Download PDF
Semin Musculoskelet Radiol 2002; 06(3): 173-182
DOI: 10.1055/s-2002-36714
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Vitamin D Metabolism, Rickets, and Osteomalacia

Jacqueline L. Berry, Michael Davies, Andrew P. Mee
  • Vitamin D Research Group, University School of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom
Further Information

Publication History

Publication Date:
23 January 2003 (online)

Also available at
    Permissions and Reprints

ABSTRACT

Rickets in the growing child or adolescent and osteomalacia in the adult develop in a variety of clinical situations and have in common an absence or delay in the mineralization of growth cartilage and in newly formed bone collagen. Classically, deficiency of vitamin D, which is essential for the absorption of dietary calcium, has been the major cause. However, rickets is also seen as a result of hereditary defects in critical vitamin D signaling molecules. Disturbances of phosphate metabolism can also lead to signs of rickets and osteomalacia, notably X-linked hypophosphatemic rickets, and oncogenic osteomalacia. Extrarenal synthesis of 1,25-dihydroxyvitamin D, such as that associated with granulomatous disease, can also lead to disturbances in calcium metabolism, with associated skeletal and nonskeletal changes.

KEYWORD

Vitamin D - rickets - osteomalacia - X-linked hypophosphatemic rickets - oncogenic osteomalacia

REFERENCES

  • 1 Mawer E B. The sunshine vitamin-how a dose of sunshine forms vitamin D.  Biol Sci Rev . 1990;  2 2-7
    PubMedGoogle Scholar
  • 2 Holick M F. Photobiology of vitamin D. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 33-39
    Google Scholar
  • 3 Stanbury S W, Mawer E B, Lumb G A. Some aspects of vitamin D metabolism in man. In: Taylor S, ed. Endocrinology London: Heinemann Medical Books 1971: 487-499
    Google Scholar
  • 4 Horst R L, Reinhardt T A. Vitamin D metabolism. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 13-31
    Google Scholar
  • 5 Okuda K I, Usui E, Ohyama Y. Recent progress in enzymology and molecular biology of enzymes involved in vitamin D metabolism.  J Lipid Res . 1995;  36 1641-1652
    PubMedGoogle Scholar
  • 6 Fraser D R, Kodiceck E. Unique biosynthesis by kidney of a biologically active vitamin D metabolite.  Nature . 1970;  288 764-766
    PubMedGoogle Scholar
  • 7 Minghetti P P, Norman A W. 1,25(OH)2-vitamin D3 receptors: gene regulation and genetic circuitry.  Fed Am Soc Exp Biol J . 1988;  2 3043-3053
    PubMedGoogle Scholar
  • 8 Haussler M R, Haussler C A, Thompson P D. Molecular nature of the vitamin D receptor and its role in regulation of gene expression.  Rev End Met Dis . 2001;  2 203-215
    PubMedGoogle Scholar
  • 9 Adams J S, Lemire J, Gacad M A, Hewison M. Vitamin D as cytokine and haematopoetic factor.  Rev End Met Dis . 2001;  2 217-227
    PubMedGoogle Scholar
  • 10 Wasserman R H. Vitamin D and the intestinal absorption of calcium and phosphorus. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 259-273
    Google Scholar
  • 11 Barbour G L, Coburn J W, Slatopolsky E, Norman A W, Horst R L. Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D.  N Eng J Med . 1981;  305 440-443
    PubMedGoogle Scholar
  • 12 Hayes M E, Denton J, Freemont A J, Mawer E B. Synthesis of the active metabolite of vitamin D, 1,25(OH)2D3, by synovial fluid macrophages in arthritic diseases.  Ann Rheum Dis . 1989;  48 723-729
    PubMedGoogle Scholar
  • 13 Gkonos P J, London R, Hendler E D. Hypercalcemia and elevated 1,25-dihydroxyvitamin D levels in a patient with end-stage renal disease and active tuberculosis.  N Eng J Med . 1984;  311 1683-1685
    PubMedGoogle Scholar
  • 14 Fu G K, Lin D, Zhang M YH. Cloning of human 25-hydroxyvitamin D-1 α-hydroxylase and mutations causing vitamin D-dependent rickets type 1.  Mol Endocrinol . 1997;  11 1961-1970
    CrossrefPubMedGoogle Scholar
  • 15 Smith S J, Rucka A J, Berry J L. Novel mutations in the 1α-hydroxylase (p450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages.  J Bone Min Res . 1999;  14 730-739
    PubMedGoogle Scholar
  • 16 Mawer E B, Davies M. Vitamin D nutrition and bone disease in adults.  Rev End Met Dis . 2001;  2 153-164
    PubMedGoogle Scholar
  • 17 Holick M F. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health.  Curr Opin Endo Diabetes . 2002;  9 87-98
    CrossrefPubMedGoogle Scholar
  • 18 Hebert S C, Brown E M. The extracellular calcium receptor.  Curr Opin Cell Biol . 1995;  7 484-492
    CrossrefPubMedGoogle Scholar
  • 19 Hock J M, Fitzpatrick L A, Bilezikian J P. Actions of parathyroid hormone. In: Bilezikian JP, Raisz L, Rodan GA, eds. Principles of Bone Biology, 2nd edition London: Academic Press 2002: 463-481
    Google Scholar
  • 20 Mawer E B, Davies M. Bone disorders associated with gastrointestinal and hepatobiliary disease. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 831-847
    Google Scholar
  • 21 Mawer E B, Mughal Z. Rickets.  Curr Opin Ortho . 1999;  10 354-360
    PubMedGoogle Scholar
  • 22 Clements M R, Johnston L, Fraser D R. A new mechanism for induced vitamin D deficiency in calcium deprivation.  Nature . 1987;  325 62-65
    CrossrefPubMedGoogle Scholar
  • 23 Davies M, Heys S E, Selby P L, Berry J L, Mawer E B. Increased catabolism of 25-hydroxyvitamin D in patients with partial gastrectomy and elevated 1,25-dihydroxyvitamin D levels. Implications for metabolic bone disease.  J Clin Endocrinol Metab . 1997;  82 209-212
    CrossrefPubMedGoogle Scholar
  • 24 Dunnigan M G, Henderson J B. An epidemiological model of privational rickets and osteomalacia.  Proc Nutr Soc . 1997;  56 939-956
    CrossrefPubMedGoogle Scholar
  • 25 Malloy P J, Pike J W, Feldman D. The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets.  Endo Rev . 1999;  20 156-188
    PubMedGoogle Scholar
  • 26 Large D M, Mawer E B, Davies M. Dystrophic calcification, cataracts and enamel hypoplasia due to long standing, privational vitamin D deficiency.  Metab Bone Dis Rel Res . 1984;  5 215-218
    CrossrefPubMedGoogle Scholar
  • 27 Adams J E. Radiology of rickets and osteomalacia. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 619-642
    Google Scholar
  • 28 Parfitt A M. Vitamin D and the pathogenesis of rickets and osteomalacia. In: Feldman D, Glorieux FH, Pike JW, eds. Vitamin D London: Academic Press 1997: 645-662
    Google Scholar
  • 29 Scheinman S J, Guay-Woodford L M, Thakker R V, Warnock D G. Mechanisms of disease: genetic disorders of renal electrolyte transport.  N Engl J Med . 1999;  340 1177-1187
    CrossrefPubMedGoogle Scholar
  • 30 Tieder M, Arie R, Modai D, Samuel R, Weissgarten J, Liberman U A. Elevated serum 1,25-dihydroxyvitamin D concentrations in siblings with primary Fanconi's syndrome.  N Engl J Med . 1988;  319 845-849
    PubMedGoogle Scholar
  • 31 The HYP Consortium. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets.  Nat Genet . 1995;  11 130-136
    CrossrefPubMedGoogle Scholar
  • 32 Rowe P S. The role of the PHEX (PEX) gene in families with X-linked hypophosphatemic rickets.  Curr Opin Nephrol Hypertens . 1998;  7 367-376
    PubMedGoogle Scholar
  • 33 Adams J E, Davies M. Intraspinal new bone formation and spinal cord compression in familial hypophosphataemic vitamin D resistant osteomalacia.  Q J Med . 1986;  61 117-129
    PubMedGoogle Scholar
  • 34 Davies M, Kane R, Valentine J. Impaired hearing in X-linked hypophosphatemic (vitamin D resistant) osteomalacia.  Ann Int Med . 1984;  100 320-232
    PubMedGoogle Scholar
  • 35 Tieder M, Modai D, Samuel R. Hereditary hypophosphatemic rickets with hypercalciuria.  N Eng J Med . 1985;  312 611-617
    CrossrefPubMedGoogle Scholar
  • 36 Drezner M K. Phosphorous homeostasis and related disorders. In: Bilezikian JP, Raisz L, Rodan GA, eds. Principles of Bone Biology, 2nd edition London: Academic Press 2002: 321-338
    Google Scholar
  • 37 Krausz Y. Nuclear endocrinology as a monitoring tool.  Sem Nuc Med . 2001;  31 238-250
    PubMedGoogle Scholar
  • 38 Hosking D J, Chamberlain M J, Whortland-Webb W R. Osteomalacia and carcinoma of the prostate with major redistribution of skeletal calcium.  Br J Radiol . 1975;  48 451-456
    PubMedGoogle Scholar
  • 39 McClure J, Smith P S. Oncogenic osteomalacia.  J Clin Pathol . 1989;  40 446-453
    PubMedGoogle Scholar
  • 40 Rathbun J C. Hypophosphatasia, a new developmental anomaly.  Am J Dis Child . 1948;  75 822-831
    PubMedGoogle Scholar
  • 41 Whyte M P. Hypophosphatasia: nature's window on alkaline phosphatase function in man. In: Bilezikian JP, Raisz L, Rodan GA, eds. Principles of Bone Biology, 2nd edition London: Academic Press 2002: 1229-1248
    Google Scholar
  • 42 Sandler L M, Winearls C G, Fraher L J. Studies on the hypercalcemia of sarcoidosis.  Q J Med . 1984;  53 165-180
    PubMedGoogle Scholar
  • 43 Taylor R L, Lynch H J, Wysor W G. Seasonal influence of sunlight on the hypercalcemia of sarcoidosis.  Am J Med . 1963;  35 67-89
    CrossrefPubMedGoogle Scholar
  • 44 Rizzato G, Montemurro L, Fraioli P. Bone mineral content in sarcoidosis.  Semin Resp Med . 1992;  13 411-423
    PubMedGoogle Scholar
  • 45 Davies M, Mawer E B, Hayes M E, Lumb G A. Abnormal vitamin D metabolism in Hodgkin's lymphoma.  Lancet . 1985;  1 1186-1188
    PubMedGoogle Scholar
  • 46 Davies M, Hayes M E, Liu Yin A J, Berry J L, Mawer E B. Abnormal synthesis of 1,25-dihydroxyvitamin D in patients with malignant lymphoma.  J Clin Endocrinol Metab . 1994;  78 1202-1207
    CrossrefPubMedGoogle Scholar
  • 47 Seymour J F, Gagel R F, Hagemeister F B, Dimopoulos M A, Cabanillas F. Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin's lymphoma.  Ann Intern Med . 1994;  121 633-640
    PubMedGoogle Scholar