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[4] The second activation step takes place predominantly in the kidneys where 1-hydroxylase converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol), an active secosteroid hormone that binds nuclear receptors in enterocytes, osteoblasts, renal tubules, parathyroid cells, and numerous immune and endocrine cells to modulate hundreds of genes involved in calcium-phosphate homeostasis, skeletal remodelling, and immunoregulation