SIAS study

The SIAS study stands for Sensitive Imaging in Ankylosing Spondylitis study. Ankylosing spondylitis (AS) is an inflammatory disease characterized by chronic inflammation in the spine. Ultimately, patients may develop syndesmophytes, bony spikes at corners of vertebrae resulting in bony bridges. Conventional radiography is able to visualize syndesmophyte formation, which can already be detected after a one-year interval. However, two years are advised to see sufficient changes in many patients. Inflammatory changes can be detected using magnetic resonance imaging (MRI) in an earlier disease stage. The general hypothesis is that inflammation precedes bone formation; however, currently available data do not fully support this hypothesis. There is no relationship between the overall level of inflammation in the spine and the number of new syndesmophytes. Detailed analyses of vertebral inflammation and syndesmophyte formation in the same unit show that it is slightly more likely that syndesmophytes are formed in vertebrae with inflammation compared to those without inflammation. However, the majority of syndesmophytes are formed in vertebrae in which no inflammation was present over a two-year period. Recent data indicate that especially fatty infiltration might be a predictor of syndesmophyte formation. One of the hypothesis is that if there is ongoing inflammation that this will not lead to syndesmophyte information, but if the inflammation disappears and this is replaced by fatty infiltration that this will result in a syndesmophyte. In contrast, when inflammation disappears without fatty infiltration this will not result in a syndesmophyte. A hypothesis to explain that the majority of syndesmophytes develop in levels in which there was no inflammation is that the imaging methods are not sensitive enough to detect all inflammation. Anti-TNF agents are very effective in suppressing MRI inflammation, but are unable to inhibit syndesmophyte formation.

Objectives
To study the relationship between inflammation on MRI and syndesmophyte formation with very detailed imaging methods: radiography, computed tomography (CT), 3 and 7 Tesla MRI. To examine the time order of pathologic changes like inflammation, fatty degeneration, erosion and syndesmophyte formation. To assess agreement between 3 and 7 Tesla MRI in detecting inflammation. To assess agreement between CT and conventional radiography of the cervical and lumbar spine in detecting structural changes. To examine if the thoracic spine provides different information compared to the cervical and lumbar spine.

Methods
This is a prospective follow-up study using a cohort of patients with AS fulfilling the Modified New York criteria and at least one syndesmophyte in the cervical or lumbar spine on conventional radiography at baseline. Consenting patients referred to the LUMC Rheumatology clinic will have both clinical and radiological assessments. 30 patients will be studied over a two-year period with annual (MRI) and biennial (radiography, CT) imaging of the spine using well established techniques currently available at the department of Radiology at the LUMC.

Expected results
The research will clarify the targets for development of treatment to prevent syndesmophyte formation in patients with AS: either more profound suppression of inflammation or earlier start of therapy; or other targets that are directly related to bone formation.