Molecular target therapy for bone metastasis: starting a new era with denosumab, a RANKL inhibitor

Expert Opin Biol Ther. 2014 Jan;14(1):15-26. doi: 10.1517/14712598.2013.843667. Epub 2013 Oct 28.


Introduction: The skeleton is generally the primary, and sometimes the only, site of metastasis in patients with advanced solid tumors. Bone metastases are the most frequent cause of cancer-related pain and the origin of severe morbidity in patients. Among the treatment options available for the prevention of skeletal-related events (SREs) associated with bone metastasis, zoledronic acid, an antiresorptive treatment from the group of bisphosphonates, is currently the standard of care in this setting.

Areas covered: Zoledronic acid, together with denosumab (a monoclonal antibody against the receptor activator of nuclear factor kappa B ligand), is the most frequent approach for the prevention of cancer-related events in skeleton. This paper reviews several trials evaluating the efficacy of denosumab in comparison with zoledronic acid in patients with solid osteotropic tumors. In this setting of skeleton-invading cancers, denosumab was demonstrated to be superior to zoledronic acid in preventing or delaying SREs. In comparison with zoledronic acid, denosumab significantly delayed the time to first SRE by 17%.

Expert opinion: Current research on denosumab is addressed to prove the immunomodulator effect of this agent in humans. Other avenue of research is focused on its antitumor activity observed in some Phase III trials.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / mortality
  • Bone Neoplasms / prevention & control*
  • Bone Neoplasms / secondary
  • Denosumab
  • Diphosphonates / therapeutic use
  • Humans
  • Imidazoles / therapeutic use
  • Male
  • Molecular Targeted Therapy*
  • Practice Guidelines as Topic
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / metabolism
  • Treatment Outcome
  • Zoledronic Acid


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Diphosphonates
  • Imidazoles
  • RANK Ligand
  • TNFSF11 protein, human
  • Denosumab
  • Zoledronic Acid