Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength.
Abstract
Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are dominant regulators of bone resorption. Many hormones, cytokines and growth factors mediate bone resorption by altering the ratio of RANKL to OPG. RANKL and OPG expression is also altered in numerous bone diseases, and these changes can reflect disease etiology or compensatory responses to disease. RANKL stimulates osteoclast formation, function and survival, and each of these effects is inhibited by OPG. OPG suppresses bone resorption and increases the density, area and strength of both cancellous and cortical bone. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, shares the pharmacologic attributes of OPG but has a significantly longer half-life that allows less frequent administration.
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Denosumab has a significantly longer circulating half-life than OPG-Fc, which allows reduced dosing frequency.
“An important practical consideration was that denosumab had a significantly longer circulating half-life compared with OPG-Fc (430), which would allow for reduced dosing frequency.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [430]
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- Authors
- KOSTENUIK, P.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- KOSTENUIK, P
- ORCID
- KOSTENUIK, P
- Venue
- Current Opinion in Pharmacology
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 5
- Issue
- 6
- Pages
- 618-625
- ISSN
- 1471-4892 (ISSN-L)
- OpenAlex
- W2055763817
- Cited by
- 281
- References
- 54
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 14 · 2020: 8 · 2019: 11 · 2018: 8 · 2017: 9 · 2016: 17 · 2015: 16 · 2014: 11 · 2013: 13 · 2012: 19
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoprotegerin, RANKL, bone resorption, RANKL/OPG ratio, osteoclasts, bone mineral density, bone geometry, bone strength, denosumab, monoclonal antibodies, bone disease, RANK signaling
- MeSH terms
- Denosumab, Animals, Antibodies, Monoclonal, Bone Resorption, Carrier Proteins, Glycoproteins, Humans, Membrane Glycoproteins, Osteoclasts, Bone Density, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Antibodies, Monoclonal, Humanized
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