al., 1974), but its major influence is in the jejunum and ileum. When dietary calcium intake is inadequate to satisfy the body's calcium requirement, 1,25(OH)2D, along with parathyroid hormone (PTH), mobilizes monocytic stem cells in the bone marrow to become mature osteoclasts (Holick, 1995; Merke et al., 1986). The osteoclasts, in turn, are stimulated by a variety of cytokines and other factors to increase the mobilization of calcium stores from the bone (Figure 7-2). Thus, vitamin D maintains the blood calcium and phosphorus at supersaturating concentrations that are deposited in the bone as calcium hydroxyapatite.

A multitude of other tissues and cells in the body can recognize 1,25(OH)2D (Stumpf et al., 1979). Although the exact physiologic function of 1,25(OH)2D in the brain, heart, pancreas, mononuclear cells, activated lymphocytes, and skin remains unknown, its major biologic function has been identified as a potent antiproliferative and prodifferentiation hormone (Abe et al., 1981; Colston et al., 1981; Eisman et al., 1981; Smith et al., 1987). There is little evidence that vitamin D deficiency leads to major disorders in these organ and cellular systems.

Physiology of Absorption, Metabolism, and Excretion

Because dietary vitamin D is fat soluble once it is ingested, it is incorporated into the chylomicron fraction and absorbed through the lymphatic system (Holick, 1995). It is estimated that approximately 80 percent of the ingested vitamin D enters the body via this mechanism. Vitamin D is principally absorbed in the small intestine.

Vitamin D is principally excreted in the bile. Although some of it is reabsorbed in the small intestine (Nagubandi et al., 1980), the enterohepatic circulation of vitamin D is not considered to be an important mechanism for its conservation (Fraser, 1983). However, since vitamin D is metabolized to more water-soluble compounds, a variety of vitamin D metabolites, most notably calcitroic acid, are excreted by the kidney into the urine (Esvelt and DeLuca, 1981).

Once vitamin D enters the circulation from the skin or from the lymph via the thoracic duct, it accumulates in the liver within a few hours. In the liver, vitamin D undergoes hydroxylation at the 25-carbon position in the mitochondria, and soon thereafter, it appears in the circulation as 25-hydroxyvitamin D (25(OH)D) (DeLuca, 1984) ( Figure 7-1 and Figure 7-2). The circulating concentration of 25(OH)D is a good reflection of cumulative effects of exposure to sunlight and dietary intake of vitamin D (Haddad and Hahn, 1973; Holick, 1995; Lund and Sorensen, 1979). In the liver, vitamin D-25-



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