Resurrection of vitamin D deficiency and rickets
Michael F. Holick
Michael F. Holick
Published August 1, 2006
Citation Information: J Clin Invest. 2006;116(8):2062-2072. https://doi.org/10.1172/JCI29449.
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Science in Medicine

Resurrection of vitamin D deficiency and rickets

Abstract

The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.

Authors

Michael F. Holick

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Figure 3

The photoproduction and metabolism of vitamin D and the various biologic effects of 1,25(OH)2 D on calcium, phosphorus, and bone metabolism.

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The photoproduction and metabolism of vitamin D and t...
Vitamin D is either produced in the skin by exposure to UVB radiation or is ingested in the diet. Vitamin D (D represents vitamin D2 or vitamin D3) is converted by the vitamin D-25-hydroxylase (25-OHase) in the liver to 25(OH)D. 25(OH)D is converted in the kidneys by 1-OHase to 1,25(OH)2D. Once formed, 1,25(OH)2D enhances intestinal calcium and phosphorus absorption and stimulates the expression of RANKL on the osteoblasts to interact with its receptor RANK on preosteoclasts to induce mature osteoclastic activity, which releases calcium and phosphorus (HPO42–). In addition, 1,25(OH)2D inhibits the renal 1-OHase and stimulates the expression of the renal 25(OH)D-24-hydroxylase (24-OHase). The induction of the 24-OHase results in the destruction of 1,25(OH)2D into a water-soluble inactive metabolite calcitroic acid. PreD3, previtamin D.