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

Abstract

Objective. Focal fat infiltration is frequently visible on magnetic resonance imaging (MRI) of the spine in patients with ankylosing spondylitis (AS) and likely reflects postinflammatory tissue metaplasia. To support the concept of coupling between inflammation and new bone formation, we tested the hypothesis that focal fat infiltration at a vertebral corner is more likely to evolve into a de novo syndesmophyte.Methods. MRI scans were obtained at baseline and radiographs were obtained at baseline and 2 years in 100 AS patients from 2 cohorts: a clinical trial cohort (n ‫؍‬ 38) and an observational cohort (n ‫؍‬ 62). In the clinical trial cohort, patients were randomized to receive anti-tumor necrosis factor (anti-TNF) therapy or placebo for 12-24 weeks and then open-label treatment for 2 years. In the observational cohort, patients received either standard therapy (n ‫؍‬ 36) or anti-TNF therapy (n ‫؍‬ 26) for 2 years. Vertebral corner inflammation and fat infiltration were assessed independently by pairs of readers who were blinded with regard to the radiographic findings.Results. New syndesmophytes developed significantly more frequently in vertebral corners with fat in both the clinical trial (10.2%) and the observational (6.5%) cohort as compared to those without either Conclusion. Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.A hallmark of ankylosing spondylitis (AS) is the development of new bone in the spine, which typically leads to ankylosis across the disc spaces. Bone proliferation typically starts at the vertebral rim and grows in the direction of the anulus fibrosus, parallel to the vertebral axis. Ossification may extend across the vertical length of the anulus and becomes visible on radiographs as a syndesmophyte.Until recently, it was hypothesized that ankylosis occurred in response to inflammation and following a reparative process that included cartilage metaplasia. However, data from animal models of spondylarthritis (SpA), principally ankylosing enthesitis, directly challenged this hypothesis by demonstrating that anti-tumor necrosis factor ␣ (anti-TNF␣) therapy did not prevent the development of ankylosis (1). An alternative hypothesis was then proposed whereby pathogenetic factors such as altered gene expression, biomechanical factors, and bacteria trigger the concomitant expression of inflammation and new bone formation, which then proceed

Fat Metaplasia and Backfill Are Key Intermediaries in the Development of Sacroiliac Joint Ankylosis in Patients With Ankylosing Spondylitis

“…The demonstration that fat metaplasia at vertebral corners is also associated with the development of new bone supports the hypothesis that fat metaplasia, both in subchondral bone marrow and at sites of erosions, is a key intermediary in the pathophysiology of new bone formation in SpA (5,18).…”

“…Recently published MRI data suggest that resolution of inflammation (i.e., bone marrow edema) in the spine may be associated with the development of fat metaplasia in the same area and later also with the development of new syndesmophytes (5)(6)(7). The sequence of events seen on MRI that lead to the development of ankylosis in the SI joints has not yet been established, but it has been assumed based on radiography that ankylosis follows resolution of erosion.…”

Ankylosing Spondylitis – the changing role of imaging

“…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]. A second study found that fatty vertebral corner lesions, thought to be a post-inflammatory finding, predate syndesmophyte formation in affected spinal units [15]. This whole area remains of considerable interest and developments may have an effect on future treatment strategies.…”

Magnetic Resonance Imaging of Vertebral Erosion in Spondyloarthritis

“…The presence of erosion may not tell us much about disease activity, but as we already know that the presence of a syndesmophyte is a predictor of damage progression 16 , and if erosion predicts syndesmophytosis, then spinal erosion could turn out to be an earlier predictor of the same outcome. It has been shown that resolution of inflammation with anti-TNF therapy may be associated with development of new syndesmophytes 17,18,19,20 , and so it may be reasonably expected that an accelerated osteoproliferative phase would include the disappearance of erosion, as suggested in this article. Whether this progresses to ankylosis remains to be seen.…”