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Denosumab: mechanism of action and clinical outcomes.

AbstractAIMS:
To describe the mechanisms of action of denosumab, a novel antiresorptive agent, contrasting it with other antiresorptive and anabolic osteoporosis treatments.
METHODS:
Published papers related to the mechanism of action of approved osteoporosis treatments were sought through MEDLINE searches.
FINDINGS:
Osteoporotic fractures carry a substantial burden of morbidity and mortality, but pharmacotherapy can prevent such fractures in high-risk individuals. Antiresorptive drugs (e.g. bisphosphonates, oestrogen, denosumab) reduce bone turnover by distinct mechanisms. Denosumab, a recently approved therapy, is a fully human monoclonal antibody that binds the cytokine RANKL (receptor activator of NFκB ligand), an essential factor initiating bone turnover. RANKL inhibition blocks osteoclast maturation, function and survival, thus reducing bone resorption. In contrast, bisphosphonates bind bone mineral, where they are absorbed by mature osteoclasts, inducing osteoclast apoptosis and suppressing resorption. These differences in mechanism influence both the onset and reversibility of treatment.
DISCUSSION:
Effective pharmacotherapy is necessary for patients at high risk of fracture. Among the treatment options for postmenopausal osteoporosis, there are significant differences in mechanism and dosing. Denosumab acts by a novel mechanism and is administered twice yearly by subcutaneous injection. Identified by Osteoporosis Canada Clinical Practice Guidelines as a first-line agent for treatment of postmenopausal osteoporosis, denosumab represents an important addition to our treatment options.
AuthorsD A Hanley, J D Adachi, A Bell, V Brown
JournalInternational journal of clinical practice (Int J Clin Pract) Vol. 66 Issue 12 Pg. 1139-46 (Dec 2012) ISSN: 1742-1241 [Electronic] India
PMID22967310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Copyright© 2012 Blackwell Publishing Ltd.
Chemical References
  • Antibodies, Monoclonal, Humanized
  • Bone Density Conservation Agents
  • Diphosphonates
  • Teriparatide
  • Denosumab
Topics
  • Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
  • Bone Density Conservation Agents (pharmacology, therapeutic use)
  • Bone Remodeling (drug effects)
  • Denosumab
  • Diphosphonates (pharmacology)
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis, Postmenopausal (drug therapy)
  • Osteoporotic Fractures (prevention & control)
  • Practice Guidelines as Topic
  • Teriparatide (pharmacology)

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