Targeting the RANK/RANKL/OPG signaling pathway: a novel approach in the management of osteoporosis.

The discovery of the unique role of the receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin signaling pathway in the process of osteoclastogenesis has led to the targeting of this pathway as a novel therapeutic approach in the management of osteoporosis. In a phase II clinical trial, a single subcutaneous administration of denosumab, a high-affinity, high-specificity, fully human monoclonal antibody to RANKL, led to a profound and prolonged inhibition of bone resorption, which was associated with significant increases in bone mineral density in postmenopausal women. The anti-fracture efficacy, and skeletal and extraskeletal safety issues of denosumab are being addressed in ongoing phase III clinical trials. The potential of RANKL as a therapeutic target in the treatment of osteoporosis is discussed in this review.