Figure 1.

Vitamin D is synthesized in the skin or obtained from the diet. The most common and more potent form, vitamin D₃, is focused on in this review. Vitamin D₃ is converted to 25(OH)D₃ in the liver. Classical effects on calcium homeostasis begin in the kidney, where 25(OH)D₃ is converted to bioactive 1,25(OH)₂D₃. 1,25(OH)₂D₃ increases osteoclast differentiation and activation, and upregulates calcium and phosphate absorption in the gut. Concurrently with 1,25(OH)₂D₃, parathyroid hormone stimulates osteoclasts. It additionally upregulates 1α–OHase (CYP27B1) activity and calcium reabsorption in the kidney. 25(OH)D₃ and 1,25(OH)₂D₃ are both inactivated by 24–OHase (CYP24A1) and are excreted in the bile. Non-classical signaling of vitamin D₃ involves local activation of 25(OH)D₃ to 1,25(OH)₂D₃ by 1α–OHase (CYP27B1) in cells of the immune system. Figure created using BioRender.com (accessed on 28 July 2022).