The RANKL pathway and denosumab

Rheum Dis Clin North Am. 2011 Aug;37(3):433-52, vi-vii. doi: 10.1016/j.rdc.2011.07.004.


Denosumab (Prolia) is a fully human monoclonal antibody directed against receptor activator of nuclear factor-κB ligand (RANKL), which interferes with the formation, activation, and survival of osteoclasts. It was approved by the Food and Drug Administration in June 2010 as a new treatment for postmenopausal osteoporosis in women who are at high risk for fracture. Given its mechanism of action, it is an antiresorptive therapy that is administered as a 60-mg subcutaneous injection every 6 months. It is the first biologic antiresorptive therapy for osteoporosis, and the first osteoporosis therapy to show efficacy and safety in patients with renal impairment.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Bone Remodeling / drug effects*
  • Bone Remodeling / physiology
  • Denosumab
  • Female
  • Humans
  • Middle Aged
  • Nuclear Export Signals / drug effects*
  • Nuclear Export Signals / physiology
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / metabolism*
  • RANK Ligand / antagonists & inhibitors
  • RANK Ligand / metabolism*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Nuclear Export Signals
  • RANK Ligand
  • TNFSF11 protein, human
  • Denosumab