Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: Evidence of a relationship between inflammation and new bone formation

Abstract

Objective. To determine whether a vertebral corner that demonstrates an active corner inflammatory lesion (CIL) on magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) is more likely to evolve into a de novo syndesmophyte visible on plain radiography than is a vertebral corner that demonstrates no active inflammation on MRI.Methods. MRI scans and plain radiographs were obtained for 29 patients recruited into randomized placebo-controlled trials of anti-tumor necrosis factor ␣ (anti-TNF␣) therapy. MRI was conducted at baseline, 12 or 24 weeks (n ‫؍‬ 29), and 2 years (n ‫؍‬ 22), while radiography was conducted at baseline and 2 years. A persistent CIL was defined as a CIL that was found on all available scans. A resolved CIL was defined as having completely disappeared on either the second or third scan. A validation cohort consisted of 41 AS patients followed up prospectively. Anonymized MRIs were assessed independently by 3 readers who were blinded with regard to radiographic findings.Results. New syndesmophytes developed significantly more frequently in vertebral corners with inflammation (20%) than in those without inflammation (5.1%) seen on baseline MRI (P < 0.008 for all reader pairs). They also developed more frequently in vertebral corners where inflammation had resolved than in those where inflammation persisted after anti-TNF treatment. This was confirmed in the analysis of the prospective cohort, in which significantly more vertebral corners with inflammation (14.3%) compared with those without inflammation (2.9%) seen on baseline MRI developed new syndesmophytes (P < 0.003 for all reader pairs).Conclusion. Our findings indicate that a syndesmophyte is more likely to develop from a prior inflammatory lesion, supporting a relationship between inflammation and ankylosis.

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

“…The MR images were read independently by readers who recorded the presence/absence of vertebral corner fat and/or inflammation at the anterior vertebral corners of the cervical (lower part of C2 to upper part of T1) and lumbar (lower part of T12 to upper part of S1) spine. None of the T1-weighted images from scans of these 100 patients had been assessed previously, whereas STIR sequence images from 70 patients had been assessed for a previously reported study (12).…”

“…Vertebral corner fat infiltration and inflammatory lesions are often subtle and are confounded by phase-encoding artifacts, which are typically worse in the anterior lumbar spine, and limited spatial resolution in the cervical spine, where vertebrae are small and the field of view is comparatively large. We have previously reported that vertebral corner inflammatory lesions are associated with the development of new syndesmophytes after 2 years of followup (12). Consequently, the primary analysis was a comparison of the proportion of new syndesmophytes developing at each anterior vertebral corner where fat infiltration, but not inflammation, was recorded by both readers as being present at the baseline examination versus vertebral corners where neither of the two readers recorded either fat infiltration or inflammation at baseline.…”

“…In addition, several studies have now demonstrated an association between inflammation seen on MRI at baseline and the subsequent development of syndesmophytes (11)(12)(13). Consequently, we used generalized linear latent and mixed models (GLLAMMs) (25) that adjusted for within-patient dependence for the total number of vertebral corners with fat, inflammation, and syndesmophytes/ankylosis.…”

“…Three prospective studies have now shown that vertebral inflammation that is visible on MRI predicts the development of new syndesmophytes that are visible on radiographs after 2 years of followup, although it was found that new syndesmophytes also occurred at vertebral corners where the baseline MRI did not show inflammation (11)(12)(13). It is unclear whether this latter observation reflects the limited sensitivity of MRI for detecting inflammation (14) as well as the limitations of a single MRI examination in the context of a chronically evolving lesion, but it has been argued that it provides support for a pathway of new bone formation that is at least partly autonomous.…”

Ankylosing Spondylitis – the changing role of imaging

“…Other possible explanations are the fact that new bone formation is a late consequence of inflammation and thus may have a long lag time to see effect, the possibility of low grade ongoing inflammation even in those with clinical improvement on TNFα blocking therapy and the suggestion that TNFα, in the presence of active inflammation, reduces new bone formation. Thus once inflammation improves on TNFα blocking treatment, the "brake" is released and repair and new bone formation can proceed [13]. This possible link with inflammation is supported by a recent study suggesting that syndesmophyte formation is more frequent in vertebral corners in which a previous inflammatory lesion has resolved [14].…”