Metabolic, but not respiratory, acidosis increases bone PGE2levels and calcium release

Abstract

First published July 12, 2001; 10.1152/ajprenal.00355.2001.— A decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO${}_3^{-}$ ]; metabolic acidosis) or to an increase in Pco₂ (respiratory acidosis). In mammals, metabolic, but not respiratory, acidosis increases urine calcium excretion without altering intestinal calcium absorption, indicating that the additional urinary calcium is derived from bone. In cultured bone, chronic metabolic, but not respiratory, acidosis increases net calcium efflux (J_Ca), decreases osteoblastic collagen synthesis, and increases osteoclastic bone resorption. Metabolic acidosis increases bone PGE₂production, which is correlated with J_Ca, and inhibition of PGE₂ production inhibits this acid-inducedJ_Ca. Given the marked differences in the osseous response to metabolic and respiratory acidosis, we hypothesized that incubation of neonatal mouse calvariae in medium simulating respiratory acidosis would not increase medium PGE₂ levels, as observed during metabolic acidosis. To test this hypothesis, we determined medium PGE₂ levels and J_Ca from calvariae incubated at pH ∼7.1 to model either metabolic (Met; [HCO${}_3^{-}$ ] ∼11 mM) or respiratory (Resp; Pco₂ ∼83 Torr) acidosis, or at pH ∼7.5 as a control (Ntl). We found that after 24–48 and 48–51 h in culture, periods when cell-mediated J_Capredominates, medium PGE₂ levels andJ_Ca were increased with Met, but not Resp, compared with Ntl, and there was a direct correlation between medium PGE₂ levels and J_Ca. Thus metabolic, but not respiratory, acidosis induces the release of bone PGE₂, which mediates J_Ca from bone.