Ho

24,25(OH)2D3

1,25(OH)2D3 (Calcitriol)

FIGURE 15 Biosynthesis of 1a,25 dihydroxycholecalciferol.

Actions on Bone

Although the most obvious consequence of vitamin D deficiency is decreased mineralization of bone, 1,25(OH)2D3 apparently does not directly increase bone formation or calcium phosphate deposition in osteoid. Rather, mineralization of osteoid occurs spontaneously when adequate amounts of these ions are available. Ultimately, increased bone mineralization is made possible by increased intestinal absorption of calcium and phosphate. Paradoxically, perhaps, 1,25(OH)2D3 acts on bone to promote resorption in a manner that resembles the effects of PTH. Like PTH, 1,25(OH)2D3 increases both the number and activity of osteoclasts. As seen for PTH, osteoblasts, rather than mature osteoclasts, have receptors for 1,25(OH)2D3. Like PTH, 1,25(OH)2D3 stimulates osteoblastic cells to express m-CSF and RANK ligand as well as a variety of other proteins. Sensitivity of bone to PTH decreases with vitamin D deficiency; conversely, in the absence of PTH, 30-100

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