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.

Physical Activity-Dependent Regulation of Parathyroid Hormone and Calcium-Phosphorous Metabolism

“…It is negatively regulated by acute exercise and training (endurance and resistance in overweight and obese men) [ 160 , 233 ]. Numbering among the antagonists of myostatin are follistatin (FST), follistatin-like 1 (FSTL1), and decorin [ 160 , 234 ].…”

Effects of marathon race on selected myokines and sclerostin in middle-aged male amateur runners

“…Research carried out in recent years has demonstrated that sclerostin is important for bone homeostasis 2 , 36 , and its expression in osteocytes has been found to be negatively regulated by mechanical loading 37 .…”

The Role of Osteokines in Sarcopenia: Therapeutic Directions and Application Prospects

“…Muscles and bones interact to maintain their structures and functions. Thus far, we have realized that muscles and bones can receive and secrete biochemical signals in a two-way manner, thereby affecting the metabolism of the two tissues and the entire body ( Lombardi, 2019 ; Gomarasca et al, 2020 ). These signals are coordinated by a set of cytokines and growth-like factors: muscle factors secreted by muscle cells and bone factors secreted by bone cells, both of which can exert autocrine, paracrine and endocrine functions to regulate muscle and bone metabolism.…”