Circulating Osteoprotegerin and Receptor Activator for Nuclear Factor κB Ligand: Clinical Utility in Metabolic Bone Disease Assessment

Rogers, Angela; Eastell, Richard

doi:10.1210/jc.2005-0794

Cited by 215Bone Metabolism and DiseasesBone health and osteoporosis researchRheumatoid Arthritis Research and Therapies

Circulating Osteoprotegerin and Receptor Activator for Nuclear Factor κB Ligand: Clinical Utility in Metabolic Bone Disease Assessment

Rogers, Angela, Eastell, Richard·2005·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2005-0794

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Abstract

CONTEXT: The discovery of the receptor activator for nuclear factor kappaB (RANK) ligand (RANKL)/RANK signaling pathway has marked a major advance in our understanding of the mechanisms controlling osteoclastogenesis. RANKL, expressed by preosteoblasts and stromal cells, binds to RANK, expressed by cells of the osteoclast lineage, inducing a signaling cascade leading to the differentiation and fusion of osteoclast precursor cells and stimulating the activity of the mature osteoclast. The effects of RANKL are counteracted by osteoprotegerin (OPG), a soluble neutralizing decoy receptor. EVIDENCE: This paper reviews the literature surrounding the use of circulating OPG and soluble RANKL (sRANKL) measurements and assesses their potential as markers of bone disease. Original clinical and basic research articles and reviews were identified using a Pubmed search strategy (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) and cover the time period up until January 2005. Search terms osteoprotegerin, OPG, RANK, RANKL, and RANK ligand were used alone and in combination with bone, osteoporosis, and disease. EVIDENCE SYNTHESIS: Assays for detecting OPG and sRANKL in the circulation in humans have been developed, and differences in the circulating concentrations of OPG and sRANKL have been observed in different disease states. There are, however, some inconsistencies in study outcome. These may relate to differences in study design, methodology, and other unknown factors influencing the variability of these measurements. CONCLUSIONS: The clinical utility of serum OPG and sRANKL measurements as markers of disease activity requires additional investigation. In particular, rigorous testing of assays and identification of the sources of measurement variability are required.

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Many factors influencing circulating levels of OPG and RANKL have been identified.
“Many factors influencing the circulating levels of these cytokines have been identified (371).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [371]

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The functions of the avian receptor activator of NF-κB ligand (RANKL) and its receptors, RANK and osteoprotegerin, are evolutionarily conserved
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Authors: Rogers, A., & Eastell, R.
Affiliations: University of Sheffield (GB)
ORCID: Eastell, Richard
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2005-11
Volume: 90
Issue: 11
Pages: 6323-6331
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2005-0794
OpenAlex: W2107118655
Cited by: 215
References: 118
Citations by year: 2025: 3 · 2024: 6 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 11 · 2014: 7 · 2013: 12 · 2012: 16
FWCI: 7.43
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (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, RANK ligand, soluble RANKL, osteoclastogenesis, metabolic bone disease, bone turnover markers, osteoporosis, serum biomarkers, measurement variability
MeSH terms: Bone Diseases, Metabolic, Carrier Proteins, Female, Glycoproteins, Humans, Male, Membrane Glycoproteins, Neoplasms, Osteoporosis, Sex Factors, Vascular Diseases, Fracture Healing, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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Circulating Osteoprotegerin and Receptor Activator for Nuclear Factor κB Ligand: Clinical Utility in Metabolic Bone Disease Assessment

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