Regulation of bone cell function by acid-base balance

Proc Nutr Soc. 2003 May;62(2):511-20. doi: 10.1079/pns2003268.


Bone growth and turnover results from the coordinated activities of two key cell types. Bone matrix is deposited and mineralised by osteoblasts and it is resorbed by osteoclasts, multinucleate cells that excavate pits on bone surfaces. It has been known since the early 20th century that systemic acidosis causes depletion of the skeleton, an effect assumed to result from physico-chemical dissolution of bone mineral. However, our own work has shown that resorption pit formation by cultured osteoclasts was absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7.3 and show maximum stimulation at a pH of about 6.9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7.1 (which may be close to the interstitial pH in bone). In this region pH shifts of < 0.05 units can cause a doubling or halving of pit formation. In whole-bone cultures, chronic HCO3- acidosis results in similar stimulations of osteoclast-mediated Ca2+ release, with a negligible physico-chemical component. In vivo, severe systemic acidosis (pH change of about -0.05 to -0.20) often results from renal disease; milder chronic acidosis (pH change of about -0.02 to -0.05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or diabetic ischaemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive 'fail-safe' that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time.

Publication types

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

MeSH terms

  • Acid-Base Equilibrium / physiology*
  • Acid-Base Imbalance / complications*
  • Acidosis / complications
  • Acidosis / metabolism
  • Aging / metabolism
  • Bicarbonates / metabolism
  • Bone Resorption
  • Bone and Bones / cytology
  • Bone and Bones / physiology*
  • Diet
  • Humans
  • Hydrogen-Ion Concentration
  • Osteoblasts / metabolism
  • Osteoblasts / physiology
  • Osteoclasts / metabolism
  • Osteoclasts / physiology


  • Bicarbonates