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Background and objectives: Patients with ankylosing spondylitis (AS) have an increased risk of bone loss with development of osteoporosis and vertebral fractures (VFs) but also spinal new bone formation with growth of bony spurs (syndesmophytes) between the vertebrae. Measurements of spinal bone mineral density (BMD) by the routine method dual-energy x-ray absorptiometry (DXA) in anteroposterior (AP) projection can be difficult to interpret due to the spinal new bone formation. The general aims of this thesis were to study the development of bone loss and new bone formation over 5 years in patients with AS and to assess factors associated with the changes. Methods: The studies included in this thesis are based on a cohort of patients with AS according to the modified New York criteria recruited from three rheumatology clinics in western Sweden. Patients completed the same protocol at baseline and at the 5-year follow-up with assessment of BMD with DXA at the hip (femoral neck, total hip), the spine (AP, lateral) and total radius and spinal radiographs for grading of AS related spinal alterations and VFs. A group of men were randomized in an age-adjusted algorithm to undergo high-resolution peripheral quantitative computed tomography (HRpQCT) at the ultra-distal radius and tibia for assessment of volumetric BMD (vBMD), cortical area and microarchitecture. Serum hepatocyte growth factor (s-HGF) was analyzed with enzyme-linked immunosorbent assay (ELISA) in the total cohort. Results: Over 5 years, there were significant decreases in femoral neck BMD and tibia vBMD. Decreases were associated with signs of inflammation. In contrast, BMD at the total hip and the spine AP and lateral projections increased. Use of bisphosphonates was associated with increases in BMD at all measured sites except tibia. Use of tumor necrosis factor inhibitors (TNFi) was associated with increases in BMD at AP spine and tibia. Only three patients developed new VFs. AS related spinal alterations increased significantly with higher increases in men compared to women. New predictors identified for spinal radiographic progression were obesity in both sexes and use of bisphosphonates and impaired mobility in women. Among previously known predictors, baseline AS related spinal alterations was shared by sexes, whereas baseline elevated CRP and smoking were predictors in men. The biomarker s-HGF was identified as a novel independent predictor of spinal radiographic progression in men. Conclusion: The studies in this thesis suggest that the best site to assess bone loss in patients with longstanding AS is at the femoral neck and that inflammation has a negative impact on bone loss and development of AS related spinal alterations and thus is an important treatment target. The studies give further reasons to counsel the patients to stop smoking and to encourage obese patients to weight loss. Treatments with bisphosphonates and TNFi had a positive impact on BMD. Further studies are suggested regarding the role of bisphosphonates in relation to spinal radiographic progression and whether s-HGF can be useful as a predictor for spinal radiographic progression.

Additional file 1: Table S1. Comparison of the bacterial composition in patients with ankylosing spondylitis (AS, n = 150) and healthy controls (HC, n = 17). Table S2. Comparison of the bacterial composition in patients with ankylosing spondylitis (AS) with normal (≤ 50 mg/kg) versus increased (≥200 mg/kg) fecal calprotectin. Table S3. Correlations (Spearman’s Rho) between Probe Signal Intensity (PSI) of fecal bacteria and fecal calprotectin and parameters reflecting disease activity and function in 150 patients with ankylosing spondylitis. All correlations with a p-value ≤0.05 are shown. A Bonferroni corrected p-value of

Table S1. Results of the SF-36 in patients with ankylosing spondylitis and in controls from the general population. Table S2. Comparisons of variables in patients with ankylosing spondylitis with scores below or above the median PCS score. Table S3. Comparisons of variables in patients with ankylosing and spondylitis scores below or above the median MCS score. Table S4. Univariate logistic regression analyses with PCS score below the median values as dependent variable and all assessed variables as covariates. Table S5. Univariate logistic regression analyses with MCS score below the median values as dependent variable and all assessed variables as covariates. Table S6. Multivariable logistic regression analyses with PCS and MCS scores below their median values as dependent variables and demographics as covariates. (DOCX 92 kb)

BACKGROUND: Patients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD. METHODS: Fecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period. RESULTS: Fecal calprotectin >50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by