Abstract and Introduction
Abstract
Background: In patients with axial spondyloarthritis (axSpA), magnetic resonance imaging (MRI) is used to detect bone marrow edema (BME) in sacroiliac joints (SIJ) but SIJ BME are also detected in the population. Not much is known about sex differences in that regard.
Objective: To explore sex-specific differences associated with the extent of BME in the SIJ suggestive of axSpA in a general population cohort study.
Methods: Taking advantage of 793 recently evaluated MRIs of subjects < 45 years taking part in the SHIP cohort, we used negative-binomial (NB) count data regression to analyze factors associated with the extent of SIJ BME. Predictors were explored by model-based boosting (MBB), a machine learning approach.
Results: Estimates of NB regression showed strong effects of sex in interaction with age, BMI, back pain, and particularly HLA-B27. The NB regression model showed incidence rate ratios (IRR) for the main effect of sex (females vs. males): 0.94 [95% CI: 0.63; 1.41], HLA-B27: 4.32 [2.09; 9.8], and for the interaction of sex to HLA-B27: 0.22 [0.06; 0.75]. According to MBB, HLA-B27 positivity, BMI, current smoking, back pain in the last 3 months, the interaction of sex and HLA-B27, and delivery in the last 12 months were of highest importance to explain the extent of SIJ BME.
Conclusions: Different factors were associated with the extent of SIJ BME in females and males. Most importantly, HLA-B27 was relevant only in males but not in females in whom a postpartal state was important. This finding may be relevant for the pathogenesis of axSpA.
Introduction
The main result of this cohort study is that the extent of lesions in the sacroiliac joints detected by MRI (bone marrow edema) in a young population < 45 years is influenced by HLA B27, an MHC class I allele which is strongly associated with axial spondyloarthritis—only in males. This suggests that sex-related differences matter in the pathogenesis of this disease, and as a possible clinical consequence, it possibly indicates that being HLA B27+ may have to be differently interpreted in females with back pain.
While ankylosing spondylitis (AS) had been widely recognized as a male disease,[1] this is different in axial spondyloarthritis (axSpA), where the male/female ratio is more or less equal,[2] and especially in patients with non-radiographic axSpA (nr-axSpA), where the proportion of women is even higher.[3] However, there is some evidence of significant differences between male and female patients with axSpA in clinical parameters including new bone formation,[4–7] the persistence of inflammation,[8,9] and the response to anti-tumor-necrosis-factor (TNF) therapy.[10]
Using data of 793 subjects aged <45 years participating in the general population based cohort Study[11] of Health in Pomerania (SHIP) who had undergone whole body magnetic resonance imaging (MRI),[12] we have recently reported that many individuals had minor MRI findings in the sacroiliac joints (SIJ) partly ressembling lesions detected in axSpA and the spine.[13] A second analysis, in which we examined factors associated with those MRI findings, showed that a history of previous delivery and HLA-B27 were important contributors to the occurrence and extent of such SIJ changes.[14] Thereafter, we decided to stratify for participants' sex and found differences between males and females in the relevance of covariates for the extent of bone marrow edema (BME) in the SIJ. In the present study, we explored interactions of participants' sex with all previously identified predictors of SIJ BME. To increase the credibility of the results, we compared those from conventional regression techniques with the results of a machine learning approach that were obtained after resampling.
Arthritis Res Ther. 2022;24(29) © 2022 BioMed Central, Ltd.
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