199 - Osteomalacia and rickets*

1997 Vitamin D is converted in the liver by a vitamin D-25-hydroxylase (25-OHase) to form the major circulating form of vitamin D, 25-hydroxyvitamin D [25(OH)D]. There have been at least four different 25-OHases identified both in mitochrondia and in microsomes. 25(OH)D is, however, biologically inert and requires hydroxylation in the kidneys on carbon 1 by the CYP27B mitrochondrial enzyme 25-hydroxyvitamin D-1α-hydroxylase (1-OHase). This results in the formation of 1α,25-dihydroxyvitamin D [1,25(OH)2D] which is the biologically active form of vitamin D responsible for regulating calcium and phosphorus homeostasis. 1,25(OH)2D enters the circulation and is bound to the DBP and travels to its target tissues. In the small intestine, 1,25(OH)2D interacts with its vitamin D nuclear receptor (VDR) that results in the expression of several gene products including the epithelial calcium channel, calbindin9k, and a calcium dependent ATPase (see Figure 199-1). 1,25(OH)2D increases the efficiency of intestinal calcium absorption. In a vitamin D deficient state, the small intestine is able to passively absorb about 10% to 15% of dietary calcium. Vitamin D sufficiency enhances the absorption of calcium in the small intestine to about 30% to 40%. 1,25(OH)2D enhances the efficiency of intestinal calcium absorption principally in the duodenum and to less of a degree in the jejunum and ileum. 1,25(OH)2D also stimulates phosphate absorption in the jejunum and ileum. The small intestine passively absorbs about 60% of dietary phosphate. 1,25(OH)2D enhances the efficiency of phosphate absorption by an additional 20% to about 80%. When there is adequate calcium and phosphate in the diet and vitamin D sufficiency is present, the serum calcium normal range is approximately 8.6 to 10.2 mg/dL (mg%) and the serum phosphate level is approximately 2.5 to 4.5 mg/ dL. It is the calcium × phosphate product in the circulation and in the extravascular space that plays a major role in the normal mineralization of osteoid laid down by osteoblasts.