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Vitamin D: Normal Physiology and Vitamin D Therapeutics in Normal Nutrition and Various Disease States

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Calcium in Internal Medicine

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Abstract

There has been a recent explosion of new information regarding the science of vitamin D; these findings include the discovery and synthesis of new analogues or derivatives of vitamin D that have actual or potential therapeutic value in several disorders related to calcium metabolism and other conditions, such as psoriasis or malignancies, that are unrelated to calcium metabolism.

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References

  1. Holick MR Vitamin D and the kidney. Kidney Int 1987;32:912–29.

    Article  PubMed  CAS  Google Scholar 

  2. Bouillon R. Vitamin D: From photosynthesis, metabolism, and action to clinical applications. In: DeGroot LJ, Jameson JL, editors. Endocrinology. Philadelphia: W.B. Saunders, 2001; 1009–28.

    Google Scholar 

  3. Kumar R. Vitamin D. In: Bushinsky DA, editor. Renal osteodystrophy. Philadelphia: LippencottRaven Publishers, 1998;161–202.

    Google Scholar 

  4. Malluche HH, Mawad H, Koszewski NJ. Update on vitamin D and its newer analogues: Actions and rationale for treatment in chronic renal failure. Kidney Int 2002;(in press).

    Google Scholar 

  5. Feldman D, Glorieux FH, Pike JW. Vitamin D. San Diego: Academic Press, 1997;1–1285.

    Google Scholar 

  6. Mellanby E. An experimental investigation on rickets. Lancet 1919;1:407–12.

    Google Scholar 

  7. McCollum EV, Simmonds N, Becker JE, Shipley PG. An experimental demonstration of the existence of a vitamin which promotes calcium deposition. J Biol Chem 1922;53:293–8.

    CAS  Google Scholar 

  8. Goldblatt H, Soames KN. A study of rats on a normal diet irradiated daily by the mercury vapor quartz lamp or kept in darkness. Biochem J 1923;17:294–7.

    PubMed  CAS  Google Scholar 

  9. Ponchon G, Kennan AL, DeLuca HF. “Activation” of vitamin D by the liver. J Clin Invest 1969;48:2032–7.

    Article  PubMed  CAS  Google Scholar 

  10. Fraser DR, Kodicek E. Unique biosynthesis by the kidney of a biologically active vitamin D metabolite. Nature 1970;228:764–6.

    Article  PubMed  CAS  Google Scholar 

  11. Nicolayson R. Studies on the mode of action of vitamin D. III. The influence of vitamin D on the absorption of calcium and phosphorus in the rat. Biochem J 1937;31:122–9.

    Google Scholar 

  12. Weinstein RS, Underwood JL, Hutson MS, DeLuca HF. Bone histomorphometry in vitamin D- deficient rats infused with calcium and phosphorus. Am J Physiol 1984;246:E499–E505.

    PubMed  CAS  Google Scholar 

  13. Underwood JR, DeLuca H. Vitamin D is not necessary for bone growth and mineralization. Am J Physiol 1984;246:493–8.

    Google Scholar 

  14. Specker BL, Tsang RC, Hollis BW. Effect of race and diet on human-milk vitamin D and 25-hydrox- yvitamin D. Am J Dis Child 1985;139:1134–7.

    PubMed  CAS  Google Scholar 

  15. Lamberg-Allardt C, Karkkainen M, Seppanen R, et al. Low-serum 25-hydroxyvitamin D concentra-tions and secondary hyperparathyroidism in middle-aged white strict vegetarians. Am J Clin Nutr 1993;58:684–9.

    PubMed  CAS  Google Scholar 

  16. Holick MF, Shao Q, Liu WW, Chen TC. The vitamin D content of fortified milk and infant formula. N Engl J Med 1992;326:1178–81.

    Article  PubMed  CAS  Google Scholar 

  17. Holick MF, MacLaughlin JA, Clark BM, Holick SA, Potts Jr JT, Anderson RR et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 1980;210:203–5.

    Article  PubMed  CAS  Google Scholar 

  18. Holick MF, MacLaughlin JA, Doppelt SH. Factors that influence the cutaneous photosynthesis of previtamin D3. Science 1981;211:590–3.

    Article  PubMed  CAS  Google Scholar 

  19. MacLaughlin J, Holick MF. Aging decreases the capacity of the human skin to produce vitamin D3. J Clin Invest 1985;76:1536–8.

    Article  PubMed  CAS  Google Scholar 

  20. Matsuoko L, Ide L, Wortsman J, MacLaughlin JA, Holick MF. Sunscreens suppress cutaneous vitamin D3 synthesis. J Clin Endocrinol Metab 1987;64:1165–8.

    Article  Google Scholar 

  21. Holick MF. 1994 McCollum Award lecture: Vitamin D - New horizons for the twenty-first century. Am J Clin Nutr 1994;60:619–30.

    PubMed  CAS  Google Scholar 

  22. Gannagé-Yared M-H, Chemali R, Yaacoub NE, Halaby G. Hypovitaminosis D in a sunny country: Relation to lifestyle and bone markers. J Bone Miner Res 2000;15:1856–62.

    Article  PubMed  Google Scholar 

  23. Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporosis Int 1997;7:439–43.

    Article  CAS  Google Scholar 

  24. Gascon-Barre M. The vitamin D 25-hydroxylase. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;41–85.

    Google Scholar 

  25. Mawer EB, Davies M. Bone disorders associated with gastrointestinal and hepatobiliary disease. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;831–47.

    Google Scholar 

  26. Henry HL. The 25-hydroxyvitamin D 1α-Hydroxylase. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;57–85.

    Google Scholar 

  27. Bell NH. Renal and nonrenal 25-hydroxyvitamin D-1α -hydroxylases and their clinical significance. J Bone Miner Res 1998;13:350–3.

    Article  PubMed  CAS  Google Scholar 

  28. Brown EM. Physiology and pathophysiology of the extracellular calcium-sensing receptor. Am J Med 1999;106:238–53.

    Article  PubMed  CAS  Google Scholar 

  29. Coburn JW, Maung HM. Calcimimetic agents and the calcium-sensing receptor. Curr Opin Nephrol Hypertens 2000;9:123–32.

    Article  PubMed  CAS  Google Scholar 

  30. Bikle DD, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest 1984;74:1966–71.

    Article  PubMed  CAS  Google Scholar 

  31. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Int Med 1996; 124:400–6.

    CAS  Google Scholar 

  32. Spanos E, Colston KW, Evans A, Galante LS, MacAuley SJ, Maclntyre I. Effect of prolactin on vitamin D metabolism. Nature 1976;5:163–7.

    CAS  Google Scholar 

  33. Spanos E, Barrett D, Maclntyre I, Pike JN, Safilian EC, Haussler MR. Effect of growth hormone on vitamin D metabolism. Nature (London) 1978;273:2420–33.

    Article  Google Scholar 

  34. Adams ND, Garthwaite TL, Gray RW, Hagen TC, Lemann Jr J. The interrelationships among prolactin, 1,25-dihydroxyvitamin D, and parathyroid hormone in humans. J Clin Endocrinol Metab 1979; 49:628–30.

    Article  PubMed  CAS  Google Scholar 

  35. Bikle DD, Nemanic MK, Whitney JO, Ellas PW. Neonatal human foreskin keratinocytes produce 1,25- dihydroxyvitamin D3. Biochemistry 1986;25:1545–8.

    Article  PubMed  CAS  Google Scholar 

  36. Bikle DD, Halloran BP, Riviere JE. Production of 1,25-dihydroxyvitamin D3 by perfused pig skin. J Invest Dermatol 1994;102:796–8.

    Article  PubMed  CAS  Google Scholar 

  37. Adams JS. Extrarenal production of active vitamin D metabolites in human lymphoproliferative diseases. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1977; 903–21.

    Google Scholar 

  38. Dusso AS, Lopez-Hilker S, Rapp N, Slatopolsky E. Extrarenal production of calcitriol in chronic renal failure. Kidney Int 1988;34:368–75.

    Article  PubMed  CAS  Google Scholar 

  39. Reddy GS, Tserng KY. Calcitroic acid, end product of renal metabolism of 1,25-dihydroxyvitamin D3 through C-24 oxidation pathway. Biochemistry 1989;28:1763–9.

    Article  PubMed  CAS  Google Scholar 

  40. St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, Chapin K, et al. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25- dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinol 2000; 141:2658–66.

    Article  CAS  Google Scholar 

  41. St-Arnaud R. Novel findings about 24,25-dihydroxyvitamin D: an active metabolite? Curr Opin Nephrol Hypertens 1999;8:435–41.

    Article  PubMed  CAS  Google Scholar 

  42. St-Arnaud R, Glorieux FH. 24,25-dihydroxyvitamin D-Active metabolite or inactive catabolite? Endocrinol 1998;139:3371–3.

    Article  CAS  Google Scholar 

  43. Henry HL, Norman AW. Vitamin D: Two dihydroxylated metabolites are required for normal chicken egg hatchability. Science 1978;201:835–7.

    Article  PubMed  CAS  Google Scholar 

  44. Seo EG, Einhorn TA, Norman AW. 24R,25-dihydroxyvitamin D3: An essential vitamin D3 metabolite for both normal bone integrity and healing of tibial fracture in chicks. Endocrinol 1997; 138:3864–72.

    Article  CAS  Google Scholar 

  45. Hodsman AB, Wong EGC, Sherrard DJ, Brickman AS, Lee DBN, Singer FR, et al. Preliminary trials with 24,25-dihydroxyvitamin D3 in dialysis osteomalacia. Am J Med 1983;74:407–14.

    Article  PubMed  CAS  Google Scholar 

  46. Sherrard DJ, Ott SM, Andress DL, Coburn JW. Histologic response to 24,25-dihydroxyvitamin D in renal osteodystrophy. In: Norman AW, Schaefer K, Grigoleit HG, von Herrath D, Walter DE Gruyter, editors. Vitamin D: Chemical, biochemical and clinical endocrinology of calcium metabolism. Berlin, 1985;269–74.

    Google Scholar 

  47. Olgaard K, Finco D, Schwartz J, Arbelaez M, Teitelbaum S, Avioli L, et al. Effect of 24,25(OH)2D3 on PTH levels and bone histology in dogs with chronic uremia. Kidney Int 1984;26:791–7.

    Article  PubMed  CAS  Google Scholar 

  48. Ott SM, Maloney NA, Coburn JW, Alfrey AC, Sherrard DJ. The prevalence of bone aluminum deposition in renal osteodystrophy and its relation to the response to calcitriol therapy. N Engl J Med 1982;307:709–13.

    Article  PubMed  CAS  Google Scholar 

  49. Haussler MR, Whitfield GK, Haussler CA, Hsieh J-C, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325–49.

    Article  PubMed  CAS  Google Scholar 

  50. Crofts LA, Hancock MS, Morrison NA, et al. Multiple promoters direct the tissue-specific expression of novel N-terminal variant human vitamin D receptor gene transcripts. Proc Nat Acad Sci (USA) 1998;95:10529–34.

    Article  CAS  Google Scholar 

  51. Wurtz J-M, Guillot B, Moras D. 3D model of the ligand binding domain of the vitamin D nuclear receptor based on the crystal structure of holo RAR-gamma. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D: Chemistry, biology, and clinical applications of the steroid hormone. Riverside: University of California, 1997; 165–72.

    Google Scholar 

  52. Xu L, Glass CK, Rosenfeld MG. Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev 1999;9:140–7.

    Article  PubMed  CAS  Google Scholar 

  53. Krishnan AV, Feldman D. Regulation of vitamin D receptor abundance. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997; 179–200.

    Google Scholar 

  54. Marx SJ, Spiegel AM, Brown EM, Gardner DG, Downs Jr RW. A familial syndrome of decrease in sensitivity to 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 1978;47:1303–10.

    Article  PubMed  CAS  Google Scholar 

  55. Malloy PJ, Pike JW, Feldman D. Hereditary 1,25-dihydroxyvitamin D resistant rickets. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1977;765–87.

    Google Scholar 

  56. Yoshizawa T, Handa Y, Uematsu Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 1997;16:391–6.

    Article  PubMed  CAS  Google Scholar 

  57. Li YC, Amling M, Pirro AE, Preimel M, Meuse J, Baron R, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia but not alopecia in vitamin D receptor-ablated mice. Endocrinol 1998;139:4391–6.

    Article  CAS  Google Scholar 

  58. Walling MW. Intestinal Ca and phosphate absorption: Differential responses to vitamin D3 metabolites. Am J Physiol 1977;233:E488–94.

    PubMed  CAS  Google Scholar 

  59. Marcus CS, Lengemann FW. Absorption of Ca45 and Sr85 from solid and liquid food at various levels of the alimentary tract of the rat. J Nutr 1962;77:155–60.

    PubMed  CAS  Google Scholar 

  60. Wasserman RH. Vitamin D and the intestinal absorption of calcium and phosphorus. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;259–73.

    Google Scholar 

  61. Peerce BE. Identification of the intestinal Na-phosphate cotransporter. Am J Physiol 1989;256:G645–52.

    PubMed  CAS  Google Scholar 

  62. Yaegci A, Werner A, Murer H, Biber J. Effect of rabbit duodenal mRNA on phosphate transport in Xenopus laevis oocytes: Dependence on 1,25-dihydroxyvitamin D3. Pfleugers Arch 1992;422:211–16.

    Article  Google Scholar 

  63. Lee DBN, Walling MW, Gafter U, Silis V, Coburn JW. Calcium and inorganic phosphate transport in rat colon: Dissociated response to 1,25-dihydroxyvitamin D3. J Clin Invest 1980;65:1326–31.

    Article  PubMed  CAS  Google Scholar 

  64. Spielvogel AM, Farley RD, Norman AW. Studies on the mechanism of action of calciferol. Exp Cell Res 1972;74:359–66.

    Article  PubMed  CAS  Google Scholar 

  65. Goldstein DA, Horowitz RE, Petit S, Haldimann B, Massry SG. The duodenal mucosa in patients with renal failure: Response to 1,25(OH)2D3. Kidney Int 1981;19:324–31.

    Article  PubMed  CAS  Google Scholar 

  66. Omdahl J, May B. The 25-hydroxyvitamin D-24-hydroxylase. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;69–85.

    Google Scholar 

  67. Hsu CH, Patel S, Buchsbaum BL. Calcitriol metabolism in patients with chronic renal failure. Am J Kidney Dis 1991;17:185–90.

    PubMed  CAS  Google Scholar 

  68. Brandi L, Egfjord M, Olgaard K. Pharmacokinetics of 1,25(OH)2D3 and 1α(OH)D3 in normal and uremic man. Nephrol Dial Transplant 2001;(in press).

    Google Scholar 

  69. Yamamoto M, Kawanobe Y, Takahashi H, et al. Vitamin D deficiency and renal calcium transport in the rat. J Clin Invest 1984;74:507–13.

    Article  PubMed  CAS  Google Scholar 

  70. Müller D, Hoenderop JGJ, van Os CH, Bindels RJM. The epithelial calcium channel, EcaC1: molecular details of a novel player in renal calcium handling. Nephrol Dial Transplant 2001; 16:1329–35.

    Article  PubMed  Google Scholar 

  71. Silver J, Naveh-Many T, Mayer H, Schmelzer HJ, Popovtzer MM. Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat. J Clin Invest 1986;78:1296–301.

    Article  PubMed  CAS  Google Scholar 

  72. Silver J, Naveh-Many T. Vitamin D and the parathyroid glands. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;353–67.

    Google Scholar 

  73. Brown AJ, Zhong M, Finch J, Ritter C, McCracken R, Morrisey J, et al. Rat calcium sensing receptor is regulated by vitamin D but not by calcium. Am J Physiol 1996;270:F454–60.

    PubMed  CAS  Google Scholar 

  74. Rogers KV, Dunn CK, Conklin RL, Hadfield S, Petty BA, Brown EA, et al. Calcium receptor messenger ribonucleic acid levels in the parathyroid glands and kidney of vitamin D-deficient rats are not regulated by plasma calcium or 1,25-dihydroxyvitamin D3. Endocrinol 1995;136:499–504.

    Article  CAS  Google Scholar 

  75. DeLuca HF. The vitamin D story: A collaborative effort of basic science and clinical medicine. Fed Proc Am Soc Exp Biol 1988;2:224–36.

    CAS  Google Scholar 

  76. Owen TA, Aronow MS, Barone LM, et al. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: Dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinol 1991;128:1496–504.

    Article  CAS  Google Scholar 

  77. Matsumoto T, Igarashi C, Taksuchi Y, et al. Stimulation by 1,25-dihydroxyvitamin D3 of in vitro mineralization induced by osteoblast-like MC3T3–E1 cells. Bone 1991;12:27–32.

    Article  PubMed  CAS  Google Scholar 

  78. Balsan S, Garabedian M, Larchet M, Groski AM, Cournot G, Tau C, et al. Long-term nocturnal calcium infusions can cure rickets and promote normal mineralization in hereditary resistance to 1,25-dihy- droxyvitamin D. J Clin Invest 1986;77:1661–7.

    Article  PubMed  CAS  Google Scholar 

  79. Moscovici A, Gafter U, Popovtzer MM. Calcitriol pulse therapy arrests bone formation in dialysis patients with refractory secondary hyperparathyroidism (abstract). J Am Soc Nephrol 1994;5:854.

    Google Scholar 

  80. Goodman WG, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, et al. Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int 1994;46:1160–6.

    Article  PubMed  CAS  Google Scholar 

  81. Kuizon BD, Goodman WG, Jüppner H, Boechat I, Nelson P, Gales B, et al. Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int 1998;53:205–11.

    Article  PubMed  CAS  Google Scholar 

  82. Andress DL, Norris KC, Coburn JW, Slatopolsky EA, Sherrard DJ. Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. N Engl J Med 1989;321:274–9.

    Article  PubMed  CAS  Google Scholar 

  83. Li YC, Amling M, Pirro AE, et al. Targeted ablation of the vitamin D receptor: An animal model of vitamin D-dependent rickets type II with alopecia. Proc Nat Acad Sci (USA) 1997;94:9831–5.

    Article  CAS  Google Scholar 

  84. Bikle DD, Pillai S. Vitamin D, calcium and epidermal differentiation. Physiol Rev 1993;14:3–19.

    CAS  Google Scholar 

  85. Segaert S, Garmyn M, Degreef H, Bouillon R. Retinoic acid modulates the antiproliferative effect of 1,25-dihydroxyvitamin D3 in cultured human epidermal keratinocytes. J Invest Dermatol 1997; 109:46–54.

    Article  PubMed  CAS  Google Scholar 

  86. van Leeuwen JPTM, Pols HAP. Vitamin D: Anticancer and differentiation. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;1089–105.

    Google Scholar 

  87. Zhao X-Y, Feldman D. Antiproliferative mechanisms of 1α,25(OH)2D3 in human prostate cancer cells. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: Structural, biological, genetic and clinical aspects. Riverside: Printing and Reprographics, University of California, 2000;489–93.

    Google Scholar 

  88. Schwartz GG. Prostate cancer and vitamin D: From concept to clinic. A ten-year update. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: Structural, biological, genetic and clinical aspects. Riverside: Printing and Reprographics, University of California, 2000;445–52.

    Google Scholar 

  89. Cross HS, Hofer H, Bareis P, Bises G, Posner GH, Peterlik M. Vitamin D compounds and colorectal cancer: A rationale for their use in prevention and therapy. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: Structural, biological, genetic and clinical aspects. Riverside: Printing and Reprographics, University of California, 2000;495–502.

    Google Scholar 

  90. Colston KW, Berger U, Coombes RC. Possible role for vitamin D in controlling breast cancer cell pro-liferation. Lancet 1989;1:185–91.

    Google Scholar 

  91. Casteels K, Bouillon R, Waer M, Mathieu C. Immunomodulatory effects of 1,25-dihydroxyvitamin D3. Curr Opin Nephrol Hypertens 1995;4:313–18.

    Article  PubMed  CAS  Google Scholar 

  92. Lemire J. The role of vitamin D3 in immunosuppression: Lessons from autoimmunity and transplantation. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;1167–81.

    Google Scholar 

  93. Mathieu C, van Etten E, Kato S, Verstuyf A, Laureys J, Dopovere J, et al. In vitro and in vivo analysis of the immune system of the VDR-KO mice. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: Structural, biological, genetic and clinical aspects. Riverside: Printing and Reprographics, University of California, 2000;555–9.

    Google Scholar 

  94. Nemere I, Schwartz Z, Pedrozo H, et al. Identification of a membrane receptor for 1,25-dihydroxyvi-tamin D3 which mediates rapid activation of protein kinase C. J Bone Miner Res 1998;13:1353–9.

    Article  PubMed  CAS  Google Scholar 

  95. Norman AW. Receptors for 1α,25(OH)2D3: Past, present, and future. J Bone Miner Res 1998;13:1360–9.

    Article  PubMed  CAS  Google Scholar 

  96. Norman AW, Bouillon R, Farach-Carson MC, et al. Demonstration that lβ,25-dihydroxyvitamin D3 is an antagonist of the nongenomic but not genomic biological responses and biological profile of the three A-ring diastereomers of lα,25-dihydroxyvitamin D3. J Biol Chem 1993;268:20022–30.

    PubMed  CAS  Google Scholar 

  97. Song X, Bishop JE, Okamura WH, et al. Stimulation of phosphorylation of mitogen-activated protein kinase by 1α,25-dihydroxyvitamin D3 in promyelocytic NB4 leukemia cells. Endocrinol 1998;139: 457–68.

    Article  CAS  Google Scholar 

  98. Cleve H, Constants J. The mutants of the vitamin-D-binding protein: More than 120 variants of the Gc\DBP system. Vox Sang 1988;54:215–25.

    Article  PubMed  CAS  Google Scholar 

  99. Cooke NE, Haddad JG. Vitamin D binding protein. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;87–101.

    Google Scholar 

  100. Bouillon R, Van Assche FA, Van Baelen H, et al. Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. J Clin Invest 1981;67:589–96.

    Article  PubMed  CAS  Google Scholar 

  101. Viccio D, Yergey A, Obrien K, et al. Quantitation and kinetics of 25-hydroxyvitamin D3 by isotope dilution liquid chromatography/thermospray mass spectrometry. Biol Mass Spectrom 1993;22:53–8.

    Article  Google Scholar 

  102. Christensen EI, Willnow TE. Essential role of megalin in renal proximal tubule for vitamin homeostasis. J Am Soc Nephrol 1999;10:2224–36.

    PubMed  CAS  Google Scholar 

  103. Nykjaer A, Vorum H, Dragun D, Walther D, Jacobsen C, Melsen F, et al. Megalin, a member of the LDL receptor family, is essential for vitamin D homeostasis and bone formation. Cell 1999;96:507–15.

    Article  PubMed  CAS  Google Scholar 

  104. Brenza HL, DeLuca HF. Regulation of 25-hydroxyvitamin D3 lalpha-hydroxylase gene expression by parathyroid hormone and 1,25-dihydroxyvitamin D3. Arch Biochem Biophys 2000;381:143–52.

    Article  PubMed  CAS  Google Scholar 

  105. Lee WM, Galbraith RM. The extracellular actin-scavenger system and actin toxicity. N Engl J Med 1992;326:1335–41.

    Article  PubMed  CAS  Google Scholar 

  106. Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr Rev 1995;16:200–57.

    PubMed  CAS  Google Scholar 

  107. Hollis BW. Detection of vitamin D and its major metabolites. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1977;587–606.

    Google Scholar 

  108. Bouillon R. Radiochemical assays for vitamin D metabolites: Technical possibilities and clinical applications. J Steroid Biochem 1983;19:921–7.

    Article  PubMed  CAS  Google Scholar 

  109. Hollis BW. Detection of vitamin D and its major metabolites. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;587–606.

    Google Scholar 

  110. Papapoulos SE, Fraher LJ, Clemens TL, Gleed J, O’Riordan JLH. Metabolites of vitamin D in human vitamin-D deficiency: Effect of vitamin D3 or 1,25-dihydroxy-cholecalciferol. Lancet 1980;2: 612–15.

    Article  PubMed  CAS  Google Scholar 

  111. Parfitt AM. Vitamin D and the pathogenesis of rickets and osteomalacia. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;645–62.

    Google Scholar 

  112. Miller WL, Portale AA. Genetic disorders of vitamin D biosynthesis. Endocrinol Metab Clin North Am 1999;28:825–40.

    Article  PubMed  CAS  Google Scholar 

  113. Liberman UA, Marx SJ. Vitamin D-dependent rickets. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Philadelphia: Lippincott Williams & Wilkins, 1999;323–8.

    Google Scholar 

  114. Chesney RW, Hamstra AJ, Mazess RB, Rose P, DeLuca HF. Circulating vitamin D metabolite concentrations in childhood renal diseases. Kidney Int 1982;21:65–9.

    Article  PubMed  CAS  Google Scholar 

  115. Bouillon R, Auwerx JD, Lissens WD, Pelemans WK. Vitamin D status in the elderly, seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency. Am J Clin Nutr 1987;45:755–63.

    PubMed  CAS  Google Scholar 

  116. Ooms ME, Roos JC, Bezemer PD, Van Der Vijch WJF, Bouter LM, Lips P. Prevention of bone loss by vitamin D supplementation in elderly women: A randomized double blind trial. J Clin Endocrinol Metab 1995;80:1052–8.

    Article  PubMed  CAS  Google Scholar 

  117. Gloth FM. Vitamin D deficiency in homebound elderly persons. JAMA 1995;274:1683–6.

    Article  PubMed  Google Scholar 

  118. Schmidt-Gayk H, Bouillon R, Roth HJ. Measurement of vitamin D and its metabolites (calcidiol and calcitriol) and their clinical significance. Scand J Clin Lab Invest 1997;57:35–45.

    CAS  Google Scholar 

  119. Dawson-Hughes B, Harris SS, Dallal GE. Plasma calcidol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. Am J Clin Nutr 1997;65:67–71.

    PubMed  CAS  Google Scholar 

  120. Krall EA, Sahyoun N, Tannenbaum S, Dallal GE, Dawson-Hughes B. Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. N Engl J Med 1989;321:1777–83.

    Article  PubMed  CAS  Google Scholar 

  121. Peacock M, Selby PL, Francis RM, Brown WB, Hordon L. Vitamin D deficiency, insufficiency, suffi-ciency, and intoxication. What do they mean? In: Norman AW, Schaefer K, Grigoleit H-G, v.Herrath D, editors. Vitamin D: Chemical, biochemical, and clinical update. Berlin: de Gruyter, 1985;569– 70.

    Google Scholar 

  122. Chapuy MC, Meunier PJ. Vitamin D insufficiency in adults and the elderly. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;679–93.

    Google Scholar 

  123. van der Wielen RPJ, Lowik MRH, van den Berg H, de Groot LCPGM, Haller J, Moreiras O, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet 1995;346:207–10.

    Article  PubMed  Google Scholar 

  124. Webb AR, Pilbeam C, Hanafin N, Holick MF. An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. N Engl J Med 1989;321:1777–83.

    Article  Google Scholar 

  125. Kinyamu HK, Gallagher JC, Balhorn KE, Petranick KM, Rafferty KA. Serum vitamin D metabolites and calcium absorption in normal young and elderly free-living women and in women living in nursing homes. Am J Clin Nutr 1997;65:790–7.

    PubMed  CAS  Google Scholar 

  126. Glerup H, Mikkelsen K, Poulsen L, Haas E, Overbeck S, Andersen H, et al. Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calcif Tissue Int 2000;66:419–24.

    Article  PubMed  CAS  Google Scholar 

  127. Glerup H, Eriksen EF. Acroparesthesia - a typical finding in vitamin D deficiency. Br J Rheumatol 1999;39:482.

    Article  Google Scholar 

  128. Lips P, van Ginkel FC, Jongen MJM, Rubertus F, Van der Vijgh WJF, Netelenbos JC. Determinants of vitamin D status in patients with hip fracture and in elderly control subjects. Am J Clin Nutr 1987;46:1005–10.

    PubMed  CAS  Google Scholar 

  129. Leboff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 1999;281:1505–11.

    Article  PubMed  CAS  Google Scholar 

  130. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327:1637–42.

    Article  PubMed  CAS  Google Scholar 

  131. Chapuy MC, Arlot ME, Delmas PD, Meunier PJ. Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. Br Med J 1994;308:1081–2.

    CAS  Google Scholar 

  132. Khaw KT, Sneyd MJ, Compston J. Bone density, parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women. Br Med J 1992;305:373–6.

    Article  Google Scholar 

  133. Dawson-Hughes B, Dallal GE, Krall EA, Harris S, Sokoll LJ, Falconer G. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Int Med 1991;115:505–12.

    PubMed  CAS  Google Scholar 

  134. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777–783.

    Article  PubMed  CAS  Google Scholar 

  135. McKenna MJ. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992;93:69–77.

    Article  PubMed  CAS  Google Scholar 

  136. Pettifor JM, Daniels ED. Vitamin D deficiency and nutritional rickets in children. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;663–78.

    Google Scholar 

  137. Edidin DV, Levitsky LL, Shey W, Dumbuvic N, Campos A. Resurgence of nutritional rickets associated with breast-feeding and special dietary practices. Pediatrics 1980;65:232–5.

    PubMed  CAS  Google Scholar 

  138. Dwyer JT, Dietz WH, Hass G, Suskind R. Risk of nutritional rickets among vegetarian children. Am J Dis Child 1979;133:134–40.

    PubMed  CAS  Google Scholar 

  139. Rudolph M, Arulanantham K, Greenstein RM. Unsuspected nutritional rickets. Pediatrics 1980;66: 72–6.

    Google Scholar 

  140. Harris SS, Dawson-Hughes B. Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American black and white women. Am J Clin Nutr 1998;67:1232–6.

    PubMed  CAS  Google Scholar 

  141. Zeghoud F, Vervel C, Guillozo H, Walrant-Debray O, Boutignon H, Garabédian M. Subclinical vitamin D deficiency in neonates: definition and response to vitamin D supplements. Am J Clin Nutr 1997; 65:771–8.

    PubMed  CAS  Google Scholar 

  142. Zeghoud F, Ben-Mekhbi H, Garabedian M. Prevention of maternal vitamin D deficiency (one oral dose of 2.5 mg vitamin D3 at the 6th and 8th month of pregnancy): Effects on neonatal calcium home-ostasis and infantile growth. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: Structural, biological, genetic and clinical aspects. Riverside: University of California Printing and Reprographics, 2000;839–42.

    Google Scholar 

  143. Dawson-Hughes B, Harris SS. Definition of optimal 25(OH)D status for bone. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: Structural, biological, genetic and clinical aspects. Riverside: University of California Printing and Reprographics, 2000;909–15.

    Google Scholar 

  144. Shah BR, Finberg L. Single day therapy for nutritional vitamin D-deficiency rickets: A preferred method. J Pediatrics 1994;125:487–90.

    Article  CAS  Google Scholar 

  145. Lubani MM, Al-Shab TS, Al-Saleh QA, Sharda DC, Quattawi SA, Ahmed SAH, et al. Vitamin D deficiency in Kuwait: The prevalence of a preventable disease. Ann Trop Paediatr 1989;3:134–9.

    Google Scholar 

  146. Kanis JA, Russell RGG. Rate of reversal of hypercalcaemia and hypercalciuria induced by vitamin D and its 1-alpha hydroxylated derivatives. Br Med J 1977;1:78–81.

    Article  PubMed  CAS  Google Scholar 

  147. Reid IR. Steroid osteoporosis. Calcif Tissue Int 1989;45:63–7.

    Article  PubMed  CAS  Google Scholar 

  148. Ringe JD. Active vitamin D metabolites in glucocorticoid-induced osteoporosis. Calcif Tissue Int 1997;60:124–7.

    Article  PubMed  CAS  Google Scholar 

  149. Eastell R, Reid DM, Compston J, Cooper C, Fogelman I, Francis RM, et al. A UK consensus group on the management of glucocorticoid-induced osteoporosis: An update. J Intern Med 1998;124:400–6.

    Google Scholar 

  150. Reid IR. Editorial: Glucocorticoid effects on bone. J Clin Endocrinol Metab 1998;83:1860–2.

    Article  PubMed  CAS  Google Scholar 

  151. Tilyard MW, Spears GFS, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992;326:357–62.

    Article  PubMed  CAS  Google Scholar 

  152. Orimo H, Shiraki M, Hayashi T, Nakamura T. Reduced occurrence of vertebral crush fractures in senile osteoporosis treated with 1α(OH)-vitamin D3. Bone Miner 1987;3:47–52.

    PubMed  CAS  Google Scholar 

  153. Lips P. Vitamin D deficiency and osteoporosis: The role of vitamin D deficiency and treatment with vitamin D an analogues in the prevention of osteoporosis-related fractures. Eur J Clin Invest 1996;26:436–42.

    Article  PubMed  CAS  Google Scholar 

  154. Nakamura T. Vitamin D for the treatment of osteoporosis. Osteoporosis Int 1997;7:S 155–8.

    Article  Google Scholar 

  155. Winters RW, Graham JB, Williams TF, McFalls VW, Burnett CH. A genetic study of familial hypophosphatemia and vitamin D-resistant rickets with a review of the literature. Medicine (Balt) 1958; 37:97–142.

    Article  CAS  Google Scholar 

  156. Thakker RV, Read AP, Davies KE, Whyte WP, Weksberg R, Glorieux FH, et al. Bridging markers defining the map position of X-linked hypophosphatemic rickets. J Med Genet 1987;24:756–60.

    Article  PubMed  CAS  Google Scholar 

  157. Drezner MK, Lyles KW, Haussler MR, Harrelson JM. Evaluation of a role for 1,25-dihydroxyvitamin D in the pathogenesis and treatment of X-linked hypophosphatemic rickets and osteomalacia. J Clin Invest 1980;66:1020032.

    Article  Google Scholar 

  158. Harrell RM, Lyles KW, Harrelson JM, Friedman NE, Drezner MK. Healing of bone disease in X-linked hypophosphatemic rickets/osteomalacia. Induction and maintenance with phosphorus and calcitriol. J Clin Invest 1985;75:1858–68.

    Article  PubMed  CAS  Google Scholar 

  159. Bettinelli A, Bianchi ML, Mazazucchi E, Gandolini G, Appliani AC. Acute effects of calcitriol and phosphate salts on mineral metabolism in children with hypophosphatemic rickets. J Pediatrics 1991; 118:372–6.

    Article  CAS  Google Scholar 

  160. Goodyer PR, Kronick JG, Jequier S, Reade TM, Scriver CR. Nephrocalcinosis and its relationship to treatment of hereditary rickets. J Pediatrics 1987;111:700–4.

    Article  CAS  Google Scholar 

  161. Alon U, Donaldson DL, Hellerstein S, Warady BA, Harris DJ. Metabolic and histologic investigation of the nature of nephrocalcinosis in children with hypophosphatemic rickets and in the Hyp mouse. J Pediatrics 1992;120:899–905.

    Article  CAS  Google Scholar 

  162. Drezner MK, Feinglos MN. Osteomalacia due to 1,25-dihydroxy-cholecalciferol deficiency. Association with a giant cell tumor of bone. J Clin Invest 1977;60:1046–53.

    Article  PubMed  CAS  Google Scholar 

  163. Lobaugh B, Burch WM, Jr., Drezner MK. Abnormalities of vitamin D metabolism and action in the vitamin D-resistant rachitic and osteomalacic diseases. In: Kumar R, editor. Vitamin D. Boston: Mar- tinus Nijhoff, 1984;665–720.

    Google Scholar 

  164. Leicht E, Biro G, Langer H-J. Tumor induced osteomalacia: Pre- and post-operative biochemical findings. Horm Metab Res 1990;22:640–3.

    Article  PubMed  CAS  Google Scholar 

  165. Brickman AS, Coburn JW, Massry SG, Norman AW. 1,25-dihydroxyvitamin D3 in normal man and patients with renal failure. Ann Int Med 1974;80:161–8.

    PubMed  CAS  Google Scholar 

  166. Brickman AS, Coburn JW, Norman AW. Action of 1,25-dihydroxycholecalciferol, a potent kidney- produced metabolite of vitamin D3 in uremic man. N Engl J Med 1972;287:891–5.

    Article  PubMed  CAS  Google Scholar 

  167. Brickman AS, Hartenbower DL, Norman AW, Coburn JW. Actions of lα-hydroxy- and 1,25-dihy- droxyvitamin D3 on mineral metabolism in man. I. Effects on net absorption of phosphorus. Am J Clin Nutr 1977;30:1064–70.

    PubMed  CAS  Google Scholar 

  168. Slatopolsky E, Weerts C, Thielan J, Horst RL, Harter H, Martin KJ. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients. J Clin Invest 1984;74:2136–43.

    Article  PubMed  CAS  Google Scholar 

  169. Dunlay R, Rodriguez M, Felsenfeld AJ, Llach F. Direct inhibitory effect of calcitriol on parathyroid function (sigmoidal curve) in dialysis. Kidney Int 1989;36:1093–8.

    Article  PubMed  CAS  Google Scholar 

  170. Coburn JW, DiDomenico NC, Bryce GF, Bassett LW, Shupien SA, Wong EGC, et al. Prospective, double- blind trial with calcitriol in the prophylaxis of bone disease in asymptomatic dialysis patients. In: Norman AW, Schaefer K, Grigoleit H-G, v.Herrath D, editors. Vitamin D: Chemical, biochemical, and clinical endocrinology of calcium metabolism. Berlin: deGruyter, 1982;833–4.

    Google Scholar 

  171. Baker LR, Muir JW, Sharman VL, Abrams SM, Greenwood RN, Cattell WR, et al. Controlled trial of calcitriol in hemodialysis patients. Clin Nephrol 1986;26:185–91.

    PubMed  CAS  Google Scholar 

  172. Memmos DE, Eastwood JB, Talner LB, Gower PE, Curtis JR, Phillips ME, et al. Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis. Br Med J 1981;282:1919–24.

    Article  CAS  Google Scholar 

  173. Van der Merwe WM, Rodger RSC, Grant AC, Logue FC, Cowan RA, Beastall GH, et al. Low calcium dialysate and high-dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients. Nephrol Dial Transplant 1990;5:874–7.

    PubMed  Google Scholar 

  174. Fukagawa M, Kitaoka M, Yi H, Fukuda N, Matsumoto T, Ogata E, et al. Serial evaluation of parathyroid size by ultrasonography is another useful marker for the long-term prognosis of calcitriol pulse therapy in chronic dialysis patients. Nephron 1994;68:221–8.

    Article  PubMed  CAS  Google Scholar 

  175. Fukagawa M, Orazaki R, Takano K, Kaname S-Y, Ogata E, Kitoaka M, et al. Regression of parathyroid hyperplasia by calcitriol-pulse therapy in patients on long-term dialysis. N Engl J Med 1990;323: 421–2.

    Article  PubMed  CAS  Google Scholar 

  176. Tsukamoto Y, Nomura M, Takahashi Y, Takagi Y, Yoshida A, Nagaoka T, et al. The “oral 1,25-dihydroxyvitamin D3 pulse therapy” in hemodialysis patients with severe secondary hyperparathyroidism. Nephron 1991;57:23–8.

    Article  PubMed  CAS  Google Scholar 

  177. Muramoto H, Haruki K, Yoshimura A, Mimo N, Oda K, Tofuku Y. Treatment of refractory hyperparathyroidism in patients on hemodialysis by intermittent oral administration of 1,25(OH)2D3. Nephron 1991;58:288–94.

    Article  PubMed  CAS  Google Scholar 

  178. Perez-Mijares R, Gomez-Fernandez P, Almaraz-Jimenez M, Ramos-Diaz M, Rivero-Bohorquez J. Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration. Am J Nephrol 1993;13:149–54.

    Article  PubMed  CAS  Google Scholar 

  179. Martin KJ, Ballal HS, Domoto DT, Blalock S, Weindel M. Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: Preliminary observations. Am J Kidney Dis 1992;19:540–5.

    PubMed  CAS  Google Scholar 

  180. Cannella G, Bonucci E, Rolla D, Ballanti P, Moriero E, De Grandi R, et al. Evidence of healing of sec-ondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. Kidney Int 1994;46:1124–32.

    Article  PubMed  CAS  Google Scholar 

  181. Llach F, Hervas J, Cerezo S. The importance of dosing intravenous calcitriol in dialysis patients with severe hyperparathyroidism. Am J Kidney Dis 1995;26:845–51.

    Article  PubMed  CAS  Google Scholar 

  182. Malberti F, Surian M, Cosci R Effect of chronic intravenous calcitriol on parathyroid function and set point of calcium in dialysis patients with refractory secondary hyperparathyroidism. Nephrol Dial Transplant 1992;7:822–8.

    PubMed  CAS  Google Scholar 

  183. Herrmann P, Ritz E, Schmidt-Gayk H, Schäfer I, Geyer J, Nonnast-Daniel B, et al. Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: A randomized prospective trial. Nephron 1994;67:48–53.

    Article  PubMed  CAS  Google Scholar 

  184. Bechtel U, Mücke C, Feucht HE, Schiffl H, Sitter T, Held E. Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 1995;25:291–6.

    Article  PubMed  CAS  Google Scholar 

  185. Salusky IB, Goodman WG, Horst R, Segre GV, Kim L, Norris KC, et al. Pharmacokinetics of calcitriol in CAPD/CCPD patients. Am J Kidney Dis 1990;16:126–32.

    PubMed  CAS  Google Scholar 

  186. Ardissino G, Schmitt CP, Bianchi ML, Dacco V, Claris-Appiani A, Mehls O. European study group on vitamin D in children with renal failure. No difference in intestinal strontium absorption after oral or IV calcitriol in children with secondary hyperparathyroidism. Kidney Int 2000;58: 981–8.

    CAS  Google Scholar 

  187. Fischer ER, Harris DCH. Comparison of intermittent oral and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism. Clin Nephrol 1993;40:216–20.

    PubMed  CAS  Google Scholar 

  188. Quarles LD, Yohay DA, Carroll BA, Spritzer CE, Minda SA, Bartholomay D, et al. Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney Int 1994;45:1710–21.

    Article  PubMed  CAS  Google Scholar 

  189. Levine BS, Song MM. Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients. J Am Soc Nephrol 1996;7:488–96.

    PubMed  CAS  Google Scholar 

  190. Faugere M-C, Friedler RM, Malluche HH. Efficacy and limitations of pulse IV and pulse oral 1,25 vit. D therapy in treatment of hyperparathyroidism in patients on long-term dialysis (abstract). J Am Soc Nephrol 1993;4:695.

    Google Scholar 

  191. Salusky IB, Ramirez JA, Belin T, Segre GV, Goodman WG. Pulse calcitriol therapy: A prospective randomized trial (abstract). J Am Soc Nephrol 1994;5:855.

    Google Scholar 

  192. Lind L, Wengle B, Wide L, Wrege U, Ljunghall S. Suppression of serum parathyroid hormone levels by intravenous alfacalcidol in uremic patients on maintenance hemodialysis: A pilot study. Nephron 1988;48:296–9.

    Article  PubMed  CAS  Google Scholar 

  193. Brandi L, Daugaard H, Tvedegaard E, Storm T, Olgaard K. Effect of intravenous 1-alpha-hydroxyvit- amin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodial-ysis. Nephron 1989;53:194–200.

    Article  PubMed  CAS  Google Scholar 

  194. Moriniere P, Esper NE, Viron B, Judith D, Bourgeon B, Farquet C, et al. Improvement of severe sec-ondary hyperparathyroidism in dialysis patients by intravenous 1α(OH) vitamin D3, oral CaC03 and low dialysate calcium. Kidney Int 1993;43 (Suppl 41):S121–4.

    Google Scholar 

  195. Emmett M, Sirmon MD, Kirkpatrick WG, Nolan CR, Schmitt GW, Cleveland MvB. Calcium acetate control of serum phosphorus in hemodialysis patients. Am J Kidney Dis 1991;17:544–50.

    CAS  Google Scholar 

  196. Sperschneider H, Gunther K, Marzoll I, Kirchner E, Stein G. Calcium carbonate (CaC03): an efficient and safe phosphate binder in haemodialysis patients? A 3-year study. Nephrol Dial Transplant 1993;8:530–4.

    PubMed  CAS  Google Scholar 

  197. Ribeiro S, Ramos A, Brandao A, Rebelo JR, Guerra A, Resina C, et al. Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism. Nephrol Dial Transplant 1998; 13: 2037–40.

    Article  PubMed  CAS  Google Scholar 

  198. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium X phosphate product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis 1998;31:607–17.

    Article  PubMed  CAS  Google Scholar 

  199. Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: Recommendations for a change in management. Am J Kidney Dis 2000;35:1226–37.

    Article  PubMed  CAS  Google Scholar 

  200. Amann K, Gross M-L, London GM, Ritz E. Hyperphosphatemia - a silent killer of patients with renal failure? Nephrol Dial Transplant 1999;14:2085–7.

    Article  PubMed  CAS  Google Scholar 

  201. Guerin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000;15:1014–21.

    Article  PubMed  CAS  Google Scholar 

  202. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342:1478–83.

    Article  PubMed  CAS  Google Scholar 

  203. Akiba T, Marumo F, Owada A, Kurihara S, Inoue A, Chida Y, et al. Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 1998;32:238.

    Article  PubMed  CAS  Google Scholar 

  204. Abe J, Takita Y, Nakano T, Miyaura C, Suda T, Nishii Y. A synthetic analogue of vitamin D3, 22- oxa-1 Alpha,25-dihydroxyvitamin D3, is a potent modulator of in vivo immunoregulating activity without inducing hypercalcaemia in mice. Endocrinol 1989;124:2645–7.

    Article  CAS  Google Scholar 

  205. Brown AJ, Ritter CS, Finch JL, Morrissey J, Martin KJ, Murayama E, et al. The noncalcaemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion. J Clin Invest 1989;84:728–32.

    Article  PubMed  CAS  Google Scholar 

  206. Brown AJ, Finch JL, Lopez-Hilker S, Dusso A, Ritter C, Pernalete N, et al. New active analogues of vitamin D with low calcaemic activity. Kidney Int 1990;29 (Suppl.29):S22–7.

    CAS  Google Scholar 

  207. Martin KJ, González EA, Gellens M, Hamm LL, Abboud H, Lindberg J. 19-Nor-1-α-25-Dihydroxyvit- amin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol 1998;9:1427–32.

    PubMed  CAS  Google Scholar 

  208. Tan Jr AU, Levine BS, Mazess RB, Kyllo DM, Bishop CW, Knutson JC, et al. Effective suppression of parathyroid hormone by 1α-hydroxyvitaminD2 in hemodialysis patients with moderate to severe secondary hyperparathyroidism. Kidney Int 1997;51:317a–23.

    Article  Google Scholar 

  209. Frazão JM, Levine BS, Tan Jr AU, Mazess RB, Kyllo DM, Knutson JC, et al. Efficacy and safety of intermittent oral 1α (OH)-vitamin D2 in suppressing 2° hyperparathyroidism in hemodialysis patients. Dial Transplant 1997;26:583–95.

    Google Scholar 

  210. Frazão JM, Elangovan L, Maung HM, Chesney RB, Acchiardo SR, Bower JD, et al. Intermittent doxer- calciferol (1α-hydroxyvitamin D2) therapy for secondary hyperparathyroidism: Results of a modified, double blinded, controlled study. Am J Kidney Dis 2000;36:550–61.

    Article  PubMed  Google Scholar 

  211. Maung HM, Elangovan L, Frazão JM, Bower JD, Kelley BJ, Acchiardo SR, etal. Efficacy and side-effects of intermittent intravenous and oral doxercalciferol (1α-hydroxyvitamin D2) in dialysis patients with secondary hyperparathyroidism: A sequential comparison. Am J Kidney Dis 2001;37:532–43.

    Article  PubMed  CAS  Google Scholar 

  212. Dusso A, Gunawardhana S, Negrea L, Finch JL, Lopez-Hilker S, Mori T, et al. On the mechanisms for the selective action of vitamin D analogs. Endocrinol 1991;128:1687–92.

    Article  CAS  Google Scholar 

  213. Finch JL, Brown AJ, Kubodera N, Nishii Y, Slatopolsky E. Differential effects of l,25-(OH)2D3 and 22- oxacalcitriol on phosphate and calcium metabolism. Kidney Int 1993;43:561–6.

    Article  PubMed  CAS  Google Scholar 

  214. Akizawa T, Kurokawa K, Suzuki M, Akiba T, Nishizawa Y, Ohashi Y, et al. Suppression of PTH by 22- oxacalcitriol (OCT). A placebo controlled study in hemodialysis (HD) patients with secondary hyperparathyroidism (2 HPT) (abstract). J Am Soc Nephrol 1997;8:570A.

    Google Scholar 

  215. Akizawa T, Kurokawa K, Suzuki M, Akiba T, Nishizawa Y, Ohashi Y, et al. Suppressive effect of 22- oxacalcitriol (OCT) on secondary hyperparathyroidism (2 HPT) of hemodialysis (HD) patients. A double-blind comparison among four doses (abstract). J Am Soc Nephrol 1997;7:1810.

    Google Scholar 

  216. Morii H, Ogura Y, Koshikawa S, Mimura N, Suzuki M, Kurokawa K, et al. Efficacy and safety of oral falecalcitriol in reducing parathyroid hormone in hemodialysis patients with secondary hyper-parathyroidism. J Bone Miner Metab 1998;16:34–43.

    Article  CAS  Google Scholar 

  217. Coburn JW, Elangovan L. Prevention of metabolic bone disease in the pre-end-stage renal disease setting. J Am Soc Nephrol 1998;9:S71–7.

    PubMed  CAS  Google Scholar 

  218. Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K. Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int 1999;56: 1084–93.

    Article  PubMed  CAS  Google Scholar 

  219. Massry SG. Assessment of 1,25(OH2D3 in the correction and prevention of renal osteodystrophy in patients with mild to moderate renal failure. In: Norman AW, Schaefer K, Grigoleit H-G, v.Herrath D, editors. Vitamin D: A chemical, biochemical and clinical update. Berlin: de Gruyter, 1985;935–7.

    Google Scholar 

  220. Nordal KP, Dahl E. Low-dose calcitriol versus placebo in patients with predialysis chronic renal failure. J Clin Endocrinol Metab 1988;67:929–36.

    Article  PubMed  CAS  Google Scholar 

  221. Baker LRI, Abrams SML, Roe CJ, Faugere M-C, Fanti P, Subayti Y, etal. 1,25(OH)2D3 administration in moderate renal failure: A prospective double-blind trial. Kidney Int 1989;35:661–9.

    Article  PubMed  CAS  Google Scholar 

  222. Hamdy NAT, Kanis JA, Beneton MNC, Brown CB, Juttmann JR, Jordans JGM, et al. Effect of alfacalcidol on natural course of bone disease in mild to moderate renal failure. Br Med J 1995;310:358–63.

    CAS  Google Scholar 

  223. Przedlacki J, Manelius J, Huttunen K. Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. Nephron 1995;69:433–7.

    Article  PubMed  CAS  Google Scholar 

  224. Ritz E, Küster S, Schmidt-Gayk H, Stein G, Scholz C, Kraatz G, et al. Low-dose calcitriol prevents the rise in 1,84 iPTH without affecting serum calcium and phosphate in patients with moderate renal failure (prospective placebo-controlled multicentre trial). Nephrol Dial Transplant 1995; 10: 2228–34.

    PubMed  CAS  Google Scholar 

  225. Bertoli M, Luisetto G, Ruffatti A, Urso M, Romagnoli G. Renal function during calcitriol therapy in chronic renal failure. Clin Nephrol 1990;33:98–102.

    PubMed  CAS  Google Scholar 

  226. Perez A, Raab R, Chen TC, Turner AK, Holick MF. Safety and efficacy of oral calcitriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis. Br J Derm 1996;134:1070–8.

    Article  CAS  Google Scholar 

  227. Coen G, Mazzaferro S, Bonucci E, Ballanti P, Massimetti C, Donado G, et al. Treatment of secondary hyperparathyroidism of pre-dialysis chronic renal failure with low doses of 1,25(OH)2D3: humoral and histomorphometric results. Miner Electrolyte Metab 1986;12:375–82.

    PubMed  CAS  Google Scholar 

  228. Bianchi ML, Colantonio G, Campanini F, Rossi R, Valenti G, Ortolani S, et al. Calcitriol and calcium carbonate therapy in early chronic renal failure. Nephrol Dial Transplant 1994;9:1595–9.

    PubMed  CAS  Google Scholar 

  229. Nordal KP, Dahl E, Halse J, Ajitamadal A, Flatmark A. Long-term low-dose calcitriol in predialysis chronic renal failure: Can it prevent hyperparathyroid bone disease? Nephrol Dial Transplant 1995;10:203–6.

    PubMed  CAS  Google Scholar 

  230. Quarles LD, Lobaugh B, Murphy G. Intact parathyroid hormone overestimates the presence and severity of parathyroid-mediated osseous abnormalities in uremia. J Clin Endocrinol Metab 1992; 75:145–50.

    Article  PubMed  CAS  Google Scholar 

  231. Sherrard DJ, Hercz G, Pei Y, Maloney NA, Greenwood C, Manuel A, et al. The spectrum of bone disease in end-stage renal failure - An evolving disorder. Kidney Int 1993;43:435–6.

    Article  Google Scholar 

  232. Scriver CR. Vitamin D dependency. Pediatrics 1970;45:361–3.

    PubMed  CAS  Google Scholar 

  233. Coburn JW, Maung HM, Frazão JM, Elangovan L. New vitamin D analogs and calcimimetics. In: Drueke TB, Salusky IB, editors. Renal osteodystrophy. Oxford: Oxford University Press, 2002.

    Google Scholar 

  234. Brooks MG, Bell NH, Love L, Stern PH, Orfei E, Queener SF, et al. Vitamin D-dependency rickets type II. Resistance of target organs to 1,25-dihydroxyvitamin D. N Engl J Med 1978;298:996–9.

    Article  PubMed  CAS  Google Scholar 

  235. Weisman Y, Hochberg Z. Genetic rickets and osteomalacia. Curr Ther Endocrinol Metab 1994; 5:492–5.

    PubMed  CAS  Google Scholar 

  236. Holick MF. Active vitamin D compounds and analogues: A new therapeutic era for dermatology in the 21st century. Mayo Clin Proc 1993;68:925–7.

    PubMed  CAS  Google Scholar 

  237. Kragballe K, Gjertsein BT, De Hoop D, Karsmark T, van de Kerkhof PCM, Larkö O, et al. Double-blind, right-left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 1991;337:193–6.

    Article  PubMed  CAS  Google Scholar 

  238. Kragballe K. Psoriasis and other skin diseases. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997; 1213–25.

    Google Scholar 

  239. Anning ST, Dawson J, Dolby DE, Ingram JT. The toxic effects of calciferol. Q J Med 1948;17:203–28.

    PubMed  CAS  Google Scholar 

  240. Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, et al. Hypervitaminosis D associ-ated with drinking milk. N Engl J Med 1992;326:1173–7.

    Article  PubMed  CAS  Google Scholar 

  241. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66–7.

    Article  PubMed  CAS  Google Scholar 

  242. Stanbury SW. The treatment of renal osteodystrophy. Ann Int Med 1966;65:1133–8.

    PubMed  CAS  Google Scholar 

  243. Breslau NA, Zerwekh JE. Pharmacology of vitamin D preparations. In: Feldman D, Glorieux FH, Pike JW, editors. Vitamin D. San Diego: Academic Press, 1997;607–18.

    Google Scholar 

  244. Bell NH, Gill Jr JR, Barter FC. Abnormal calcium absorption in sarcoidosis: Evidence for increased sensitivity to vitamin D. Am J Med 1964;36:500–13.

    Article  PubMed  CAS  Google Scholar 

  245. Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL. Hypercalcemia in an anephric patient with sarcoidosis, evidence for extrarenal generation of 1,25 dihydroxyvitamin D. N Engl J Med 1981;305:440–6.

    Article  PubMed  CAS  Google Scholar 

  246. Adams JS, Sharma OP, Diz MM, Endres DB. Ketoconazole decreases the serum 1,25-dihydroxyvitamin D and calcium concentration in sarcoidosis-associated hypercalcemia. J Clin Endocrinol Metab 1990;70:1090–5.

    Article  PubMed  CAS  Google Scholar 

  247. Bia MJ, Insogna K. Treatment of sarcoidosis-associated hypercalcemia with ketoconazole. Am J Kidney Dis 1991;18:702–5.

    PubMed  CAS  Google Scholar 

  248. Coburn JW, Salusky IB. Renal bone diseases: clinical features, diagnosis and management. In: Bilezikian JP, Marcus R, Levine MA, editors. The Parathyroids. San Diego: Academic Press, 2001; 635–61.

    Google Scholar 

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Authors
  1. J. W. Coburn
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  2. J. M. Frazão
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Editors and Affiliations

  1. 2nd Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, 545-8585, Abeno-ku Osaka, Japan

    Hirotoshi Morii MD, PhD (Professor Emeritus) & Yoshiki Nishizawa MD, PhD (Professor Emeritus) & 

  2. Division of Nephrololgy Raulston Memorial Research Building, Room 104 Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA

    Shaul G. Massry MD (Professor of Medicine) (Professor of Medicine)

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Coburn, J.W., Frazão, J.M. (2002). Vitamin D: Normal Physiology and Vitamin D Therapeutics in Normal Nutrition and Various Disease States. In: Morii, H., Nishizawa, Y., Massry, S.G. (eds) Calcium in Internal Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-0667-8_15

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  • DOI: https://doi.org/10.1007/978-1-4471-0667-8_15

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