9. RA

The role of hypovitaminosis D in the pathogenesis of rheumatoid arthritis has been the topic of interest in the recent past. Lower vitamin D levels possess increased risk for RA [53]. 1,25(OH)2D3 contributes to the regulation of matrix metalloproteinase and prostaglandin E2 production by synovial fibroblasts and articular chondrocytes in RA [54].

High rates of vitamin D deficiency have been observed in patients with rheumatic diseases. A study demonstrated that in patients with RA, VDD was seen in 64% and insufficiency in 28%. Similarly, in spondyloarthritis (SpA) patients 48% had VDD and 35% had insufficiency [55]. The prevalence of VDD is quite in RA patients. The COMEDRA study showed that 55.8% of RA patients had vitamin D insufficiency and 3.6% had deficiency [56]. Eighty-four percent of RA patients were VDD in a recently published study by Meena. It also showed a significant inverse correlation between serum vitamin D levels and RA disease activity [57]. A metaanalysis by Lee and Bae supported this result suggesting that the vitamin D level is associated with susceptibility to RA and RA activity [58]. Similarly, a negative association between serum vitamin D and RA disease activity was demonstrated in few studies [59–62]. Levels of 25(OH)D3 were also found to be negatively correlated to CRP and ESR [62]. However, relationship between 25(OH)D and levels of rheumatoid factor or anti-cyclic citrullinated peptide antibodies has not been established yet [63].

The COMORA study showed that vitamin D was insufficient in 54.6% and deficient in 8.5% of the RA patients. Low levels of vitamin D were associated with disease activity of RA and corticosteroid dosage and comorbidities like lung disease and osteoporosis therapy [64].

### 10. CTD

In comparison to healthy adults, VDD is more prevalent in people with autoimmune diseases including connective tissue diseases (CTDs) [65]. It may also have a pivotal role in progression of undifferentiated CTDs to well-defined and more severe disease [65]. There are few evidences which showed the antifibrotic property of vitamin D [66]. Low vitamin D levels are also associated with more severe disease, low diffusing capacity for carbon monoxide (DLCO), and advanced-stage nailfold capillaroscopy changes in patients with scleroderma [67, 68]. However, a recent meta-analysis revealed that though VDD is quite common in scleroderma patients, it does not correlate to the disease activity [69].

Over the years, it has been proven that vitamin D is necessary for optimum muscle and bone health. In CTDs, vitamin D levels correlate with intensity of muscle weakness [68, 70]. It may also be considered as one of the risk factors in developing myositis [71]. However, the role of vitamin D in myositis or other CTDs has not been established yet. Studies have shown that in fibromyalgia, VDD is correlated with pain and disease activity [72] and correction of deficiency improves the symptoms [73].