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Regulation of bone cell function by acid–base balance

Published online by Cambridge University Press:  05 March 2007

Tim Arnett
Tim Arnett*
Affiliation:
Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK
*
Corresponding author: Dr Timothy R. Arnett, fax +44 20 7679 7349, [email protected]
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Abstract

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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.

Keywords

OsteoclastsOsteoblastsBoneAcidpH
Type
Macronutrient Group Symposium on ‘Protein intake and chronic disease’
Information
Proceedings of the Nutrition Society , Volume 62 , Issue 2 , May 2003 , pp. 511 - 520
Copyright
Copyright © The Nutrition Society 2003

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