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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) 2 D 3
Author(s) -
Morony Sean,
Capparelli Casey,
Lee Richard,
Shimamoto Grant,
Boone Thomas,
Lacey David L.,
Dunstan Colin R.
Publication year - 1999
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1999.14.9.1478
Subject(s) - bone resorption , osteoclast , endocrinology , medicine , parathyroid hormone , osteoprotegerin , bone remodeling , resorption , osteoporosis , hyperparathyroidism , chemistry , calcium , receptor , activator (genetics)
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 D 3 ) 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.