Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

Abstract

Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG) and receptor activator for nuclear factor-κB (RANK) ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, the RANK/RANKL/OPG pathway is described. The multiple interactions of various factors (hormones, cytokines, growth factors, and vitamins) with the OPG/RANK/RANKL pathway are also commented on. Finally, the effects of denosumab, a human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts, and of strontium ranelate are also described. Indeed, these two new drugs afford appreciable assistance in daily care practice, helping to prevent bone loss in patients with osteoporosis.

Keywords: OPG; RANK; RANKL; denosumab; osteoporosis; osteoprotegerin; strontium ranelate.

Figure 1

Bone turnover through the OPG/RANK/RANKL pathway. The osteoclast precursor matures into a multinucleated cell under the influence of numerous factors such as cytokines, hormones, and growth factors. The multinucleated cell differentiates into an activated osteoclast in the presence of MCSF and RANKL. Once activated, the osteoclast starts degrading the bone surface, forming a lacuna. OPG, the decoy receptor of RANKL, inhibits the continuous binding of RANKL on RANK, therefore leading the osteoclast to its apoptosis. Thereafter, bone formation starts with preosteoblasts that have matured into osteoblasts in order to constitute new bone.