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Background:The prevalence of osteoporosis in inflammatory rheumatic diseases such as psoriatic arthritis (PsA) has not been sufficiently clarified yet, and the data in the literature are heterogeneous. In addition, it is still unclear to what extent patients with PsA differ in terms of bone density from patients with other forms of spondyloarthritis such as ankylosing spondylitis (AS).Objectives:In an interim analysis of the Rh-GIOP Study (ClinicalTrials.gov IdentifierNCT02719314), we observed that PsA patients demonstrated more frequently normal bone density than any other patient group analyzed (suffering from e.g. rheumatoid arthritis or systemic sclerosis). The main objective of this investigation was to compare bone density data from patients with PsA and AS, as both diseases belong to the spondyloarthritis group. 1100 patients with inflammatory rheumatic diseases provided the basis of Rh-GIOP, a prospective study monitoring glucocorticoid (GC)-induced osteoporosis in patients with rheumatic diseases. Rh-GIOP was established in 2015 at the Charité University Hospital. Bone mineral density data were measured by dual x-ray absorptiometry (DXA).Methods:92 patients with PsA (65% female) were compared with 51 patients suffering from AS (35% female). Potential risk and protective factors (e.g. data on GC treatment, anti-rheumatic therapy), laboratory parameters (e.g. Vitamin D, alkaline phosphatase, calcium and inflammatory markers) and functional status (e.g. Health Assessment Questionnaire, sporting activities, back pain) were compared between these groups. Statistical analysis was performed descriptively using mean and standard deviation, t-tests for metric variables, and chi-square tests for nominal variables. Due to the heterogeneous gender distribution, an additional statistical matching was performed to compare patients matched by age and gender.Results:Patients with PsA displayed significantly higher minimal T-scores than patients with AS (p=0.003) even though patients with AS were younger and more often male (pConclusion:Our results demonstrate that patients with PsA display higher bone density compared to age and gender matched patients with ankylosing spondylitis. Possible influencing factors could be the higher frequency of csDMARD use, higher BMI or the lower frequency of back pain in PsA patients. Multivariate tests and additional biomarker investigations in larger cohorts are necessary to corroborate these findings and to identify underlying pathogenic differences which could serve for an explanation.Disclosure of Interests:Desiree Freier: None declared, Edgar Wiebe: None declared, Robert Biesen: None declared, Thomas Buttgereit: None declared, Sandra Hermann: None declared, Timo Gaber: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

Background:Osteoporosis is a skeletal disease characterized by the loss of bone density resulting in an increased fracture risk. Female sex, advanced age, Caucasian ancestry, previous history of fractures, menopause and certain genetic factors predispose for osteoporosis. In addition, recent studies could prove that chronic inflammatory diseases such as Rheumatoid Arthritis (RA) and long-term treatment with higher doses of glucocorticoids (GCs) represent independent risk factors for the development of osteoporosis. On the other hand, the intake of vitamin D, a calcium-rich diet and physical exercise can be protective. Data describing the prevalence of osteoporosis in patients with other rheumatic diseases like psoriatic arthritis (PsA) are lacking.Objectives:We compared the prevalence of osteopenia and osteoporosis in patients with RA and PsA, respectively, based on data obtained from our ongoing prospective monocentric study Rh-GIOP investigating glucocorticoid (GC)-induced osteoporosis in patients with different rheumatic diseases (NCT02719314).Methods:Bone mineral density data measured by dual x-ray absorptiometry (DXA) in patients with PsA (n=92) were compared with data measured in 92 age- and gender-matched patients with RA. The results were analysed with respect to clinical and laboratory parameters such as data on GC treatment (frequency, duration defined as start of treatment until timepoint of measurement, actual and cumulative dose), csDMARD and bDMARD (including as well tsDMARDs) therapy, serological parameters (Vitamin D, alkaline phosphatase, calcium, inflammatory markers and rheumatoid factor) and functional status (e.g. Health Assessment Questionnaire (HAQ), sporting activities). Statistical analyses were performed descriptively using mean and standard deviation, t-tests for metric variables, and chi-square tests for nominal variables. For subgroup analyses with less than 30 patients per group, tests for non-normally distributed data were used due to the lower test power.Results:RA patients showed significantly lower means of bone density values (minimal T-score, p=0.03) than PsA patients leading to a higher frequency of osteopenic bone densities (pConclusion:The lower bone density in RA patients seems not to be fully explained by higher GCCD, disease duration or higher levels of inflammation. However, RA patients had a higher frequency of current GC intake. Additionally, differences in bone density between the two groups could be related to the higher number of bDMARD therapies in PsA patients, but further investigations like multivariate analyses with higher numbers of patients are necessary. Furthermore there is more need for research on possible molecular and genetic factors in PsA, which are protecting from low bone density.Disclosure of Interests:Desiree Freier: None declared, Edgar Wiebe: None declared, Robert Biesen: None declared, Thomas Buttgereit: None declared, Sandra Hermann: None declared, Timo Gaber: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

Background:Rheumatoid arthritis (RA) is associated with increased systemic bone loss, leading to a high risk for fragility fractures. Especially anti-citrullinated protein antibody (ACPA) positivity is considered a risk factor for local bone erosions and systemic bone loss1.Objectives:The purpose of this study was to compare ACPA positive versus ACPA negative RA patients in terms of the prevalence of osteoporosis and fragility fractures and to identify differences in underlying risk factors that influence bone health.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic rheumatic diseases or psoriasis treated with glucocorticoids (GC). In this cross-sectional analysis, we performed a matched-pair analysis, matching 114 ACPA positive to 114 ACPA negative RA patients according to age (5-year-steps), sex, and body mass index (BMI, 2-unit-steps). Descriptive analyses were performed, with values displayed as mean ± standard deviation for continuous variables. Non-parametric tests were used at a two-sided significance level of 5% to compare differences in underlying and potential risk factors without adjustment for multiple testing.Results:At same mean age (63.9 ±10.2 years) and BMI (27.9 ±5.6kg/m2), the matched groups had a female proportion of 82.5%. APCA positive patients had a significantly longer mean disease duration (13.9 vs 9.9 years, pConclusion:In a cross-sectional analysis of our cohort, the prevalence of osteoporosis and fragility fractures was similar between ACPA positive and ACPA negative RA patients, despite longer disease duration and GC-treatment in ACPA positive patients. This is remarkable since it implies that ACPA negative patients are at a similar risk for osteoporosis and associated fractures. Optimal management of disease activity with or without GCs may represent a mainstay in preventing disease-related comorbidities such as osteoporosis.References:[1]Steffen, U., Schett, G., & Bozec, A. (2019). How Autoantibodies Regulate Osteoclast Induced Bone Loss in Rheumatoid Arthritis. Frontiers in immunology, 10, 1483. doi:10.3389/fimmu.2019.01483Disclosure of Interests:Edgar Wiebe: None declared, Desiree Freier: None declared, Dörte Huscher: None declared, gloria dallagiacoma: None declared, Robert Biesen: None declared, Sandra Hermann: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

Background:Rheumatic diseases are associated with increased systemic bone loss and fracture risk related to chronic inflammation, disease-specific, general and demographic risk factors as well as treatment with glucocorticoids (GC). Yet, there is evidence that GCs may, by adequately suppressing systemic inflammation, also have a positive effect on bone mineral density (BMD) and fracture risk1.Objectives:The purpose of this study was to investigate the prevalence of osteoporosis and fragility fractures in patients with inflammatory rheumatic diseases and to analyze the impact that treatment with GCs, other known risk factors and preventive measures have on bone health in these patients.Methods:Rh-GIOP is an ongoing prospective observational study collecting and analyzing disease- and bone-related data from patients with chronic inflammatory rheumatic diseases and psoriasis treated with GCs. In this cross-sectional analysis, we evaluated the initial visit of 1091 patients. A multivariate linear regression model with known or potentially influential factors adjusted for age and sex was used to identify predictors of BMD as measured by dual-energy X-ray absorptiometry (DXA). Multiple imputation was applied for missing baseline covariate data.Results:In the total cohort of 1091 patients (75% female of which 87.5% were postmenopausal) with a mean age of 62.1 (±13.2) years, the prevalence of osteoporosis by DXA was 21.7%, while fragility fractures have occurred in 31.2% of the study population (6.7% vertebral, 27.7% non-vertebral). Current GC therapy was common (64.9%), with a median daily dose of 5.0mg [0.0;7.5], a mean life-time total GC dose of 17.7g (±24.6), and a mean GC therapy duration of 7.8 years (±8.5). Bisphosphonates were the most commonly used anti-osteoporotic drug (12.6%).Multivariate analysis showed that BMD as expressed by the minimum T-Score at all measured sites was negatively associated with higher age, female sex and menopause as well as Denosumab and Bisphosphonate treatment. A positive association with BMD was found for body mass index as well as current and life-time (cumulative) GC dose. While comedication with proton-pump-inhibitors significantly predicted low bone mass, concomitant use of non-steroidal anti-inflammatory drugs showed a positive association with BMD. Of the measured bone-specific laboratory parameters, higher alkaline phosphatase levels were determinants of low DXA-values, while the association was positive for gamma-glutamyltransferase.BMD was neither predicted by duration of GC treatment nor by treatment with disease modifying anti-rheumatic drugs.Predictive variables for BMD differed at the respective anatomical site. While treatment with Denosumab predicted low bone mass at the lumbar spine and not at the femoral neck, the opposite was true for health assessment questionnaire (HAQ) score. Current and life-time GC-dose as well as direct sun-exposure of more than 30 minutes daily were positively associated with bone mass at the femoral sites only.Conclusion:This cross-sectional analysis of a prospective cohort study quantified the prevalence of osteoporosis and identified predictive variables of BMD in patients with rheumatic diseases.Multivariate analyses corroborated low BMD to be predicted by traditional factors like age, female sex and menopause but showed current and well as life-time GC dose to be positively associated with BMD in our cohort of patients with chronic inflammatory rheumatic diseases. This suggests that optimal management of disease activity with GCs might be beneficial in order to avoid bone loss due to inflammation.References:[1]Güler-Yüksel et al. “Glucocorticoids, Inflammation and Bone.” Calcified Tissue International (January 08 2018).Disclosure of Interests:Edgar Wiebe: None declared, Desiree Freier: None declared, Dörte Huscher: None declared, Robert Biesen: None declared, Sandra Hermann: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi.

Background and objectives Flow cytometry offers quantification of multidimensional characteristics at single cell level for millions of cells. Multiplex flow cytometry or mass cytometry enable to screen for dozens of antigens on a single cell. Conventional analysis of such data requires user defined gating and is time consuming. Using the new bioinformatics tools immunoClust for automated and user-independent analysis, we investigated the complexity of phenotypic changes of immune cells upon migration from peripheral blood (PB) to synovial fluid (SF) in rheumatoid arthritis (RA). Materials and methods Seven paired samples of PB and SF from RA patients were stained in 10 different antibody cocktails and data investigated by the newly developed immunoClust pipeline for sample specific populations and differences between PB and SF. Population clustering and comparative meta-clustering assume finite mixture models and use Expectation Maximisation (EM)-iterations with integrated classification likelihood (ICL) criterion to stabilise the number of reasonable clusters. For meta-clustering, a probability measure on Gaussian distributions was invented, which is based on the Bhattacharyya Coefficients. Meta-clusters were manually annotated and classified. The clustering tools of immunoClust are available as open source R-package in Bioconductor. Results Automated clustering with 46 different surface markers detected all major leukocyte subsets and several activation markers in PB and SF samples including neutrophils, eosinophils, T-cells and sub-populations, monocytes, B-cells, NK-cells and dendritic cells. The comparison revealed about 10 highly significant changes per staining cocktail. For example the percentage of monocytes/macrophages was doubled in SF and dominated by CD16+ cells, the frequencies of effector/memory subpopulations of lymphocytes were increased and naive T-cells and B-cells were almost completely absent. In addition several unexpected populations like CCR7+ monocytes were found in SF only. Conclusion In conclusion, the results give a reasonable starting point to face the next field of research for marker detection and prediction analysis. The data will be further exploited for changes in cell activation and differentiation in SF in order to screen for these populations also in PB. This approach is not only applicable to fluorescence-based flow data but could be also used for multi-parametric data sets generated by mass spectrometry-based cytometry (CyTOF).

Background In addition to joint swelling and tenderness, patients with rheumatoid arthritis (RA) commonly experience morning symptoms of joint stiffness associated with pain that result in impaired function causing morbidity and productivity loss with early disease as well as those with low disease activity or remission1. However, the degree of morning stiffness has never been described. Objectives Although RA patients recognize morning stiffness as being one of the four most significant symptoms to manage, validated morning stiffness patient-reported outcome (PRO) measures are lacking. Therefore, we have developed an approach to objectively quantify finger joint stiffness. The device has been approved by the ethical committee for the use in patients, and has also already obtained a national technical certification. We here present the first results of an ongoing study with this device. Methods So far, nine female postmenopausal RA patients affected by morning stiffness of at least one hour agreed to participate in this study and underwent repetitive measurements of evening and on following morning cycle. These measurements quantified the passive resistance of an affected MCP joint against an externally applied torque while the finger was fixed in the device and passively moved from a completely extended position (referred to as 0°) to a flexed position of 60°. Measurement related sensors and advanced analysis algorithms for the investigation of resulting hysteresis curves enabled both the stiffness and dissipated energy to be evaluated at definite flexion-extension angles. A one-way ANOVA was then applied to test for differences in both parameters between repetitive evening and morning measurements. Results The stiffness of the MCP joint (given in Nm/°) showed highest absolute values at extreme positions, i.e. at 0° and 60°, while lower values were detected at angles in between (Figure 1). At all flexion angles except 0°, stiffness was – as expected – always more pronounced in the morning (red bars) compared with evening measurements (blue bars). The difference found at 40° was statistically significant (p=0.038). Similar results (not shown) were obtained for dissipated energy with a significantly higher value in the morning than in the evening at a flexion angle of 50° (p=0.047). Conclusions Even though the number of patients examined was low and the individual variation of absolute values between subjects is (known to be) considerable, our findings indicate that our approach is capable to differentiate stiffness and dissipated energy in the morning from that measured in the evening. The quantification of these parameters offers for the first time an option for objective evaluation the possibility to objectively evaluate and quantify this important patient-reported outcome in RA. Furthermore, such biomechanical assessments are also very likely able to quantify treatment effects on morning stiffness in the future. References Da Silva, JAP et al.: Impact of impaired morning function on the lives and well-being of patients with rheumatoid arthritis. Scand J Rheumatol. Vol. 125 (2011), pp. 6-11. Acknowledgements This study was funded by Horizon Pharma, USA. Disclosure of Interest H. Boeth: None declared, G. Duda: None declared, D. Hinzmann: None declared, S. Hermann: None declared, W. Taylor: None declared, R. Ehrig: None declared, T. Witaschek: None declared, F. Buttgereit Grant/research support from: Dr. Buttgereit received consultancy fees, honoraria and travel expenses from Merck Serono, Horizon Pharma (formerly Nitec Pharma) and Mundipharma International Ltd, and grant support from Merck Serono and Horizon Pharma