Fatty lesions don’t explain new bone formation in AS: Study

More research needed into effect of inflammation on bone growth in spine

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by Lindsey Shapiro |

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The effects of inflammation on the later development of new bone outgrowths in certain parts of the spine in ankylosing spondylitis (AS) patients are largely not explained by the intermediate formation of fatty deposits, according to a new study.

The findings, which take into account data from two clinical studies, are in contrast to an existing hypothesis that inflammation followed by fat deposition were needed for abnormal bone to grow in these areas.

As noted by the researchers, future studies should investigate exactly how inflammation leads to bone growth even in the absence of fat deposits.

“Since only a small part of the effect of inflammation on [new bone] formation is explained by fatty lesions, getting more insight into how inflammation leads to [bone outgrowths] should be the priority,” the team wrote.

The study, “Do fatty lesions explain the effect of inflammation on new syndesmophytes in patients with radiographic axial spondyloarthritis? Results from the SIAS cohort and ASSERT trial,” was published in RMD Open.

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An inflammatory disease involving the bones and joints, AS is marked by a range of different musculoskeletal abnormalities and inflammatory lesions in the spine.

A common imaging finding in ankylosing spondylitis is the presence of inflammation in the corners of the main structural units of the spine, called vertebral bodies.

This so-called vertebral corner inflammation, or VCI, is associated with the formation of syndesmophytes, or abnormal bone outgrowths, in those areas. Over time, this can result in ankylosis — a hallmark of advanced AS in which bones fuse together due to new bone growth, causing sections of the spine to become rigid.

It has been proposed that for VCI to lead to syndesmophyte formation, an intermediate event is needed in which fatty deposits accumulate in vertebral corners. Indeed, vertebral corner fatty deposits or VCFD have been associated with syndesmophyte growth both alone and in association with VCI.

Now, a team of scientists from across Europe more closely examined the potentially causative role of VCI and VCFD in syndesmophyte formation.

To do so, the scientists looked at data from two previous clinical studies that collected information related to these imaging findings: the Sensitive Imaging in Ankylosing Spondylitis (SIAS) observational study and the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) randomized clinical trial (NCT00207701).

Ultimately, the new analysis involved 49 SIAS participants and 2,667 vertebral corners, as well as 168 ASSERT participants, with 2,918 evaluated vertebral corners. All data was culled over a two-year period.

VCI was evident in 7% of vertebral corners of SIAS participants and 5% of those in ASSERT at the first evaluated time point. After two years, new syndesmophytes had formed in 5% and 3% of corners for SIAS and ASSERT participants, respectively.

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Findings ‘very small and non-significant’

The researchers also looked at imaging findings from an intermediate time point — after one year in the SIAS trial and after six months in ASSERT.

These findings indicated that the new fatty deposits at this intermediate time point were more common in vertebral corners that had shown inflammation in the earlier assessment.

A mathematical model was used to predict how often VCI caused new bone formation two years later, and how many of these cases were mediated by intermediate VCFD formation.

Overall, the presence of VCI at the start of the SIAS study increased the probability that a person would have a new symdesmophyte in that corner two years later by 9.3%.

Of this 9.3%, 0.2% of it could be attributed to cases where intermediate VCFD had been observed after one year.

Similar observations were made in ASSERT participants. Among them, VCI increased the odds of new bone formation after two years by 7.3% — 0.8% of which could be attributed to intermediate fat formation observed after six months.

Our findings can have several implications for future studies and clinical practice.

“The contribution of new VCFD as an intermediate on syndesmophyte formation was, in both studies, very small and non-significant,” the researchers wrote, noting that findings were comparable between the studies despite a large number of differences in study design.

The analyses were not controlled for certain clinical factors that could influence the findings, marking a study limitation, according to the authors.

“Our findings can have several implications for future studies and clinical practice,” the researchers wrote.

Given that the findings do not overall support VCFD as a good marker for syndesmophyte development, “future studies should focus on the biological pathways through which VCI directly leads to syndesmophyte formation,” the team concluded.