Machine learning models with time-series clinical features to predict radiographic progression in patients with ankylosing spondylitis.

Objective: Ankylosing spondylitis (AS) is chronic inflammatory arthritis causing structural damage and radiographic progression to the spine due to repeated and continuous inflammation over a long period. This study establishes the application of machine learning models to predict radiographic progression in AS patients using time-series data from electronic medical records (EMRs). Methods: EMR data, including baseline characteristics, laboratory findings, drug administration, and modified Stoke AS Spine Score (mSASSS), were collected from 1,123 AS patients between January 2001 and December 2018 at a single center at the time of first (T1), second (T2), and third (T3) visits. The radiographic progression of the (n+1)th visit (Pn+1=(mSASSSn+1-mSASSSn)/(Tn+1-Tn)≥1 unit per year) was predicted using follow-up visit datasets from T1 to Tn. We used three machine learning methods (logistic regression with the least absolute shrinkage and selection operation, random forest, and extreme gradient boosting algorithms) with three-fold cross-validation. Results: The random forest model using the T1 EMR dataset best predicted the radiographic progression P2 among the machine learning models tested with a mean accuracy and area under the curves of 73.73% and 0.79, respectively. Among the T1 variables, the most important variables for predicting radiographic progression were in the order of total mSASSS, age, and alkaline phosphatase. Conclusion: Prognosis predictive models using time-series data showed reasonable performance with clinical features of the first visit dataset when predicting radiographic progression.

Radiographic involvement of cervical facet joints in ankylosing spondylitis: a longitudinal analysis in correlation with vertebral body lesions.

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.

Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis.

This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) (January 2001-December 2018) to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data, including serum ALP levels, were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels calculated for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, those having the highest beta coefficient with the mSASSS were selected in the correlation between ALP and longitudinal mSASSS. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients (mean follow-up, 8.20 [standard deviation: 2.85] years). The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level at 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (ß = 0.021, 95% confidence interval: 0.017-0.025, p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.

Clinical and genetic factors associated with radiographic damage in patients with ankylosing spondylitis.

OBJECTIVES: To identify clinical and genetic factors associated with severe radiographic damage in patients with ankylosing spondylitis (AS). METHODS: We newly generated genome-wide single nucleotide polymorphism data (833K) for 444 patients with AS. The severity of radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). To identify clinical and genetic factors associated with severe radiographic damage, multiple linear regression analyses were performed. Human AS-osteoprogenitor and control-osteoprogenitor cells were used for functional validation. RESULTS: The significant clinical factors of final mSASSS were baseline mSASSS (ß=0.796, p=3.22×10-75), peripheral joint arthritis (ß=-0.246, p=6.85×10-6), uveitis (ß=0.157, p=1.95×10-3), and smoking (ß=0.130, p=2.72×10-2) after adjusting for sex, age and disease duration. After adjusting significant clinical factors, the Ryanodine receptor 3 (RYR3) gene was associated with severe radiographic damage (p=1.00×10-6). For pathway analysis, the PI3K-Akt signalling pathway was associated with severe radiographic damage in AS (p=2.21×10-4, false discovery rate=0.040). Treatment with rhodamine B, a ligand of RYR3, dose-dependently induced matrix mineralisation of AS osteoprogenitors. However, the rhodamine B-induced accelerated matrix mineralisation was not definitive in control osteoprogenitors. Knockdown of RYR3 inhibited matrix mineralisation in SaOS2 cell lines. CONCLUSIONS: This study identified clinical and genetic factors that contributed to better understanding of the pathogenesis and biology associated with radiographic damage in AS.

The impact of smoking status on radiographic progression in patients with ankylosing spondylitis on anti-tumor necrosis factor treatment.

Background: Ankylosing spondylitis (AS) is characterized by back pain which can lead to spinal ankylosis. Anti-tumor necrosis factor (TNF) dramatically alleviates symptoms, but spinal damage can still be progressive even during anti-TNF treatment. Smoking is a one of well-known risk factors for structural damage in AS. However, it has not been confirmed that smoking can affect radiographic progression even during anti-TNF treatment. Objective: To investigate factors associated with radiographic progression during anti-TNF treatment with a focus on smoking status which is known as one of poor prognostic factors for AS. Materials and methods: We conducted a retrospective cohort study of AS patients who began the first-line anti-TNF treatment between 2001 and 2018 according to availability of smoking data. All enrolled patients were observed until the last visit, the first-line anti-TNF discontinuation, or December 2019. Radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The mSASSS progression rate (units/year) was calculated using the baseline mSASSS, the final mSASSS during observation period, and the duration between them. Univariable and multivariable logistic regression analyses were performed to identify associated factors of mSASSS progression rate > 1 unit/year. Results: Among 459 AS patients, 185 (40.3%) patients were never smokers, 62 (13.5%) were ex-smokers and 212 (46.2%) were current smokers at baseline. Ex- and current smokers had higher mSASSS progression rates than never smokers [never smoker 0.1 (0.0-0.7), ex-smoker 0.6 (0.0-1.5), and current smoker 0.6 (0.0-1.5) units/year, P < 0.001]. In the multivariable logistic analysis, current smoking [adjusted odds ratio (OR) 1.69, 95% CI 1.01-2.82, P = 0.047] and higher baseline mSASSS [adjusted OR 1.03, 95% CI 1.01-1.04, P < 0.001] were associated with a mSASSS progression rate > 1 unit/year. Conclusion: Current smoking is a modifiable risk factor for radiographic progression in patients with AS on anti-TNF treatment. Quitting smoking should be strongly recommended.

A pilot study on deep learning-based grading of corners of vertebral bodies for assessment of radiographic progression in patients with ankylosing spondylitis.

Background: Radiographs are widely used to evaluate radiographic progression with modified stoke ankylosing spondylitis spinal score (mSASSS). Objective: This pilot study aimed to develop a deep learning model for grading the corners of the cervical and lumbar vertebral bodies for computer-aided detection of mSASSS in patients with ankylosing spondylitis (AS). Methods: Digital radiographic examination of the spine was performed using Discovery XR656 (GE Healthcare) and Digital Diagnost (Philips). The disk points were detected between the bodies using a key-point detection deep learning model from the image obtained in DICOM (digital imaging and communications in medicine) format from the cervical and lumbar spinal radiographs. After cropping the vertebral regions around the disk point, the lower and upper corners of the vertebral bodies were classified as grade 3 (total bony bridges) or grades 0, 1, or 2 (non-bridges). We trained a convolutional neural network model to predict the grades in the lower and upper corners of the vertebral bodies. The performance of the model was evaluated in a validation set, which was separate from the training set. Results: Among 1280 patients with AS for whom mSASSS data were available, 5,083 cervical and 5245 lumbar lateral radiographs were reviewed. The total number of corners where mSASSS was measured in the cervical and lumbar vertebrae, including the upper and lower corners, was 119,414. Among them, the number of corners in the training and validation sets was 110,088 and 9326, respectively. The mean accuracy, sensitivity, and specificity for mSASSS scoring in one corner of the vertebral body were 0.91604, 0.80288, and 0.94244, respectively. Conclusion: A high-performance deep learning model for grading the corners of the vertebral bodies was developed for the first time. This model must be improved and further validated to develop a computer-aided tool for assessing mSASSS in the future.

Relationship Between Inflammation and Radiographic Progression in Patients With Ankylosing Spondylitis Attaining a BASDAI of Less Than 4 During Tumor Necrosis Factor Inhibitor Treatment.

OBJECTIVE: To determine the relationship between inflammation and radiographic progression over time in patients with ankylosing spondylitis (AS) attaining a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of < 4 during tumor necrosis factor inhibitor (TNFi) treatment. METHODS: Medical records data of patients with AS with BASDAI scores of < 4 during TNFi treatment were analyzed at 6-month intervals from January 2001 to December 2018. To determine the relationship between the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and C-reactive protein (CRP) over time, we fitted linear mixed models with mSASSS as the response variable, baseline mSASSS and the cumulative sum of CRP with different lag times (6, 12, 18, 24, 30, and 36 months) as fixed effects, and patients as random effects. Associations between mSASSS and the cumulative sum of CRP, or the lag times with the highest beta coefficients, were further investigated with linear mixed models that included additional clinical variables. RESULTS: A total of 2956 intervals were obtained from 333 patients. Among different lag times, the cumulative sum of log CRP in the previous 18 to 36 months associated with mSASSS showed significant beta coefficients. In the final linear mixed model, the cumulative sum of log CRP in the previous 24 months was significantly associated with mSASSS at 24 months (ß 0.04, 95% CI 0.01-0.07, P = 0.004). CONCLUSION: Remnant inflammation correlates with radiographic progression, even in patients attaining a BASDAI of < 4 during TNFi treatment. CRP is a surrogate marker for radiographic progression despite clinical improvement with TNFi treatment.

Age-stratified trends in the progression of spinal radiographic damage in patients with ankylosing spondylitis: a longitudinal study.

Objective: The objective of this study was to investigate spinal radiographic progression in specific age ranges of ankylosing spondylitis (AS) patients. Methods: Longitudinal data for 1125 AS patients at a single hospital from 2000 to 2018 were retrospectively reviewed. Radiographic intervals were obtained from patients with consecutive spinal radiographs. The radiographic progression rate was defined as the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change per year within each interval. Using generalized estimating equations (GEEs), estimated marginal means were calculated for the mSASSS progression rate across age groups after adjusting for potential confounders. Results: We obtained 4016 radiographic intervals and stratified them into five groups based on patient age at the interval start: <20 (n = 122); 20-29 (n = 1124); 30-39 (n = 1690); 40-49 (n = 794); and ⩾50 years (n = 286). The mean (SD) mSASSS progression rate for all the intervals was 0.8 (1.9). The GEE-estimated mean mSASSS progression rate increased with age, peaking in the 30-39 age group with a value of 1.15 [95% confidence interval (CI) 1.03, 1.27], and decreased slightly thereafter. In the presence of risk factors, rapid progression occurred at earlier ages: the GEE-estimated mean mSASSS progression rate in those with elevated C-reactive protein levels and preexisting syndesmophytes was 2.82 (95% CI 1.93, 3.71) in the 20-29 age group. Conclusion: Spinal structural damage in AS seems to progress most rapidly when patients are age 30-39 years. An awareness of the trends in radiographic progression with advancing age could improve understanding of the natural course of AS.

Early control of C-reactive protein levels with non-biologics is associated with slow radiographic progression in radiographic axial spondyloarthritis.

AIM: Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics. METHODS: Patients with radiographic axial spondyloarthritis who were followed up for 18 years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3 months were included. Patients with a CRP level of <0.8 mg/dL or 50% of the baseline CRP at 3 months were assigned to the controlled CRP group (n = 351), and the remaining patients were assigned to the uncontrolled CRP group (n = 452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups. RESULTS: The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term ß = -.499, 95% confidence interval -0.699 to -0.300). CONCLUSION: Controlled CRP achieved in response to initial treatment with non-biologic agents for 3 months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3 months after initial non-biologic treatment is a good predictor of radiographic progression.

Use of Quantitative Vertebral Bone Marrow Fat Fraction to Assess Disease Activity and Chronicity in Patients with Ankylosing Spondylitis.

OBJECTIVE: We quantitatively measured the fat fraction (FF) in the vertebrae of patients with ankylosing spondylitis (AS) using magnetic resonance imaging (MRI) and investigated the role of FF as an indicator of both active inflammation and chronicity. MATERIALS AND METHODS: A total of 52 patients with AS who underwent spinal MRI were retrospectively evaluated. The FF values of the anterosuperior and anteroinferior corners of the bone marrow in the L1-S1 spine were assessed using the modified Dixon technique. AS activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), AS Disease Activity Score (ASDAS), and serum inflammatory marker levels. AS disease chronicity was assessed by AS disease duration and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Univariable and multivariable regression analyses were conducted to investigate the correlation between FF and other clinical characteristics. RESULTS: The mean FF ± standard deviation of the total lumbar spine was 43.0% ± 11.3%. At univariable analysis, spinal FF showed significant negative correlation with BASDAI (ß = -0.474, p = 0.002) and ASDAS with C-reactive protein (ASDAS-CRP; ß = -0.478, p = 0.002) and a significant positive correlation with AS disease duration (ß = 0.440, p = 0.001). After adjusting for patient age, sex, and total mSASSS score, spinal FF remained significantly negatively correlated with BASDAI (ß = -0.543, p < 0.001), ASDAS-CRP (ß = -0.568, p < 0.001), and ASDAS with erythrocyte sedimentation rate (ß = -0.533, p = 0.001). Spinal FF was significantly lower in patients with very high disease activity (ASDAS-CRP > 3.5) than in those with only high disease activity (2.1 ≤ ASDAS-CRP ≤ 3.5) (p = 0.010). CONCLUSION: Spinal FF may help assess both AS disease activity and chronicity.

Low BASDAI score alone is not a good predictor of anti-tumor necrosis factor treatment efficacy in ankylosing spondylitis: a retrospective cohort study.

BACKGROUND: The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated. METHODS: We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan-Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy. RESULTS: Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011). CONCLUSIONS: A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.

Conventional disease-modifying antirheumatic drugs therapy may not slow spinal radiographic progression in ankylosing spondylitis: results from an 18-year longitudinal dataset.

OBJECTIVES: The clinical benefit of conventional disease-modifying antirheumatic drugs (cDMARDs) for treating ankylosing spondylitis (AS) is generally limited to improvements in peripheral arthritis. However, cDMARDs could be conditionally considered as alternatives to established drugs for improving axial manifestations in exceptional circumstances. However, there are few studies of the impact of cDMARDs on radiographic progression outcomes. Therefore, we investigated the effectiveness of cDMARDs on radiographic progression in AS. METHODS: Among 1280 AS patients at a single hospital from 2000 to 2018, 301 who had been treated with sulfasalazine (SSZ) or methotrexate (MTX) were enrolled. For each patient, the entire follow-up period was split into 1-year intervals. Each interval was classified as either an "on-cDMARD" interval, which was a period of treatment with SSZ alone, MTX alone, or a combination of SSZ and MTX, or an "off-cDMARD" interval, which was a period without cDMARD treatment. Radiographic progression was scored using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The relationship between cDMARD use and radiographic progression within the intervals, defined as the rate of mSASSS progression, was investigated using linear models with adjustment for potential confounding covariates and for clustering among observations from the same patient. RESULTS: The 732 on-cDMARD intervals and 1027 off-cDMARD intervals were obtained from enrolled patients. In multivariable regression analysis, there was no significant association between cDMARDs and the rate of mSASSS progression (ß = -0.081, p = 0.418). The mean adjusted mSASSS change per year was 0.610 from on-cDMARD intervals and 0.691 from off-cDMARD intervals. CONCLUSION: Treatment with cDMARDs may not reduce radiographic progression in AS patients.

Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence.

OBJECTIVES: Tumour necrosis factor inhibitors (TNFis) have been suggested to slow radiographic progression in patients with ankylosing spondylitis. However, limitations such as variations in disease activity, complex drug administration and short follow-up duration make it difficult to determine the effect of TNFis on radiographic progression. The aim of the study was to investigate whether long-term treatment with TNFis can reduce radiographic progression in patients with ankylosing spondylitis using 18-year longitudinal real-world data. METHODS: This retrospective study was conducted between January 2001 and December 2018 at a single centre. Among the 1280 patients whose electronic medical records were reviewed, data of 595 patients exposed to TNFis at least once were included. Among them, time intervals of TNFi exposure or non-exposure were determined in 338 patients ('on the TNFis' or 'off the TNFis' intervals, respectively). The difference in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change rate between 'on the TNFis' and 'off the TNFis' intervals was investigated. RESULTS: We obtained 2364 intervals of 338 patients (1281 'on the TNFis' and 1083 'off the TNFis' intervals). In the marginal structural model for inverse probability of treatment weighting, the change rate of mSASSS significantly decreased with the use of TNFis (ß=-0.112, p=0.004), and the adjusted mSASSS changes were 0.848 and 0.960 per year during 'on the TNFis' and 'off the TNFis' intervals, respectively. CONCLUSION: Compared with treatment without TNFis, treatment with TNFis slowed radiologic progression significantly.

Digital tomosynthesis as a new diagnostic tool for evaluation of spine damage in patients with ankylosing spondylitis.

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 < 0.001) and thoracolumbar (p = 0.003) junctions. With regard to facet joint damage, erosion/sclerosis of facet joints was better depicted by DTS than by radiographs in the cervical (54.4 vs. 22.1%, p < 0.001) and lumbar spine (72.1 vs. 11.8%, p < 0.001). DTS depicted more subtle damage of spinal vertebrae in patients with AS than radiographs did. Moreover, erosion/sclerosis of facet joints was better detected with DTS than with radiographs.

Loss of anterior concavity of the first sacrum can predict spinal involvement in ankylosing spondylitis.

In this study, we evaluated the frequency of squaring of the first sacrum (S1), defined as the loss of anterior concavity, in patients with ankylosing spondylitis (AS). We also determined the interobserver reliability in the assessment of S1 squaring and the relationships of S1 squaring with MRI findings and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). To this end, we performed a retrospective study of 100 patients with AS (mean age 33.2 years; range 19-57 years) and 100 control patients (mean age 35.6 years; range 19-50 years). Four experienced radiologists independently assessed the presence of S1 squaring in the AS and control groups. The frequencies of S1 squaring as scored by the four observers were 47, 48, 46, and 42 in the AS group and 3, 6, 4, and 6 in the control group. The interobserver agreement among the four observers with respect to S1 squaring was excellent (κ value 0.80) in the AS group and fair to good (κ value 0.61) in the control group. In patients with AS, the presence of S1 squaring showed fair to good agreement with the MRI changes (κ value 0.74). Moreover, the mSASSSs of patients with versus without S1 squaring were significantly different (mean 23.9 vs 7.0, p < 0.001). In conclusion, S1 squaring is relatively common in patients with AS. Moreover, S1 squaring is closely correlated with MRI changes and significantly associated with the mSASSS. Assessment of S1 squaring could be a simple method that is potentially useful for predicting early spinal structural involvement in patients with AS.

Radiologic Changes in the Symphysis Pubis of Male Patients with Ankylosing Spondylitis.

OBJECTIVE: We aimed to evaluate the involvement of the symphysis pubis in patients with ankylosing spondylitis (AS), and to assess the correlations between symphysis pubis changes and clinical findings. METHODS: We retrospectively evaluated a total of 222 male patients with AS who underwent pelvic and cervical/lumbar spine radiography at the Hanyang University Hospital for Rheumatic Diseases from August 2004 to February 2014. Radiographs were examined by 2 experienced radiologists, and radiographic damage was scored as follows: 0 (no damage), 1 (subtle irregularity and/or subchondral sclerosis), 2 (erosion), 3 (partial ankylosis), and 4 (total ankylosis). We evaluated the patients' clinical characteristics and analyzed their correlations with radiographic symphysis pubis changes. RESULTS: The mean patient age was 30.5 ± 8.3 years and mean disease duration was 7.1 ± 4.6 years; 105 patients (47.3%) exhibited radiologic damage in the symphysis pubis. Moreover, 75, 28, 0, and 2 patients had scores of 1, 2, 3, and 4, respectively. When comparing the normal (score 0) and abnormal (score 1-4) symphysis pubis groups, the latter had a longer symptom duration (10.1 ± 7.0 vs 7.6 ± 5.8 yrs, p = 0.004) and higher modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; 18.6 ± 17.0 vs. 14.3 ± 13.4, p = 0.038). Moreover, a significant correlation was noted between the radiographic symphysis pubis damage score and mSASSS (r(2) = 0.147, p = 0.029). CONCLUSION: Among male patients with AS, 47.3% exhibited symphysis pubis involvement. Moreover, a correlation was observed between the radiographic symphysis pubis and spine changes.

Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis.

BACKGROUND AND OBJECT: Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS. METHODS: A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke' Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates. RESULTS: We identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74 × 10(-4)) and rs1235192 [OR 1.92, p = 1.17 × 10(-3)]) adjusted by covariates. CONCLUSION: This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS.