title: Cortisol inhibits acid-induced bone resorption in vitro.
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 E(2) 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; [HCO(3)(-)] = 10.6 +/- 0.3 mM) or neutral (Ntl; pH = 7.43 +/- 0.01; [HCO(3)(-)] = 26.2 +/- 0.5 mM) medium, with or without 1 microM cortisol (Cort), and net calcium efflux and medium prostaglandin E(2) (PGE(2)) levels and osteoclastic beta-glucuronidase activity were determined. Compared with Ntl, Cort alone decreased calcium efflux, medium PGE(2), 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 PGE(2) levels and beta-glucuronidase activity compared with Acid alone. There was a significant direct correlation between medium PGE(2) concentration and net calcium efflux (r = 0.944; n = 23; P < 0.0001), between osteoclastic beta-glucuronidase activity and net calcium efflux (r = 0.663; n = 40; P < 0.001), and between medium PGE(2) concentration and beta-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 PGE(2) 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.
authors.affiliation: Department of Medicine, Nephrology Unit, University of Rochester School of Medicine, Rochester, New York 14642, USA. Nancy_Krieger@URMC.Rochester.edu
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Krieger
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Frick
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
mesh_terms: D000143:Acids; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced* / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008815:Mice, Inbred Strains; D009924:Organ Culture Techniques; D009994:Osmolar Concentration; D010313:Partial Pressure
chemical_list: D000143:Acids; D001639:Bicarbonates; D003470:Culture Media; D002245:Carbon Dioxide; D005966:Glucuronidase; D015232:Dinoprostone; D002118:Calcium; D006854:Hydrocortisone