Influence of vitamin D on bones and muscle

Vitamin D is converted in the liver to 25-hydroxyvitamin D, which represents the storage form and is the most abundant circulating metabolite. The further activation (1-alpha-hydroxylation) leads to the hormone 1aEuro alpha,25-dihydroxyvitamin D (calcitriol), which takes place in the kidneys under hormonal control and contributes to circulating calcitriol but some target organs (such as bone) can produce calcitriol in an autocrine/paracrine fashion. Muscle and bone are the classical target organs for calcitriol. The hormone calcitriol has direct effects on muscle tissue, which are mediated by the nuclear vitamin D receptor (VDR) and also by non-genomic pathways (membrane receptors). Calcitriol modulates differentiation of muscle cells and stimulates protein synthesis. Vitamin D deficiency leads to muscle weakness, which is prominent in patients with rickets and osteomalacia; however, even subclinical vitamin D deficiency is associated with diminished muscle function. In populations with vitamin D deficiency (e. g. elderly people), controlled intervention studies with vitamin D demonstrated improved muscle function and reduction in falls. In bone, calcitriol exerts anabolic and catabolic effects. Calcitriol stimulates intestinal absorption of calcium and phosphate providing mineral supply for bone mineralization. Calcitriol also has direct effects on proliferation and differentiation of bone cells. Calcitriol stimulates alkaline phosphatase and regulates bone matrix proteins (such as osteocalcin and osteopontin); therefore, calcitriol regulates mineralization in a direct manner. In high concentrations calcitriol also stimulates bone resorption. People with severe vitamin D deficiency have a higher risk for fractures. Vitamin D supplementation can reduce the risk of fractures. The best evidence exists for the daily administration of 800-2000 IU of vitamin D. Active vitamin D metabolites (also called vitamin D receptor agonists), such as calcitriol, alfacalcidol (1-alpha-hydroxyvitamin D) and paricalcitol are used for the pharmacological treatment of metabolic bone diseases and in these conditions reduce falls, improve muscle function and reduce the risk of fractures.