Intervertebral disc and vertebral endplate subchondral changes associated with Modic 1 changes of the lumbar spine: a cross-sectional study

Modic 1 signal changes detected on magnetic resonance imaging (MRI) encompass clinical [1‐3], radiological [4, 5] and biological [3] features, which allows for defining a specific subgroup of patients with chronic low back pain (cLBP) [6, 7]. Elementary MRI and histopathological alterations involving intervertebral disc (IVD) and vertebral endplate subchondral bone (VESB) associated with Modic 1 changes, were first described and classified by Modic et al., in the late 1980s, in 474 patients [4, 5]. Briefly, Modic 1 changes are characterized by VESB decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images, whereas Modic 2 changes show VESB increased signal intensity on T1-weighted images and isointense or slightly increased signal intensity on T2-weighted images [5]. Along with VESB changes, changes in IVD related to degenerative disc disease (DDD) also occur, and include intervertebral space narrowing (IVSN) and disc herniation [5, 8].

In Modic et al. study, Modic 1 VESB changes were consistently associated with DDD features. Correlation with the grade of DDD was not assessed [5]. Yu et al. recently reported that Modic changes were correlated with Pfirrmann grades of lumbar DDD. These grades were significantly higher with Modic 1 than Modic 0 or 2 changes. However, grades I, II and III DDD-associated Modic signals were not described [9]. Only few studies have addressed the spatio-temporal pattern between VESB changes and DDD. In a prospective observational study of 344 people from the Danish general population, who underwent MRI at baseline and at 4-year follow-up, levels with DDD, bulges or herniations predicted new MRI VESB signal changes. Severity of DDD was also associated with the extent of Modic changes [10]. Conversely, in another one-year follow-up prospective study of 54 patients, lumbar levels with Modic 1 changes predicted increased incidence of VESB deformation, IVSN and change in disc signal intensity [11]. Findings from another prospective MRI study of 24 cLBP patients were consistent [12].

Modic changes can also occur with only mild DDD features. In a retrospective study of 150 patients, the prevalence of Modic changes in patients with no IVSN and no hyperostosis was 16.9%, and 29.7% in patients with hyperostosis only [13]. In another study, the prevalence of all Modic changes at the level of a normal IVD was 9.9% [14], while the prevalence Modic 1 changes without IVSN was 29% [12]. Altogether, published data suggest that Modic 1 changes are most frequently associated with advanced DDD, but that they can also occur at the level of a normal IVD or with only mild DDD features. Whether this finding reflects either two different stages of the same dynamic process or two different subsets of Modic 1 changes remain unclear.

We hypothesized that Modic 1 changes associated with less advanced DDD may represent a subset of VESB changes, different from those accompanying advanced DDD. Therefore, we designed a cross-sectional study in order to compare Modic 1 changes associated with advanced DDD to those associated with less advanced DDD.

In our cross-sectional study of 101 Modic 1 changes involving the lumbar level, we compared IVD and VESB changes associated with advanced DDD to those associated less advanced DDD. We found that ≤50%-IVSN Modic 1 were rather found in young men at L5/S1 level and are associated with less frequent osteophytes, while >50%-IVSN Modic 1 were rather found in older women at L4/L5 level.

IVSN has been considered a hallmark of DDD [5, 16]. Its frequency, when Modic changes are present, is up to 90.1% [14]. Some authors reported Modic changes without or with minimum IVSN [12‐14]. The prevalence of this phenotype ranges from 9.9% [14] to 29.7% [13]. Variability between studies is due in part to heterogeneous definition and assessment methods of IVSN and to the absence of analysis by Modic change type. No studies have described the demographic and imaging phenotype in these patients. In our study, Modic 1 patients with relatively conserved disc height differed, namely ≤50%-IVSN, significantly differed from those with >50%-IVSN, and overall from Modic 1 population described in the literature [17]. ≤50%-IVSN Modic 1 patients were younger and the men to women ratio was higher than those with >50%-IVSN. In addition, ≤50%-IVSN Modic 1 changes were less often associated with osteophytes and more often located at L5/S1 level, as compared with >50%-IVSN Modic 1 changes, which were more frequent at L4/L5 level. On multivariate analysis, predictors of >50%-IVSN Modic 1 changes were location at L4/L5 level, and variables reflecting more advanced DDD, such as anterior disc herniation and lateral osteophytes. Osteophyte formation has been described by some authors as a compensation mechanism to distribute the increasing axial and shear forces (due to instability) on a larger articulating surface [18]. Therefore, one can assume that differences in osteophyte formation between >50%- and ≤50%-IVSN Modic 1 might reflect differential biomechanical factors. Current hypotheses of Modic 1 changes include biochemical and biomechanical stress [19], along with local infection [20‐22] and genetic predisposition [23, 24]. ≤50%-IVSN and >50%-IVSN Modic 1 groups, may reflect successive stages of the same dynamic process. However, based on the specific demographic findings of our study, one can also hypothesize, that these two groups might represent distinct subsets of Modic 1 patients, that might involve different physiopathological processes. The cross-sectional design of our study did not allow to further address this hypothesis. Proper phenotyping of Modic 1-associated cLBP patients may help guide clinical decisions and develop more targeted treatments [7].

Our study had several limitations. Our sample size was small. Because some events were rarely observed, our statistical analysis lacked power. However, because we focused on only Modic 1 changes, our sample of ≤50%-IVSN Modic 1 changes was larger than in previously published studies and allowed us to compare this subgroup of Modic 1 patients to those with more advanced DDD stages. As well, cases were selected solely from a systematic screening of a computerized database, regardless of clinical presentation. Therefore, we could not address clinical correlates of the MRI phenotype. In addition, MRI cases were from a tertiary care radiology facility and not representative of the whole French primary care population, because patients were more likely referred for a specific condition or symptom. A more comprehensive classification of DDD would probably have been obtained by using the Pfirrmann grading system of lumbar DDD [16]. However, we focused on only some DDD features that we thought were relevant to address our hypothesis. Our method to assess IVSN had some limitations. Indeed, we assessed decreased disc height only on the mid-sagittal view. Methods to quantify IVD height have not been standardized, and they especially do not take into account more localized IVSN. Some authors have recently developed the disc height index to objectively quantify disc height. However, this index needs further validation [25]. Images were analyzed in consensus by the 2 assessors. They should have ideally been read independently. Finally, the cross-sectional design of our study did not allow for addressing the predictive value of observed changes on clinical and structural outcomes, namely, accelerating the DDD process and cLBP symptoms.

≤50%-IVSN Modic 1 patients differ from >50%-IVSN Modic 1 patients on some demographic and IVD and VESB features. Overall, these patients were younger, more often men, had less advanced DDD features, and changes were more often located at L5/S1 level. Whether these findings reflect either two different stages of the same dynamic process or two phenotypically distinct subsets of Modic 1 changes has to be further assessed.