Aortic-vertebral interaction in inflammation.

Abstract

Dear editor, We read with great interest the article by Chen et al., in which the aortic-vertebral interaction was proposed in the context of inflammation.1 The study suggested that inflammation may promote ossification and was linked to a large aorta ipsilateral ratio of the osteophytes. This topic has significant clinical relevance, and future cohort studies covering various aspects are needed to further validate the findings in this study. First, it is important to note that baseline demographics and comorbidities may have influenced the study observations. At Shanghai Renji Hospital between 2013 and 2021, the percentage of male participants in the Takayasu's arteritis (TKA) group, the ankylosing spondylitis (AS) group, the coronary artery disease (CAD), and the diffuse idiopathic skeletal hyperostosis (DISH) group were 38.7%, 65.4%, 70%, and 60%, respectively, compared to 50% in the healthy controls (HC). Male sex may have been a potential confounder, as previous research has suggested that males are at a greater risk of AS, CAD, and DISH2 than females. Therefore, adjusting or stratifying for sex3 could provide insights into whether male sex was a mediator or a confounder in the causal relationship between inflammation and radiographic phenotypes. In addition, since inflammation was proposed as a key component in this study, it would be valuable to consider the presence of inflammatory diseases or autoimmune diseases4-7 such as rheumatoid arthritis,8-12 psoriasis,13-15 psoriatic arthritis,16-18 Sjogren's syndrome,19, 20 fibromyalgia,21, 22 periodontitis,22-28 or other diseases with osteophytes such as osteoarthritis,23, 29, 30 as potential effect modifiers. The second issue to be addressed is the potential impact of unmeasured confounders on the observed findings. For example, the article did not report on the common medications used to manage AS and TKA, which are known to reduce C-reactive protein (CRP) levels and heterotopic ossification. These medications include nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used to manage AS and recommended as a prophylactic regimen for postoperative heterotopic ossification.31, 32 Similarly, the use of tumor necrosis factor (TNF) alpha inhibitors and interleukin-17 inhibitors may inhibit tenascin-C from affecting aorta-vertebrae remodeling.1 Additionally, low doses of corticosteroids have been found to significantly reduce CRP levels,33 which can also affect the aorta ipsilateral ratio or observed radiographic progression. Therefore, stratification or adjustment of treatments and medications may clarify whether the observed results were caused by the disease or were modified by the use of medications in these patients. Such analyses could provide evidence regarding the safety and efficacy of NSAIDs, steroids, and biologic disease-modifying antirheumatic drugs (DMARDs)8, 16, 32, 34 in patients with AS, TKA, DISH, or CAD, which could improve patient care and patient education21, 35, 36 on drug safety.37-40 Last but not least, as this was a cross-sectional study, without longitudinal data, as in cohort studies,41-43 acquired during follow-ups,44-46 the causal effect of inflammation on the observed radiographic findings may not be ascertained. In conclusion, longitudinal studies considering baseline demographics and treatment effects may provide more details into the aortic-vertebrae interaction. All authors (YHC, WHT, YCC, KHC, and KSM) provided their ideas and critical contribution. YHC, WHT, and YCC contributed to the writing and editing of the manuscript. KHC and KSM contributed equally as corresponding authors. This research was not sponsored by a specific project grant. None. The authors declare no conflicts of interest.