Evidence of inflammation on spinal MRIs was "marginally predictive" of new syndesmophyte formation 2 years later at the vertebral sites where inflammation was observed, in a study of over 100 patients with ankylosing spondylitis.
However, growth of syndesmophytes that were present at vertebral sites at baseline was not associated with evidence of inflammation on MRIs, reported Dr. Désirée van der Heijde, of Leiden University Medical Center, Leiden, the Netherlands, and her associates, in the March issue of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012;71:369-73).
Courtesy of Dr. Pedro Machado
STIR magnetic resonance image of the upper spine of a patient with ankylosing spondylitis, showing inflammatory lesions (bright signal) in multiple vertebral units.
"MRI inflammation in a vertebral unit slightly increases the likelihood of finding a new syndesmophyte in the same vertebral unit 2 years later, but does not predict the growth of already existing syndesmophytes," they wrote. The finding that most of the syndesmophytes grew in the vertebral units with no MRI evidence of inflammation suggests that "the relationship between MRI inflammation and syndesmophyte formation is not straightforward," they added.
The goal of the study was to address the association between inflammation of a vertebral unit (defined as "the region between two virtual lines through the middle of each vertebra") on MRI and the subsequent formation and growth of syndesmophytes, the excessive bone formation that represents the structural damage seen in ankylosing spondylitis (AS). The processes behind the formation of syndesmophytes in AS are not well understood and are not inhibited by treatment with tumor necrosis factor (TNF) blockers, despite the dramatic effects these agents have on inflammation, they noted.
They used data that included spinal MRI activity scores, from a random sample of people enrolled in ASSERT (AS Study for the Evaluation of Recombinant Infliximab Therapy), a 24-week study published in 2005 that compared infliximab to placebo in patients with active AS and followed patients in a open extension period up to 102 weeks, during which time everyone was treated with infliximab (Arthritis Rheum. 2005;52:582-91).
They analyzed information from 1,827 to 2,070 vertebral units from 177 to 183 patients, (the numbers varied, depending on the case definition and the reader of the MRI). MRI images of all 23 vertebral units of the spine – C2 to S1 – were scored on a scale of 0 to 3 (the presence of inflammation in a vertebral unit was defined as a score greater than 0), and a score from 4 to 6 if erosions were also evident.
After adjusting for possible confounders, the risk of developing a syndesmophyte in a vertebral unit with MRI evidence of inflammation was increased 1.5- to 2-fold, a statistically significant increase, they said.
Depending on the syndesmophyte definition used, the reader of the MRI, and the MRI case definition, 6%-32% of new syndesmophytes developed at the vertebral sites with evidence of active inflammation and 68%-94% of new syndesmophytes developed at the vertebral sites that had no evidence of active inflammation. Similar findings were observed for the syndesmophytes that were present at baseline: 0%-30% of the syndesmophytes that were present at baseline and grew were at sites of active inflammation, and 70%-100% of the syndesmophytes that grew "did so in vertebral units without inflammation," they reported.
"The subtle association between MRI activity and new syndesmophytes is in conflict with the absence of an effect of TNF blockers on structural damage," the authors wrote. One explanation they proposed was that the formation of syndesmophytes is "a post-inflammatory repair reaction that may only be inhibited if a TNF blocker is started early before inflammation gives way to repair."
Based on the finding that evidence of inflammation at the vertebral unit "only marginally predicts" the formation of new syndesmophytes at that site, "if inflammation is indeed the principle trigger of repair responses, a strong case can be made for early and aggressive anti-inflammatory treatment," they speculated. However, they added, "if inflammation and repair are independent pathways triggered by common factors, new therapies targeting the pathologically enhanced repair responses need to be developed."
One of the eight authors was supported by a grant from the Fundação para a Ciência e a Tecnologia (FCT); otherwise, the authors had no disclosures to report.