The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Denosumab: mechanism of action and clinical outcomes
Open accessAbstract
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.
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Cites
Writing Group for the Women's Health Initiative Investigators (2002) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.288.3.321 · Cited by 15,889
Neer, R. M., Arnaud, C. D., Zanchetta, J. R., Prince, R., Gaich, G. A., Reginster, J.-Y., Hodsman, A. B., Eriksen, E. F., Ish-Shalom, S., Genant, H. K., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105103441904 · Cited by 4,602
Black, D. M., Cummings, S. R., Karpf, D. B., Cauley, J. A., Thompson, D. E., Nevitt, M. C., Bauer, D. C., Genant, H. K., Haskell, W. L., Marcus, R., et al. (1996) · The Lancet · doi:10.1016/s0140-6736(96)07088-2 · Cited by 3,846
Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis
Cummings, S. R., Martin, J. S., McClung, M. R., Siris, E. S., Eastell, R., Reid, I. R., Delmas, P., Zoog, H. B., Austin, M., Wang, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809493 · Cited by 3,489
Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis
Black, D. M., Delmas, P. D., Eastell, R., Reid, I. R., Boonen, S., Cauley, J. A., Cosman, F., Lakatos, P., Leung, P. C., Man, Z., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa067312 · Cited by 2,986
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,568
Effect of Risedronate on the Risk of Hip Fracture in Elderly Women
McClung, M. R., Geusens, P., Miller, P. D., Zippel, H., Bensen, W. G., Roux, C., Adami, S., Fogelman, I., Diamond, T., Eastell, R., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200102013440503 · Cited by 1,918
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Advances in the regulation of osteoclasts and osteoclast functions
Boyce, B. F. (2013) · Journal of Dental Research · doi:10.1177/0022034513500306 · Cited by 457
RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling
Tobeiha, M., Moghadasian, M. H., Amin, N., & Jafarnejad, S. (2020) · BioMed Research International · doi:10.1155/2020/6910312 · Cited by 309
Long-term and sequential treatment for osteoporosis
Foessl, I., Dimai, H. P., & Obermayer-Pietsch, B. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00866-9 · Cited by 273
Adverse events to monoclonal antibodies used for cancer therapy: Focus on hypersensitivity responses
Baldo, B. (2013) · OncoImmunology · doi:10.4161/onci.26333 · Cited by 191
Can we prevent BRCA1-associated breast cancer by RANKL inhibition?
Kotsopoulos, J., Singer, C., & Narod, S. A. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-4029-z · Cited by 37
Metadata
- Authors
- Hanley, D. A., Adachi, J. D., Bell, A., & Brown, V.
- Venue
- International Journal of Clinical Practice
- Publisher
- Hindawi Limited
- Published
- 2012-09-12
- Volume
- 66
- Issue
- 12
- Pages
- 1139-1146
- ISSN
- 1368-5031 (ISSN-L)
- 1742-1241
- OpenAlex
- W1621696727
- Cited by
- 377
- References
- 51
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
