Clinical potential of RANKL inhibition for the management of postmenopausal osteoporosis and other metabolic bone diseases

J Clin Densitom. Apr-Jun 2008;11(2):325-38. doi: 10.1016/j.jocd.2008.02.002. Epub 2008 Apr 2.

Abstract

Osteoporosis affects millions of people worldwide, causing decreases in bone strength and a marked increase in fracture risk. Current therapies increase bone mineral density and reduce the risk of fractures, but dosing requirements are often considered inconvenient, and patient compliance with therapy is poor. This review will discuss recent discoveries in bone biology, which have demonstrated that the interaction of osteoprotegerin (OPG), receptor activator of nuclear factor--kappa B (RANK), and RANK ligand (RANKL) is critical for the regulation of bone remodeling. Collectively, these preclinical studies have shown that endogenous RANKL inhibition by OPG underlies the normal mechanism for maintaining the correct balance between bone resorption and bone formation. Multiple clinical trials are in progress to investigate the therapeutic potential of RANKL inhibition by denosumab, a fully human monoclonal anti-RANKL antibody, in the treatment of postmenopausal osteoporosis and other bone loss diseases. The results of these human trials will also be discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Bone Density / drug effects
  • Bone Density / physiology
  • Bone Density Conservation Agents / pharmacology
  • Bone Diseases, Metabolic / drug therapy
  • Bone Remodeling / drug effects
  • Bone Remodeling / physiology
  • Denosumab
  • Female
  • Fractures, Bone / physiopathology
  • Fractures, Bone / prevention & control*
  • Humans
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Osteoprotegerin / physiology
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / pharmacology
  • RANK Ligand / physiology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Osteoprotegerin
  • RANK Ligand
  • Denosumab