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The resources listed below represent a collection of scientific articles discussing research on the effects of chronic, low-grade metabolic acidosis on bone, including studies relating acid-base balance to osteopenia and osteoporosis. These sources represent an expanding database of observations that support pH balance as a necessary component of full bone health.
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Alexy, U., T. Remer, et al. (2005). Long-term protein intake and dietary potential renal acid load are associated with bone modeling and remodeling at the proximal radius in healthy children. Am J Clin Nutr 82:1107-14.
Amanzadeh, J., Gitomer, W.L., et al. (2003). Effect of high protein diet on stone-forming propensity and bone loss in rats. Kidney Int 64(6): 2142-9. PMID: 14633136
Arnett, T. R. and D. W. Dempster. 1986. Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrin 119:119–124.
Arnett, T. (2003). Regulation of bone cell function by acid-base balance. Proc Nutr Soc 62(2): 511-20. PMID: 14506899
Arnett, T. R., Spowage, M. (1996). Modulation of the resorptive activity of rat osteoclasts by small changes in extracellular pH near the physiological range. Bone 18(3): 277-9. PMID: 8703584
Bäckman, T. (1999). Acid-base balance, dentinogenesis, and dental caries. Faculty of Medicine, University of Oulu, Finland.
Ballard, T. L., Clapper, J.A., et al. (2005). Effect of protein supplementation during a 6-mo strength and conditioning program on insulin-like growth factor I and markers of bone turnover in young adults. Am J Clin Nutr 81(6): 1442-8. PMID: 15941900
Barzel, U.S., Jowsey, J. (1969). The effects of chronic acid and alkali administration on bone turnover in adult rats. Clin Sci 36(3): 517-24. PMID: 5795240
Barzel, U.S., Massey, L.K. (1998). Excess dietary protein can adversely affect bone. J Nutr 128(6): 1051-3. PMID: 9614169
Brandao-Burch, A., J.C. Utting, I.R. Orriss, et al. (2005). Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77: 167-174.
Breslau, N.A., Brinkley, L., et al. (1988). Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab 66(1): 140-6. PMID: 2826524
Buclin, T., Cosma, M., et al. (2001). Diet acids and alkalis influence calcium retention in bone. Osteoporos Int 12(6): 493-9. PMID: 11446566
Budde, R.A., Crenshaw, T.D. (2003). Chronic metabolic acid load induced by changes in dietary electrolyte balance increased chloride retention but did not compromise bone in growing swine. J Anim Sci 81(1): 197-208. PMID: 12597391
Burket, J. C., J. MacLeay, et al. (2010). Variations in cancellous bone tissue composition and mechanical properties with a model of osteoporosis and treatment in sheep. Presentation number SU0048, ASBMR Conference, Toronto, Canada.
Bushinsky, D.A. (1987). Effects of parathyroid hormone on net proton flux from neonatal mouse calvariae. Am J Physiol 252(4 Pt 2): F585-9. PMID: 3031997
Bushinsky, D.A. (1989). Internal exchanges of hydrogen ions: bone. In: Seldein D.W., Giebisch, G., eds. The regulation of acid-base balance. New York: Raven Press, pp. 69-88.
Bushinsky, D.A. (1995). Stimulated osteoclastic and suppressed osteoblastic activity in metabolic but not respiratory acidosis. Am J Physiol 268(1 Pt 1): C80-8. PMID: 7840163
Bushinsky, D.A. (1996). Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol 271(1 Pt 2): F216-22. PMID: 8760264
Bushinsky, D.A. (2001). Acid-base imbalance and the skeleton. Eur J Nutr 40(5): 238-44. http://www.saeure-basen-forum.de/pdf/symp2001/bushinsky.pdf
Bushinsky, D.A., Coe, F.L. (1985). Hyperkalemia during acute ammonium chloride acidosis in man. Nephron 40(1): 38-40. PMID: 3923378
Bushinsky, D.A., Gavrilov, K., et al. (1997). Effect of metabolic acidosis on the potassium content of bone. J Bone Miner Res 12(10): 1664-71. PMID: 9333127
Bushinsky, D.A., Gavrilov, K., et al. (1996). Effects of osteoclastic resorption on bone surface ion composition. Am J Physiol 271(4 Pt 1): C1025-31. PMID: 8897806
Bushinsky, D.A., Krieger, N.S., et al. (1983). Effects of pH on bone calcium and proton fluxes in vitro. Am J Physiol 245(2): F204-9. PMID: 6881337
Bushinsky, D.A., Lechleider, R.J. (1987). Mechanism of proton-induced bone calcium release: calcium carbonate-dissolution. Am J Physiol 253(5 Pt 2): F998-1005. PMID: 2825542
Bushinsky, D.A., Levi-Setti, R., et al. (1986). Ion microprobe determination of bone surface elements: effects of reduced medium pH. Am J Physiol 250(6 Pt 2): F1090-7. PMID: 3717349
Bushinsky, D.A., Nilsson, E.L. (1995). Additive effects of acidosis and parathyroid hormone on mouse osteoblastic and osteoclastic function. Am J Physiol 269(6 Pt 1): C1364-70. PMID: 8572164
Bushinsky, D.A., Sessler, N.E. (1992). Critical role of bicarbonate in calcium release from bone. Am J Physiol 263(3 Pt 2): F510-5. PMID: 1415579
Bushinsky, D.A., Sessler, N.E., et al. (1994). Proton-induced physicochemical calcium release from ceramic apatite disks. J Bone Miner Res 9(2): 213-20. PMID: 8140934
Bushinsky, D.A., Sessler, N.E., et al. (1992). Greater unidirectional calcium efflux from bone during metabolic, compared with respiratory, acidosis. Am J Physiol 262(3 Pt 2): F425-31. PMID: 1558159
Bushinsky, D.A., Smith, S.B., et al. (2002). Acute acidosis-induced alteration in bone bicarbonate and phosphate. Am J Physiol Renal Physiol 283(5): F1091-7. PMID: 12372785
Bushinsky, D.A., Smith, S.B., et al. (2003). Chronic acidosis-induced alteration in bone bicarbonate and phosphate. Am J Physiol Renal Physiol 285(3): F532-9. PMID: 12759230
Canas, F., Terepka, A.R., et al. (1969). Potassium and milieu interieur of bone. Am J Physiol 217(1): 117-20. PMID: 5785866
Carter, J.D., Vasey, F.B., et al. (2006). The effect of a low-carbohydrate diet on bone turnover. Osteoporos Int 17(9): 1398-403. PMID: 16718399
Cochran, M., Wilkinson, R. (1975). Effect of correction of metabolic acidosis on bone mineralisation rates in patients with renal osteomalacia. Nephron 15: 98-110.
Dargent-Molina, P., S. Sabia, et al. (2008). Proteins, dietary acid load, and calcium and risk of post-menopausal fractures in the E3N French Women Prospective Study. J Bone Miner Res 23(12):1915-22.
Dawson-Hughes, B., S.S. Harris, N.J. Palermo, et al. (2009). Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab 94: 96-102.
Dawson-Hughes, B., Harris, S.S., et al. (2008). Alkaline diets favor lean tissue mass in older adults. Am J Clin Nutr 87(3): 662-5. PMID: 18326605
Dawson-Hughes, B., Harris, S.S., et al. (2004). Effect of dietary protein supplements on calcium excretion in healthy older men and women. J Clin Endocrinol Metab 89(3): 1169-73. PMID: 15001604
Dawson-Hughes, B., Harris, S.S. (2002). Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am J Clin Nutr 75(4): 773-779. ID: 11916767
Devine, A., Prince, R.L., et al. (1996). Nutritional effect of calcium supplementation by skim milk powder or calcium tablets on total nutrient intake in postmenopausal women. Am J Clin Nutr 64(5): 731-7. PMID: 8901793
Domrongkitchaiporn, S., Pongsakul, C., et al. (2001). Bone mineral density and histology in distal renal tubular acidosis. Kidney Int 59(3): 1086-93. PMID: 11231364
Domrongkitchaiporn, S., Pongsakul, C., et al. (2002). Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis. Kidney Int 62(6): 2160-6. PMID: 12427141
Duff, T.L., Whiting, S.J. (1998). Calciuric effects of short-term dietary loading of protein, sodium chloride and potassium citrate in prepubescent girls. J Am Coll Nutr 17(2): 148-54. PMID: 9550458
Fenton, T.R., A.W. Lyon, M. Eliaziw, et al. (2009). Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance. J Bone Miner Res 24: 1835-1840.
Fenton, T. R., A. W. Lyon, M. Eliasziw, et al. (2009). Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis. Nutr J 8:41.
Fenton, T. R., M. Eliasziw, et al. (2010). Bone fractures or the loss of bone mineral density: A prospective cohort study. BMC Musculo Dis 11:88.
Frassetto, L., R.C. Morris Jr., and A. Sebastian. (1997). Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab 82: 254-259.
Frassetto, L., R.C. Morris, Jr. and A. Sebastian. (2004). Diet acid load and bone health. In Nutritional Aspects of Osteoporosis, 2nd ed. Ed. P. Burckhardt, B. Dawson-Hughes and R.P. Heaney. San Diego, CA: Elsevier Academic Press.
Frassetto, L., Morris, R.C. Jr., et al. (1997). Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab 82(1): 254-9.
Frassetto, L., Morris, R.C. Jr., et al. (2005). Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. J Clin Endocrinol Metab 90(2): 831-4. PMID: 15572425
Frassetto, L., Sebastian, A. (1996). Age and systemic acid-base equilibrium: analysis of published data. J Gerontol A Biol Sci Med Sci 51(1): B91-9. PMID: 8548506
Frassetto, L.A., Morris, R.C. Jr., et al. (1996). Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline. Am J Physiol 271(6 Pt 2): F1114-22.
Frassetto, L.A., Nash, E., et al. (2000). Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion. Kidney Int 58(2): 748-52. PMID: 10916098
Frassetto, L.A., Todd, K.M., et al. (1998). Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr 68(3): 576-83. PMID: 9734733
Frassetto, L.A., Todd, K.M., et al. (2000). Worldwide incidence of hip fracture in elderly women: relation to consumption of animal and vegetable foods. J Gerontol Biol Sci Med Sci 55(10): M585-92. PMID: 11034231
Frick, K.K., Bushinsky, D.A. (1998). Chronic metabolic acidosis reversibly inhibits extracellular matrix gene expression in mouse osteoblasts. Am J Physiol 275(5 Pt 2): F840-7. PMID: 9815143
Frick, K.K., Bushinsky, D.A. (2003). Metabolic acidosis stimulates RANKL RNA expression in bone through a cyclo-oxygenase-dependent mechanism. J Bone Miner Res 18(7): 1317-25. PMID: 12854843
Frings-Meuthen, P., N. Baecker, and M. Heer. (2008). Low-grade metabolic acidosis may be the cause of sodium-chloride induced exaggerated bone resorption. J Bone Miner Res 23: 517-524.
Green, J., Kleeman C.R. (1991). The role of bone in the regulation of systemic acid-base balance. Contrib Nephrol 91: 61-76. PMID: 1800012
Grinspoon, S.K., Baum, H.B., et al. (1995). Decreased bone formation and increased mineral dissolution during acute fasting in young women. J Clin Endocrinol Metab 80(12): 3628-33. PMID: 8530611
Grinspoon, S.K., Baum, H.B., et al. (1995). Decreased bone formation and increased mineral dissolution during acute fasting in young women. J Clin Endocrinol Metab 80(12): 3628-33. PMID: 8530611
Hardcastle, A. C., L. Aucott, et al. (2011). Dietary patterns, bone resorption and bone mineral density in early post-menopausal Scottish women. Eur J Clin Nutr 65:378-85.
Heaney, R., Weaver, C., et al. (1993). Absorbability of calcium from brassica vegetables: broccoli, bok choy, and kale. J Food Sci 58(6): 1378-80.
Heersche, J.N., Bellows, C.G., et al. (1998). The decrease in bone mass associated with aging and menopause. J Prosthet Dent 79(1): 14-6. PMID: 9474535
Hegarty, V.M., May, H.M., et al. (2000). Tea drinking and bone mineral density in older women. Am J Clin Nutr 71(4): 1003-7. PMID: 10731510
Henriksen, K., Sorensen, M.G., et al. (2006). Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification. J Bone Miner Res 21(1): 58-66. PMID: 16355274
Hood, V.L., Tannen, R. L. (1998). Protection of acid-base balance by pH regulation of acid production. N Engl J Med 339(12): 819-26. PMID: 9738091
Hu, J. F., Zhao, X.H., et al. (1993). Dietary intakes and urinary excretion of calcium and acids: a cross-sectional study of women in China. Am J Clin Nutr 58(3): 398-406. PMID: 8237852
Jaffe, R. and S. E. Brown. 2000. Acid alkaline balance and its effect on bone health. Int. J. Integ. Med. 2(6).
Jajoo, R., Song, L., et al. (2006). Dietary acid-base balance, bone resorption, and calcium excretion. J Am Coll Nutr 25(3): 224-30. PMID: 16766781
Jehle, S., Zanetti, A., et al. (2006). Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol 17(11): 3213-22. PMID: 17035614
Kalhoff, H., Manz, F. (2001). Nutrition, Acid-Base Status and Growth in Early Childhood. Eur J Nutr 40(5): 221-30. http://www.saeure-basen-forum.de/pdf/symp2001/kalhoff_manz.pdf
Kerstetter, J. E., Mitnick, M.E., et al. (1999). Changes in bone turnover in young women consuming different levels of dietary protein. J Clin Endocrinol Metab 84(3): 1052-5. PMID: 10084594
Klevay, L. M., Wildman, R.E. (2002). Meat diets and fragile bones: inferences about osteoporosis. J Trace Elem Med Biol 16(3): 149-54. PMID: 12437150
Kocian, J., Brodan, V. (1979). Simultaneous correction of Ca deficiency and acidosis in fasting obese patients as a prevention of bone demineralisation. Nutr Metab 23(5): 391-8. PMID: 481830
Komarova, S.V., Pereverzev, A., et al. (2005). Convergent signaling by acidosis and receptor activator of NF-kappaB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts. Proc Natl Acad Sci U S A 102(7): 2643-8. PMID: 15695591
Krieger, N. S., Frick, K.K., et al. (2002). Cortisol inhibits acid-induced bone resorption in vitro. J Am Soc Nephrol 13(10): 2534-9. PMID: 12239242
Krieger, N. S., Sessler, N.E., et al. (1992). Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro. Am J Physiol 262(3 Pt 2): F442-8. PMID: 1558161
Krieger, N. S., Sukhatme, V.P., et al. (1990). Conditioned medium from ras oncogene-transformed NIH 3T3 cells induces bone resorption in vitro. J Bone Miner Res 5(2): 159-64. PMID: 2180257
Krieger, N, S. Yee, et al. (2009). Metabolic acidosis stimulates RGS2 and inhibits RGS16 in osteoblasts. Presentation number SU0208, ASBMR 31st Annual Meeting, Colorado.
Kurtz, I., Maher, T. et al. (1983). Effect of diet on plasma acid-base composition in normal humans. Kidney Int 24(5): 670-80. PMID: 6663989
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Lemann, J., Jr., Bushinsky, D.A., et al. (2003). Bone buffering of acid and base in humans. Am J Physiol Renal Physiol 285(5): F811-32. PMID: 14532161
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MacDonald, H.M., New, S.A., et al. (2005). Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women. Am J Clin Nutr 81(4): 923-33. PMID: 15817873
MacDonald, H.M., New, S.A., et al. (2004). Nutritional associations with bone loss during the menopausal transition: Evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr. 79: 155-65
Manz, F. (2001). History of nutrition and acid-base physiology. Eur J Nutr 40(5): 189-99. http://www.saeure-basen-forum.de/pdf/symp2001/manz.pdf
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New, S.A., H.M. MacDonald, M.K. Campbell, et al. (2004). Lower estimates of net endogenous non-carbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women. Am J Clin Nutr 79: 131-138.
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