The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Denosumab and bisphosphonates: Different mechanisms of action and effects
Open accessAbstract
To treat systemic bone loss as in osteoporosis and/or focal osteolysis as in rheumatoid arthritis or periodontal disease, most approaches target the osteoclasts, the cells that resorb bone. Bisphosphonates are currently the most widely used antiresorptive therapies. They act by binding the mineral component of bone and interfere with the action of osteoclasts. The nitrogen-containing bisphosphonates, such as alendronate, act as inhibitors of farnesyl-pyrophosphate synthase, which leads to inhibition of the prenylation of many intracellular signaling proteins. The discovery of RANKL and the essential role of RANK signaling in osteoclast differentiation, activity and survival have led to the development of denosumab, a fully human monoclonal antibody. Denosumab acts by binding to and inhibiting RANKL, leading to the loss of osteoclasts from bone surfaces. In phase 3 clinical studies, denosumab was shown to significantly reduce vertebral, nonvertebral and hip fractures compared with placebo and increase areal BMD compared with alendronate. In this review, we suggest that the key pharmacological differences between denosumab and the bisphosphonates reside in the distribution of the drugs within bone and their effects on precursors and mature osteoclasts. This may explain differences in the degree and rapidity of reduction of bone resorption, their potential differential effects on trabecular and cortical bone, and the reversibility of their actions.
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Cites
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670 · cited 3×
“In vitro, the combination of RANKL andM-CSF is required for optimal osteoclast survival [17].”
BackgroundDenosumab 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
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
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
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“However, when RANKL is produced by activated T cells during inflammatory processes such as colitis and rheumatoid arthritis (RA) in the absence of other immune molecule deficits, antagonizing RANK/RANKL signaling has no effect on proliferation or activation of inflammatory cells [93–97].”
BackgroundYoshida, H., Hayashi, S.-I., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L. D., & Nishikawa, S.-I. (1990) · Nature · doi:10.1038/345442a0 · Cited by 1,789
Ten Years' Experience with Alendronate for Osteoporosis in Postmenopausal Women
Bone, H. G., Hosking, D., Devogelaer, J.-P., Tucci, J. R., Emkey, R. D., Tonino, R. P., Rodriguez-Portales, J. A., Downs, R. W., Gupta, J., Santora, A. C., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa030897 · Cited by 1,347
Chesnut, C. H., Skag, A., Christiansen, C., Recker, R., Stakkestad, J. A., Hoiseth, A., Felsenberg, D., Huss, H., Gilbride, J., Schimmer, R. C., et al. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040325 · Cited by 1,229
Denosumab in postmenopausal women with low bone mineral density.
McClung, M. R., Lewiecki, E. M., Cohen, S. B., Bolognese, M. A., Woodson, G. C., Moffett, A. H., Peacock, M., Miller, P. D., Lederman, S. N., Chesnut, C. H., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa044459 · Cited by 1,228
Cited by
WNT signaling in bone homeostasis and disease: From human mutations to treatments
Baron, R., & Kneissel, M. (2013) · Nature Medicine · doi:10.1038/nm.3074 · Cited by 2,093
Self-citationKhosla, S., Oursler, M. J., & Monroe, D. G. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.03.008 · Cited by 943
Denosumab: mechanism of action and clinical outcomes
Hanley, D. A., Adachi, J. D., Bell, A., & Brown, V. (2012) · International Journal of Clinical Practice · doi:10.1111/ijcp.12022 · Cited by 377
Japanese Allied Committee on Osteonecrosis of the Jaw, Yoneda, T., Hagino, H., Sugimoto, T., Ohta, H., Takahashi, S., Soen, S., Taguchi, A., Nagata, T., Urade, M., et al. (2017) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-016-0810-7 · Cited by 308
The WNT system: background and its role in bone
Lerner, U. H., & Ohlsson, C. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12368 · Cited by 228
Metadata
- Authors
- Baron, R., Ferrari, S., & Russell, R. G. G.
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 48
- Issue
- 4
- Pages
- 677-692
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W1997823019
- Cited by
- 715
- References
- 30
- FWCI
- 27.33
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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