Hyperostosis induced by the bisphosphonate (2-PEBP) in the oophorectomized rat.
To prevent the high turnover bone remodeling associated with acute estrogen deficiency, the bisphosphonate [2-(2-pyridinyl) ethylidene-BP] (2-PEBP) was administered to oophorectomized (OX) rats. Three groups of 15 rats each (250 g) were studied. Group (Gp) A was sham operated, Gp B was OX, and Gp C received 2-PEBP (1.72 mg/kg/day) intraperitoneally for 3 days commencing 4 days postoophorectomy. Oophorectomy was confirmed with serum estradiol measurements. Blood samples were collected on days -7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), PTH, and serum bone gla protein (BGP). Rats received tetracycline for bone histomorphometric labeling. All results were compared to Gp A. Body weight increased significantly in Gps B and C (P less than 0.005 by day 28). There was no significant difference in Ca2+, and PTH levels in Gps B and C were similar to Gp A. BGP levels were significantly higher on day 28 in Gp B (P less than 0.05). In Gp C, BGP levels were significantly decreased on days 7, 21, and 28 (P less than 0.03). Gp B revealed increased bone turnover without loss of bone volume (BV/TV). BV/TV was significantly increased in Gp C despite a decrease in parameters of bone formation and normal osteoclast number. In conclusion, 2-PEBP in the OX rat inhibited bone resorption more than formation with resultant hyperostosis. Serum BGP appeared to be a good marker of the changes observed on bone histomorphometry.
Movsowitz
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C
Division of Endocrinology and Metabolism, Albert Einstein Medical Center, Philadelphia, PA 19141.
Epstein
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Fallon
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Ismail
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F
Thomas
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S
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001846:Bone Development / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D005260:Female; D015576:Hyperostosis / Q000139:chemically induced* / Q000503:physiopathology; D015675:Osteocalcin / Q000097:blood; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013977:Tibia / Q000473:pathology
D004164:Diphosphonates; D010281:Parathyroid Hormone; D015675:Osteocalcin; D004958:Estradiol; C054229:2-(2-pyridyl)ethylidine-1,1-bisphosphonate; D002118:Calcium