Denosumab for bone diseases: translating bone biology into targeted therapy

Eur J Endocrinol. 2011 Dec;165(6):833-40. doi: 10.1530/EJE-11-0454. Epub 2011 Aug 18.


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.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bone Diseases / drug therapy*
  • Bone Diseases / metabolism*
  • Bone Diseases / pathology
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Denosumab
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends*
  • Humans
  • RANK Ligand / administration & dosage*
  • RANK Ligand / therapeutic use*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • RANK Ligand
  • Denosumab