Exercise-Dependent Modulation of Bone Metabolism and Bone Endocrine Function: New Findings and Therapeutic Perspectives

Abstract

Physical inactivity is the fourth leading cause of mortality worldwide; regardless of geographic location and income, it is a contributing risk factor to the other three causes. Physical activity is really a drug, a poly-pill; its “regular use” can reduce this risk throughout the activation of a plethora of responses in virtually all the body tissues. The beneficial effects of physical activity on cardiovascular function and hemodynamics are mainly mediated by skeletal muscle, adipose tissue and the immune system via the usage, delivery and distribution of metabolic substrates and improvement in inflammatory status. There is emerging evidence for exercise-dependent changes in bone metabolism as well; with improved bone quality, reduced fracture risk and increased bone endocrine function, the last of which modulates energy metabolism through its effects on pancreatic islet cells, skeletal muscle and adipose tissue. Bone endocrine function relies on the integration of biomechanical stimuli and endocrine signals from other organs and tissues. Here I review current concepts about exercise-dependent modulation of bone endocrine function and its beneficial effects on whole-body metabolism. Several molecular mechanisms have been identified that support this exercise-stimulated bone-mediated metabolic effect and, among these, Wnt signaling, fibroblast growth factor-23, bone morphogenic protein-7, osteocalcin, RANK/RANKL/OPG axis, and lipocalin-2 gave the largest evidences. In conclusion, beside the controversies surrounding technical aspects of the exercise, the efficacy of physical activity in preventing/treating metabolic and inflammatory dysfunctions also passes throughout the bone.