Body mass index and extent of MRI-detected inflammation: opposite effects in rheumatoid arthritis versus other arthritides and asymptomatic persons

An increased BMI is associated with higher inflammatory markers in the general population [1], and a higher risk for RA development [2]. A high BMI within RA, however, is associated with less severe radiographic joint damage [3–6]. Because joint destruction is the result of persistent inflammation, the present cross-sectional study assessed the association between BMI and MRI-detected inflammation and showed that RA patients with a high BMI had less MRI-detected inflammation. More specifically, patients had less severe synovitis and BME. This inverse association was not observed in early arthritis patients with other inflammatory diagnoses and in asymptomatic volunteers. This suggests that the inverse association between BMI and local joint inflammation is confined to RA and may explain the previously reported observation of less severe radiographic progression in obese RA patients.

The mechanism underlying this inverse association is unknown. It can be speculated that adipocytokines play a role. It could be that the composition of the adipocytokines is different between various diseases; for example, the balance between low molecular weight versus high molecular weight adiponectin might be different. Another possibility is that the interaction between adipocytokines and immune cells is different within RA compared with other diseases. However, we have no data to support these speculations and further studies are needed to unravel the biologic mechanism underlying our observation.

To the best of our knowledge RA is the only disease in which obese patients have less severe inflammation and progression. Also, the effect of obesity for RA is two-fold. Despite the association with less severe MRI-detected inflammation and less severe radiographic progression, obesity has been associated with a higher risk for developing RA and a lower risk for reaching persistent remission [2, 12]. Furthermore, a lower chance to achieve a low disease activity has also been observed in RA patients that use synthetic DMARDs and biological DMARDs [13–15]. Of note, when evaluating the components of the disease activity score, the effect was only present for subjective measures (tender joint count and patient global assessment) and not for objective measures of inflammation (CRP, erythrocyte sedimentation rate, and swollen joint count) [13].

Also in the present study we observed no association between BMI and either the CRP levels or the number of swollen joints. This illustrates that local inflammation is different from systemic inflammation and also underlines that MRI is a more sensitive method to detect local inflammation than physical examination of joints. Apparently the less severe radiographic progression in RA is paralleled by less severe local inflammation, which is detected when local inflammation is measured using a sensitive method. As such, the results of the present study suggest that MRI is not only valuable as an outcome measure in clinical trials but that MRI studies may also help to increase our pathophysiological understanding of RA.

In line with recommendations of the ESSR [16], BME was evaluated on T1 Gd, which is different from the RAMRIS methodology using T2. Our scan protocol omitted T2 because previous studies have shown that these sequences perform equally well in the depiction of BME [17, 18] and the T1 Gd sequence allows a shorter imaging time for the patients. The present finding of similar effects of BMI in BME as observed in two different studies in which BME was assessed on different sequences (Baker et al. [3] used short tau inversion recovery (or T2 precontrast) sequences) support the notion that the findings are not influenced by the sequence used to depict BME.

This study has limitations. The BMI was used as an estimate of the adipose tissue, but differences in BMI are not only caused by differences in adipose tissue but also by differences in, for instance, muscle mass. There are methods that could make more accurate estimations in this respect, such as waist circumference, bioelectrical impedance, or computed tomography. Another important limitation is that long-term follow-up was not yet available for the RA patients who had undergone MRI. Therefore we could not assess whether our findings at disease presentation might explain the association of BMI with less severe radiographic joint progression. In addition we could not determine the association of BMI with other disease outcomes, such as persistent remission.