The Role of Calcitriol in Bone Metabolism

In addition to the role of bone mineral as a structural component of bone, it can be regarded as a major reserve of calcium for the body. In an adult, the skeleton contains 25 mol of calcium, whereas the total extracellular fluids contain only about 25 mmol. Parathyroid hormone, calcitonin, and calcitriol regulate the 

Physiologically, the response of bone to calcitriol is resorption of bone mineral and matrix protein. Both calcitriol and parathyroid hormone increase bone resorption in vivo and in bone organ culture, but have no effect on the activity of isolated osteoblasts. In addition to direct stimulation of the resorptive activity of osteoblasts, calcitriol increases osteoclastic activity. This is not because of a direct effect of calcitriol on osteoclasts, which lack calcitriol 

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Vitamin D3 is transported to liver where it undergoes a hydroxylation at C-25 into 1a,25-dihydroxyvitamin D3 (calcitriol) (Fig. 64). In the kidney, it undergoes further hydroxylations at different sites, depending on the serum Ca + concentration. The most biologically active metabolite of vitamin D3 is calcitriol, which plays important roles in the regulation of calcium and phosphorus metabolism. It is used for treating bone diseases, but is also involved in the cell proliferation and the inducement of cell differentiation [151]. 

There is evidence that 24-hydroxycalcidiol has physiological functions distinct from those of calcitriol, and the regulation of the 24-hydroxylase suggests that it functions to provide a metabolically active product, as well as diverting calcidiol away from calcitriol synthesis (Henry, 2001). Studies of knockout mice lacking the 24-hydroxylase show that 24-hydroxycalcidiol has a role in both in-tramembranous bone formation during development and the suppression of parathyroid hormone secretion (St-Arnaud, 1999 van Leeuwen et al., 2001). 

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