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.
Hamdy
Neveen A T
NA
Leiden University Medical Center, Department of Endocrinology & Metabolic Diseases, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. N.A.T.Hamdy@lumc.nl
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000069448:Denosumab; D006801:Humans; D007279:Injections, Subcutaneous; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000069448:Denosumab