Clinical Investigation

Kidney International (1984) 26, 752–759; doi:10.1038/ki.1984.212

Dietary calcium and serum 1,25-(OH)2-vitamin D concentrations as determinants of calcium balance in healthy men

William J Maierhofer1, Jacob Lemann Jr1, Richard W Gray1 and Herman S Cheung1

1Departments of Medicine and Biochemistry and The Clinical Research Center, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee, Wisconsin

Correspondence: Dr J Lemann Jr, Nephrology Section, Department of Medicine, Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226, USA

Received 25 November 1983; Revised 4 June 1984.

Top

Abstract

Dietary calcium and serum 1,25-(OH)2-vitamin D concentrations as determinants of calcium balance in healthy men. We previously reported that experimental elevations of serum 1,25-(OH)2-vitamin D [1,25-(OH)2-D] concentrations produced by the chronic oral administration of calcitriol, 0.75 microg every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum 1,25-(OH)2-D and iPTH concentrations, Ca and PO4 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 plusminus 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 plusminus 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0,5 microg every 6 hr. For all six subjects, serum 1,25-(OH)2-D levels averaged 89 plusminus 25 pM during control and 143 plusminus 26 pM during calcitriol. Net intestinal Ca absorption and urinary Ca excretion rose during calcitriol but Ca balances did not change, averaging +2.2 plusminus 2.2 mmoles/day during control and +4.3 plusminus 2,2 mmoles/day during calcitriol for the subjects fed 22 mmoles Ca/day and - 1.6 plusminus 1.5 mmoles Ca/day during control and - 1.7 plusminus 2.0 mmoles Ca/day during calcitriol for the subjects fed 9 mmoles Ca/day. Urinary hydroxyproline excretion also did not change. Thus, when serum 1,25-(OH)2-D levels are elevated, the availability of dietary Ca appears to prevent more negative Ca balances and increased urinary hydroxyproline excretion suggesting that net bone resorption is not stimulated.

Le calcium alimentaire et les concentrations sériques de 1,25-(OH)2-vitamine D déterminants de la balance calcique chez des hommes sains. Nous avons préalablement rapporté que des élévations expérimentales des concentrations sériques de 1,25-(OH)2-D par administration chronique orale de calcitriol, 0,75 microg toutes les 6 heures à des hommes sains ingérant des régimes n'apportant que 4 mmoles Ca/jour stimulent la résorption osseuse nette, ce qui est mis en évidence par des balances Ca plus négatives et par des débits d'excrétion urinaire d'hydroxyproline plus élevés. Afin de déterminer si une augmentation de l'apport en Ca alimentaire modifie cette réponse, nous avons comparé les concentrations sériques de 1,25-(OH)2-D et d'iPTH, les balances Ca et PO4 et l'excrétion urinaire d'hydroxyproline chez trois hommes sains adaptés à des régimes apportant 22,3 plusminus 1,3 mmoles Ca/jour et chez trois hommes sains adaptés à des régimes apportant 9,3 plusminus 0,7 mmoles Ca/jour avant et pendant l'administration orale continue de calcitriol, 0,5 microg toutes les 6 heures. Pour les six sujets, les niveaux sériques de 1,25-(OH)2-D étaient en moyenne de 89 plusminus 25 pM pendant le contrôle et de 143 plusminus 26 pM pendant le calcitriol. L'absorption intestinale nette de Ca et l'excrétion urinaire de Ca se sont élevées pendant le calcitriol, mais les balances Ca n'ont pas changé, étant en moyenne de +2,2 plusminus 2,2 mmoles/jour pendant le contrôle et de 4,3 plusminus 2,2 mmoles/jour pendant le calcitriol chez les sujets ingérant 22 mmoles Ca/jour et de - 1,6 plusminus 1,5 mmoles Ca/jour pendant le contrôle et de 1,7 plusminus 2,0 mmoles Ca/jour pendant le calcitriol chez les sujets ingérant 9 mmoles Ca/jour. L'hydroxyproline urinaire aussi ne s'est pas modifiée. Ainsi, lorsque les niveaux sériques de 1,25-(OH)2-D sont élevés, la disponibilité du calcium alimentaire parait prévenir des balances Ca plus négatives et une excrétion urinaire d'hydroxyproline élevée, suggérant que la résorption osseuse nette n'est pas stimulée.

Top

References

  1. Adams ND, Gray RW, Lemann J Jr, Cheung HS: Effects of calcitriol administration on calcium metabolism in healthy men. Kidney Int 21:90–97, 1982
  2. Maierhofer WJ, Gray RW, Cheung HS, Lemann J Jr: Bone resorption stimulated by elevated serum 1,25-(OH)2-vitamin D concentrations in healthy men. Kidney Int 24:555–560, 1983 | PubMed | ISI | ChemPort |
  3. Holick MF, Garabedian M, Deluca HF: 1.25-Dihydroxycholecalciferol: Metabolite of vitamin D3 active on bone in anephric rats. Science 176:1146–1147, 1972
  4. Raisz LG, Trummel CL, Holick MF, Deluca HF: 1,25-dihydroxycholecalciferol: A potent stimulator of bone resorption in tissue culture. Science 175:768–769, 1972 | PubMed | ISI | ChemPort |
  5. Kaplan RA, Haussler MR, Deftos LH, Bone H, Pak CYC: The role of 1,25-dihydroxyvitamin D in the mediation of intestinal hyperabsorption of calcium in primary hyperparathyroidism and absorptive hypercalciuria. J Clin Invest 64:729–736, 1979
  6. Shen FH, Bayling DJ, Nielsen RL, Sherrard DJ, Ivey JL, Haussler MR: Increased serum 1,25-dihydroxyvitamin D in idiopathic hypercalciuria. J Lab Clin Med 90:955–962, 1977 | PubMed | ISI | ChemPort |
  7. Gray RW, Wilz DR, Caldas AH, Lemann J Jr: The importance of phosphate in regulating plasma 1,25-(OH)2-vitamin D levels in humans: studies in healthy subjects, in calcium-stone formers and in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 45:299–306, 1977 | PubMed | ISI | ChemPort |
  8. Pak CYC, Ohata M, Lawrence EC, Snyder W: The hypercalciurias: Causes, parathyroid functions, and diagnostic criteria. J Clin Invest 54:387–400, 1975
  9. Alhava EM, Juuti M, Karjalainen P: Bone mineral density in patients with urolithiasis. Scand J Urol Nephrol 10:154–156, 1976
  10. Bordier P, Ryckewart A, Gueris J, Rasmussen H: On the pathogenesis of so-called idiopathic hypercalciuria. Am J Med 63:398–409, 1977 | PubMed | ChemPort |
  11. Lemann J Jr: Idiopathic hypercalciuria, in Contemporary Issues in Nephrology: Nephrolithiasis, edited by Coe FL, Brenner BM, Stein JH, New York, Churchill Livingstone, 1980, vol 5, chap 5, pp 88–115
  12. Hughes MR, Baylink DJ, Jones PG, Haussler MR: Radioligand receptor assay for 25-hydroxyvitamin D2/D3 and 1alpha, 25-dihydroxyvitamin D2/D3. J. Clin Invest 58:61–70, 1976 | PubMed | ChemPort |
  13. Eisman JA, Hamstra AJ, Kream BE, Deluca HF: 1,25-Dihydroxyvitamin D in biological fluids; A simplified and sensitive assay. Science 193:1021–1023, 1976
  14. Lambert PW, Taft DO, Hodgson SF, Lindmark EA, Witrak BJ, Roos BA: An improved method for the measurement of 1,25-(OH)2-D3 in human plasma. Endocrin Res Commun 5:293–310, 1978
  15. Taylor CM, Hann J, St. John J, Wallace JE, Mawer EB: 1,25-Dihydroxycholecalciferol in human serum and its relationship with other metabolites of vitamin D3. Clin Chem Acta 96:1–8, 1979
  16. Lund BJ, Lund BI, Sorenson OH: Measurement of circulating 1,25-dihydroxyvitamin D in man. Changes in serum concentrations during treatment with 1alpha-hydroxycholecalciferol. Acta Endocrinol 91:338–350, 1979
  17. Clemens TL, Hendy GN, Papapoulos SE, Fraher LJ, Cane AD, O'Riordan JLH: Measurement of 1,25-dihydroxycholecalciferol in man by radioimmunoassay. Clin Endocrinol 11:225–234, 1979
  18. Mason RS, Lissner D, Grunstein HS, Posen S: A simplified assay for dihydroxylated vitamin D metabolites in human serum: Application to hyper and hypovitaminosis D. Clin Chem 26:444–450, 1980
  19. Bishop JE, Norman AW, Coburn JW, Roberts PA, Henry HL: Studies on the metabolism of calciferol. XVI. Determination of 25-hydroxyvitamin D, 24,25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in single two-milliliter plasma sample. Mineral Electrolyte Metab 3:181–189, 1980
  20. Bouillon R, Demoor P, Baggiolini EG, Uskokovic MR: A radioimmunoassay for 1,25-dihydroxycholecalciferol. Clin Chem 26:562–567, 1980
  21. Yamaoka K, Seino Y, Ishida M, Ishida T, Shimotsuji T, Tanaka Y, Kurose H, Matsuda S, Satomura K, Yabuuchi H: Effect of dibutyryl adenosine 3'5'-monophosphate administration on plasma concentrations of 1,25-dihydroxyvitamin D in pseudohypoparathyroidism type I. J Clin Endocrinol Metab 53:1096–1100, 1981
  22. Maierhofer WJ, Gray RW, Lemann J Jr: Phosphate deprivation increases serum 1,25-(OH)2-vitamin D concentrations in healthy men. Kidney Int 25:571–575, 1984 | PubMed | ISI | ChemPort |
  23. Malm OJ: Calcium requirement and adaptation in adult men. Scand J Clin Lab Invest 10(Suppl 36):35–39, 1958
  24. Brickman AS, Hartenbower DL, Norman AW, Coburn JW: Actions of 1 alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on mineral metabolism in men. Am J Clin Nutr 30:1064–1069, 1977 | PubMed | ISI | ChemPort |
  25. Dietary Intake Source Data, United States, 1971–1974: U.S. Department of Health, Education, and Welfare, Public Health Service, Office of Health Research, Statistics, and Technology, National Center for Health Statistics, Washington, D.C., 1979
  26. Nordin BEC (Ed): Calcium, Phosphate and Magnesium Metabolism, Edinburgh, Churchill Livingstone, 1976, pp 471–472

Extra navigation

.
ADVERTISEMENT