title: RANKL inhibition: clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases.
abstract: BACKGROUND
  Receptor activator of NF-kappaB ligand (RANKL) binds to RANK on the surface of osteoclast precursors and enhances their differentiation, survival and fusion, activates mature osteoclasts and inhibits their apoptosis. Osteoprotegerin (OPG) is the decoy receptor of RANKL. Disruption of the RANK/RANKL/OPG axis is implicated in bone metastases.
  
  
  OBJECTIVE
  A review of the role of RANKL signaling in bone development and the rationale for targeting RANKL in treatment of bone metastases and myeloma bone disease.
  
  
  CONCLUSIONS
  In preclinical models of solid tumors and myeloma, RANKL inhibition reduced osteoclast numbers and subsequent bone resorption, prevented development of osteolytic lesions and decreased tumor burden. Preliminary clinical studies with denosumab, an anti-RANKL fully human monoclonal antibody, in patients with solid tumors with bone metastases and myeloma showed that targeting RANKL reduces osteoclastogenesis, bone resorption markers and skeletal-related events, supporting further study of this molecule and others with anti-RANKL activity.
authors.affiliation: Alexandra University Hospital, University of Athens School of Medicine, Department of Clinical Therapeutics, 5 Marathonomahon street, Drosia Attikis, 14572, Athens, Greece. eterpos@hotmail.com
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Eleni
authors.initials: E
authors.lastname: Efstathiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Christoulas
authors.forename: Maria
authors.initials: M
authors.lastname: Roussou
authors.forename: Eirini
authors.initials: E
authors.lastname: Katodritou
authors.forename: Meletios-Athanassios
authors.initials: MA
authors.lastname: Dimopoulos