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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #65686
Title: 24,25 DIHYDROXYVITAMIN D SUPPLEMENTATION CORRECTS HYPOPHOSPHATEMISM AND IMPROVES SKELETAL ABNORMALITIES IN X-LINKED HYPOPHOSPHATEMIC RICKETS

Author
item CARPENTER, THOMAS - YALE UNIV. SCHOOL OF MED.
item KELLER, MARC - YALE UNIV. SCHOOL OF MED.
item SCHWATZ, DANA - YALE UNIV. SCHOOL OF MED.
item MITNICK, MARY - YALE UNIV. SCHOOL OF MED.
item SMITH, CYNTHIA - YALE UNIV. SCHOOL OF MED.
item ELLISON, ALICE - YALE UNIV. SCHOOL OF MED.
item CAREY, DENNIS - SCHNEIDER CHILDRENS HOSP.
item COMITE, FLORENCE - YALE UNIV. SCHOOL OF MED.
item Horst, Ronald
item TRAVERS, ROSE - SHRINERS HOSP., CANADA

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: X-linked hypophosphatemia is a genetic disease in humans which results in abnormal bone development. This disorder is not common, with estimated occurrence between 1/100,000 to 1/1,000,000 live births. This disorder was once called "vitamin D-resistance rickets," a reference to the poor therapeutic response to doses of vitamin D used to treat vitamin D deficiency. Subsequently, administration of pharmacological dosages of vitamin D were recommended, but it was soon apparent that this form of treatment was not very effective. In particular, stature and growth were not improved, and frequent episodes of vitamin D intoxication were encountered, resulting in renal damage. The present study was designed to determine if a new, less toxic, form of vitamin D3, called 24,25-hydroxyvitamin D3, could be used in preventing the abnormal bone formation. The results clearly demonstrated that bone development improved significantly when children with X-linked hypophosphatemia were supplemented with 24,25-dihydroxyvitamin D3. The use of this less toxic form of vitamin D represents a significant advance in the management of this chronic debilitating disease. The results will be of particular interest and importance to clinicians and medical researchers studying this disease.

Technical Abstract: Standard treatment for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions, and is often complicated by hyperparathyroidism. 24,25(OH)2D3 has been reported to have beneficial effects on the skeletal disease in a murine model of XLH. We, therefore, undertook a placebo controlled trial of 24,25(OH2D3 supplementation of standard treatment in patients with XLH. 15 subjects with XLH receiving standard treatment [1,25(OH)2D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one year later. 24,25(OH)2D3 supplementation was then begun, and studies repeated one year later. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-hour period. Children underwent radiographic assessment of lower extremity rachitic abnormalities and renal ultrasonography. Adults underwent iliac crest biopsies before and after 24,25(OH)2D3 treatment. 24,25(OH)2D3 normalized parathyroid hormone (PTH) values in 9 subjects (peak PTH was 46.5 +/- 6.6 pM at entry, 42.3 +/- 5.9 pM after placebo, and 23.3 +/- 5.4 pM after 24,25(OH)2D3, but serum calcium or phosphorus did not change significantly.