Development Of New Syndesmophytes Research Articles

No relationship between bone mineral density and syndesmophyte formation at the same level in the lumbar spine of patients with radiographic axial Spondyloarthritis

ObjectiveTo investigate if in radiographic axial Spondyloarthritis (r-axSpA) low vertebral bone mineral density (BMD) is associated with development of new syndesmophytes at the same vertebral level.MethodsIn a post-hoc analysis from...

Elevated serum level of hepatocyte growth factor predicts development of new syndesmophytes in men with ankylosing spondylitis.

ObjectivesTo study baseline serum hepatocyte growth factor (s-HGF) as a predictor of spinal radiographic progression overall and by sex and to analyse factors correlated to changes in s-HGF in patients with AS.MethodsAt baseline and the 5-year follow-up, s-HGF was analysed with ELISA. Spinal radiographs were graded according to modified Stoke Ankylosing Spondylitis Spinal Score. Radiographic progression was defined as ≥2 modified Stoke Ankylosing Spondylitis Spinal Score units/5 years or development of ≥1 syndesmophyte. Logistic regression analyses were used.ResultsOf 204 baseline participants, 163 (80%) completed all examinations at the 5-year follow-up (54% men). Baseline s-HGF was significantly higher in men who developed ≥1 syndesmophyte compared with non-progressors, median (interquartile range) baseline s-HGF 1551 (1449–1898) vs 1436 (1200–1569) pg/ml, P = 0.003. The calculated optimal cut-off point for baseline s-HGF ≥1520 pg/ml showed a sensitivity of 70%, a specificity of 69% and univariate odds radio (95% CI) of 5.25 (1.69, 14.10) as predictor of development of ≥1 new syndesmophyte in men. Baseline s-HGF ≥1520 pg/ml remained significantly associated with development of ≥1 new syndesmophyte in men in an analysis adjusted for the baseline variables age, smoking, presence of syndesmophytes and CRP, odds radio 3.97 (1.36, 11.60). In women, no association with HGF and radiographic progression was found. Changes in s-HGF were positively correlated with changes in ESR and CRP.ConclusionIn this prospective cohort study elevated s-HGF was shown to be associated with development of new syndesmophytes in men with AS.

Spinal Radiographic Progression in Early Axial Spondyloarthritis: Five-Year Results From the DESIR Cohort.

ObjectiveTo analyze the progression of spinal radiographic damage in patients with early axial spondyloarthritis (SpA).MethodsAxial SpA patients from the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort with 5‐year spinal (cervical and lumbar) radiographs available (n = 549) were included. Two‐ and 5‐year modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) progression and development of new syndesmophytes (net change: the number of patients with positive change minus the number of patients with negative change divided by the total number of patients) were assessed in subgroups defined at baseline according to the Assessment of SpondyloArthritis international Society axial SpA criteria and its arms, modified New York criteria (mNYC) and the presence of syndesmophytes.ResultsMean ± SD mSASSS progression was 0.2 ± 0.9 at 2 years and 0.4 ± 1.8 at 5 years. Five‐year progression was higher in the imaging arm (mean ± SD 0.6 ± 2.3), magnetic resonance imaging (MRI)+/mNYC+ (mean ± SD 1.3 ± 4.0), than in the clinical arm only (mean ± SD 0.1 ± 0.7), and highest in patients with syndesmophytes (mean ± SD 2.7 ± 5.0). At 5 years, 7% of all patients had a net change of any new syndesmophyte; this value was 10% for the imaging arm (mNYC+/MRI+ with 18%), 17% for mNYC+ patients, and 42% for patients with syndesmophytes.ConclusionSpinal radiographic progression, although limited in early axial SpA, can be captured after 2 years. Inflammation and damage in the sacroiliac joint are associated with higher radiographic progression. The presence of baseline syndesmophytes already strongly predicts the development of further structural damage early in the disease.

Low bone mineral density predicts the formation of new syndesmophytes in patients with axial spondyloarthritis

BackgroundThis study aimed to investigate whether the presence of low bone mineral density (BMD) in patients with axial spondyloarthritis (axSpA) predicts formation of new syndesmophytes over 2 years.MethodsOne hundred and nineteen patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. All patients were under 50 years of age. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was assessed by two trained readers blinded to the patients’ data. BMD (lumbar spine, femoral neck or total hip) at baseline was assessed using dual-energy absorptiometry. Low BMD was defined as Z score ≤ − 2.0. Spinal radiographic progression was defined as worsening of the mSASSS by ≥ 2 points over 2 years. Logistic regression analyses were performed to identify predictors associated with development of new syndesmophytes and spinal radiographic progression.ResultsAt baseline, 19 (16%) patients had low BMD. New syndesmophytes had developed in 22 (21%) patients at 2-year follow-up. New syndesmophyte formation after 2 years occurred more in patients with low BMD than in those with normal BMD (p = 0.047). In the multivariable analysis, current smoking, existing syndesmophytes and low BMD at baseline were associated with spinal radiographic progression (OR (95% CI) 3.0 (1.1, 7.7), 4.6 (1.8, 11.8) and 3.6 (1.2, 11.2), respectively). The presence of syndesmophytes at baseline and low BMD were predictors of new syndesmophytes over the following 2 years (OR (95% CI) 5.5 (2.0, 15.2) and 3.6 (1.1, 11.8), respectively).ConclusionsLow BMD and existing syndesmophytes at baseline were independently associated with the development of new syndesmophytes in young axSpA patients.

A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis

BackgroundKnowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex.MethodsSwedish patients with AS, age (mean ± SD) 50 ± 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples.ResultsOf 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 ± 2.8 vs. 1.2 ± 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression ≥ 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women.ConclusionThis first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.Trial registrationClinicalTrials.gov, NCT00858819. Registered on 9 March 2009. Last updated 28 May 2015.

The contribution of imaging in the diagnosis and treatment of axial spondyloarthritis.

The concept of axial Spondyloarthritis (axSpA) includes patients with non-radiographic axSpA and ankylosing spondylitis (AS). Inflammatory and chronic/structural changes of the sacroiliac joints and the spine are pathognomonic in patients who are diagnosed with axSpA. In the last years, the evaluation of the natural course of axSpA has been in the focus of research, especially with respect to the relationship between inflammation or postinflammatory changes [detected by magnetic resonance imaging (MRI)] and bone formation (detected by conventional radiographs). Based on the analysis of spinal MRI data, development of new syndesmophytes is directly associated with the parallel occurrence of inflammatory and postinflammatory (fatty) changes in the edges of the vertebral bodies. In contrast, vertebral edges that show only inflammation but no transformation into fatty lesions show a decreased relative risk for development of new bone formation over time. An inhibitory effect on radiographic progression had not been demonstrated during the first 2years of continuous anti-TNFa treatment, however, very recently first studies reported a decreased rate of radiographic progression when patients were continuously treated with TNFa-blockers for a time period of ≥4years. These data are crucial in the understanding of the long-term clinical course of patients with axSpAin daily practice. According to these results, it becomes obvious that anti-inflammatory treatment, especially by using tumor-necrosis-factor alpha (TNFa)-blockers, has the best effect on the radiographic outcomes when it is started in anearly disease stage, where only inflammation is driving the disease activity and where structural, postinflammatory changes have not yet occurred.

The predictors of development of new syndesmophytes in female patients with ankylosing spondylitis

Objectives: The formation of spinal syndesmophytes is an important outcome measure in ankylosing spondylitis (AS) but the predictors of new syndesmophyte development in female AS patients are unknown. This longitudinal study aimed to assess the rate and predictors of development of new syndesmophytes over a 2-year period in female AS patients.Method: Clinical and radiographic data were collected at baseline and after 2 years in 67 female AS patients. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Univariate logistic regression analyses were performed to identify predictors associated with new syndesmophyte development.Results: Eleven (16%) patients had syndesmophytes at baseline. Nine (13.4%) patients had developed new syndesmophytes in their lumbar spines after 2 years. In the univariate logistic regression analyses, older age, longer disease duration, severe sacroiliitis, elevated C-reactive protein (CRP) levels at baseline, and one or more pre-existing syndesmophytes were associated with the occurrence of new syndesmophytes. After adjustment for baseline SASSS, increases in SASSS were statistically significantly higher in patients with elevated baseline CRP levels (p = 0.002) than in patients with normal CRP at baseline.Conclusions: Older age, longer disease duration, severe sacroiliitis, the baseline presence of syndesmophytes, and elevated levels of CRP are predictors of the development of new syndesmophytes in female AS patients.

FRI0127 Eular Recommendations for the Use of Imaging in Spondyloarthritis in Clinical Practice

ObjectivesTo develop evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis.MethodsThe task force comprised an expert group of 21 rheumatologists, radiologists and...

SP0143 Ten Eular Recommendations for Use of Imaging in Spondyloarthritis Clinical Practice

A task force convened by the European League Against Rheumatism (EULAR) comprising rheumatologists, radiologists and methodologists from 11 countries developed 10 recommendations, based on both evidence obtained through systemic literature...

OP0218 Erosions and Sclerosis, but not Squaring Predict the Development of New Syndesmophytes: A 12-Year Longitudinal Analysis

BackgroundErosions, sclerosis and squaring are included in the modified Stoke Ankylosing Spondylitis (AS) Spine Score (mSASSS). However, their value in predicting the development of new syndesmophytes has not been established,...

SAT0250 Validation of a New Scoring Method for the Evaluation of Fat Lesions in the Spine of Patients with Axial Spondyloarthritis: The Canada-Denmark Fat Spondyloarthritis Spine Score (FASSS)

BackgroundFat lesions (FL) have been shown to follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA) (1), and to predict development of new syndesmophytes (2). Thus,...

The FAt Spondyloarthritis Spine Score (FASSS): development and validation of a new scoring method for the evaluation of fat lesions in the spine of patients with axial spondyloarthritis

IntroductionStudies have shown that fat lesions follow resolution of inflammation in the spine of patients with axial spondyloarthritis (SpA). Fat lesions at vertebral corners have also been shown to predict development of new syndesmophytes. Therefore, scoring of fat lesions in the spine may constitute both an important measure of treatment efficacy as well as a surrogate marker for new bone formation. The aim of this study was to develop and validate a new scoring method for fat lesions in the spine, the Fat SpA Spine Score (FASSS), which in contrast to the existing scoring method addresses the localization and phenotypic diversity of fat lesions in patients with axial SpA.MethodsFat lesions at pre-specified anatomical locations at each vertebral endplate (C2 lower-S1 upper) were assessed dichotomously (present/absent) on spine MRIs. Two readers independently evaluated MRIs obtained at two time points for 58 patients (Exercise 1), followed by optimization of scoring methodology and reader calibration. Thereafter, the same readers read 135 pairs of MRI scans (Exercise 2; including the 58 pairs from exercise 1 randomly mixed with 77 new pairs).ResultsIn Exercise 2, the mean (SD) baseline FASSS score for the two readers was 22.5(29.6) and 21.1(28.0), respectively, and the FASSS change score was 4.2(10.6) and 6.0(12.2). Inter-reader reliability assessed as intra-class correlation coefficients (ICCs) for status and change scores were excellent (0.96 (95% CI (0.94 to 0.97)) and very good (0.86 (0.80 to 0.90)), respectively. The smallest detectable change (SDC) was 3.7 for the 135 patients. Good reliability of change scores was also observed for MRI scans conducted one year apart (ICC 0.74 (95% CI 0.44 to 0.89) and SDC 4.5). For the 58 MRI-pairs assessed in both exercises, inter-reader reproducibility for the total FASSS status score improved from very good (ICCs: 0.89 (95% CI: 0.81 to 0.93) in exercise 1 to excellent in exercise 2 (0.96 (0.93 to 0.98)), and improved substantially for the total change score (from 0.67 (0.51 to 0.80) to 0.83 (0.73 to 0.90).ConclusionsFASSS meets essential validation criteria for quantification of a common structural abnormality in clinical trials of axial spondyloarthritis.

MRI and X-ray in axial spondyloarthritis: the relationship between inflammatory and structural changes

Demonstration of an association between inflammation and spinal ankylosis has been challenging. Until the advent of MRI, prospective study was not possible due to inaccessibility of tissue. Recent studies using MRI have described an association between the presence of bone edema at vertebral corners on MRI and the subsequent development of syndesmophytes at the corresponding vertebral corners on radiography. Although reports have also highlighted the development of new syndesmophytes where the baseline MRI shows no inflammation, MRI has limited sensitivity for detection of spinal inflammation that is clearly evident on histopathology. There are also crucial methodological challenges because radiographic assessment is limited to the anterior corners of the cervical and lumbar spine while MRI lesions in the cervical spine are often small while spurious inflammatory signal is common in the lumbar spine. Follow-up MRI evaluation in two independent studies has also shown that inflammatory lesions that resolve after anti-TNF therapy are more prone to develop into syndesmophytes. It may be possible that very early inflammatory lesions resolve completely without sequelae if anti-TNF therapy is introduced before new bone formation becomes largely autonomous. For an individual patient the overall development of new bone during anti-TNF therapy may therefore depend on the balance between the number of early and more mature inflammatory lesions. Clinical trials of anti-TNF agents in early spondyloarthritis together with prospective MRI studies will allow more detailed testing of this hypothesis as a major priority for the research agenda in spondyloarthritis.

Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: A study of radiographic progression, inflammation on magnetic resonance imaging, and c

To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy. MRIs were evaluated according to the Berlin sacroiliac (SI) joint and spine inflammation scoring method at baseline, week 22, and week 46. Radiographs were evaluated using the modified Stoke Ankylosing Spondylitis Spine Score at baseline and week 46. Patients with new syndesmophytes were identified. Biomarker levels in patients were compared to levels in healthy subjects. Higher pretreatment MRI inflammation scores for SI joints and/or lumbar spine were associated with higher baseline CTX-II levels, but not with higher levels of biomarkers of inflammation and bone turnover. During treatment with TNFα inhibitors, a decrease in MRI inflammation scores from baseline to week 22 was associated with larger percentage decreases in and a normalization of CRP and IL-6 levels as compared to an increase or no change in MRI scores. Development of new syndesmophytes was associated with larger percentage decreases in CRP and IL-6 levels and an increase in osteocalcin level, and with normalization of CRP and IL-6 levels from baseline to week 22. Persistent systemic inflammation was associated with radiographic nonprogression. Our findings indicate that inflammation on baseline MRI is associated with higher CTX-II levels. Radiographic progression is associated with decreased systemic inflammation, as assessed by IL-6 and CRP levels and MRI, supporting the notion of a link between the resolution of inflammation and new bone formation in SpA patients during anti-TNFα therapy.

Development of new syndesmophytes and bridges in ankylosing spondylitis and their predictors: a longitudinal study

BackgroundStructural damage of the spine in ankylosing spondylitis (AS) is associated with worse physical function and impaired spinal mobility. Knowledge about predictors of new syndesmophyte formation is limited.ObjectivesTo assess the...

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

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. 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. 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 feature on baseline MRI (3.1% [P = 0.008] and 1.4% [P = 0.0002], respectively). Adjusting for within-patient variations in baseline syndesmophytes/ankylosis, vertebral corners that were fat-positive/inflammation-positive significantly predicted new syndesmophytes, with an odds ratio (OR) of 7.6 (95% confidence interval [95% CI] 1.5-38.5 [P = 0.01]), while a model that included baseline variations in both fat and inflammation showed an OR of 5.8 (95% CI 2.2-15.3 [P < 0.001]) for inflammation and an OR of 1.9 (95% CI 0.9-4.1 [P = 0.1]) for fat. Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.

Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis: Evidence of a relationship between inflammation and new bone formation

To determine whether a vertebral corner that demonstrates an active corner inflammatory lesion (CIL) on magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) is more likely to evolve into a de novo syndesmophyte visible on plain radiography than is a vertebral corner that demonstrates no active inflammation on MRI. MRI scans and plain radiographs were obtained for 29 patients recruited into randomized placebo-controlled trials of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy. MRI was conducted at baseline, 12 or 24 weeks (n=29), and 2 years (n=22), while radiography was conducted at baseline and 2 years. A persistent CIL was defined as a CIL that was found on all available scans. A resolved CIL was defined as having completely disappeared on either the second or third scan. A validation cohort consisted of 41 AS patients followed up prospectively. Anonymized MRIs were assessed independently by 3 readers who were blinded with regard to radiographic findings. New syndesmophytes developed significantly more frequently in vertebral corners with inflammation (20%) than in those without inflammation (5.1%) seen on baseline MRI (P<or=0.008 for all reader pairs). They also developed more frequently in vertebral corners where inflammation had resolved than in those where inflammation persisted after anti-TNF treatment. This was confirmed in the analysis of the prospective cohort, in which significantly more vertebral corners with inflammation (14.3%) compared with those without inflammation (2.9%) seen on baseline MRI developed new syndesmophytes (P<or=0.003 for all reader pairs). Our findings indicate that a syndesmophyte is more likely to develop from a prior inflammatory lesion, supporting a relationship between inflammation and ankylosis.