The RANK-RANK-L-OPG pathway: trait d’union between bone and muscle

Abstract

From an operational point of view, the musculoskeletal system can be considered a single organ that, displaying great plastic capacity, continuously remodels itself in response to various functional demands, which change over the course of human life. Many factors, mechanical and biochemical, underlie the constant interaction between bone and muscle. Among the main biochemical signals mediating this crosstalk, the receptor activator of the nuclear factor kappa-Β (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) system regulates not only bone remodeling but also muscle mass and performance, as well as its response to physiological or pathological stressing conditions. Administration of OPG or monoclonal antibodies (denosumab) against RANK-L improves skeletal mass and strength, and also plays an important role in reducing the risk of falls and improving the outcome of diseases involving skeletal and myocardial muscles. KEY WORDS: Bone, muscle, RANK, RANKL, OPG, denosumab.