title: Denosumab: anti-RANKL antibody.
abstract: Denosumab (anti-receptor activator of nuclear factor-kappaB ligand antibody) is a novel agent, a fully human monoclonal antibody that inhibits osteoclastic-medicated bone resorption by binding to osteoblast-produced RANKL. By reducing RANKL binding to the osteoclast receptor RANK, bone resorption and turnover decrease. In phase 2 dose-ranging studies, denosumab had a rapid onset and offset effect. Also, in patients who had received 2 years of denosumab and were discontinued for the third year, rechallenge with denosumab during the fourth year demonstrated a return of responsiveness to denosumab that mimicked the initial treatment. Phase 3 pivotal fracture data were recently presented with positive outcome data; denosumab (60 mg subcutaneously every 6 months) significantly reduced vertebral, nonvertebral, and hip fracture risk compared with placebo, and had an excellent safety profile through 3 years of use. Denosumab will offer a novel approach to managing postmenopausal osteoporosis, one that should be associated with a high adherence rate and global fracture risk reduction.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Colorado Center for Bone Research, 3190 South Wadsworth Boulevard, Lakewood, CO 80227, USA. millerccbr@aol.com
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation; D000069448:Denosumab; D006801:Humans; D010010:Osteoclasts / Q000166:cytology; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000517:prevention & control; D053245:RANK Ligand / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D000069448:Denosumab