A review of denosumab for the treatment of osteoporosis

Abstract

Osteoporosis is an age-related systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility. Bone remodeling involves two types of cells: osteoblasts and osteoclasts. Receptor activator of nuclear factor-κB ligand (RANKL) is a key regulator of the formation and function of bone-resorbing osteoclasts, and its cell surface receptor, receptor activator of nuclear factor-κB (RANK), is expressed by both osteoclast precursors and mature osteoclasts. Denosumab is a fully human monoclonal anti-RANKL antibody that inhibits the binding of RANKL to RANK, thereby decreasing osteoclastogenesis and bone-resorbing activity of mature osteoclasts. Although there are many medications available for the treatment of osteoporosis, inhibition of RANKL by denosumab has been shown to significantly affect bone metabolism. Denosumab appears to be a promising, highly effective, and safe parenteral therapy with good adherence for osteoporosis. Moreover, denosumab may be cost-effective therapy compared with existing alternatives. Therefore, in this review, we focus on studies of denosumab and the risks and benefits identified for this type of treatment for osteoporosis.

Keywords: OPG; RANKL; bone resorption; osteoclast.

Figure 1

The mechanism of action of denosumab on bone metabolism. Notes: Denosumab (a fully human monoclonal anti-RANKL antibody) binds to osteoblast-produced RANKL, thereby preventing RANKL from binding to the osteoclast receptor, RANK. By preventing RANKL from binding to RANK, there is less osteoclastogenesis and bone-resorbing activity so that bone resorption is markedly suppressed. Abbreviations: c-Fms, colony stimulating factor-1 receptor; M-CSF, macrophage colony-stimulating factor; RANK, receptor activator of nuclear factor-κB; RANKL, receptor activator of nuclear factor-κB ligand.