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Cortisol Inhibits Acid-Induced Bone Resorption In Vitro

Department of Medicine, Nephrology Unit, University of Rochester School of Medicine, Rochester, New York.

Correspondence to Dr. Nancy S. Krieger, Associate Research Professor of Medicine and of Pharmacology and Physiology, University of Rochester School of Medicine, Nephrology Unit, 601 Elmwood Avenue, Box 675, Rochester, NY 14642. Phone: 585-275-5123; Fax: 585-442-9201;

ABSTRACT. Metabolic acidosis increases urine calcium excretion without an increase in intestinal calcium absorption, resulting in a net loss of bone mineral. In vitro, metabolic acidosis has been shown to initially induce physicochemical mineral dissolution and then enhance cell-mediated bone resorption. Acidic medium stimulates osteoblastic prostaglandin E₂ production, which mediates the subsequent stimulation of osteoclastic bone resorption. Glucocorticoids are also known to decrease bone mineral density, and metabolic acidosis has been shown to increase glucocorticoid production. This study tested the hypothesis that glucocorticoids would exacerbate acid-induced net calcium efflux from bone. Neonatal mouse calvariae were cultured in acid (Acid; pH = 7.06 ± 0.01; [HCO₃^-] = 10.6 ± 0.3 mM) or neutral (Ntl; pH = 7.43 ± 0.01; [HCO₃^-] = 26.2 ± 0.5 mM) medium, with or without 1 µM cortisol (Cort), and net calcium efflux and medium prostaglandin E₂ (PGE₂) levels and osteoclastic -glucuronidase activity were determined. Compared with Ntl, Cort alone decreased calcium efflux, medium PGE₂, and osteoclast activity; Acid led to an increase in all three parameters. The addition of Cort to Acid led to a reduction of calcium efflux, medium PGE₂ levels and -glucuronidase activity compared with Acid alone. There was a significant direct correlation between medium PGE₂ concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between osteoclastic -glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE₂ concentration and -glucuronidase activity (r = 0.976; n = 4; P < 0.01). Thus, in vitro cortisol inhibits acid-induced, cell-mediated osteoclastic bone resorption through a decrease in osteoblastic PGE₂ production. These results suggest that the osteopenia observed in response to metabolic acidosis in vivo is not due to an increase in endogenous cortisol production. E-mail: Nancy_Krieger@URMC.Rochester.edu

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673