Our patient population demonstrated high rates of vitamin D insufficiency (50%) that were in accordance with data from national population-based studies, underscoring the relatively high prevalence of vitamin D insufficiency in African-Americans [10
]. Recognizing the limitations of making comparisons across studies, the frequency of vitamin D insufficiency in reproductive-aged African American women with RA (56%) appears to be higher than that previously reported in a national study (NHANES-III) of a similar non-RA population (42%) [11
]. In contrast to our a priori hypothesis, we observed no conclusive associations of vitamin D concentrations with disease activity or severity. Although baseline pain, swollen joints, and DAS-28 scores were inversely associated with vitamin D concentration in univariate analyses, these associations failed to meet statistical significance following multivariate adjustments, suggesting that this association is explained primarily by differences in age and season of assessment. Although of borderline significance and potentially representing a spurious finding, the association of 25(OH)-D concentration with RF seropositivity was not anticipated.
The results observed in this study with respect to the association of vitamin D status and self-reported pain may not be surprising given conflicting literature regarding hypovitaminosis D and musculoskeletal pain. Previous studies have suggested a link between low vitamin D and musculoskeletal pain [25
], and some have even suggested that patients with chronic pain should be routinely screened for hypovitaminosis D [27
]. More recently, the notion of an association between pain and vitamin D status has been refuted [28
]. Furthermore, treatment of hypovitaminosis D does not appear to be effective in management of patients with chronic pain [29
Our results conflict with those of Patel and colleagues [8
], a report that showed evidence of an inverse relationship between vitamin D concentrations and measures of disease activity in early inflammatory arthritis both at baseline and after 1 year of follow-up. Specifically, these investigators observed inverse associations between 25(OH)-D and baseline tender joint counts, Disease Activity Score 28-joint assessment (DAS28) score, and HAQ score, with only the associations with HAQ score remaining significant after 1 year of follow-up. Interestingly, associations of vitamin D status with pain scores were not examined in this population [8
]. There are several factors that may account for the differences observed between the present study and previous findings, mainly with respect to differences in the study populations (i.e. RA in the present study vs. inflammatory arthritis, African-Americans vs. Northern Europeans, and differences in exposure to therapies including glucocorticoids and DMARDs). Patients in the study of Patel et al were ‘treatment naive’ at baseline, enrolled within six months of disease onset with a cumulative DMARD use of less than six weeks in duration. In contrast, patients in the present study had disease durations of up to two years at enrollment and most patients had received therapy for their RA for at least a limited duration of time, reflected in the high rate of DMARD and current or past glucocorticoid use. Recognizing these potentially important study differences, our results call in to question the role of vitamin D status as an important disease modifier, at least in this population.
As noted, the results of this investigation are specific to African-Americans with recent onset RA, which limits the generalizability of these findings. Despite its high prevalence, the precise impact of hypovitaminosis D in African Americans has not been well established and preliminary data suggests that the physiological effects of vitamin D concentration may differ by race/ethnicity. Compared to Caucasians, African Americans appear to be less sensitive to changes in circulating 25(OH)-D with respect to bone mineral density [30
]. It is conceivable that African Americans may also be less sensitive than Caucasians to the effects of vitamin D status in relation to its effects on other disease pathways including systemic inflammation in RA. Further studies aimed at improving our understanding of racial/ethnic differences in the anti-inflammatory effects of vitamin D could provide insight into RA pathogenesis with potential application to other diseases in which hypovitaminosis D has been implicated.
It is worth noting that the threshold used to define vitamin D insufficiency (≤37.5 nmol/L) in this study might be considered conservative. This threshold was used primarily to facilitate historical comparisons with reports from other African American populations [11
]. Recently, different authors have argued in support of optimal 25(OH)-D levels as high as 75 to 80 nmol/L, levels based primarily on fracture prevention data also derived from older Caucasian populations [23
]. As our data clearly illustrate, using higher thresholds renders hypovitaminosis D nearly universal among African Americans with recent-onset RA. Indeed, an optimal threshold and the potential benefit of increased vitamin D intake in African Americans remain to be defined [32
]. Given the potential consequences of vitamin D deficiency with the risk of other chronic diseases including diabetes, multiple sclerosis, malignancy, and heart disease [33
], its health implications in African Americans (including those with RA) may extend well beyond bone health and musculoskeletal disease.
There are limitations to this study. Study participants were enrolled in the Southeast U.S. where sun exposure rates (and resulting vitamin D concentrations) may differ significantly with other populations from other geographic regions. It is possible, for instance, that African Americans with RA from northern latitudes may have a substantially higher prevalence of hypovitaminosis D. Our study also lacks from limited follow-up, as vitamin D status was assessed only at baseline, and disease activity recorded at enrollment and after 3 years of disease duration with the latter available for a majority of patients. Although study participants had a limited disease duration at the time of enrollment, it is impossible to exclude the possibility of unmeasured confounding from different RA treatments received, varying amounts of sun exposure, and dietary intake of vitamin D. However, we would anticipate that confounding secondary to the effect of RA on mobility, sun exposure, and nutritional status would have resulted in even stronger associations with measures of disease activity, particularly HAQ scores. Despite its limitations, the study has notable strengths. This is the largest study to date examining the impact of vitamin D status in African Americans with RA, a vastly understudied population. Although vitamin D concentrations do not appear to play a major role in RA disease activity in this population, the high prevalence of hypovitaminosis D underscores the critical need for additional studies examining the longer term effects of vitamin D status in African Americans with RA.
In summary, Vitamin D insufficiency is common in African Americans with recent-onset RA, affecting approximately half of this population. Associations of lower concentrations of circulating vitamin D with increased pain, higher swollen joint counts, and DAS-28 values in this group appear to be primarily related to differences in season, age, and gender and were not significant in multivariate analyses. In contrast to reports of Northern Europeans with early inflammatory arthritis, there are not strong associations of 25(OH)-D concentration with symptoms or disease severity in African Americans with RA.