title: Denosumab for bone diseases: translating bone biology into targeted therapy.
abstract: Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.
authors.affiliation: Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine III, Technical University Medical Center, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Tsourdi
authors.forename: Tilman D
authors.initials: TD
authors.lastname: Rachner
authors.forename: Martina
authors.initials: M
authors.lastname: Rauner
authors.forename: Christine
authors.initials: C
authors.lastname: Hamann
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001847:Bone Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D000069448:Denosumab; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D006801:Humans; D053245:RANK Ligand / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D000069448:Denosumab