Effects of in vivo metabolic acidosis on midcortical bone ion composition

Chronic metabolic acidosis increases urine calcium excretion without alteri ng intestinal calcium absorption, suggesting that bone mineral is the sourc e of the additional urinary calcium. During metabolic acidosis there appear s to be an influx of protons into bone mineral, lessening the magnitude of the decrement in pH. Although in vitro studies strongly support a marked ef fect of metabolic acidosis on the ion composition of bone, there are few in vivo observations. We utilized a high-resolution scanning ion microprobe w ith secondary ion mass spectroscopy to determine whether in vivo metabolic acidosis would alter bone mineral in a manner consistent with its purported role in buffering the increased proton concentration. Postweanling mice we re provided distilled drinking water with or without 1.5% NH4Cl for 7 days; arterial blood gas was then determined. The addition of NH4Cl led to a fal l in blood pH and HCO3- concentration. The animals were killed on day 7, an d the femurs were dissected and split longitudinally. The bulk cortical rat ios Na/Ca, K/Ca, total phosphate/carbon-nitrogen bonds [(PO2 + PO3)/CN], an d HCO3-/CN each fell after 1 wk of metabolic acidosis. Because metabolic ac idosis induces bone Ca loss, the fall in Na/Ca and K/Ca indicates a greater efflux of bone Na and K than Ca, suggesting H substitution for Na and K on the mineral. The fall in (PO2 + PO3)/CN indicates release of mineral phosp hates, and the fall in HCO3-/CN indicates release of mineral HCO3-. Each of these mechanisms would result in buffering of the excess protons and retur ning the systemic pH toward normal.