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Acid-base regulation of bone metabolism

Arnett, TR; (2007) Acid-base regulation of bone metabolism. International Congress Series , 1297 pp. 255-267. 10.1016/j.ics.2006.08.005.

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Abstract

It has been known for almost a century that systemic acidosis causes depletion of the skeleton-an effect assumed to result from physicochemical dissolution of bone mineral. However, our work has shown that resorption pit formation by cultured osteoclasts is dependent on extracellular acidification. Osteoclasts are almost inactive above pH 7.4 and show maximum acid-activation at about pH 6.9. Within this pH range, small shifts in H+ concentration can cause large changes in resorption. Bone mineralisation by cultured osteoblasts is inhibited in a reciprocal manner by acidosis. In vivo, acidosis can occur systemically as a result of renal, bronchial or gastrointestinal disease, diabetes, severe (anaerobic) exercise, excessive protein intake, ageing, or the menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumours or ischaemia (due to increased anaerobic metabolism and reduced perfusion). The robust functional responses of bone cells to extracellular pH changes probably represent a primitive 'failsafe' to correct systemic acidosis by releasing alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The association of acidosis with hypoxia led us to investigate the effects of oxygen tension on bone cell function. We found that hypoxia causes impressive stimulation of osteoclast formation, independent of pH changes, whereas osteoblast growth and differentiation are blocked. Our results provide strong evidence for the critical role of the vasculature in the maintenance of bone health. © 2006 Elsevier B.V. All rights reserved.

Type: Article
Title: Acid-base regulation of bone metabolism
DOI: 10.1016/j.ics.2006.08.005
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/44568
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