PEDIATRICS Vol. 57 No. 5 May 1976, pp. 729-741
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Vitamin D: The Discovery of Its Metabolites and Their Therapeutic Applications

Mary G. Beale M.D.1, James C. M. Chan M.D.1, Susan B. Oldham Ph.D.1, and Hector F. DeLuca Ph.D.1

1 Department of Child Health and Development, George Washington University School of Medicine, and the Department of Nephrology, Children's Hospital National Medical Center, Washington, D.C., the Department of Biochemistry and Medicine, University of Southern California School of Medicine, Los Angeles, and the Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison

Our understanding of the role of vitamin D in calcium-phosphorus metabolism has changed considerably in the last decade. Studies performed in tissue culture, animal, and man have firmly established that the natural compound requires hydroxylation in the liver at the C-25 position and in the kidney at the C-1 position to form the biologically active derivative 1,25-(OH)2D3. These hydroxylation reactions are finely regulated to maintain normal calcium-phosphorus homeostasis: We now regard 1,25-(OH)2D3 as a hormone which is released by the kidney during periods of hypocalcemia. This hormone acts on the intestinal mucosa to facilitate calcium absorption and on bone to increase calcium mobilization. Its function in other tissues is still being evaluated.

The active metabolites of vitamin D and several closely related analogs have been synthesized. It has been clearly demonstrated that 1,25-(OH)2D3 and 1agr-OH-D3 promote healing in uremic bone disease. Administration of small amounts of these compounds has corrected the biochemical disturbances in vitamin D-dependency and hypoparathyroidism. Limited clinical experience with 25-OH-D3 and 1,25-(OH)2D3 in children with familial hypophosphatemia has failed to show convincing evidence of a therapeutic effect. Further clinical studies are needed to fully evaluate the therapeutic potential of this new family of compounds.

Submitted on July 9, 1975
Accepted on October 3, 1975




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