Vitamin D deficiency

Clinical information

Vitamin D is a fat-soluble hormone which plays an essential role in the intestinal absorption of calcium and in bone resorption. There are 2 different types of vitamin D, which differ by the side chain of the molecules. Vitamin D₃ (cholecalciferol) and vitamin D₂ (ergocalciferol). Vitamin D₃ is either synthesised in the skin on exposure to UVB radiation or obtained from certain foods of animal origin, such as oily fish. Vitamin D₂, on the other hand, is obtained from food of vegetable origin, e. g. mushrooms, and is the most common prescribed supplement.

Both forms (D₂ and D₃) are either stored in the adipose tissues or converted in the liver (and other tissues) to the storage form 25-hydroxyvitamin D, 25(OH)D₂ and 25(OH)D₃, respectively, which is stored in muscles. The total concentration of 25-OH D₂ and 25-OH D₃ together is considered a reliable indicator of a person’s vitamin D status.

For 25-OH vitamin D to have an effect, it first needs to undergo a second hydroxylation which takes place primarily in the kidney. Only after that it is present in the active form, i.e. 1,25(OH)₂ D (1,25-dihydroxyvitamin D). Once formed, 1,25(OH)₂ D forms a complex with the vitamin D receptor (VDR) in the cells of the target tissues.

The VDR is involved in sustaining normocalcaemia by influencing bone and skeletal muscle biology. Once the 1,25D-VDR complex is formed, it in turn acts on the vitamin D responsive elements (VDRE) to regulate target gene activity / gene expression. In so doing, it increases calcium absorption from food intake, reduces loss of calcium via the kidneys and, in more severe cases, stimulates parathyroid hormone (PTH) production which induces bone resorption and release of calcium from the bones.

Moreover, vitamin D plays a key role in various physiological processes, ranging from the modulation of the immune response to the regulation of brain development and activity in adulthood. Hence, vitamin D has long been studied in many pathological conditions, either as a risk factor or a serum biomarker for disease severity.

Diagnostics

While 1,25-dihydroxy vitamin D is the biologically active form of vitamin D, 25-OH-Vitamin D makes up for the largest proportion of the vitamin D-related metabolites in blood and is thus the best indicator for the individual vitamin D status.

Numerous metabolic processes are regulated by vitamin D. Vitamin D plays an important part in the bone metabolism since it maintains the physiological calcium and phosphate levels in the serum and stimulates the resorption of calcium and phosphate in the intestine. Vitamin D deficiency therefore leads to reduced bone mineralisation, which manifests as rickets in children and as osteomalacia in adults.

Moreover, the combined determination of 25-OH vitamin D, parathyroid hormone and calcitonin levels may provide information on whether or not bone metabolism disorders or diseases are present.