The Role of Abnormal Vitamin D Metabolism in X-Linked Hypophosphatemic Rickets and Osteomalacia

  • Marc K. Drezner
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 178)


The contemporary theory for the pathogenesis of X-linked hypophosphatemic rickets/osteomalacia (XLH) has as its central tenet that a primary defect in transepithelial transport of phosphate in the kidney accounts for all of the biochemical and skeletal abnormalities characteristic of the disease. Consistent with this view phosphorus depleted animals develop abnormalities in bone morphology similar to those observed in XLH and treatment of affected subjects with orthophosphate promotes healing of the rickets and linear growth in childhood. Moreover, apparent localization of the proposed defect in renal phosphate wasting to the parathyroid hormone sensitive locus of the proximal renal tubule1,2 lends further support to the primacy of a renal phosphate leak in the pathogenesis of XLH.


Phosphate Transport Hypophosphatemic Rickets Affected Subject Renal Phosphate Phosphate Depletion 
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. 1.
    H. S. Tennenhouse, C. R. Scriver, R. R. McInnes, and F. H. Glorieux, Renal handling of phosphate in vivo and in vitro by the X-linked hypophosphatemic male mouse: evidence for a defect in the brush border membrane, Kidney Int. 14: 236 (1978).CrossRefGoogle Scholar
  2. 2.
    H. S. Tennenhouse and C. R. Scriver, Renal brush border membrane adaptation to phosphorus deprivation in the Hyp/y mouse, Nature 281: 225 (1979).CrossRefGoogle Scholar
  3. 3.
    F. H. Glorieux, C. L. Morin, R. Travers, E. E. Delvin, and R. Poirer, Intestinal phosphate transport in familial hypophosphatemic rickets, Pediatr. Res. 10: 691 (1976).Google Scholar
  4. 4.
    K. W. Lyles, J. M. Harrelson, and M. K. Drezner, The efficiacy of vitamin D 2 and oral phosphorus therapy in X-linked hypophosphatemic rickets and osteomalacia, J. Clin. Endocrinol. Metab. 54: 307 (1982).CrossRefGoogle Scholar
  5. 5.
    K. W. Lyles, A. G. Clark, and M. K. Drezner, Serum 1,25-dihydroxyvitamin D levels in subjects with X-linked hypo- phosphatemic rickets and osteomalacia, Calc. Tissue Int. 34: 125 (1982).CrossRefGoogle Scholar
  6. 6.
    E. E. Delvin and F. H. Glorieux, Serum 1,25-dihydroxyvitamin D concentration in hypophosphatemic vitamin D resistant rickets, Calc. Tissue Int. 33: 173 (1981).CrossRefGoogle Scholar
  7. 7.
    C. R. Scriver, T. M. Reade, H. F. DeLuca, and A. J. Hamstra, Serum 1,25-dihydroxyvitamin D levels in normal subjects and in patients with hereditary rickets or bone disease, N. Engl. J. Med. 299: 976 (1978).PubMedCrossRefGoogle Scholar
  8. 8.
    R. W. Chesney, R. B. Mazess, P. Rose, A. J. Hamstra, and H. F. DeLuca, Supranormal 25-hydroxyvitamin D and subnormal 1,25-dihydroxyvitamin D: their role in X-linked hypophosphatemic rickets, Am. J. Dis. Child 134: 140 (1980).PubMedGoogle Scholar
  9. 9.
    M. R. Haussler, M. Hughes, D. Baylink, E. T. Littledike, D. Cork, and M. Pitt, Influence of phosphate depletion on the biosynthesis and circulating level of 1,25-dihydroxyvitamin D, Adv. Exp. Med. Biol. 81: 233 (1977).PubMedGoogle Scholar
  10. 10.
    B. Lobaugh and M. K. Drezner, Abnormal regulation of renal 25-hydroxyvitamin D-la-hydroxylase activity in the X-linked hypophosphatemic mouse, J. Clin. Invest. 71: 400 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    J. Cunningham, H. Gomes, Y. Sieno, and L. R. Chase, Abnormal 24-hydroxylation of 25-hydroxyvitamin D in the X-linked hypophosphatemic mouse, Endocrinology 112: 633 (1983).PubMedCrossRefGoogle Scholar
  12. 12.
    M. Tieder, R. Samuel, A. Halabe, R. Arie, D. Modai, D. Gabízon, and U. A. Liberman, Autosomal recessive hypophosphatemic rickets, elevated 1,25-(OH)2-D serum levels and hypercalciuria - a new syndrome, Calc. Tissue Int. (Abstr. Am. Soc. Bone and Mineral Res) In press (1983).Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Marc K. Drezner
    • 1
  1. 1.Duke University Medical CenterDurhamUSA

Personalised recommendations