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Abstract Background The inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS. Methods We analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments. Results Patients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed. Conclusions Evidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden.

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10-115; OR, 14.90; 95% CI, 11.83-18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29-2.22) and HLA-B27 positivity (PFDR = 1.45 × 10-33; OR, 28.79; 95% CI, 16.83-49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

Purpose of Review: This study aims to review recent studies on risk factors for syndesmophyte growth in ankylosing spondylitis (AS) and on treatment effects. Recent Findings: New genetic studies, including a genome-wide association study, provided only limited evidence of specific genetic associations with radiographic severity. Measures of inflammation, including vertebral osteitis and C-reactive protein level, were strongly associated with radiographic progression, while studies of adipokines had mixed results. Mesenchymal stem cells from HLA-B27 positive AS patients were found to promote vertebral ossification via a pathway of B27 misfolding, retinoic acid receptor-β activation, and increased bone alkaline phosphatase. Low vertebral trabecular bone density is associated with syndesmophyte growth, with reciprocal effects when bridged. Several observational studies suggested radiographic severity was reduced by treatment with tumor necrosis factor inhibitors, particularly when longer than 2 years. Summary: Syndesmophyte development in AS is the result of a complex, incompletely understood, interplay of inflammatory and mechanical factors. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression.

Imaging plays a crucial role in diagnosing and forecasting treatment outcomes in axial spondyloarthritis. Conventional radiography may overlook patients in the initial stages of the disease, while MRI is sensitive in identifying inflammation early on. Computed tomography reliably detects structural abnormalities. Practicing rheumatologists must possess a fundamental understanding of interpreting both active inflammatory and structural lesions in axial spondyloarthritis., Competing Interests: Disclosure V. Mohan and M.C. Hwang have no financial or nonfinancial disclosures relevant to the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background S100A4 is a member of calcium binding S100 protein family well known for its role in cancer progression and metastasis. Nevertheless, S100A4 also serves as a negative regulator of bone formation. Dickkopf-1 (DKK-1), marker of bone remodelling, is also implicated in the process of syndesmophyte formation in ankylosing spondylitis. The aim of our study was to evaluate plasma levels of S100A4 in patients with axial spondyloarthritis and to determine the potential association of S100A4 with disease severity, clinical manifestations and with bone changes in a cross-sectional study. Methods Fifty-eight patients with axial spondyloarthritis and 40 healthy controls were studied. Biological samples were analysed for S100A4 and Dickkopf-1. Disease activity was assessed according to the Bath Ankylosing Spondylitis Disease Activity Index. C-reactive protein (CRP) was used as a marker of inflammation. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Results The plasma levels of S100A4 were significantly higher in patients with axial spondyloarthritis compared to heathy controls (p

Abstract 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

Abstract 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.

The breadth of bone lesion types seen in spondyloarthritis is unprecedented in medicine and includes increased bone turnover, bone loss and fragility, osteitis, osteolysis and erosion, osteosclerosis, osteoproliferation of soft tissues adjacent to bone and spinal skeletal structure weakness. Remarkably, these effects can be present simultaneously in the same patient. The search for a potential unifying cause of effects on the skeleton necessarily focuses on inflammation arising from the dysregulation of immune response to microorganisms, particularly dysregulation of TH17 lymphocytes, and the dysbiosis of established gut and other microbiota. The compelling notion that a common antecedent pathological mechanism affects existing bone and tissues with bone-forming potential (entheses), simultaneously with variable effect in the former but bone-forming in the latter, drives basic research forward and focuses our awareness on the effects on these bone mechanisms of the increasing portfolio of targeted immunotherapies used in the clinic. [ABSTRACT FROM AUTHOR]

To investigate the longitudinal relationship between trabecular bone loss and spinal progression in axial spondyloarthritis (axSpA). Patients enrolled in the Incheon Saint Mary's axSpA prospective observational cohort were evaluated. The number of syndesmophytes was assessed by two trained readers at baseline and at 2 and 4 years follow-up. Trabecular bone loss was assessed using the trabecular bone score (TBS). Disease activity measures included the BASDAI, ASDAS, CRP, and ESR. The relationship between trabecular bone loss and radiographic damage was investigated using generalized estimating equation models with 2 year time lags. Of the 245 patients included (80% males; mean (SD) age, 37 (12) years), 26 (11%) had mild trabecular bone loss (1.23–1.31) and 25 (10%) had severe trabecular bone loss (≤1.23) at baseline. Trabecular bone loss was associated with longitudinal radiographic spinal progression. Those with severe trabecular bone loss at baseline had an average 0.42 more syndesmophytes/2 years than those with normal TBS. Multivariate analysis revealed that severe trabecular bone loss compared with normal TBS resulted in an additional 0.4 syndesmophytes over 2 years. Adjusting for significant clinical factors revealed that both mild and severe trabecular bone loss were independent risk factors for new syndesmophyte formation over the next 2 years (OR [95% CI] = 2.4 [1.1–5.1]) and OR [95% CI] = 4.0 [1.6–9.7], respectively). Trabecular bone loss is longitudinally associated with spinal progression of axSpA. The more severe the trabecular bone loss, the stronger the effect on the progression of the spine. [ABSTRACT FROM AUTHOR]

Background Context: Positron emission tomography (PET) is a potential imaging technique for the diagnosis of AS. The visualization of physiological change makes PET potentially suitable for early detection of inflammatory processes, even before anatomical changes occur. Thus, PET might provide specificity via the use of receptor targeting tracers and allows quantification of disease activity in order to accurately monitor therapeutic effects.Purpose: To examine fluorine-18 sodium fluoride (18F-NaF) PET/computed tomography (PET/CT) findings in patients with inflammatory low back pain and evaluate the utility of this modality in the diagnosis of ankylosing spondylitis (AS) according to the Assessment of SpondyloArthritis International Society (ASAS) criteria.Study Design: Retrospective cohort study.Patients Sample: Sixty-eight patients who underwent 18F-NaF PET/CT imaging between April 2015 and April 2017 for evaluation of inflammatory low back pain.Outcome Measures: We defined AS-positive lesions on PET/CT as symmetric sacroiliac joint uptake that suggests sacroiliitis, syndesmophytes on the spine, and enthesopathy at any site.Methods: All patients were evaluated using the ASAS criteria and assigned to either the AS or the control group. The diagnostic criteria of AS on PET/CT images were defined as 18F-NaF PET/CT images with at least one of AS-positive findings.Results: The diagnostic rate of AS was 72.1% among the 68 patients according to the ASAS criteria. The baseline characteristics between the two groups differed significantly in terms of serum C-reactive protein levels and the presence of human leucocyte antigen-B27. Compared to the control group, in the AS group, 39 patients (79.5%) exhibited typical 18F-NaF PET/CT-positive findings, such as enthesopathy (65.3%, p=.003), syndesmophytes (61.2%, p=.006) and symmetric sacroiliitis (67.3%, p=.001). PET-positive findings had significantly higher area under the curve values than did single 18F-NaF PET/CT- positive findings, and they had the best performance for concordant diagnosis according to the ASAS criteria.Conclusions: 18F-NaF PET/CT yielded significantly different findings between the two groups according to the ASAS criteria and is useful for diagnosing AS. [ABSTRACT FROM AUTHOR]

Objectives: 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. Patients and methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine whether smoking was associated with the cumulative radiographic spinal damage and radiographic progression in patients with ankylosing spondylitis (AS). Thus, we conducted a systematic review and meta-analysis of the available studies to date. Methods: An electronic search was conducted from inception to June 21, 2016, in EMBASE, the MEDLINE/ PubMed Cochrane Central Register of Controlled Trials databases. Cross-sectional and longitudinal cohort studies investigating the association between smoking and cumulative spinal structural damage or radiographic progression were included. The outcome of interest was the presence of syndesmophytes in cross-sectional studies and radiographic progression in longitudinal studies. The quality assessment was done using the Agency for Healthcare Research and Quality checklist. The authors of potentially relevant studies were contacted regarding the unpublished data. Data from eligible cross-sectional studies were extracted and arranged in a 2x2 table. The odds ratios (ORs) and 95% confidence intervals (CIs) for the dichotomous outcome of interest were computed. Results: The combined data of eight eligible cross-sectional studies for the assessment of association between smoking and cumulative spinal structural damage suggested a significant association (OR, 2.02; 95% CI, 1.51-2.70). No significant heterogeneity was detected between studies (I2=23.0%, p=0.25). The heterogeneity of the longitudinal study data did not permit us to undertake a meta-analysis. Hence, a qualitative review was performed. Conclusion: The results of our meta-analysis show that smoking is associated with increased cumulative spinal structural damage in patients with AS. Therefore, rheumatologists should encourage patients with AS to quit smoking. [ABSTRACT FROM AUTHOR]

Objectives: The 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.Methods: We 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.Results: In 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.Conclusions: Syndesmophytes 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. [ABSTRACT FROM AUTHOR]

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<.001). 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. [ABSTRACT FROM AUTHOR]

• Costovertebral joint is commonly involved in axial spondyloarthritis (axSpA). • Costovertebral joint involvement is associated with disease features of axSpA. • Low-dose CT is recommended for evaluating costovertebral joint abnormalities. To evaluate costovertebral joint involvement in patients with axial spondyloarthritis (axSpA) and to assess its association with disease features. We included 150 patients from the Incheon Saint Mary's axSpA observational cohort who underwent whole spine low-dose computed tomography (ldCT). Costovertebral joint abnormalities were scored by two readers on a scale of 0–48 based on the presence or absence of erosion, syndesmophyte, and ankylosis. The interobserver reliability of costovertebral joint abnormalities was assessed using intraclass correlation coefficients (ICCs). Associations between costovertebral joint abnormality scores and clinical variables were evaluated using a generalized linear model. Two independent readers found costovertebral joint abnormalities in 74 (49%) patients and 108 (72%) patients. The ICCs of scores for erosion, syndesmophyte, ankylosis, and total abnormality were 0.85, 0.77, 0.93, and 0.95, respectively. For both readers, total abnormality score was correlated with age, symptom duration, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS functional index (BASFI), CT syndesmophyte score (CTSS), and number of bridging spines. Multivariate analyses showed age, ASDAS, CTSS to be independently associated with total abnormality scores in both readers. The frequency of ankylosed costovertebral joint was 10.2% (reader 1) and 17.0% (reader 2) in patients without radiographic syndesmophytes (n = 62), and 10.3% (reader 1) and 17.2% (reader 2) in patients without radiographic sacroiliitis (n = 29). Costovertebral joint involvement was common in patients with axSpA, even in the absence of radiographic damage. LdCT is recommended for evaluating structural damage in patients with clinically suspected costovertebral joint involvement. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether body mass index (BMI) is associated with parameters of disease activity and clinical manifestations in axial spondyloarthritis (axSpA). Methods: Demographic, clinical, and radiological features and disease activity indexes from 789 axSpA patients (619 males and 170 females) were obtained from the Korean College of Rheumatology BIOlogics (KOBIO) registry. BMI (kg/m2) was classified into normal (BMI <23.0), overweight (23.0-BMI <25.0), and obese (BMI -25.0). Disease activity indexes included Bath ankylosing spondylitis disease activity index (BASDAI), erythrocyte sediment rate (ESR), C-reactive protein (CRP), and ankylosing spondylitis disease activity score (ASDAS). Results: The mean BMI in patients with axSpA was 23.3 ± 3.5. 50.2% of all patients were overweight or obese. Overweight/obese patients had more syndesmophyte and less peripheral arthritis than those in normal BMI patients (p<0.001 and p<0.030, respectively). BMI was not associated with disease activity indexes in axSpA patients. Patients with syndesmophyte had higher BMI than those without syndesmophyte (24.2 ± 3.6 vs. 22.9 ± 3.3, p<0.001). Multivariate logistic regression analysis showed that increased BMI was closely related with the presence of syndesmophyte (OR=1.086, 95% CI 1.031-1.143, p=0.002). Conclusions: Our results imply that increased BMI is significantly associated with the presence of syndesmophyte, but not with disease activity in axSpA. [ABSTRACT FROM AUTHOR]

Inflammatory arthritides, such as rheumatoid arthritis (RA) and spondyloarthritides (SpA) have been associated with both localized bone resorption and/or formation, and generalized osteoporosis. Systemic inflammation may be the major driver for bone loss in arthritis. In RA and peripheral SpA the RANK-RANKL-OPG network is involved in bone resorption, while in axial SpA the Wnt-β-catenin axis and its inhibitors (DKK-1, sclerostin) are the most relevant. Targeted therapies including biologics and small molecule tyrosine kinase inhibitors may interfere with inflammatory bone metabolism. Most of these compounds are able to slow down radiographic progression and osteoporosis in arthritides. In very early cases of non-radiological SpA, there may be a window of opportunity allowing to prevent syndesmophyte formation. The inability of targeted therapies to increase the production of DKK-1 and sclerostin may explain the lack of efficacy of TNF inhibitors to halt syndesmophyte formation in SpA. Further clinical trials are needed to better understand the bone effects of targeted therapies. [ABSTRACT FROM AUTHOR]

Background: The inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS., Methods: We analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments., Results: Patients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed., Conclusions: Evidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden., (© 2023. The Author(s).)

Objectives: To compare the cardiovascular disease (CVD) risk between axial spondyloarthritis (axSpA) patients and matched controls, and to identify factors associated with increased CVD risk in axSpA patients. Methods: This cross-sectional study enrolled 185 axSpA patients who fulfilled the Assessment for Spondyloarthritis (ASAS) criteria and 925 age- and sex-matched controls. None of the subjects had a previous history of CVD or diabetes mellitus. Traditional CVD risk factors were assessed and the 10-year CVD risk was calculated using the Framingham risk score (FRS). Estimated 10-year CVD risk was compared between axSpA patients and matched controls. Disease activity and radiographic progression in the sacroiliac joint and spine of axSpA patients were evaluated at the time of CVD risk assessment. Results: High-density lipoprotein (HDL) cholesterol levels were lower in axSpA patients than in the matched controls (p=0.004); however, systolic blood pressure was higher (p50.001). The FRS was 5.0 ± 6.6% for controls and 6.3 ± 8.7% for axSpA patients (p=0.046). Both the grade of sacroiliitis on X-ray and the number of syndesmophytes correlated with the FRS (p=0.009 and p=0.001, respectively), but disease activity variables did not. The FRS was significantly higher in axSpA patients with a greater number of syndesmophytes (p=0.035). Multivariate analysis identified the number of syndesmophytes as being independently associated with the FRS (p50.001). Conclusions: The FRS was higher in axSpA patients than in a matched general population. Radiographic progression in the spine was associated with a high estimated 10-year CVD risk. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis is an inflammatory rheumatoid disease with severe osteoporosis affecting the spine with a tendency to fracture. Cervical spine fractures resulting in posterior mediastinal hematoma are rare. We present a patient with widened mediastinum secondary to fracture of a cervical ankylosing spondylitis and discuss its presentation and the current literature on the disease. [ABSTRACT FROM AUTHOR]

Objective. 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. Methods. 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. Results. Among 60 IDSs with at least two syndesmophytes at baseline (range 2–6), there was substantial heterogeneity in both absolute (P < 0.0001) 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 by >100 mm3. 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). Conclusion. 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. [ABSTRACT FROM AUTHOR]

Abstract: We performed a pilot study to compare vertebral fracture assessments (VFA) and lateral X-rays in terms of inter- and intraobserver reliability and degree of correlation for the detection of syndesmophytes in ankylosing spondylitis (AS). We recruited 19 patients with AS and recent lumbar or cervical lateral X-rays with at least one syndesmophyte. Each patient underwent dual-energy X-ray absorptiometry with measurement of bone mineral density and dorso-lumbar VFA. Intra- and interreader reliability for VFA and X-rays were measured using 2 independent, blinded observers and Cohen's kappa values. An adapted modified Stoke Ankylosing Spondylitis Spinal Score (amSASSS) was generated with each method, and these 2 values correlated. For X-rays, intraobserver and interobserver agreement were 94.3% (κ = 0.83) and 98.6% (κ = 0.96), respectively; for VFA, corresponding values were 92.8% (κ = 0.79) and 93.8% (κ = 0.82). Overall agreement between the 2 techniques was 88.6% (κ = 0.72). The Pearson correlation coefficient for the 2 methods was 0.95 for the modified Stoke Ankylosing Spondylitis Spinal Score . Per dual-energy X-ray absorptiometry−generated bone mineral density, >50% of patients were osteopenic and 10% osteoporotic. In terms of reproducibility and correlation with X-rays, performing a VFA appears to be a candidate for assessing radiographic damage in AS, thought further research is necessary to justify this indication. [Copyright &y& Elsevier]