The role of osteoprotegerin (OPG) in exercise-induced skeletal muscle adaptation

Abstract Objectives The purpose of this narrative review is to offer an updated perspective on the current research on the glycoprotein Osteoprotegerin (OPG), including its potential therapeutic impact and mechanisms of action, and interaction with bone and muscle tissues. Content As health and social care advances people are living longer, with projections suggesting that in 2050 there will be 2 billion people who are aged over 60 years. Yet musculoskeletal health still declines into older age and as a result there is an increase in the proportion of older populations that spend more time with persistent disabilities. Although physical exercise is repeatedly demonstrated to minimise detrimental effects of ageing, it is not always a feasible intervention, and other directions must be considered. Summary and outlook OPG, a glycoprotein decoy receptor for the receptor activator of nuclear factor kappa-β ligand (RANKL) is a key regulator of bone formation yet emerging evidence has presented its potential to offer positive outcomes in regard to the preservation of skeletal muscle mass and function. Animal models have shown that OPG levels increase during exercise, and independently acts to restore losses of muscle strength and reduce bone resorption. Interventions to increase circulating OPG alongside exercise may act as a therapeutic target to combat the decline in quality of life in older age in humans. Further research is needed on the mechanisms of its action and interaction in humans in combination with exercise.