Clinical Significance

Vitamin D is a fat-soluble steroid hormone precursor that is mainly produced in the skin by exposure to sunlight. Vitamin D is biologically inert and must undergo two successive hydroxylations in the liver and kidney to become the biologically active 1,25‑dihydroxyvitamin D. 

The two most important forms of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). In contrast to vitamin D3, the human body cannot produce vitamin D2 which is taken up with fortified food or given by supplements. In blood vitamin D3 and D2 are bound to the vitamin D binding protein (VDBP) and transported to the liver where both are hydroxylated to form 25‑hydroxyvitamin D. It is commonly agreed that 25‑hydroxyvitamin D is the metabolite to determine the overall vitamin D status as it is the major storage form of vitamin D in the human body. This primary circulating form of vitamin D is biologically inactive with levels approximately 1000‑fold greater than the circulating 1,25‑dihydroxyvitamin D. The half-life of circulating 25‑hydroxyvitamin D is 2‑3 weeks. 

Most of the 25‑hydroxyvitamin D, measurable in blood circulation, is 25‑hydroxyvitamin D3 whereas 25‑hydroxyvitamin D2 reaches measurable levels only in patients taking vitamin D2 supplements. Vitamin D2 is considered to be less effective. 

Vitamin D is essential for bone health. In children, severe deficiency leads to bone-malformation, known as rickets. Milder degrees of insufficiency are believed to cause reduced efficiency in the utilization of dietary calcium. Vitamin D deficiency causes muscle weakness; in elderly, the risk of falling has been attributed to the effect of vitamin D on muscle function. Vitamin D deficiency is a common cause of secondary hyperparathyroidism. Elevations of parathyroid hormone levels, especially in elderly vitamin D deficient adults can result in osteomalacia, increased bone turnover, reduced bone mass and risk of bone fractures. Low 25‑hydroxyvitamin D concentrations are also associated with lower bone mineral density. In conjunction with other clinical data, the results may be used as an aid in the assessment of bone metabolism. 

_{Source: Roche cobas Elecsys Vitamin D total III method sheet, V 3.0 2025-01}