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Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

Objectives To investigate the occurrence of facet joint ankylosis in the spine of patients with radiographic axial spondyloarthritis (r-axSpA) using low dose computed tomography (ldCT), and to examine the association between facet joint ankylosis and functional impairment. Methods A group of 126 patients with r-axSpA was selected from Incheon Saint Mary's axSpA observational cohort and whole spine ldCT data were examined. Facet joint (right and left, C2–S1) ankylosis was scored from 0–46 (total). The presence of facet joint ankylosis was assessed by two readers, each blinded to the patient data. The inter-reader reliability of facet joint ankylosis scoring was assessed using intraclass correlation coefficients (ICCs). The CT Syndesmophyte Score (CTSS) was assessed. Lumbar spinal mobility was evaluated using the modified Schober test. Functional impairment was measured using the Bath AS functional index (BASFI). Results The ICCs of ankylosed facet joint scores at the cervical, thoracic, lumbar and whole spine were 0.84, 0.88, 0.92 and 0.90, respectively. Facet joint ankylosis was most common in the thoracic spine. Scores for the whole spine correlated positively with the ASDAS, mSASSS and the syndesmophyte score. Multivariate analysis revealed that facet joint ankylosis was significantly associated with decreased lumbar motion. For both readers, the scores for the whole spine were independently associated with BASFI after adjusting for syndesmophyte score and disease activity. Conclusions Facet joint ankylosis in patients with r-axSpA was associated with functional impairment and spinal mobility. Facet joints should be incorporated into a structural damage assessment method.

Objectives Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes. Methods IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI and BASMI were assessed and spinal radiographs were scored for r-axSpA-related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden. Results A total of 155 patients comprising 69% men and 31% women, age [mean (s.d.)] 55.5 (11.4) years and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients [median (interquartile range), 12.9 (7.9–17.9) U/ml] compared with controls [10.9 (7.2–14.6) U/ml, P = 0.003]. IgA anti-CD74 was above the cut-off level of 20 U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls (P = 0.002). Multivariable logistic regression analyses revealed ≥1 syndesmophyte associated with IgA anti-CD74 (odds ratio 5.64; 95% CI: 1.02, 35.58; P = 0.048) adjusted for hsCRP, smoking, BMI, sex and age. No distinct pattern of IgA anti-CD74 over time was revealed. Conclusion Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes, which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.

Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, has demonstrated low radiographic progression over 4 years in patients with ankylosing spondylitis (AS). An adalimumab (tumor necrosis factor [TNF] inhibitor) biosimilar, GP2017 (SDZ-ADL; Sandoz), has been approved by the European Medicines Agency (July 2018) for use in all same indications as adalimumab, including AS. Adalimumab has also shown low long-term radiographic progression in patients with AS. Direct comparison of radiographic progression in AS between IL-17A and TNF inhibitors has not been studied. SURPASS is the first head-to-head, Phase IIIb, randomized, biologic-controlled study in AS to compare effects of secukinumab versus SDZ-ADL on spinal radiographic progression. Overall, 858 biologic-naive patients with AS with elevated high-sensitivity C-reactive protein (≥ 5 mg/L) and/or at least one syndesmophyte in the cervical/lumbar spine at baseline (without total ankylosis) were randomized (1:1:1) to subcutaneous (sc) secukinumab (300 or 150 mg) or SDZ-ADL (40 mg). Secukinumab will be administered at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks until week 100. SDZ-ADL will be administered every 2 weeks from baseline until week 102. Patients and investigators will be unblinded to drug but blinded to secukinumab doses. Spinal X-rays will be obtained at baseline, and weeks 52 and 104, sacroiliac joint (SIJ) X-rays at baseline and week 104, and magnetic resonance imaging (MRI) of SIJs and spine at baseline, weeks 16, 52, and 104. The primary endpoint is to demonstrate superiority of secukinumab (300 or 150 mg) treatment versus SDZ-ADL regarding proportion of patients with no radiographic progression (change from baseline in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤ 0.5) at week 104. Secondary endpoints include change from baseline in mSASSS, proportion of patients with syndesmophyte at baseline who develop no new syndesmophytes, reduction of osteitis on MRI of SIJs and spine (Berlin method). Assessment of SpondyloArthritis International Society (ASAS) 20/40 responses, ASAS partial remission, and AS Disease Activity Score (ASDAS) inactive disease (ASDAS

The conceptual paradigm of axial spondyloarthritis (axSpA) has evolved and now comprises an expanded spectrum that includes more females and patients with little or no radiographic changes in sacroiliitis or syndesmophyte formation in the spine.1 This broadened paradigm is often, but not always, characterized by an inflammatory magnetic resonance imaging (MRI) signature.

Machine learning is applied to characterize the risk and predict outcomes in multi-dimensional data. The prediction of radiographic progression in axial spondyloarthritis (axSpA) remains limited. Hence, we tested the feasibility of supervised machine learning algorithms to predict radiographic progression in axSpA.This is a retrospective and hospital-based study. Clinical and laboratory data obtained from two independent axSpA groups were used as training and testing datasets. Radiographic progression over 2 years was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and mSASSS worsening by ≥ two units was defined as progression. Seven machine learning models with different algorithms were fitted, and their performance for the testing dataset was assessed using receiver-operating characteristic (ROC) and precision-recall (PR) curve.The training and testing groups had equivalent characteristics, and radiographic progression was identified in 25.3% and 23.7%, respectively. The generalized linear model (GLM) and support vector machine (SVM) were the top two best-performing models with an average area-under-curve (AUC) of ROC of over 0.78. SVM had the higher AUC of PR compared with GLM (0.56 versus 0.51). Balanced accuracy was over 65% in all models. mSASSS was the most informative variable, followed by the presence of syndesmophyte(s) at the baseline and sacroiliac joint grades.Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA. Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients.Key Points• Clinical and radiographic data-driven predictive models showed reasonable performance in the prediction of radiographic progression in axSpA.• Further modelling with larger and more detailed data could provide an excellent opportunity for the clinical translation of the predictive models to the management of high-risk patients.

Background: Ankylosing spondylitis (AS) is an inflammatory autoimmune disorder that manifested with sacroiliitis at its early stage and developed extensive inflammation with syndesmophytes of the lumbar, thoracic and cervical spines at its later stage. In the present study, we characterized the trunk isometric strength in patients with AS with different disease severity, defined by the radiological images. Methods: In a cross-sectional study conducted in a university-affiliated hospital, thirty-eight male AS patients (23 in the early AS group whose radiological findings showed no syndesmophyte, Modified Stoke Ankylosing Spinal Score (m-SASSS

Ankylosing spondylitis (AS) is a chronic inflammatory disease that leads to spinal ankylosis. The receptor activator of the nuclear factor-kappa (RANK), RANK ligand, and osteoprotegerin (OPG) (RANK/RANKL/OPG) pathway plays critical roles in bone metabolism and the immune system. The current study was aimed at investigating whether six single-nucleotide polymorphisms (SNPs) within the RANK, RANKL, and OPG genes essential for bone homeostasis are associated with AS. Genotype distributions, allele and haplotype frequencies, were compared between 1120 AS patients and 1435 healthy controls and among AS patients with stratification by syndesmophyte formation, onset age, and HLA-B27 positivity. We found that RANKL SNPs were associated with AS syndesmophyte formation. Notably, the RANKL SNP haplotype rs7984870C/rs9533155G/rs9525641C was negatively associated with AS susceptibility and appeared to protect against syndesmophyte formation in AS. Functionally, RANKL promoter SNPs (rs9525641 C/T and rs9533155 G/C) affected DNA-protein complex formation and promoter activity in promoter reporter analyses. The OPG SNP haplotype rs2073618G/rs3102735T was significantly associated with HLA-B27 negativity in AS patients. Furthermore, AS patients with syndesmophyte formation had significantly lower levels of soluble RANKL levels than those without syndesmophyte formation. Our data suggested a role for RANKL in AS susceptibility and severity.

Background The effects of sacroiliitis and syndesmophyte formation on the cross-correlation between spine and hip joint kinematics in ankylosing spondylitis (AS) are poorly understood. Objective To investigate the cross-correlation between spine and hip joint kinematics differs in healthy individuals and ankylosing spondylitis patients during trunk lateral flexion. Methods Fifty AS patients and thirty-nine healthy adults (controls) were recruited from a medical center. The patients were divided into two subgroups, namely the sacroiliitis (n = 28) and syndesmophyte (n = 22) subgroups. An inertial motion system was used to record kinematic data of spine, pelvic and hip joints during lateral trunk flexion. The maximal cross-correlation coefficient (CCF) and time lag of motion between the spine and hip joint were analyzed. Results The syndesmophyte group had the smallest range of motion in all recorded motion. The sacroiliitis group exhibited higher thoracic flexion, pelvic pitch, and pelvic rotation than the other two groups. In the syndesmophyte group, the CCF between lumbar lateral flexion (LLF) and hip abduction were weakly and LLF and hip rotation were strongly correlated. Considering in time sequence, LLF occurred earlier than hip abduction and hip rotation during trunk lateral flexion; however, both AS subgroups exhibited longer time lags than in the control group. Conclusion The cross-correlation between spine and hip joint kinematics differs in healthy individuals and AS patients during trunk lateral flexion. The motion pattern changes in patients with AS of differing severity may also alter the loads on the spine and hip joints.

Objective To investigate the prevalence of and factors associated with metabolic syndrome (MetS) in patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS). Methods This cross-sectional study included PsA or AS patients who attended Siriraj Hospital (Bangkok, Thailand) during March 2014 to October 2017. The Harmonized MetS definition was used to diagnose MetS. Demographic, clinical, and spinal radiographic data were collected. Logistic regression was used to identify factors associated with MetS. Results Among 319 patients, 153 had AS and 166 had PsA. MetS was present in 43% of PsA and 19% of AS (p > 23 (odds ratio [OR]: 3.7), female gender (OR range: 3.8–3.9), and the number of syndesmophytes or ankylosis [SynAnk] (OR: 1.1) were associated with MetS among PsA patients. For AS patients, BMI > 23 (OR: 9.1) and age > 40 (OR: 4.3) were associated with MetS. Disease activity index was not associated with MetS. Conclusions MetS was significantly more prevalent in PsA than in AS. Structural change of the spine was associated with MetS in PsA. PsA patients with being female, BMI > 23 or evidence of spinal change should be informed to screen for MetS. AS patients with age > 40 or BMI > 23 should be informed to screen for MetS.

Objectives To 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. Methods At 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. Results Of 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. Conclusion In this prospective cohort study elevated s-HGF was shown to be associated with development of new syndesmophytes in men with AS.

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 the ASSERT trial (infliximab vs placebo), dual-energy X-ray absorptiometry was used to measure baseline BMD (g/cm2) of the lumbar spine L1 to L4. Syndesmophyte formation was assessed in the same vertebrae on conventional radiographs defined as an increase in modified Stoke Ankylosing Spondylitis Spine Score from 0 or 1 to 2 or 3 after 2 years. Radiographs were scored by two readers. Generalised estimating equations (GEE) adjusted for within-patient correlation across multiple vertebrae, taking potential confounders into account.ResultsWe analysed 599 vertebrae in 165 r-axSpA patients (78% male, mean (SD) age 38 (10) years, 67% with at least one syndesmophyte anywhere in the spine). In total, 24 to 74 new syndesmophytes developed in 9 (5%) to 30 (18%) patients and 13 (2%) to 39 (7%) vertebrae, if either a syndesmophyte was seen by both or only one of the readers (ie, specific and sensitive definitions) respectively. In multivariable analyses, no association was found between baseline local vertebral BMD and new syndesmophyte formation after 2 years: adjOR (95% CI): 0.56 (0.01, 44.45) (specific definition) and 0.26 (0.03, 2.63) (sensitive definition).ConclusionIn patients with active and established r-axSpA, with an observed low incidence of lumbar spine syndesmophyte formation over 2 years, no relationship was found between baseline BMD and new radiographic syndesmophyte formation at the same vertebra.

Objectives To evaluate the occurrence and progression of facet joint ankylosis in the whole spine using low-dose CT (ldCT) in radiographic axial spondyloarthritis (r-axSpA) and compare progression of facet joint ankylosis and syndesmophytes. Methods Patients with r-axSpA from the Sensitive Imaging in Ankylosing Spondylitis (SIAS) cohort underwent ldCT at baseline (n = 60) and 2 years (n = 53). Facet joints (right and left, levels C2-S1) were scored as ankylosed, not ankylosed or unable to assess. Joints that were frequently poorly visible (>15% missing), were excluded. Inter-reader reliability on the patient level was assessed with intraclass correlation coefficients (ICCs) and smallest detectable change (SDC). Ankylosis was assessed at joint level and patient level for both timepoints. Syndesmophytes were assessed with CT syndesmophyte score. Results Levels C5-T2 were difficult to assess and excluded from all further analyses. Facet joint ICCs were good to excellent for status scores (0.72–0.93) and poor to excellent for progression scores (0.10–0.91). Facet joint ankylosis was detected at every level but most frequently in the thoracic joints. In total, 48% of patients showed 2-year progression. Most progression occurred in the thoracic segment. Using SDCs as cutoff, 18% of patients had progression of facet joint ankylosis only, whereas 20% of patients had progression of syndesmophytes only. Conclusion This is the first study evaluating facet joints in the whole spine by ldCT in r-axSpA. Facet joint ankylosis was detected most often in the thoracic spine. Assessing facet joints in addition to syndesmophytes detected substantially more patients with damage progression over two years.

The purpose of this review is to report on the current status of evaluation of enthesitis with sonography. Sonography can visualize peripheral entheses in great detail since most of them are superficial. Visualization of entheses has provided insights into the pathophysiology of enthesitis and highlighted the interconnectivity of stress dissipation mechanisms about the enthesis. The primary use of entheseal sonography presently revolves around diagnostic use. There is increasing awareness of biomechanical confounders that lead to entheseal changes, which are more prevalent in males, patients with higher body mass index, and those who are more active—though there are several approaches to mitigate biomechanical confounders in sonographic evaluation. Entheseal sonography may also provide prognostic information in predicting the severity of axial syndesmophyte formation. Although entheseal outcome scoring systems are available, there is sparse data on its use as an outcome tool, and hence, this is a fertile area for future research.

International audience; Background: Ankylosing spondylitis (AS) patients seems to be at risk of osteoporosis but bone screening is not often performed. The objective was to evaluate the effect of vertebral ankylosis on scanographic bone attenuation coefficient (SBAC) on lumbar vertebrae in AS patients. Patients and methods: This study included AS patients fulfilling New York criteria who underwent both thoraco-abdomino-pelvic computed tomography and X-rays during routine follow-up. The modified stoke ankylosing spondylitis spinal score (mSASSS) was scored on X-rays, and the presence of at least one syndesmophyte (mSASSS≥2) defined mSASSS+ patients. Ankylosis of a lumbar vertebra was defined by the presence of bone bridges to its two adjacent vertebrae. The SBAC was measured from L1 to L5, and the fracture threshold was set at SBAC£145 HU. Results: A total of 73 AS patients were included (mean age: 60.3 (±10.7) years, 65 men (89%)). Sixty patients (82.2%) were mSASSS+; 13 patients (17.8%) presented ankylosis of at least one lumbar vertebra. The SBAC of each lumbar vertebra was not significantly different between mSASSS-and mSASSS+ patients. The SBAC was lower for patients with at least one bone bridge than for patients without (p

Objective To investigate whether spinal radiographic progression relates to structural damage at the sacroiliac level in axial spondyloarthritis (axSpA). Methods Patients classified as nonradiographic (nr-) and radiographic (r-) axSpA in the Swiss Clinical Quality Management cohort with radiographs performed every 2 years, scored according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), were included. The relationship between classification status and spinal progression during 2 years was investigated using binomial generalized estimating equations models with adjustment for sex, ankylosing spondylitis disease activity score (ASDAS) and tumour necrosis factor inhibitor treatment. Baseline spinal damage was considered an intermediate variable and included in sensitivity analyses. Results In total, 88 nr-axSpA and 418 r-axSpA patients contributed to data for 725 radiographic intervals. R-axSpA patients were more frequently male, had a longer disease duration and higher structural damage at baseline. Mean (SD) mSASSS change over 2 years was 0.16 (0.62) units in nr-axSpA and 0.92 (2.78) units in r-axSpA, p = 0.01. Nr-axSpA was associated with a significantly lower progression in 2 years (defined as an increase in ≥2 mSASSS units) in adjusted analyses (OR 0.33, 95%CI 0.13; 0.83), confirmed with progression defined as the formation of ≥1 syndesmophyte. Mediation analyses revealed that sacroiliitis exerted its effect on spinal progression indirectly by being associated with the appearance of a first syndesmophyte (OR 0.09, 95%CI 0.02; 0.36 for nr-axSpA vs r-axSpA). Baseline syndesmophytes were predictors of further progression. Conclusion Spinal structural damage is mainly restricted to patients with r-axSpA, leading to relevant prognostic and therapeutic implications.

Objective Familial Mediterranean Fever (FMF) is an autoinflammatory disease that is commonly present with recurrent episodes of fever, peritonitis, pleuritis or arthritis. Enthesitis and sacroilitis can also be seen in FMF. Spondylitis is a less common manifestation of joint involvement in FMF and there are controversial publications about whether this involvement is FMF-related or coincidentally. The aim of this study was to provide a comparison between ankylosing spondylitis (AS) patients and FMF patients with AS. Methods A total of 404 patients who 360 of them was AS and 44 was FMF patients with AS (in accordance with Tel Hashomer) patients with AS (in accordance with modified New York criteria) were included in this study. All cases were evaluated retrospectively and patient's demographic and clinical data were recorded. Results The mean age was 34.5 ± 8.6 years and 61.4% of patients were female in FMF group. In AS group, the mean age was 41.2 ± 10.8 years and 67.8% of patients were male. In AS group, 92% of patients had inflammatory back pain, 51% had hip pain, 30% had heel pain, 14% had peripheral arthritis and 11% had uveitis. In FMF group, 98% of patients had inflammatory back pain, 59% had hip pain, 48% had heel pain, 43% had peripheral arthritis and 4.5% had uveitis. Syndesmophyte and enthesitis on X-ray were seen in 18% and 22% of AS patients, and 7% and 41% of FMF patients with AS, respectively. There were significant differences between AS patients and FMF patients with AS in terms of heel pain (P: .017), peripheral arthritis (P: .000) and enthesitis (P: .006). Conclusion Peripheral arthritis and enthesitis were more frequent, and uveitis and syndesmophyte were less frequent in FMF patients with spondylitis than AS patients. When we look at gender differences, clinical and genetic features, it seems to be different condition from AS.

Observational study [Abstract] Objective: To describe the radiographic phenotype of axial spondyloarthritis (SpA) according to the presence of HLA-B27. Methods: An international collaboration compared the radiographic phenotype of axial SpA according to HLA-B27 status. Patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA) were collected. Radiographs were read centrally, blinded to clinical details. The symmetry of the sacroiliac joints and lumbar syndesmophytes and the morphology of syndesmophytes (typical marginal versus atypical chunky), together with the modified Stoke Ankylosing Spondylitis Spine Score and the Psoriatic Arthritis Spondylitis Radiographic Index, were recorded. Results: A total of 244 patients with PsA and 198 patients with AS were included. In PsA, 60 patients (25%) were HLA-B27 positive while in AS, 148 patients (75%) were HLA-B27 positive. Patients with HLA-B27 were younger and more often male and had a longer duration of disease. In multivariable logistic regression, HLA-B27 was significantly associated with syndesmophyte symmetry (odds ratio [OR] 3.02 [95% confidence interval (95% CI) 1.38, 6.61]) and marginal syndesmophytes (OR 1.97 [95% CI 1.16, 3.36]) but not with sacroiliac symmetry. Mean radiographic scores were higher for patients with HLA-B27. Conclusion: Patients with axial SpA who are positive for HLA-B27 have more severe radiographic damage, more marginal syndesmophytes, and more frequent syndesmophyte symmetry compared to patients who are negative for HLA-B27.

Objective To analyze the progression of spinal radiographic damage in patients with early axial spondyloarthritis (SpA). Methods Axial SpA patients from the DESIR (Devenir des Spondylarthropathies Indifferenciees Recentes) 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. Results Mean ± 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. Conclusion Spinal 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.

BackgroundEvolution of endoscopic surgery provides equivalent results to open surgery with advantages of minimal invasive surgery. The literature on technique Uniportal Full endoscopic contralateral approach is scarce.MethodsThe endoscopic contralateral approach technique applies for patients presenting with double crush syndrome with foraminal and extraforminal stenosis. The key steps focus on contralateral ventral overriding superior articular process decompression, foraminal and extraforaminal discectomy, and lateral vertebral syndesmophyte decompression leading to enlargement of the contralateral foramen and extraforamen size.ConclusionThe Uniportal Full endoscopic contralateral approach is a good alternative to open surgery or minimally invasive microscopic surgery through direct endoscopic visualization of the entire route of exiting nerve with no neural retraction allowing both lateral recess and foraminal and extraforaminal decompression all in one approach.

ObjectivesTo compare the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) with the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) for conventional radiographs (CR) in patients with ankylosing spondylitis (AS).MethodsPatients with AS in the Sensitive Imaging in Ankylosing Spondylitis cohort had lateral cervical and lumbar spine CR and whole spine ldCT at baseline and 2 years. CR and ldCT images were scored by two readers, paired by patient, blinded to time order, per imaging modality. For the total score analysis, we used average scores of readers per corner on CR or quadrant on ldCT. For the syndesmophyte analysis we used individual reader and consensus scores, regarding new or growing syndesmophyte at the same corner/quadrant.Results50 patients were included in the syndesmophyte analysis and 37 in the total score analysis. Mean (SD) status scores for mSASSS (range 0–72) and CTSS (range 0–552) at baseline were 17.9 (13.8) and 161.6 (126.6), and mean progression was 2.4 (3.8) and 17.9 (22.1). Three times as many patients showed new or growing syndesmophytes at ≥3 quadrants on ldCT compared with ≥3 corners on CR for individual readers; for consensus this increased to five times. In 50 patients, 36 new or growing syndesmophytes are seen on CR compared with 151 on ldCT, most being found in the thoracic spine.ConclusionsldCT, covering the whole spine, detects more progression in the form of new and growing syndesmophytes in patients with AS compared with CR, which is limited to the cervical and lumbar spine. Most progression occurred in the thoracic spine.

Objective: To investigate whether the impact of long-term treatment (> 3 years) with TNF inhibitors (TNFi) on radiographic progression in AS is associated with the level of acute phase reactants during therapy. Methods: One hundred and one consecutive AS patients under TNFi [65 men; age: 41.6 ± 11 years (mean ± SD), with symptom duration: 17 ± 10 years] were included in this retrospective study. Lateral X-rays of cervical and lumbar spine, obtained before TNFi initiation, were compared to those obtained after a period of 7 ± 2.5 (range: 3–15) years. The levels of CRP and ESR were evaluated every 6 months. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) assessed the radiographic damage. New syndesmophyte formation or ΔmSASSS-score/year ≥ 1 unit/year was defined as radiographic progression. Results: Forty-seven patients (46.5%) showed radiographic progression. ΔmSASS-score/year was positively correlated with both, baseline CRP (r = 0.35, P < 0.001) and ESR (r = 0.3, P < 0.01), as well as with time-averaged CRP (r = 0.3, P < 0.01). Furthermore, ΔmSASS-score/year was significantly higher (P < 0.0001) in patients with syndesmophytes at baseline [0.9 (0.4–1.8), median (IQR)] compared to those without [0 (0–0.4)]. In the multivariate logistic regression analysis, independent risk factors for spinal radiographic progression during TNFi treatment were the presence of syndesmophytes at baseline (OR: 14.7, 95%CI:4.9–44) and the time-averaged CRP > 5 mg/L (OR:7.6, 95%CI: 2.5–23). No gender differences were observed. Conclusion: In AS patients with long standing disease, radiographic progression during TNFi treatment is significantly associated with higher levels of time-averaged CRP.

Patients with spondyloarthritis (SpA) have an elevated incidence of osteoporosis and are at increased risk of pathological vertebral fracture. Evaluation of bone density by dual energy X-ray absorptiometry (DXA) has its limits in fracture prediction, already known in this population. One hypothesis is that the presence of lumbar syndesmophyte could overestimate the spine bone mineral density (BMD). Trabecular bone score (TBS) is a new texture measurement correlated with bone microarchitecture. Previous studies have shown that TBS is mildly impacted by osteoarthritis and thus could be a predictor of fracture better than spine BMD. We aimed to evaluate a male population of SpA with BMD and TBS measurement and see the impact of lumbar syndesmophytes.Two cohorts of SpA male patients (Lausanne, Sofia) with SpA disease, clinical and bone parameters (femoral neck and total spine BMD+spine TBS) were merged. We compared BMD and TBS results regarding to the presence/absence of syndesmophytes.Our study concerned 51 men [29 with lumbar syndesmophytes (L1 to L4,≥1), 22 without], fulfilling the European Spondyloarthropathy Study Group (ESSG) and the Assessment of SpondyloArthritis international Society (ASAS) criteria. Mean age was 52.18 years old (no difference between the 2 groups) and mean body mass index (BMI) 27.47kg/mOur results showed that SpA men with and without syndesmophytes have lower results compared to the normal population regarding hip BMD, spine TBS and spine BMD except for men with syndesmophytes who have a normal BMD spine T-score. These results suggest that TBS is not influenced by the syndesmophytes in opposite to spine BMD and could be measured in this population in addition to the neck BMD to assess the bone fragility.

Background Previous research indicates a role of adipokines in inflammation and osteogenesis. Hence adipokines might also have a pathophysiological role in inflammation and new bone formation in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the role of adipokine serum levels as predictors of radiographic spinal progression in patients with AS. Methods A total of 120 patients with definite AS who completed a 2-year follow up in the ENRADAS trial were included in the current study. Radiographic spinal progression was defined as: (1) worsening of the modified Stoke Ankylosing Spondylitis spine (mSASSS) score by ≥2 points and/or (2) new syndesmophyte formation or progression of existing syndesmophytes after 2 years. Serum levels of adipokines (adiponectin (APN) and its high molecular weight form (HMW-APN), chemerin, leptin, lipocalin-2, omentin, resistin, visfatin) were measured using enzyme-linked immunosorbent assays. Results There was a significant association between radiographic spinal progression and both leptin and HMW-APN. Baseline serum levels of both adipokines were lower in patients who showed radiographic spinal progression after 2 years. This association was especially evident in men; they had generally lower leptin and HMW-APN serum levels as compared to women. The inverse association between adipokines and radiographic spinal progression was confirmed in the logistic regression analysis: the odds ratios (OR) for the outcome “no mSASSS progression ≥2 points” were 1.16 (95% CI 1.03 to 1.29) and 1.17 (95% CI 0.99 to 1.38), for leptin and HMW-APN, respectively; for “no syndesmophyte formation/progression” the respective OR were 1.29 (95% CI 1.11 to 1.50) and 1.18 (95% CI 0.98 to 1.42), adjusted for the presence of syndesmophytes at baseline, C-reactive protein at baseline, sex, body mass index (BMI), non-steroidal anti-inflammatory drugs intake score over 2 years, and smoking status at baseline. Conclusion Serum leptin and HMW-APN predict protection from spinal radiographic progression in patients with AS. Women generally have higher leptin and HMW-APN serum levels that might explain why they have less structural damage in the spine as compared to male patients with AS. Trial registration EudraCT: 2007-007637-39. ClinicalTrials.gov, NCT00715091 . Registered on 14 July 2008.

Objective.We evaluated the whole-spine computed tomography (CT) findings in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome to improve our understanding of this rare disease.Methods.Whole-spine CT images obtained in 69 patients with SAPHO were reviewed. For each individual, a total of 25 vertebrae were evaluated for the distribution of affected vertebrae, CT manifestations of vertebral lesions, symmetry and location of distribution of the lesions on vertebrae, involvement pattern, and narrowing of adjacent intervertebral disc space. Paravertebral ligamentous ossifications, apophyseal joint disorders, and costovertebral joint disorders were also evaluated.Results.All the 69 patients with SAPHO exhibited abnormalities on whole-spine CT. Sixty-four had vertebral lesions, 52 had paravertebral ossifications, and 47 had both. The vertebral lesions were observed in 441 vertebrae, with a predilection for thoracic spine. The lesions exhibited a mixture of cortical erosion, reactive osteosclerosis of surrounding cancellous bone, and syndesmophyte. They may be confined to the vertebral corner (65.1%) or be extensive, involving the endplate (34.9%). Corner lesions could start in any part of the epiphyseal ring. The lesions were asymmetrically distributed. The affected vertebrae were more consecutively involved in a “kissing” appearance (78.2%). Intervertebral disc spaces were usually normal or mildly narrowed. There were 320 foci of paravertebral ossifications observed, with a predilection for the supraspinous ligament. Paravertebral ossifications were delicate and segmental. Ossifications throughout annulus fibrosis and apophyseal joint were not observed.Conclusion.Our investigation of the distributional, morphological features and the involvement pattern of spinal lesions in patients with SAPHO demonstrated distinct CT characteristics.

We aimed to compare digital tomosynthesis (DTS) with radiographs for the assessment of spinal bone damage in patients with ankylosing spondylitis (AS). The study comprised 68 patients with AS who underwent both DTS and radiographs of the cervical and lumbar spine on the same day. Spinal bone damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and the presence of facet joint damage. The Wilcoxon signed-rank test and McNemar's test were used to compare spinal bone damage between the two modalities. In 68 AS patients with mean 4.5 years of disease duration, the mean mSASSS was 11.7 ± 11.3 with radiographs and 13.1 ± 11.5 with DTS (p = 0.001). A grade 1 (erosion, sclerosis, or squaring) score in the mSASSS system was higher with DTS than with radiographs (p = 0.001), but grade 2 (syndesmophyte) and grade 3 (bridge) scores (p > 0.005 each) were not. In particular, the grade 1 score was higher with DTS than with radiographs at the cervicothoracic (p

The present study evaluated the severity of syndesmophytes and its correlation with the spinopelvic and clinical outcomes in patients with ankylosing spondylitis (AS).The data from 41 consecutive patients with AS who had undergone pedicle subtraction osteotomy surgery at our institution were reviewed. The computed tomography syndesmophyte score (CTSS), a novel method of evaluating the severity of syndesmophytes, was applied to assess the syndesmophytes of the whole, cervical, thoracic, and lumbar spine. The measured spinopelvic parameters included global kyphosis, sagittal vertical axis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope. The Oswestry disability index questionnaire, C-reactive protein, and erythrocyte sedimentation rate were used to evaluate the clinical outcome. The Pearson correlation test was performed to identify correlations between syndesmophyte severity and the spinopelvic and clinical parameters.The Pearson correlation analysis demonstrated that the whole CTSS (WCTSS), cervical CTSS, thoracic CTSS, and lumbar CTSS (LCTSS) correlated significantly with each other (P0.05). All the CTSSs correlated positively with age, disease duration, and pelvic tilt (P0.05). In addition, both sagittal vertical axis and lumbar lordosis were significantly related to the WCTSS, cervical CTSS, and LCTSS (P0.05). The Oswestry disability index correlated negatively with the WCTSS (r = -0.312; P0.05), thoracic CTSS (r = -0.314; P 0.05), and LCTSS (r = -0.343; P0.05).In advanced AS, old age and a long disease duration are risk factors for the progression of syndesmophytes. The progression of syndesmophytes might contribute to spinal sagittal malalignment. With serious syndesmophytes, pelvic retroversion seems to be the major compensatory mechanism for spinal sagittal malalignment.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS.Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months.TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP.Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.

Background The purpose of the present study was to demonstrate whether alcohol consumption could predict spinal structural damage in axial spondyloarthritis (axSpA) in a prospective cohort study. Methods AxSpA patients were enrolled from a single tertiary hospital in a prospective cohort. Baseline data were collected, and 2-year follow-up radiographic data were collected. We analyzed the progression of spinal structural damage in 278 axSpA patients and grouped them into alcohol drinkers and non-drinkers. Baseline and follow-up characteristics were compared between the two groups. Univariable and multivariable logistic regression analyses were performed to reveal predictors of spinal structural damage. Results Changes in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and syndesmophyte count over the 2-year period were more prominent in the alcohol drinker group than in the non-drinker group (2.7 ± 3.6 vs 1.5 ± 2.8, P = 0.007, 0.9 ± 1.3 vs 0.4 ± 1.2, P = 0.003). The alcohol drinker group showed more frequent significant mSASSS changes (≥ 2 units for 2 years follow-up) and new syndesmophyte/progression of pre-existing syndesmophytes than the non-drinker group (60.7% vs 29.2%, P

Ankylosing spondylitis (AS) is a form of arthritis that can lead to fusion of vertebrae and sacroiliac joints following syndesmophyte formation. The etiology of this painful disease remains poorly defined due to its complex genetic background. There are no commonly accepted methods for early diagnosis of AS, nor are there any effective or efficient clinical treatments. Several noncoding RNAs (ncRNAs) have been linked to AS pathogenesis and inflammation via selective binding of their downstream targets. However, major gaps in knowledge remain to be filled before such findings can be translated into clinical treatments for AS. In this review, we outline recent findings that demonstrate essential roles of ncRNAs in AS mediated via multiple signaling pathways such as the Wnt, transforming growth factor-β/bone morphogenetic protein, inflammatory, T-cell prosurvival, and nuclear factor-κB pathways. The summary of these findings provides insight into the molecular mechanisms by which ncRNAs can be targeted for AS diagnosis and the development of therapeutic drugs against a variety of autoimmune diseases.

Objective Uveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors. Methods DESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: P less than 0.05. Results After 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI: 15.4–22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84–1.74]/100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI. Conclusion Five-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.

Objective.Serum C-reactive protein (CRP) associates with radiographic progression in patients with ankylosing spondylitis (AS) untreated with tumor necrosis factor (TNF) antagonists. We assessed correlations between serum CRP and radiographic progression/magnetic resonance imaging (MRI)-detected inflammation after 2 years of anti-TNF therapy.Methods.Patients with active AS receiving golimumab (GOL)/placebo through Week 16 (early escape) or Week 24 (crossover by design), followed by GOL through 4 years, had sera/images obtained through Week 208. Lateral spinal radiographs and spinal MRI were scored with the modified Stoke AS Spine Score (mSASSS) and the AS spine MRI activity (ASspiMRI-a) score, respectively. ANOVA assessed differences based on CRP levels and mSASSS progression. The relationships between CRP levels and mSASSS/ASspiMRI-a were assessed by Spearman correlation and logistic regression.Results.Of the randomized GO-RAISE patients, 299 (84.0%) had pre- and posttreatment spinal radiographs. Larger proportions of patients with Week 104 CRP ≥ 0.5 mg/dl (n = 47) versus < 0.5 mg/dl (n = 236, 40.4% vs 22.9%, p = 0.0121) had mSASSS changes ≥ 2 at Week 104. Across several visits, serum CRP demonstrated weak associations with mSASSS change (rs ≤ 0.21, p < 0.05, n = 262–293) and moderate associations with ASspiMRI-a change (rs = −0.33 to 0.54, p < 0.05, n = 65–89). Higher baseline CRP was associated with increased risk for syndesmophytes at Week 104/Week 208, and large, short-term decreases in CRP from baseline to Week 14/Week 24 also yielded increased syndesmophyte formation risk.Conclusion.Elevated CRP after 2 years of anti-TNF treatment correlated with greater radiographic progression risk at 4 years. Elevated CRP at baseline or Week 14/Week 24 of anti-TNF treatment weakly predicted subsequent radiographic progression and modestly predicted residual spinal inflammation in patients with AS treated with anti-TNF. Findings are useful regarding new treatment options in patients treated with anti-TNF. ClinicalTrials.gov: NCT00265083.

Objectives To better understand the effect of TNF-α inhibitors (TNFi) on new bone formation in ankylosing spondylitis (AS) patients. Methods We systematically searched the articles in EMBASE and PubMed. Results Fifteen articles were enrolled. In all the 9 TNFi-treated cohorts, the vertebral corners with inflammatory lesions at baseline were at higher risk to develop new syndesmophytes than those without inflammatory lesions, although a few syndesmophytes also developed at the vertebral corners without inflammatory lesions at baseline. The advanced inflammatory lesions including fat deposition on baseline MRI showed a higher risk for syndesmophyte formation than the acute inflammatory lesions. Because the number of analyzed vertebral corners were too small, it might not be true that new syndesmophytes developed more frequently at the corners with inflammatory lesions completely resolved than those with persistent inflammation after TNFi treatment. Four studies with 2-year follow-up revealed null effect of TNFi on radiographic progression compared with historical controls with lower disease activity, and 3 studies with ≥ 4-year follow-up proved inhibitory effect of TNFi on new bone formation in AS patients. Patients with a delay of > 10 years in starting TNFi therapy were more likely to experience radiographic progression as compared to those who started earlier. Conclusions In TNFi treated AS patients, baseline inflammation is linked with syndesmophyte development. An earlier initiation of TNFi therapy may slow the radiographic progression in AS, and TNFi may lose its benefit of retarding new bone formation at advanced stage of AS especially after the focal fat infiltration or syndesmophyte formation.

Objective The aim of this work was to investigate the association between disease activity measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) and radiographic spinal progression in patients with early axial spondyloarthritis (axSpA). Methods Altogether, 178 patients with definite axSpA (100 with ankylosing spondylitis and 78 with non-radiographic axSpA) were included. Spinal radiographs (baseline and year 2) were assessed according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and for the presence of syndesmophytes. Clinical and lab data were collected at baseline and every 6 months thereafter. Time-averaged (over 2 years) values of the C-reactive protein based ASDAS were calculated. Results There was a clear positive association between disease activity according to ASDAS and radiographic spinal progression. In the logistic regression analysis, mSASSS progression by ≥2 points over 2 years was significantly associated with the time-averaged ASDAS: unadjusted OR=1.64 (95% CI 1.03 to 2.62), adjusted (for presence of syndesmophytes at baseline, smoking status and intake of non-steroidal anti-inflammatory drugs) OR=1.80 (95% CI 1.04 to 3.13). Syndesmophyte formation/progression demonstrated an even stronger association with the time-averaged ASDAS: unadjusted OR=2.62 (95% CI 1.46 to 4.68), adjusted OR=2.45 (95% CI 1.26 to 4.77). Conclusions Persisting high disease activity according to the ASDAS is associated with accelerated radiographic spinal progression in early axSpA.

ObjectivesThe aorta inhibits paravertebral ossification in diffuse idiopathic skeletal hyperostosis. We investigated if syndesmophytes in ankylosing spondylitis (AS) occurred less often at the vertebral rim near the aorta.MethodsWe performed thoracolumbar CT scans in 60 subjects in this cross-sectional study. The mid-thoracic spine was also scanned in 22 subjects. We divided the rim of each intervertebral disc space (IDS) into 72 angular sectors, each of 5°. We computed syndesmophyte height in each sector, and the distance from the sector to the aorta. We evaluated if syndesmophyte size or frequency in a sector was associated with its distance from the aorta.ResultsIn the 180° region of the vertebral rim centered on the sector closest to the aorta, syndesmophyte height and/or frequency varied with the distance of the sector to the aorta, with the lowest frequency and smallest mean syndesmophyte height at the sector along the rim nearest the aorta. Additionally, syndesmophytes were less common in subjects and at IDSs where the aorta was anatomically closer to the vertebra. No syndesmophytes were present in the sector closest to the aorta in subjects whose aorta-vertebral distance was less than 2 mm, but syndesmophytes were progressively more common among subjects whose aortas lay further from the rim.ConclusionsSyndesmophytes occurred less commonly and were smaller at the thoracolumbar vertebral rim near the aorta. These findings suggest that mechanical factors extrinsic to the spine and not solely vertebral inflammation, influence syndesmophyte development in AS.

Ankylosing spondylitis (AS) is a type of axial inflammation. Over time, some patients develop spinal ankylosis and permanent disability; however, current treatment strategies cannot arrest syndesmophyte formation completely. Here, we used mesenchymal stem cells (MSCs) from AS patients (AS MSCs) within the enthesis involved in spinal ankylosis to delineate that the HLA-B27–mediated spliced X-box–binding protein 1 (sXBP1)/retinoic acid receptor-β (RARB)/tissue-nonspecific alkaline phosphatase (TNAP) axis accelerated the mineralization of AS MSCs, which was independent of Runt-related transcription factor 2 (Runx2). An animal model mimicking AS pathological bony appositions was established by implantation of AS MSCs into the lumbar spine of NOD-SCID mice. We found that TNAP inhibitors, including levamisole and pamidronate, inhibited AS MSC mineralization in vitro and blocked bony appositions in vivo. Furthermore, we demonstrated that the serum bone-specific TNAP (BAP) level was a potential prognostic biomarker to predict AS patients with a high risk for radiographic progression. Our study highlights the importance of the HLA-B27–mediated activation of the sXBP1/RARB/TNAP axis in AS syndesmophyte pathogenesis and provides a new strategy for the diagnosis and prevention of radiographic progression of AS.

Background This 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. Methods One 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. Results At 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). Conclusions Low BMD and existing syndesmophytes at baseline were independently associated with the development of new syndesmophytes in young axSpA patients.

Background Ankylosing spondylitis causes structural damage and motion restriction in spine. The study was designed to assess structural damage and incoordination pattern between the spine and hip during trunk lateral bending in ankylosing spondylitis. Methods Twenty-three healthy adults and 39 adults with ankylosing spondylitis were recruited from a tertiary care medical centre. Patients with ankylosing spondylitis were divided into two subgroups: sacroiliitis or lumbar-level syndesmophytes (n = 27) and thoracic or cervical-level syndesmophytes (n = 12). An inertia motion system was used to record three-dimensional kinematic data during trunk lateral bending. Findings Significant differences were observed in lumbar spine syndesmophyte scores, sacroiliitis severity and Bath Ankylosing Spondylitis Metrology Index between the subgroups. The cervical supraspinous ligaments thickness revealed difference between the ankylosing spondylitis and control group, but the Glasgow Ultrasound Enthesitis Scoring System did not revealed difference. Motion analysis revealed that the ankylosing spondylitis group had a larger hip, cervical rotation and smaller lumbar-hip rhythm than the control group; however, the other motions of the spine and hip were smaller. The sacroiliitis or lumbar-level syndesmophytes group had the largest thoracic rotation among the three groups. Interpretation The different lumbar-hip rhythm between ankylosing spondylitis patients depends on syndesmophyte formation levels. Cervical rotation, the Schober test, the chest expansion test, and lumbar–hip rhythm can indicate the levels of bone damage in ankylosing spondylitis. Clinical examination of ankylosing spondylitis should include kinematic measures of both the spine and hips in the early disease stage.

We review new insights to syndesmophyte growth in axial spondyloarthritis revealed by computed tomography (CT). CT allows full reliable quantitation of syndesmophytes. About 70% of patients had detectable growth in syndesmophyte volume or height in 1 year. Syndesmophyte growth is not uniform, but can be highly heterogeneous even within the same disc space of the same patient. Syndesmophytes are not randomly distributed around the vertebral rim but have preferred locations (posterolateral and anterolateral) which vary along the spine. The frequency of syndesmophyte involvement also varies along the spine. It is highest at the thoracolumbar junction and higher in the thoracic than lumbar spine. CT syndesmophyte quantitation is a promising tool for studies of medications or biomarkers and their relations with syndesmophyte progression. The localization and growth patterns of syndesmophytes suggest importance for local factors such as mechanical stress.

ObjectivesTo develop the CT Syndesmophyte Score (CTSS) for low-dose CT (ldCT) to assess structural damage in the spine of patients with ankylosing spondylitis (AS) and test its reliability.MethodsPatientswith AS in the SIAS cohort had whole spine ldCT at baseline and 2 years. Syndesmophytes were scored in coronal and sagittal planes in eight quadrants per vertebral unit (VU) as absent=0, Results49 patients (mean age 50 years (SD 9.8), 84% men, 88% human leucocyte antigen B27 positive) were included. Mean (SD) scores of reader 1 were: whole spine baseline status score 163 (126) and change score 16 (21), spinal segment baseline status scores 30 (41), 97 (77) and 36 (36) and change scores 2 (7), 12 (18) and 3 (4) for the cervical, thoracic and lumbar spine, respectively. Scores of reader 2 were similar. Whole spine status score ICC was 0.99 and 0.97–0.98 for spinal segments. Whole spine change score ICC was 0.77 and 0.32–0.75 for spinal segments. Whole-spine SDC was 14.4. Score distribution pattern per VU was similar between readers.ConclusionsUsing the CTSS, new bone formation in the spine of patients with AS can be assessed reliably. Most progression was seen in the thoracic spine.

Purpose of review Computed tomography (CT) is increasingly being used in ankylosing spondylitis (AS) for imaging the spine and sacroiliac joint (SIJ). We review new insights to diagnosis and evaluation revealed by the use of CT. Recent findings Studies using low-dose CT in AS to detect syndesmophytes can image the entire spine, but semiquantitative scoring of the scans by human readers decreases the reliability and validity of this method. The thoracic spine is the segment most involved with syndesmophytes. Syndesmophytes are not randomly distributed around the vertebral rim but have preferred locations, which vary with the vertebral level and may be related to biomechanics. Examination of SIJ on abdominal CT scans has found structural changes of sacroiliitis in up to 35% of patients with inflammatory bowel disease. The significance of monosodium urate crystal deposition in the pelvis of axial spondyloarthritis patients without coexisting gout is uncertain. Summary Low-dose CT is a promising tool in AS. Studies of biomarkers or medications and their relations with syndesmophyte progression should take the thoracic spine into account. Abdominal CT scans are useful for detecting changes related to sacroiliitis.

Objectives: We quantified the expression of six well-characterized microRNAs (miRNAs) in peripheral blood mononuclear cells to see whether they can predispose to syndesmophytes in ankylosing spondylitis (AS) patients. Methods: This is a cross-sectional study involving 46 AS patients (23/23 with/without syndesmophytes) and 22 healthy controls. miRNAs expression was quantified by real-time PCR. Results: Six examined miRNAs were comparably expressed between AS patients without syndesmophytes and healthy controls (p > .05). Relative to AS patients without syndesmophytes, patients with syndesmophytes had significantly higher levels of miR-29a, miR-335-5p, miR-27a and let-7i (p = .001, .002, .013 and .029, respectively). Nine significant contributors associated with syndesmophytes in AS, including smoking, AS duration, human leukocyte antigen B27, erythrocyte sedimentation rate, C-reactive protein, miR-335-5p, miR-27a, miR-218 and sacroiliitis, were identified. The addition of miR-335-5p, miR-27a and miR-218 can significantly improve the accuracy of baseline risk factors. Based on the nine significant contributors, a nomogram was constructed, with good prediction accuracy (C-index: 0.86, p Conclusion: We provide evidence for the predisposition of miR-335-5p, miR-27a and miR-218 to syndesmophytes in AS patients, indicating a contributory role of miRNAs in the pathogenesis of syndesmophytes. Further validation is warranted.

Current emphasis on diagnosing axial spondyloarthritis (axSpA) in early stage enforced the search for sensitive and specific diagnostic algorithms with the use of imaging methods. The aim of this review was to summarise current recommendations concerning the use of imaging techniques in diagnostics and monitoring of axSpA as well as to outline possible future directions of the development in this field. MEDLINE database was searched between March and April 2018. In the first phase, such keywords were applied: ‘ASAS’, ‘EULAR’, ‘ASAS-EULAR’, ‘ASAS/OMERACT’, ‘axial spondyloarthritis’, while in the second step: ‘axial spondyloarthritis’, ‘ankylosing spondylitis’, ‘magnetic resonance imaging’, ‘computed tomography’, and ‘radiography’, ‘imaging’. An up-to-date summary of European League Against Rheumatism (EULAR) recommendations enriched with recent updates of Assessment of Spondyloarthritis International Society (ASAS) diagnostic criteria regarding imaging in axSpA course was created. Moreover, we outlined the role of new in this field, promising imaging techniques, such as diffusion-weighted imaging and dynamic contrast-enhanced sequences in magnetic resonance imaging (MRI) or low-dose computed tomography (CT). As precise monitoring of axSpA activity is vital, we reviewed the most precise methods: semiquantitative scores (e.g., Spondyloarthritis Research Consortium of Canada scores or CT Syndesmophyte Score) and quantitative analysis of MRI-based apparent diffusion coefficient or perfusion maps and enhancement curves. According to EULAR and ASAS recommendations, radiography and MRI still remain basic methods of axSpA diagnostics and monitoring. However, the knowledge of state-of-the-art international guidelines combined with the awareness of emerging imaging methods is the key to effective management of axSpA.

Background Short-term studies have demonstrated good surgical outcomes after pedicle subtraction osteotomy (PSO) in ankylosing spondylitis (AS) patients, but there is a paucity of literature focused on middle-term results, especially regarding patterns of loss of correction. The objective of this study is to assess the durability of surgical outcomes and the patterns of loss of correction in thoracolumbar kyphosis secondary to AS following lumbar PSO with over 5-year follow-up. Methods We performed a retrospective review of 155 consecutive AS patients undergoing lumbar PSO from January 2001 to December 2011. Twenty-four patients were included with an average follow-up of 6.9 years (range, 5–15 years). Radiographical evaluations included global kyphosis (GK), lumbar lordosis (LL), sagittal vertical axis, spinal-sacral angle, kyphosis of proximal non-fused segments (KPNS), angle of fused segments (AFS), osteotomized vertebra angle (OVA), distal intervertebral disc wedging (DIDW) and proximal junctional angle. Meanwhile, clinical outcomes were assessed by the Oswestry disability index (ODI) and Numerical rating scale (NRS). Results The average correction per PSO segment was 34.9°. Significant improvement in sagittal parameters were found postoperatively, and no obvious deterioration was noticed during the follow-up. Mild loss of correction in GK (2.82°) and LL (3.77°) were observed at the final follow-up (P 0.05). The ODI and NRS improved significantly from 20.6 and 6.6 preoperatively to 5.9 and 2.3 at the final follow-up (P

Objective.The biologically active molecule used in positron emission tomography (PET) for depiction of osteoblastic activity is 18F-labeled fluoride (18F-F). We examined whether inflammatory or chronic changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) and the spines of patients with active ankylosing spondylitis (AS) are linked to osteoblastic activity, assessed by PET/MRI.Methods.Thirteen patients with AS (mean age 37.8 ± 11.4 yrs, Bath AS Disease Activity Index > 4, no anti-TNF treatment) underwent 3-Tesla whole-spine and SIJ PET/MRI. Two independent readers recorded pathologic changes related to vertebral (VQ) or SIJ quadrants (SQ). Final scores were based on reader agreement.Results.A total of 104 SQ and 1196 VQ were examined. In SIJ, bone marrow edema (BME) was seen in 44.2%, fat deposition (FD) in 42.3%, and 18F-F in 46.2% SQ. BME alone was associated with 18F-F in 78.6% and FD alone in only 7.7% SQ, while the combination BME/FD was associated with 18F-F in 72.2% SQ. Erosions, sclerosis, and ankylosis alone were rarely associated with 18F-F. In the spine, BME alone was seen in 9.9%, FD in 18.2%, and 18F-F in 5.4% VQ. BME alone was associated with 18F-F in 14.3% and FD alone in 8.7% VQ, while the combination BME/FD was associated with 18F-F in 40.6% VQ.Conclusion.In this study of hybrid 18F-F PET/MRI of patients with active AS, we show that BME rather than chronic changes is associated with osteoblastic activity, while the combination of BME and FD showed the highest 18F-F uptake. The use of PET/MRI in prediction of future syndesmophyte formation in AS needs further exploration in prospective studies.

Objective.Using the 3-D imaging capability of computed tomography (CT), we developed an algorithm quantitating syndesmophyte height along the entire vertebral rim. We investigated its reliability and sensitivity to change, performed a 2-year longitudinal study, and compared it to CT measures of syndesmophyte volume.Methods.We performed thoracolumbar spine CT scans on 33 patients at baseline, Year 1, and Year 2, and computed syndesmophyte height in 4 intervertebral disc spaces (IDS). Height was computed every 5° (72 angular sectors) along the vertebral rim. These 72 measures were summed to form the circumferential height per IDS, and results from 4 IDS were summed to provide results per patient. To assess reliability, we compared results between 2 scans performed on the same day in 9 patients. Validity was assessed by associations with spinal flexibility.Results.Coefficient of variation for circumferential syndesmophyte height was 0.893% per patient, indicating excellent reliability. Based on the Bland-Altman analysis, an increase in circumferential height of more than 3.44% per patient represented a change greater than measurement error. At years 1 and 2, mean (SD) circumferential syndesmophyte height increases were 10.2% (11.7%) and 16.1% (14.0%), respectively. Sensitivity to change was 0.72 and 0.87 at years 1 and 2, respectively. Circumferential syndesmophyte height correlated with the Schober test (r = −0.56, p = 0.0003) and lateral thoracolumbar flexion (r = −0.73, p < 0.0001).Conclusion.CT-based circumferential syndesmophyte height had excellent reliability and good sensitivity to change. It was more highly correlated with spine flexibility than syndesmophyte volume. The algorithm shows promise for longitudinal studies of syndesmophyte growth.

ObjectivesTo describe the evolution of radiographic abnormalities of the spine in patients with ankylosing spondylitis (AS).MethodsPatients with AS were followed prospectively with 2 yearly radiographs for 12 years. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) was scored by two readers (R1 and R2). New syndesmophytes at uninvolved vertebral corners were computed. Radiographic progression was investigated using generalised estimating equations.Results809 radiographs (presenting 520 at 2 yearly intervals) from 186 patients (70% men, mean age 43 (SD 12) years, mean 20 (SD 12) years since symptom onset and 83% HLA-B27 positive) were included. Mean mSASSS at baseline was 11.6 (16.2). While the course of progression in individual patients was highly variable, and still occurred in patients with decades of symptom duration, mean 2 year progression was 2.0 (3.5) mSASSS units. Over the entire follow-up, at least one new syndesmophyte was found in 55% (R1) and 63% (R2) of patients (38% (R1) and 39% (R2) of all intervals). In 24% of patients (39% of intervals), there was no progression. A progression ≥5 mSASSS units occurred in 22% of patients (or in 12% of intervals). At the group level, a linear time course model fitted the data best, with a constant rate over the entire 12 year interval of 0.98 mSASSS units/year. Radiographic progression occurred significantly faster in men, in HLA-B27 positive patients and in patients with a baseline mSASSS≥10.ConclusionsLong term radiographic progression in AS is highly variable in the individual patient, more severe in HLA-B27 positive men and still occurs after decades of disease. At the group level, however, progression in AS follows an approximately linear course.

Syndesmophytes in AS typically grow slowly, but it is not known whether growth is uniform among syndesmophytes in the same intervertebral disc space (IDS) or among different IDSs in the same patient or if growth is heterogeneous. We examined the dynamics of syndesmophyte growth over 24 months using CT, with the main aim of determining if syndesmophytes in the same IDS or the same patient grow at similar rates.We performed lumbar spine CT scans on 33 patients and measured syndesmophytes in four IDSs using a validated computer algorithm. Scans were done at baseline and 12 and 24 months. We compared absolute and percentage changes in volume from baseline to 12 months and to 24 months among syndesmophytes in the same IDS and among four IDSs of each patient. We also examined whether growth among all IDSs differed between study years.Among 60 IDSs with at least two syndesmophytes at baseline (range 2-6), there was substantial heterogeneity in both absolute (P0.0001) and percentage (P = 0.0002) volume increases among syndesmophytes in the same IDS. Several IDSs had both syndesmophytes with no growth and syndesmophytes that increased by100 mm(3). Similarly there was significant heterogeneity in syndesmophyte growth among IDSs of individual patients. Increases in total syndesmophyte volume for each patient also tended to differ between study years (P = 0.07).Syndesmophytes in AS do not all grow continuously. Rates of growth over 24 months commonly differ between syndesmophytes in the same IDS and between different IDSs in the same patient, suggesting that local factors regulate syndesmophyte growth.

Objective Periostin has been shown to be involved in bone anabolism through the regulation of Wnt-β-catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes. Methods Ninety-seven consecutive AS patients (78% male) and 48 healthy controls (75% male) were included in the study. Serum periostin, dickkopf-1 (DKK-1), sclerostin and vascular endothelial growth factor (VEGF) levels were measured using commercially available enzyme-linked immunosorbent assay kits. Disease-related characteristics of patients were assessed using Ankylosing spondylitis disease activity score – C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index, Bath AS Functional Index and Bath AS metrology index. Radiographs were scored using the modified New York criteria and modified Stokes AS spinal score (mSASSS). Results Compared with control subjects, patients with AS had significantly lower serum levels of periostin (P < 0.001) and sclerostin (P < 0.001), but higher serum levels of VEGF (P < 0.001) and high-sensitivity CRP (P < 0.001). Serum periostin (P = 0.005) and sclerostin levels (P = 0.016) were significantly lower in patients with very high disease activity according to ASDAS-CRP. Current age (P = 0.009), age at symptom onset (P = 0.021) and hip joint involvement (P = 0.012) were independently associated with the development of syndesmophyte, in contrast to biomarkers of bone metabolism that we evaluated. Conclusion Our results suggest that periostin is down-regulated in AS patients with highly active disease and may contribute to disease pathogenesis through an interaction with Wnt signaling.

Objective.To determine the extent of thoracic involvement with syndesmophytes in ankylosing spondylitis (AS) relative to lumbar involvement.Methods.We performed thoracolumbar spine computed tomography (CT) and lumbar radiography on 18 patients. We quantitated syndesmophytes in 11 intervertebral disc spaces and related these to the presence of syndesmophytes on lumbar radiographs.Results.Syndesmophytes were slightly more common in the thoracic than in the lumbar spine and bridging was significantly more common. Thoracic syndesmophytes were universally present in patients without visible lumbar syndesmophytes on either radiographs or CT.Conclusion.Syndesmophytes predominate in the thoracic spine. Lumbar radiographs underestimate the degree of thoracic involvement.