Effects of in vivo metabolic acidosis on midcortical bone ion composition

Am J Physiol. 1999 Nov;277(5):F813-9. doi: 10.1152/ajprenal.1999.277.5.F813.


Chronic metabolic acidosis increases urine calcium excretion without altering intestinal calcium absorption, suggesting that bone mineral is the source of the additional urinary calcium. During metabolic acidosis there appears 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 effect of metabolic acidosis on the ion composition of bone, there are few in vivo observations. We utilized a high-resolution scanning ion microprobe with 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 were provided distilled drinking water with or without 1.5% NH(4)Cl for 7 days; arterial blood gas was then determined. The addition of NH(4)Cl led to a fall in blood pH and HCO(-)(3) concentration. The animals were killed on day 7, and the femurs were dissected and split longitudinally. The bulk cortical ratios Na/Ca, K/Ca, total phosphate/carbon-nitrogen bonds [(PO(2) + PO(3))/CN], and HCO(-)(3)/CN each fell after 1 wk of metabolic acidosis. Because metabolic acidosis 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 (PO(2) + PO(3))/CN indicates release of mineral phosphates, and the fall in HCO(-)(3)/CN indicates release of mineral HCO(-)(3). Each of these mechanisms would result in buffering of the excess protons and returning the systemic pH toward normal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis / chemically induced
  • Acidosis / metabolism*
  • Ammonium Chloride
  • Animals
  • Anions / metabolism
  • Bone Density
  • Cations / metabolism
  • Femur / metabolism*
  • Ions
  • Mice
  • Protons


  • Anions
  • Cations
  • Ions
  • Protons
  • Ammonium Chloride