Abstract
Although vitamin D has been reported to have pleiotropic effects including effects on the immune system and on cancer progression, the principal action of vitamin D is the maintenance of calcium and phosphate homeostasis. The importance of vitamin D in this process is emphasized by the consequences of vitamin D deficiency which includes rickets in children and osteomalacia in adults. Vitamin D deficiency has also been reported to increase the risk of falls and osteoporotic fractures. Although vitamin D fortification of foods (including dairy products) has contributed to a marked decrease in rickets in the Western world, vitamin D deficiency in children and adults is still prevalent world-wide. This review summarizes new developments in our understanding of vitamin D endocrine system and addresses clinical syndromes related to abnormalities in vitamin D metabolism and action. In addition, the current understanding of the evaluation of vitamin D deficiency and sufficiency and recommendations for achieving vitamin D sufficiency are discussed.
•Mutations in CYP2R1, CYP27B1, CYP24A1 and CYP3A4 cause human disease•VDR binding sites can be located at a range of locations; within introns and at distal intergenic regions of regulated genes•The principal action of vitamin D in maintaining calcium homeostasis is intestinal calcium absorption, although during negative calcium balance 1,25(OH)2D3 can promote bone resorption to prioritize maintenance of blood calcium at the expense of skeletal integrity•Evidence supports beneficial effects of 1,25(OH)2D3 beyond mineral homeostasis, such as immune function and cancer, although randomized clincial trials indicate that the benefits of vitamin D supplementation are generally limited to those with suboptimal vitamin D levels at baseline•Development of rickets/osteomalcia is dependent on calcium intake as well as vitamin D status but optimal calcium and vitamin D levels may be different for different racial groups