Cited by 187Bone Metabolism and DiseasesBone health and osteoporosis researchRheumatoid Arthritis Research and Therapies

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A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3.

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Morony, Sean, Capparelli, Casey, Lee, Richard, Shimamoto, Grant, Boone, Thomas, Lacey, David L., Dunstan, Colin R.·1999·Journal of Bone and Mineral Research

DOI 10.1359/jbmr.1999.14.9.1478

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Abstract

Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation and activity and appears to be a critical regulator of bone mass and metabolism. In the current study, mice were challenged with various cytokines and hormones (interleukin-1β, tumor necrosis factor-α, parathyroid hormone, parathyroid hormone-related protein, and 1α,25-dihydroxyvitamin D3) that are known to increase bone resorption and cause hypercalcemia and treated concurrently with either a recombinant chimeric Fc fusion form of human OPG, with enhanced biological activity (cOPG) (2.5 mg/kg/day) or vehicle. Mice receiving these bone-resorbing factors became hypercalcemic by day 3 after commencing treatment and had increased bone resorption as evidenced by elevated osteoclast numbers on day 5. Concurrent cOPG treatment prevented hypercalcemia (p < 0.05) and maintained osteoclast numbers in the normal range (p < 0.001). The demonstration that cOPG can inhibit bone resorption suggests that this molecule may be useful in the treatment of diseases including hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, and inflammatory bone disease, which are characterized, in part, by increases in osteoclastic bone resorption.

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Authors: Morony, S., Capparelli, C., Lee, R., Shimamoto, G., Boone, T., Lacey, D. L., & Dunstan, C. R.
Affiliations: Amgen (United States) (US)
Corresponding author: Dunstan, Colin R.
ORCID: Lee, Richard
Boone, Thomas
Dunstan, Colin R.
Venue: Journal of Bone and Mineral Research
Publisher: Oxford University Press (OUP)
Published: 1999-09-01
Volume: 14
Issue: 9
Pages: 1478-1485
ISSN: 0884-0431 (ISSN-L)
1523-4681
DOI: 10.1359/jbmr.1999.14.9.1478
OpenAlex: W2050716165
Cited by: 187
References: 43
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2022: 2 · 2020: 3 · 2019: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 7
FWCI: 6.73
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Journal of Bone and Mineral Research (publishedVersion)
PubMed (publishedVersion)
Funders: Amgen
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, hypercalcemia, bone resorption, osteoclasts, IL-1β, TNF-α, parathyroid hormone, parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, inflammatory bone disease, bone metabolism
MeSH terms: Animals, Bone and Bones, Bone Resorption, Calcitriol, Calcium, Cell Count, Glycoproteins, Humans, Hypercalcemia, Interleukin-1, Isomerism, Male, Osteoclasts, Parathyroid Hormone, Proteins, Radiography, Tumor Necrosis Factor-alpha, Weight Loss, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Parathyroid Hormone-Related Protein, Mice, Osteoprotegerin

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A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3.

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