercise modalities and durations on these processes are also critically evaluated. Finally, this review addresses current limitations in existing research and highlights future directions, including the optimization of exercise interventions targeting mitophagy and the integration of multi-omics approaches. These findings offer a theoretical basis for designing precise exercise regimens and combined therapeutic approaches in the management of osteoporosis.