Disclosures David Hanley: Research Support: Alliance (Procter & Gamble, Aventis), Amgen, Eli Lilly, Merck, NPS Pharmaceuticals, Novartis; Advisory Boards: Amgen, Eli Lilly, Novartis, Warner-Chilcott; Speaker Honoraria: Amgen, Eli Lilly, Merck, Novartis, Warner-Chilcott. Jonathan D. Adachi: Consultant/Speaker: Amgen, Eli Lilly, GSK, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi Aventis, Warner Chilcott; Clinical trials: Amgen, Eli Lilly, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi Aventis, Warner Chilcott. Alan Bell: Relevant to this paper, Dr Bell has received consultant and/or speaker fees from Amgen and Sanofi Aventis and research grants from Amgen. Vivien Brown: Relevant to this paper, Dr Brown has received consultant and/or speaker fees from Amgen.
Denosumab: mechanism of action and clinical outcomes
Version of Record online: 12 SEP 2012
© 2012 Blackwell Publishing Ltd
International Journal of Clinical Practice
Volume 66, Issue 12, pages 1139–1146, December 2012
How to Cite
Hanley, D. A., Adachi, J. D., Bell, A. and Brown, V. (2012), Denosumab: mechanism of action and clinical outcomes. International Journal of Clinical Practice, 66: 1139–1146. doi: 10.1111/ijcp.12022
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
Linked Comment: Ahmed. Int J Clin Pract 2012; 66: 1129-31.
- Issue online: 20 NOV 2012
- Version of Record online: 12 SEP 2012
Aims: 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.