Vitamin D in rheumatoid arthritis—towards clinical application

Abstract

In addition to its well-documented involvement in mineral homeostasis, vitamin D seems to have broad effects on human health that go beyond the skeletal system. Prominent among these so-called nonclassical effects of vitamin D are its immunomodulatory properties. In vitro studies have shown anti-inflammatory effects of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active form of vitamin D. In addition, epidemiological analysis of patients with established inflammatory disease identified associations between vitamin D deficiency (low serum concentrations of inactive 25-hydroxyvitamin D, abbreviated to 25(OH)D) and inflammatory conditions, including rheumatoid arthritis (RA). The association of vitamin D deficiency with RA severity supports the hypothesis of a role for vitamin D in the initiation or progression of the disease, or possibly both. However, whether 25(OH)D status is a cause or consequence of RA is still incompletely understood and requires further analysis in prospective vitamin D supplementation trials. The characterization of factors that promote the transition from preclinical to clinical phases of RA has become a major focus of research, with the aim to facilitate earlier diagnosis and treatment, and improve therapeutic outcomes. In this Review, we aim to describe the current knowledge of vitamin D and the immune system specifically in RA, and discuss the potential benefits that vitamin D might have on slowing RA progression.

Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases

“…It also decreases Th 17 -induced osteoclast activity and RA-associated bone resorption by inducing expression of RANK ligand on fibroblast-like synoviocytes and osteoblasts. [7] Articular damage is further prevented by vitamin D because it inhibits interleukin 1A-mediated production of matrix metalloproteinases. [49] Moreover, vitamin D also increases regulatory T cells, wich are impaired in RA.…”

“…[3] Based on this finding, many researchers have investigated correlations between vitamin D serum levels and the presence/activity of rheumatic conditions. [1,4–6] With its increasing visibility, clinical repercussions of vitamin D supplementation have been studied in rheumatic diseases such as systemic lupus erythematosus (SLE) [1,4] and rheumatoid arthritis (RA) [7] and in non-rheumatic conditions such as tuberculosis [8] and psoriasis. [2] The results, then, prompted research on known and novel biomolecular and cellular functions of vitamin D. [2,3] …”

Radiographic damage in hands and wrists of patients with juvenile idiopathic arthritis after 29 years of disease duration

“…Nutritional factors which influence mineral homeostasis, differentiation of the osteoblasts and the immune system, such as vitamin D and vitamin A, have not previously been included in long-term studies of radiographic outcome in JIA [15, 16]. …”

High Vitamin D Levels May Downregulate Inflammation in Patients with Behçet’s Disease

“…Vitamin D (Vit D) is a major fat-soluble vitamin that is essential for normal immune function and a large body of evidence now implicates Vit D in the pathogenesis of several inflammatory diseases including BD [2–16]. The main source of Vit D is from the ultraviolet B- (UVB-) induced synthesis in the skin, which is then activated via two hydroxylation steps in the liver and kidney.…”