Cortisol Inhibits Acid-Induced Bone Resorption In Vitro

Abstract

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 β-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 β-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 β-glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE2 concentration and β−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