In addition to its role in calcium hemostasis and bone metabolism, vitamin D also appears to be an important regulator of immune function. However, its role in modulating RA disease activity has not been studied. Here, Patel et al (Arthritis Rheum 2007; 56(7): 2143) explore the effects of serum vitamin D levels on clinical response in patients with early inflammatory polyarthritis.
Methods
Patients in region of Norfolk, UK with early inflammatory arthritis, defined as having synovitis of 2 or more peripheral joints for at least 4 weeks, were recruited into the Norfolk Arthritis Register (NOAR). Vitamin D metabolites (25-hydroxy vitamin D (25OH vD) and 1,25-dihydroxy vitamin D (1,25OH2 vD)) were measured at baseline and compared in patients according to clinical features at baseline and outcome at 1 year.
Results
206 Early inflammatory arthritis patients were included. Two-thirds were women with a mean age of 59 years. At baseline, 35% of patients fulfilled ACR classification criteria for RA, while 45% fulfilled these criteria at 1 year.
At baseline, subjects fulfilling ACR criteria for RA had significantly lower mean 1,25OH2 vD levels compared to those who did not meet RA criteria. For 25OH vD, a trend to lower levels was observed for subjects who did and did not fulfill ACR criteria (p=0.06). In regression models of baseline data, each 10 ng/mL increase in 25OH vD was associated with a 42.7% lower tender joint count, a 25% lower CRP, a 0.30 lower DAS28 score, and a 39% lower odds of being in the higher HAQ group. Each 10 pg/mL increase in 1,25OH2 vD was associated with a 21% lower odds of being in the higher HAQ group.
At 1 year, baseline 25OH and 1,25OH2 levels were both significantly lower in subjects fulfilling ACR criteria for RA. In regression models, each 10 ng/mL increase in baseline 25OH vD was associated with a 46.3% decrease in tender joint count at 1 year and a 41% lower odds of being in the higher HAQ group. Each 10 pg/mL increase in baseline 1,25OH2 vD was associated with a 26% lower odds of being in the higher HAQ group. Findings were similar in analyses adjusted for DMARD use of the first year.
Conclusions
Lower levels of vitamin D metabolites were associated with clinical outcomes in patients with early inflammatory polyarthritis.
Editorial Comment
These are interesting findings that bring to light the possible role of vitamin D in the modulation of RA disease symptoms and activity. A previous study identified an association between low vitamin D levels and incident RA (Merlino Arthritis Rheum 2004; 50; 72) . This study suggests that the dangers of low vitamin D may extend beyond the initiation of disease and affect whether inflammatory arthritis develops into a fully fledged RA phenotype. It is important to note that clinically defined “Hypovitaminosis D” is very common (particularly in this cohort deriving from the UK with its preponderance of cloudy days) and that more than 75% of the cohort presented here would meet criteria for vitamin D deficiency (25OH vD < 30 ng/mL). Thus, it would be interesting to see if these findings were more robust in a cohort in which higher vitamin D levels were more prevalent. The findings that low vitamin D levels were more associated with tender joints and HAQ, but not swollen joints could suggest that vitamin D may affect pain perception rather than act as an immunomodulator. However, these effects are difficult to parse out given the overlaps in standard clinical assessment tools in RA. Although vitamin D supplementation is warranted in patients with low levels, it is not clear from this or available studies whether supplementation with vitamin D replacement can alter disease outcomes in RA.
