RANKL inhibition has a dual effect on bone mass and muscle strength

Bones and skeletal muscles are often considered as one functional entity, referred to as the musculoskeletal system. Muscles weaken (sarcopenia) along with bone loss (osteoporosis) with advancing age, thereby increasing the risk of fragility fractures. Osteoclasts are the cells responsible for bone resorption and when their activity overcomes the activity of their counterparts, the osteoblasts, bone are weakened. RANKL is a molecule essential for osteoclast proliferation, maturation, activity, and survival. Thus, RANKL activation predisposes to bone loss while its inhibition increases bone mass. RANKL exerts its actions through its receptor RANK on the osteoclast surface. However, RANKL and its receptor RANK are also expressed in the myocytes and experimental studies suggest that their activation inhibits myogenic differentiation, which leads to skeletal muscle dysfunction and loss.

In a study published in the Journal of Clinical Investigation, the member of ECTS Academy Nicolas Bonnet and colleagues studied the effects of RANKL overexpression and inhibition on both osteoporotic mice and humans and found that overexpression and thus stimulation of RANKL results in reduced muscle mass and strength, while RANKL inhibition had the exact opposite effect. Furthermore, authors found that insulin sensitivity in the muscles is improved upon RANKL inhibition. Authors came to the conclusion that besides being used as a treatment for osteoporosis, RANKL inhibition could also represent a novel therapeutic approach for sarcopenia, thus shooting two birds with one stone.

See the original article here: https://www.jci.org/articles/view/125915