We have found that vitamin D deficiency (25(OH)D values <20 ng/ml) is common in RA patients affecting 43% of the entire cohort. Our results are similar to those reported by others in smaller sample sizes, with a prevalence of vitamin D deficiency ranging from 30 to 63% [10
In our study the proportion of patients with vitamin D deficiency rises to 52% in patients not taking vitamin D supplements, but it was also unacceptably high in women on approximately 400 or 800 U vitamin D daily supplements, that is, 33 and 31% respectively. These latter proportions rise considerably if the threshold 25(OH)D levels are set to 30 ng/ml, but they are very similar to those we observed in control women representative of the general population and this indicates that vitamin D deficiency is, at least in Italy, a general problem.
From a careful analysis of a large number of epidemiological studies it was recently found that the optimal 25(OH)D concentrations for bone health and extra-skeletal benefits are between 36 to 40 ng/ml% [23
]. These levels were achieved only by 9% of our patients (results not shown) and this indicates that, at least in RA patients, in order to achieve 25(OH)D levels above 38 ng/ml in more than 90% of the population, the daily dose of vitamin D should be substantially higher than 800 U per day.
As expected, the logarithmic values of 25(OH)D were negatively (P < 0.04) correlated with the logarithmic levels of PTH, but only in patients not on vitamin D supplements.
In non-supplemented patients, 25(OH)D levels were associated with several variables. Sun exposure and BMI are well established risk factors for vitamin D deficiency and these associations are confirmed in the present study [24
The scope of this study was to evaluate to what extent vitamin D deficiency was related in RA patients with the severity of the disease. The inverse relationships between vitamin D levels and disease activity or functional impairment are of interest but not of obvious interpretation. Similar relationships have been found also by others. Cutolo et al.
reported a significant inverse association between 25(OH)D and DAS28 in patients with active RA and Patel et al.
found an inverse relationship between 25(OH)D levels and tender joint count, DAS28, and HAQ score only at disease onset, but not in patients with a disease duration longer than one to two years [16
]. Though our study population included a large variety of disease activity, treatments and disease durations, the correlations we found were all highly significant and this is likely explained by the size of our study, 6- to 10-fold larger than previous studies. We found that the worse the direct or indirect indices of disease activity, the lower the 25(OH)D levels or the higher the proportion of patients with vitamin D deficiency. Thus, the proportion of patients with vitamin D deficiency was around 30% lower in patients on disease remission or judged as good responders to treatment or for a DAS28 <3.1. In addition, both functional indices and mobility ADL were negatively associated with 25(OH)D levels with a P
At a first glance, the most obvious explanation for these findings is that patients with very active disease are at higher risk of vitamin D deficiency rather than the other way around. Indeed, we found an association between sun exposure time and achievement of disease remission, good treatment response, Steinbrocker's functional state, HAQ and swollen joint counts. This indicates that patients with uncontrolled RA and/or with severe functional impairment are less prone to spend time outdoors in sunshine and are, therefore, at higher risk of vitamin D deficiency. Thus, the conclusions drawn in previous cross-sectional studies regarding the immunomodulatory role played by vitamin D in inflammatory arthritis, should be interpreted with caution, if 25(OH)D values are not adjusted for the known risk factors for vitamin D deficiency [16
]. However, when the correlations between disease activity scores and vitamin D deficiency were reanalysed by adjusting the 25(OH)D levels for sun exposure and BMI, the association remained statistically significant for Steinbrocker's functional state, DAS28, treatment response, HAQ score and mobility ADL. These results indicate that patients with very active RA are at higher risk of vitamin D deficiency for similar BMI and sun exposure, for reasons that remain unknown.
The main strength of this study is its size. There are also important limitations. The large heterogeneity in terms of specific treatments and disease duration hampers the interpretation of some associations but it is of help for defining the risk of developing vitamin D deficiency. Our control group was identified a posteriori and it was not perfectly matched since it does not include men and women aged 50 to 60 years.