| 1. |
- Deminger, Anna, 1973, et al.
(författare)
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A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis
- 2018
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex. Methods: Swedish patients with AS, age (mean +/- SD) 50 +/- 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples. Results: Of 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 +/- 2.8 vs. 1.2 +/- 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression >= 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women. Conclusion: This first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.
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| 2. |
- Deminger, Anna, 1973, et al.
(författare)
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Factors associated with changes in volumetric bone mineral density and cortical area in men with ankylosing spondylitis : a 5-year prospective study using HRpQCT
- 2022
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:1, s. 205-216
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Patients with ankylosing spondylitis (AS) have impaired volumetric bone mineral density (vBMD) assessed with high-resolution peripheral computed tomography (HRpQCT). This first longitudinal HRpQCT study in AS shows that cortical and trabecular vBMD decreased at tibia and that signs of inflammation were associated with cortical bone loss at tibia and radius.Introduction: Patients with ankylosing spondylitis (AS) have reduced volumetric bone mineral density (vBMD) in the peripheral skeleton assessed with high-resolution peripheral quantitative computed tomography (HRpQCT). The aims were to investigate longitudinal changes in vBMD, cortical area, and microarchitecture and to assess factors associated with changes in vBMD and cortical area in men with AS.Methods: HRpQCT of radius and tibia was performed in 54 men with AS at baseline and after 5 years. Univariate and multivariable linear regression analyses were used.Results: At tibia, there were significant decreases exceeding least significant changes (LSC) in cortical and trabecular vBMD, mean (SD) percent change −1.0 (1.9) and −2.7 (5.0) respectively (p<0.001). In multivariable regression analyses, increase in disease activity measured by ASDAS_CRP from baseline to follow-up was associated with decreases in cortical vBMD (β −0.86, 95% CI −1.31 to −0.41) and cortical area (β −1.66, 95% CI −3.21 to −0.10) at tibia. At radius, no changes exceeded LSC. Nonetheless, increase in ASDAS_CRP was associated with decreases in cortical vBMD, and high time-averaged ESR was associated with decreases in cortical area. Treatment with TNF inhibitor ≥ 4 years during follow-up was associated with increases in cortical vBMD and cortical area at tibia, whereas exposure to bisphosphonates was associated with increases in cortical measurements at radius. No disease-related variables or treatments were associated with changes in trabecular vBMD.Conclusion: The findings in this first longitudinal HRpQCT study in patients with AS strengthen the importance of controlling disease activity to maintain bone density in the peripheral skeleton.
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| 3. |
- Deminger, Anna, 1973, et al.
(författare)
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Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline : results from a 5-year prospective study
- 2017
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Ingår i: Arthritis Research & Therapy. - London, United,Kingdom : BioMed Central. - 1478-6354 .- 1478-6362. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes.METHODS: In a longitudinal study, BMD in Swedish AS patients, 50 ± 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes.RESULTS: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, β = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (β = 3.15, p = 0.012).CONCLUSION: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.
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| 4. |
- Jansson, John-Olov, 1954, et al.
(författare)
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Leukemia inhibitory factor reduces body fat mass in ovariectomized mice
- 2006
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Ingår i: Eur J Endocrinol. - : Oxford University Press (OUP). - 0804-4643. ; 154:2, s. 349-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Ovariectomized (OVX) mice are known to gain body fat while exposure to estrogens decreases fat mass. We have previously shown that estrogen replacement therapy enhances the expression of receptors for the cytokine, leukemia inhibitory factor (LIF). LIF and other cytokines acting via the gp130 signal transducing receptor have been reported to decrease obesity. In the present study, we investigated whether LIF treatment can reduce obesity in OVX mice. DESIGN: Eight-week-old female C57Bl/6 mice were OVX or sham-operated. The mice were treated with LIF, 30 microg/kg or PBS via daily i.p. injections for 15 days (n = 9-10). METHODS: Dual X-ray absorptiometry and computerized tomography. RESULTS: We found that LIF treatment of OVX mice caused a significant reduction in the weight of white fat depots (P = 0.017) and serum leptin levels (P = 0.011). LIF also caused a significant decrease in brown fat mass (P = 0.036). Treatment with LIF decreased thymus weight but did not affect crown-rump length, femur length, trabecular bone mineral density or the weight of several non-fat organs including the uterus. CONCLUSION: The cytokine, LIF, decreases body fat mass in OVX mice, suggesting that estrogen signaling is not required for this effect.
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| 5. |
- Klingberg, Eva, et al.
(författare)
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A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin
- 2019
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map (TM) Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1-5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (<= 50 mg/kg, n = 57) and increased (>= 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI >= 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS.
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| 6. |
- Klingberg, Eva, et al.
(författare)
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A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis
- 2017
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- 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 < 200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin. Conclusions: Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD
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| 7. |
- Klingberg, Eva, et al.
(författare)
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Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study
- 2019
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Ingår i: Arthritis Res Ther. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundObesity is over-represented in patients with psoriatic arthritis (PsA) and associated with higher disease activity, poorer effect of treatment and increased cardiovascular morbidity. Studies on the effects of weight loss are however needed. This study aimed to prospectively study the effects of weight loss treatment with very low energy diet (VLED) on disease activity in patients with PsA (CASPAR criteria) and obesity (body mass index BMI 33kg/m(2)).MethodsVLED (640kcal/day) was taken during 12-16weeks, depending on pre-treatment BMI. Afterwards, an energy-restricted diet was gradually reintroduced. Weight loss treatment was given within a structured framework for support and medical follow-up.Treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs was held constant from 3months before, until 6months after baseline.Patients were assessed with BMI, 66/68 joints count, Leeds enthesitis index, psoriasis body surface area (BSA), questionnaires and CRP at baseline, 3 and 6months. Primary outcome was the percentage of patients reaching minimal disease activity (MDA) and secondary outcomes were reaching Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology (ACR) response criteria.ResultsTotally 41/46 patients completed the study, 63% women, median age 54years (IQR 48-62). At baseline increased BMI was associated with higher disease activity and poorer function.The median weight loss was 18.7kg (IQR 14.6-26.5) or 18.6% (IQR 14.7-26.3) of the baseline weight. A majority of the disease activity parameters improved significantly after weight loss, including 68/66 tender/swollen joints count, CRP, BSA, Leeds enthesitis index, HAQ and patient VAS for global health, pain and fatigue. A larger weight loss resulted in more improvement in a dose-response manner. The percentage of patients with MDA increased from 29 to 54%, (p=0.002). PsARC was reached by 46.3%. The ACR 20, 50 and 70 responses were 51.2%, 34.1% and 7.3% respectively.ConclusionsShort-term weight loss treatment with VLED was associated with significant positive effects on disease activity in joints, entheses and skin in patients with PsA and obesity. The study supports the hypothesis of obesity as a promotor of disease activity in PsA.Trial registrationClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016retrospectively registered
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| 8. |
- Wallenius, Ville, 1970, et al.
(författare)
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Interleukin-6-deficient mice develop mature-onset obesity.
- 2002
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 8:1, s. 75-9
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Tidskriftsartikel (refereegranskat)abstract
- The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obesity that was partly reversed by IL-6 replacement. The obese Il6-/- mice had disturbed carbohydrate and lipid metabolism, increased leptin levels and decreased responsiveness to leptin treatment. To investigate the possible mechanism and site of action of the anti-obesity effect of IL-6, we injected rats centrally and peripherally with IL-6 at low doses. Intracerebroventricular, but not intraperitoneal IL-6 treatment increased energy expenditure. In conclusion, centrally acting IL-6 exerts anti-obesity effects in rodents.
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| 9. |
- Wilhelmson, Anna S K, et al.
(författare)
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Testosterone is an endogenous regulator of BAFF and splenic B cell number
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibro-blastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an alpha-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.
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| 10. |
- Almehed, Katarina, 1966, et al.
(författare)
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Health-related quality of life in systemic lupus erythematosus and its association with disease and work disability.
- 2010
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Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 39:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine the health-related quality of life (HRQOL) and its relationship to disease variables, vertebral fractures, and employment status in female patients with systemic lupus erythematosus (SLE). Methods: HRQOL was assessed with the Swedish version of the Medical Outcomes Study (MOS) 36-Item Short Form Survey (SF-36) in female patients (n=163) and in age- and sex-matched controls (n=1045). Associations between the SF-36 score and demographics, disease variables, prevalent vertebral fractures, and employment status were analysed. Results: The SLE patients, aged 20 to 82 years, scored significantly lower than the controls on all SF-36 subscales. Patients with vertebral fractures were older, had greater disease damage, and lower physical functioning (PF) than patients without fractures. Of the SLE patients of working age (n=142), 54% worked full or part time. These patients scored their HRQOL significantly higher (better) than patients not working. Being able to work was significantly associated with low age and high scores in PF and role physical (RP): the area under the receiver operating characteristic (ROC) curve for these variables was 0.82, confidence interval 0.75-0.89. Conclusions: HRQOL is substantially lower in SLE than in the general population but working ability indicates better health. We encourage further research regarding the effects on HRQOL by preventive actions taken against work disability in SLE.
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