Decreased bone carbonate content in response to metabolic, but not respiratory, acidosis

D. A. Bushinsky, B. C. Lam, R. Nespeca, N. E. Sessler and M. D. Grynpas Nephrology Unit, University of Rochester School of Medicine, New York 14642. In vitro cultured neonatal mouse calvariae release calcium and buffer the medium proton concentration in response to a decrease in the medium pH caused by a reduction in bicarbonate concentration ([HCO3-]), a model of metabolic acidosis, but not to an equivalent decrease in pH caused by an increase in the partial pressure of carbon dioxide (PCO2), a model of respiratory acidosis. We have postulated that the medium is in equilibrium with the carbonated apatite in bone. To determine whether bone carbonate is depleted during models of acidosis, we cultured calvariae in control medium (pH approximately 7.4, PCO2 approximately 43, [HCO3-] approximately 26) or in medium in which the pH was equivalently reduced by either a decrease in [HCO3-] (metabolic acidosis, pH approximately 7.1, [HCO3-] approximately 13) or an increase in PCO2 (respiratory acidosis, pH approximately 7.1, PCO2 approximately 86) and determined net calcium flux (JCa) and bone carbonate content. We found that compared with control, after 3, 24, and 48 h there was a decrease in bone carbonate content during metabolic but not during respiratory acidosis. Compared with control, at 3 h JCa increased with both respiratory and metabolic acidosis; however, at 24 and 48 h JCa increased only with metabolic acidosis. JCa was correlated inversely with percent bone carbonate content in control and metabolic acidosis at all time periods studied (r = -0.809, n = 23, P < 0.001). Thus a model of metabolic acidosis appears to increase JCa from bone, perhaps due to the low [HCO3-] inducing bone carbonate dissolution.