The Effects of High Phosphorus Intake on Calcium Homeostasis

  • Mona S. Calvo
Part of the Advances in Nutritional Research book series (ANUR, volume 9)


Osteoporosis and related bone fractures are recognized as a serious cause of morbidity and mortality, largely among elderly women. The most preventable cause of fractures is low bone mass (Riggs and Melton, 1992), which is thought to be dependent on both the current rate of bone loss and peak bone mass (i.e., the amount of bone present at skeletal maturity) (Riggs and Melton, 1986). The most cost-effective approach to reducing the risk of osteoporosis is to maximize peak bone mass by optimizing bone accretion during teen and early adult life and later to slow the rate of bone loss with increasing age (Riggs and Melton, 1986, 1992; Ott, 1990; Matkovic et al., 1990).


Bone Mineral Content Calcium Intake Secondary Hyperparathyroidism Dietary Calcium Peak Bone Mass 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albanese, A.A., Lorenze, E.J., Edelson, A.H., Tarlow, A., Wein, E.H., and Carroll, L., 1986, Effects of dietary calcium:phosphorus ratios on utilization of dietary calcium for bone synthesis in women 20–75 years of age, Nutr. Rep. Int. 33: 879.Google Scholar
  2. Anderson, J.J.B., 1991, Nutritional biochemistry of calcium and phosphorus, J. Nutr. Biochem. 2: 300.CrossRefGoogle Scholar
  3. Anderson, G.H., and Draper, H.H., 1972, Effect of dietary phosphorus on calcium metabolism in intact and parathyroidectomized adult rats, J. Nutr. 102: 1123.Google Scholar
  4. Anderson, M.P., Hunt, R.D., Griffiths, H.F., McIntyre, K.W., and Zimmerman, R.E., 1977, Long-term effect of low dietary calcium:phosphate ratio on the skeleton of cebus albifrons monkeys, J Nutr. 107: 834.Google Scholar
  5. Baran, D., Sorensen, A., Grimes, J., Lew, R., Karellas, A., Johnson, B., and Roche, J., 1990, Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a three-year prospective study, J. Clin. Endocrinol. Metab. 70: 264.CrossRefGoogle Scholar
  6. Behlen, P., 1986, Calcium in women’s diets, Nat. Food Rev. 34: 16.Google Scholar
  7. Bell, R.R., Draper, H.H., Tzeng, D.Y.M., Shin, H.K., and Schmidt, G.R., 1977, Physiological responses of human adults to foods containing phosphate additives, J. Nutr. 107: 42.Google Scholar
  8. Bell, R.R., Tzeng, D.Y., and Draper, H.H., 1980, Long-term effects of calcium phosphorus and forced exercise on the bones of mature mice, J. Nutr. 110: 1161.Google Scholar
  9. Broadus, A.E., Magee, J.S., Mallette, L.E., Horst, R.L., Lang, R., Jensen, P.S., Gertner, J.M., and Baron, R., 1983, A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism, J. Clin. Endocrinol. Metab. 56: 953.CrossRefGoogle Scholar
  10. Calvo, M.S., 1993, Dietary phosphorus, calcium metabolism and bone, J. Nutr. 123: 1627.Google Scholar
  11. Calvo, M.S., and Heath, H. III., 1988, Acute effects of oral phosphate-salt ingestion on serum phosphorus, serum ionized calcium and parathyroid hormone in young adults, Am. J. Clin. Nutr. 47: 1025.Google Scholar
  12. Calvo, M.S., Harstad, L., Laakso, K.J., and Heath, H. III, 1987, Chronic low calcium (Ca), high phosphorus (P) intake during adolescence causes secondary hyperparathyroidism (2HPT) and reduces bone mass in female beagles, J. Bone Mineral Res. 2: s464 (abstract).Google Scholar
  13. Calvo, M.S., Kumar, R., and Heath, H. III., 1988, Elevated secretion and action of serum parathyroid hormone in young adults consuming high phosphorus, low calcium diets assembled from common foods, J Clin. Endocrinol. Metab. 66: 823.CrossRefGoogle Scholar
  14. Calvo, M.S., Kumar, R., and Heath, H. III., 1990, Persistently elevated parathyroid hormone secretion and action in young woman after four weeks of ingesting high phosphorus low calcium diets, J. Clin. Endocrinol. Metab. 70: 1334.CrossRefGoogle Scholar
  15. Calvo, M.S., Eastell, R., Offord, K.P., Bergstrahl, E.J., and Burritt, M.F., 1991, Circadian variations in ionized calcium and intact parathyroid hormone: evidence for sex differences in calcium homeostasis, J. Clin. Endocrinol. Metab. 72: 69.CrossRefGoogle Scholar
  16. Cheema, C., Grant, B.F., and Marcus, R., 1989, Effects of estrogen on circulating “free” and total 1,25-dihydroxyvitamin D and on the parathyroid vitamin D axis in postmenopausal women, J. Clin. Invest. 83: 537.CrossRefGoogle Scholar
  17. Chinn, H. I., 1981, Effects of dietary factors on skeletal integrity in adults: calcium, phosphorus, vitamin D and protein, Life Sciences Research Office, Federation of American Societies for Experimental Biology, Bethesda.Google Scholar
  18. Clark, I., 1969, Importance of dietary Ca:PO4 ratios on skeletal Ca, Mg and PO, metabolism, Am. J. Physiol. 217: 865–70.Google Scholar
  19. Cook, S.D., Skinner, H.B., and Haddad, R.J. Jr., 1983, A quantitative histologic study of osteoporosis produced by nutritional secondary hyperparathyroidism in dogs, Clin. Orthop. Relat. Res. 175: 105.Google Scholar
  20. Dawson-Hughes, B., Dallai, G.E., Krall, E.A., Sadowski, L., Sayhoun, N., and Tannenbaum, S., 1990, A controlled trial of the effect of calcium supplementation on bone density in menopausal women, N. Engl. J. Med. 323: 878.CrossRefGoogle Scholar
  21. Dawson-Hughes, B., Harris, S., and Dallai, G.E., 1991, Serum ionized calcium, as well as phosphorus and parathyroid hormone, is associated with the plasma 1,25-dihydroxyvitamin D3 concentration in normal postmenopausal women, J. Bone Mineral Res. 6: 461.CrossRefGoogle Scholar
  22. DeLuca, H.F., Castillo, L., Jee, W.S., Oldham, S., and Grummer, R.H. 1976, Studies on high phosphate diets. Food Research Institute Annual Report, University of Wisconsin-Madison, 1976: 394.Google Scholar
  23. Draper, H.H., and Bell, R.R., 1979, “Nutrition and osteoporosis,” in Advances in Nutritional Research ( H. Draper, ed.), pp. 79–106, Plenum Press, New York.CrossRefGoogle Scholar
  24. Draper, H.H., and Scythes, C.A., 1981, Calcium, phosphorus and osteoporosis, Fed. Proc. 40: 2434.Google Scholar
  25. Draper, H.H., Sie, T-L., and Bergan, J.G., 1972, Osteoporosis in aging rats induced by high phosphorus diets, J. Nutr. 102: 1133.Google Scholar
  26. Dziezak, J.D., 1990, Phosphates improve many foods, Food Technol. 90: 80.Google Scholar
  27. Elders, P.J.M., Netelenbos, J.C., Lips, P., van Ginkel, F.C., Khoe, E., Leeuwenkamp, O.R., Hackeng, W.H.L., and van der Stelt, P.F., 1991, Calcium supplementation reduces vertebral bone loss in perimenopausal women: A controlled trial in 248 women between 46 and 55 years of age, J. Clin. Endocrinol. Metab. 73: 533.CrossRefGoogle Scholar
  28. Goldsmith, R.S, Jowsey, J., Dube, W.J., Riggs, B.L., Arnaud, C.D., and Kelly, P.J., 1976, Effects of phosphorus supplementation on serum parathyroid hormone and bone morphology in osteoporosis, J. Clin. Endocrinol. Metab. 43: 523.CrossRefGoogle Scholar
  29. Greger, J.L., and Krystofiak, M., 1982, Phosphorus intake of Americans, Food Technol. 36: 78.Google Scholar
  30. Guenther, P.M., 1986, Beverages in the diets of American teenagers, J. Am. Diet. Assoc. 86: 493.Google Scholar
  31. Harris, W.H., Heaney, R.P, Davis, L.A, Weinberg, E.H., Coutts, R.D., and Schiller, A.L., 1976, Stimulation of bone formation in vivo by phosphate supplementation, Calcif. Tissue Res. 22: 85.CrossRefGoogle Scholar
  32. Hasling, C., Sondegaard, K., Charles, P., and Mosekilde, L., 1992, Calcium metabolism in postmenopausal osteoporotic women is determined by dietary calcium and coffee intake, J. Nutr. 122: 1119.Google Scholar
  33. Heaney, R., 1988, “Nutritional Factors in Bone Health,” in: Osteoporosis: Etiology, Diagnosis, and Management ( B. L. Riggs and L.J. Melton III, eds.), pp. 359–372, Raven Press, New York.Google Scholar
  34. Heaney, R.P., and Recker, R., 1982, Effects of nitrogen, phosphorus, and caffeine on calcium balance in women, J. Lab Clin. Med. 99: 46.Google Scholar
  35. Heaney, R., Gallagher, C., Johnston, C., Neer, R., Parffit, M., and Whedon, G., 1982, Calcium nutrition and bone health in the elderly, Am. J. Clin. Nutr. 36: 986.Google Scholar
  36. Hegsted, M., Schuette, S.A., Zemel, M.B., and Linkswiler, H.M., 1981, Urinary calcium and calcium balance in young men as affected by level of protein and phosphorus intake, J. Nutr. 111: 553.Google Scholar
  37. Herbert, L.A., Lemann, J., Petersen, J.R., and Lennon, E.J., 1966, Studies of the mechanism by which phosphate infusion lowers serum calcium concentration, J. Clin. Invest. 48: 1886.CrossRefGoogle Scholar
  38. Hulley, S.B., Vogel, J.M., Donaldson, C.J., Bayers, J.H., Friedman, R.J., and Rosen, S.N., 1971, The effect of supplemental oral phosphate on bone mineral changes during prolonged bed rest, J. Clin. Invest. 50: 2506.CrossRefGoogle Scholar
  39. Human Nutrition Information Service, U.S. Department of Agriculture, 1983, Food intakes: individuals in 48 states, year 1977–78. U.S. Department of Agriculture, Washington, DC, (Nationwide food consumption survey 1977–78, report #1–1.)Google Scholar
  40. Ittner, J., Dambacher, M.A., Muff, R., Ruegsegger, P., Trechsel, U., and Fisher, J.A., 1986, Reduced parathyroid hormone response to peroral phosphate in osteoporotic patients, Miner. Electrolyte Metab. 12: 199.Google Scholar
  41. Jowsey, J., and Balasubramaniam, P., 1972, Effect of phosphate supplements on soft tissue calcification and bone turnover, Clin. Sci. 42: 289.Google Scholar
  42. Jowsey, J., Reiss, E., and Canterbury, J.M., 1974, Long-term effects of high phosphate intake on parathyroid hormone levels and bone metabolism, Acta Orthop. Scand. 45: 801.CrossRefGoogle Scholar
  43. Krishnarao, G.V.G., and Draper, H.H., 1972, Influence of dietary phosphate on bone resorption in senescent mice, J. Nutr. 102: 1143.Google Scholar
  44. Krook, L., Lutwak, L., Henrikson, P-A., Kallfelz, F., Hirsch, C., Romanus, B., Belanger, L.F., Marier, J.R., and Sheffy, B.E., 1971, Reversibility of nutritional osteoporosis: physicochemical data on bones from an experimental study in dogs, J. Nutr. 101: 233.Google Scholar
  45. Krook, L., Whalen, J.P., Lesser, G.V., and Berens, D.L., 1975, Experimental studies on osteoporosis, Methods Achiev. Exp. Pathol. 7: 72.Google Scholar
  46. LaFlamme, G.H, and Jowsey, J., 1972, Bone and soft tissue changes with oral phosphate supplements, J. Clin. Invest. 51: 2834.CrossRefGoogle Scholar
  47. Life Sciences Research Office, Federation of American Societies for Experimental Biology, 1989, Nutrition Monitoring in the United States—An Update Report on Nutrition Monitoring, Prepared for the U.S. Department of Agriculture and the U.S. Department of Health and Human Services. DHHS Publication No. (PHS) 89–1255. Public Health Service. U.S. Government Printing Office, Washington, DC.Google Scholar
  48. Lukert, B.P., Carey, M., McCarthy, B., Tiemann. S., Goodnight, L., Helm, M., Hassanein, R., Stevenson, C., Stoskopf, M., and Doolan, L., 1987, Influence of nutritional factors on calcium-regulating hormones and bone loss, Calcif. Tissue Int. 40: 119.Google Scholar
  49. Luz Villa, M., Packer, E., Cheema, M., Holloway, L., and Marcus, R., 1991, Effects of aluminium hydroxide on the parathyroid-vitamin D axis of postmenopausal women, J Clin. Endocrinol. Metab. 73: 1256.CrossRefGoogle Scholar
  50. Mallette, L.E., LeBlanc, A.D., Pool, J.L., and Mechanick, J.I., 1989, Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate, J. Bone Mineral Res. 4: 143.CrossRefGoogle Scholar
  51. Malm, O.J., 1953, On phosphate and phosphoric acid as dietary factors in the calcium balance of man, Scand. J. Clin. Lab. Invest. 5: 75.CrossRefGoogle Scholar
  52. Marcus, R., 1982, The relationship of dietary calcium to the maintenance of skeletal integrity in man. An interface of endocrinology and nutrition, Metabolism 31: 93.CrossRefGoogle Scholar
  53. Marie, P.J., Pettifor, J.M., Ross, F.P., and Glorieux, F.N., 1982, Histological osteomalacia due to dietary calcium deficiency in children, N. Engl. J. Med. 307: 584.CrossRefGoogle Scholar
  54. Matkovic, V., 1991, Calcium metabolism and calcium requirements during skeletal modeling and consolidation of bone mass, Am. J Clin. Nutr. 54: 245s.Google Scholar
  55. Matkovic, V., and Dekanic, D., 1989, “Developing strong bones: the teenage female,” in: Clinical Disorders of Bone and Mineral Metabolism ( M. Kleerekoper and S.M. Krane, eds.), pp. 165–70, Mary Liebert, Inc, New York.Google Scholar
  56. Matkovic, V., Fontana, D., Tominac, C., Lehmann, J., and Chestnut, C., 1986, Influence of calcium on peak bone mass: a pilot study, J. Bone Mineral Res. 1: s168 (abstract).Google Scholar
  57. Matkovic, V., Fontanna, D., Tominac, C., Goel, P., and Chestnut, C.H., 1990, Factors that influence peak bone mass formation: a study of calcium balance and the inheritance of bone mass in adolescent females, Am. J. Clin. Nutr. 52: 878.Google Scholar
  58. Mazess, R.B., and Mather, W., 1974, Bone mineral content of North Alaskan Eskimos, Am. J. Clin. Nutr. 27: 916.Google Scholar
  59. Mazess, R.B., and Mather, W., 1975, Bone mineral content in Canadian Eskimos, Human Biol. 47: 45.Google Scholar
  60. National Research Council, 1989, Recommended Dietary Allowances. 10`h ed. National Academy Press, Washington, DC.Google Scholar
  61. Oenning, L.J., Vogel, J., and Calvo, M.S., 1988, Accuracy of methods estimating calcium and phosphorus intake in daily diets, J Am. Diet. Assoc. 88: 1076.Google Scholar
  62. Ott, S.M., 1990, Editorial: attainment of peak bone mass, J. Clin. Endocrinol. Metab. 71: 1082A.CrossRefGoogle Scholar
  63. Packer, E., Holloway, L., Newhall, K., Kanwar, G., Butterfield, G., and Marcus, R., 1990, Effects of estrogen on daylong circulating calcium, phosphorus, 1,25-dihydroxyvitamin D, and parathyroid hormone in postmenopausal women, J. Bone Mineral Res. 5: 877.CrossRefGoogle Scholar
  64. Pettifor, J.M., Marie, P.J., Sly, M.R., du Bruyn, D.B., Ross, F., Isdale, J.M., De Klerk, W., and van der Walt, W.H., 1984, The effects of differing dietary calcium and phosphorus contents on mineral metabolism and bone histomorphometry in young vitamin D-replete baboons, Calcif. Tissue Int. 36: 668.CrossRefGoogle Scholar
  65. Portale, A.A., Booth, B.E., Halloran, B.P., and Morris, R.C., Jr., 1984, Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency, J Clin. Invest. 73: 1580.CrossRefGoogle Scholar
  66. Portale, A.A., Halloran, B.P., Murphy, M.M., and Morris, R.C., Jr., 1986, Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans, J. Clin. Invest. 77: 7.CrossRefGoogle Scholar
  67. Portale, A.A., Halloran, B.H., and Morris, R.C., Jr., 1987, Dietary intake of phosphorus modulates the circadian rhythm in serum concentration of phosphorus, J. Clin. Invest. 80: 1147.CrossRefGoogle Scholar
  68. Portale, A.A., Halloran, B.P., and Morris, R.C., Jr., 1989, Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men, J. Clin. Invest. 83: 1494.CrossRefGoogle Scholar
  69. Raisz, L.G., and Lorenzo, J.A. 1980, “Interactions of hormones, ions, and drugs in the regulation of osteoclastic bone resorption,” in: Phosphate and Minerals in Health and Disease, Advances in Experimental Medicine and Biology ( S. G. Massry, E. Ritz, and H. Jahns, eds.), pp. 579–96, Plenum Press, New York.Google Scholar
  70. Reid, I.R., Ames, R.W., Evans, M.C., Gamble, G.D., and Sharpe, Si.,. 1993, The effect of calcium supplementation on bone loss in postmenopausal women, N. Engl. J. Med. 328: 460.CrossRefGoogle Scholar
  71. Reiss, E., Canterbury, J.M., Bercovitz, M.A., and Kaplan, E.L., 1970, The role of phosphate in the secretion of parathyroid hormone in man, J. Clin. Invest. 49: 146.CrossRefGoogle Scholar
  72. Riggs, B.L., and Melton, L.J., 1986, Involutional osteoporosis, N. Engl. J. Med. 314:1676. Riggs, B.L., and Melton, L.J., 1992, Prevention and treatment of osteoporosis, N. Engl. J. Med. 327: 620.Google Scholar
  73. Ritskes-Hoitinga, J., Lemmens, A.G., Danse, L.H.J.C., and Beynen, A.C., 1989, Phosphorusinduced nephrocalcinosis and kidney function in female rats, J. Nutr. 119: 1423.Google Scholar
  74. Saville, P. D., and Krook, L., 1969, Gravimetric and isotopic studies in nutritional hyperparathyroidism in beagles, Clin. Orthop. 62: 15.Google Scholar
  75. Schaafsma, G., and Visser, R., 1980, Nutritional interrelationships between calcium, phosphorus, and lactose in rats, J. Nutr. 110: 1101.Google Scholar
  76. Schryver, H.F., Hintz, H.F., and Craig, P.H., 1971, Calcium metabolism in ponies fed a high phosphorus diet, J. Nutr. 101: 259.Google Scholar
  77. Sie, T-L., Draper, H.H., and Bell, R.R., 1974, Hypocalcemia, hypoparathyroidism and bone resorption in rats induced by dietary phosphate, J. Nutr. 104: 1195.Google Scholar
  78. Silverberg, S.J., Shane, E., Clemens, T.L., Dempster, D.W., Segre, G.V., Lindsay, R., and Bilezikian, J.P., 1986, The effect of oral phosphate administration on major indices of skeletal metabolism in normal subjects, J. Bone Mineral Res. 1: 383.CrossRefGoogle Scholar
  79. Silverberg, S. J., Shane, E., Luz del la Cruz, R.N., Segre, G.V., Clemens, T.L., and Bilezikian, J.P., 1989, Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis, N. Engl. J. Med. 320: 277.CrossRefGoogle Scholar
  80. Smith, D.A, and Nordin, B.E.C., 1964, The effect of high phosphorus intake on total and ultra-filtrable plasma calcium and on phosphate clearance, Clin. Sci. 26: 479.Google Scholar
  81. Spencer, H., Menczel, J., Lewin, I., and Samachson, J., 1965, Effect of high phosphorus intake on calcium and phosphorus metabolism in man, J. Nutr. 86: 125.Google Scholar
  82. Spencer, H., Kramer, L., Osis, D., and Norris, C., 1978, Effect of phosphorus on the absorption of calcium and on the calcium balance in man, J. Nutr. 108: 447.Google Scholar
  83. Tylaysky, F.A., and Anderson, J.J.B., 1988, Dietary factors in bone health of elderly lactoovovegetarians and omnivorous women, Am. J. Clin. Nutr. 48: 842.Google Scholar
  84. Van den Berg, C.J., Kumar, R., Wilson, D.M., Heath, H. III, and Smith, L,H., 1980Google Scholar
  85. Orthophosphate therapy decreases urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations in idiopathic hypercalciuria, J. Clin. Endocrinol. Metab. 51:998.Google Scholar
  86. Yano, K., Heilbrun L, Wasnich R., Hankins, J., and Voegel, J., 1985, The relation between diet and bone mineral content of multiple skeletal sites in elderly Japanese-American men and women living in Hawaii, Am. J. Clin. Nutr. 42: 877.Google Scholar
  87. Yates, J.A., Oreffo, R.O.C., Mayor, K., and Mundy, G.R., 1991, Inhibition of bone resorption by inorganic phosphate is mediated by both reduced osteoclast formation and decreased activity of mature osteoclasts, J. Bone Mineral Res. 6: 473.CrossRefGoogle Scholar
  88. Zemel, M.B., and Linkswiler, H.M., 1981, Calcium metabolism in the young adult male as affected by level and form of phosphorus intake and level of calcium intake, J Nutr. 111: 315.Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Mona S. Calvo
    • 1
  1. 1.Department of Health and Human ServicesPublic Health Service, Food and Drug AdministrationUSA

Personalised recommendations