Biomarkers predict progressive spinal damage in ankylosing spondylitis

Jun 8 2012

By Laura Cowen

German researchers have discovered five biomarkers that may predict the progression of structural damage in the spine of patients with ankylosing spondylitis (AS) who are already at high risk for disease progression.

The findings, presented at the European League Against Rheumatism Annual Congress of Rheumatology in Berlin, Germany, show that levels of matrix metalloproteinase (MMP)3, bone-morphogenetic protein (BMP)2, procollagen type II N-propeptide (PIINP), vascular endothelial growth factor (VEGF), and osteoprotegerin (OPG) are associated with AS structural damage.

Denis Poddubnyy (Charité Universitätsmedizin Berlin, Germany) and colleagues studied 64 patients with AS who were considered high risk for radiographic disease progression due to the presence of radiographic spinal damage (syndesmophytes) at baseline.

The researchers measured baseline levels of MMP3, BMP2, PIINP, VEGF, and OPG, as well as C-reactive protein (CRP), sclerostin, Dickkopf 1 (DKK1), periostin, BMP7, PINP, collagen type 2 cross-linked C-telopeptide, bone alkaline phosphatase, receptor activator of nuclear factor kappa-B ligand, cartilage oligomeric matrix protein, and bone sialoprotein in each of the study participants.

These biomarkers were chosen because they have previously been linked to syndesmophyte formation in patients with AS who had not yet shown evidence of radiographic progression.

The team then took spine radiographs after 2 years of follow up to look for disease progression, defined as new syndesmophytes formation or growth of the existing syndesmophytes, in each of the patients.

At this time, the patients were divided into two groups, progressors (n=26) and nonprogessors (n=38).

Poddubnyy reported that compared with nonprogressors, progressors had significantly higher baseline levels of CRP (17.1 vs 8.7 mg/L) and MMP3 (40.2 vs 19.5 ng/mL), which "confirmed a predictive value of markers of active inflammation regarding radiographic spinal progression," he said.

Furthermore, in patients with both syndesmophytes and elevated CRP at baseline, serum levels of MMP3, BMP2, PIINP, VEGF were significantly higher, and OPG significantly lower in progressors than in nonprogressors.

Nonsignificant protective trends were also observed found also for sclerostin, DKK1, and periostin, but no differences were observed for the other biomarkers tested.

"Knowing more about why certain patients have disease progression is hugely important. Not only will this help us stratify our patients due to risk but may, in the future, pave the way for more treatment options that target specific markers to be developed," Poddubnyy concluded in a press statement.

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