Regulation of bone cell function by acid–base balance

Proceedings of the Nutrition Society - Tập 62 Số 2 - Trang 511-520 - 2003
T Arnett1
1Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Martin, 1994, Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy, Cancer Research, 54, 5670

10.1038/ki.1984.64

10.1093/ajcn/71.1.142

Goto, 1918, Mineral metabolism in experimental acidosis, Journal of Biological Chemistry, 36, 355, 10.1016/S0021-9258(18)86403-1

10.1007/BF02554835

10.1002/jbmr.5650101002

10.1111/j.1749-6632.1999.tb11274.x

10.1016/S0002-9343(99)80310-6

Frick, 1998, Chronic metabolic acidosis reversibly inhibits extracellular matrix gene expression in mouse osteoblasts, American Journal of Physiology, 275, F840

10.1002/jbmr.5650051102

10.1016/0169-6009(90)90026-C

10.1079/PNS2002159

Santhanagopal, 1999, Insulin-like growth factor I rapidly enhances acid efflux from osteoblastic cells, American Journal of Physiology, 277, E423

10.1111/j.1469-7793.1998.495bh.x

Ginty, 1998, The effect of short-term calcium supplementation on biochemical markers of bone metabolism in healthy young adults, British Journal of Nutrition, 80, 437, 10.1017/S0007114598001500

10.1056/NEJM199406233302502

Frassetto, 1996, Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline, American Journal of Physiology, 271, F1114

10.1016/8756-3282(95)00486-6

10.1016/0002-9343(82)90179-6

Cooke, 1955, Osteoporosis, Lancet, i, 929

10.1152/ajpcell.1995.268.1.C80

Bushinsky, 1989, Net calcium efflux from live bone during chronic metabolic, but not respiratory, acidosis, American Journal of Physiology, 256, F836

10.1084/jem.56.6.823

10.1007/s00223001107

10.1074/jbc.272.42.26346

10.1016/S0022-5347(05)66414-2

10.1210/endo-119-1-119

10.1096/fj.00-0395com

Bushinsky, 1983, Effects of pH on bone calcium and proton fluxes in vitro, American Journal of Physiology, 245, F204

10.1007/s001980170095

10.1079/BJN19970187

Albright, 1948, The Parathyroid Glands and Metabolic Bone Disease, 242

Morrison, 1998, pH effects on osteoclast formation and activation, Bone, 22

Bridgeman, 1996, Blood supply to the human femoral diaphysis in youth and senescence, Journal of Anatomy, 188, 611

10.1172/JCI105467

Bushinsky, 1985, Cellular contribution to pH-mediated calcium flux in neonatal mouse calvariae, American Journal of Physiology, 248, F785

Frassetto, 1996, Age and systemic acid-base equilibrium: analysis of published data, Journal of Gerontology, 51, B91

Gibbons, 2001, Hypoxia is a powerful stimulator of bone resorption, Journal of Bone and Mineral Research, 16

Bushinsky, 1992, Greater unidirectional calcium efflux from bone during metabolic, compared with respiratory, acidosis, American Journal of Physiology, 262, F425

Barzel, 1969, The effects of chronic acid and alkali administration on bone turnover in adult rats, Clinical Science, 36, 517

10.1056/NEJM199009273231305

Bushinsky, 1987, Mechanism of protoninduced bone calcium release: calcium carbonate-dissolution, American Journal of Physiology, 253, F998

10.1016/B978-0-12-068702-2.50008-8

10.1007/BF02556313

10.1002/jbmr.5650060508

Cooke, 1955, Osteoporosis, Lancet, i, 878

10.1016/0002-9343(68)90252-0

10.1016/S0092-8674(00)81569-X

10.1359/jbmr.2000.15.3.550

Meghji, 2001, pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis, American Journal of Physiology, 280, E112

Orr-Walker, 1999, Hormone replacement therapy causes a respiratory alkalosis in normal postmenopausal women, Journal of Clinical Endocrinology and Metabolism, 84, 1997

10.1007/s002230001172

10.1038/ki.1991.2

10.1093/ajcn/73.1.5

10.1002/jcp.1041540309

10.1007/BF02556314

Goldhaber, 1987, H + stimulation of cell-mediated bone resorption in tissue culture, American Journal of Physiology, 253, E90

10.1210/endo-120-2-602

10.1074/jbc.272.10.6354

Thông tin
Thông tin xuất bản

Proceedings of the Nutrition Society

Tập 62 Số 2

511-520

Thông tin tác giả