POS1002 BASELINE CALPROTECTIN AND VISFATIN LEVELS PREDICT RADIOGRAPHIC SPINAL PROGRESSION AFTER 2 YEARS IN ANKYLOSING SPONDYLITIS PATIENTS ON TNF INHIBITOR THERAPY

Background:Radiographic spinal progression determinates functional status and mobility in ankylosing spondylitis (AS)1.Objectives:To analyse whether biomarker of inflammation, bone turnover and adipokines at baseline or their change after 3 months or 2 years can predict spinal radiographic progression after 2 years in AS patients treated with TNF-α inhibitors (TNFi).Methods:Consecutive AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort2 starting TNFi between 2004 and 2012 were included. The following serum biomarkers were measured at baseline, 3 months and 2 years of follow-up with ELISA: - Markers of inflammation: calprotectin, matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF) - Markers of bone turnover: bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide (sCTX), osteocalcin (OC), osteoprotegerin (OPG), procollagen typ I and II N-terminal propeptide (PINP; PIINP), sclerostin. - Adipokines: high molecular weight (HMW) adiponectin, leptin, visfatinTwo independent readers assessed spinal radiographs at baseline and 2 years of follow-up according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Radiographic spinal progression was defined as mSASSS change ≥2 units or the formation of ≥1 new syndesmophyte over 2 years. Logistic regression was performed to examine the association between biomarker values at baseline, their change after 3 months and 2 years and radiographic spinal progression. Multivariable models for each biomarker were adjusted for mSASSS or syndesmophytes at baseline, elevated CRP (≥5mg/l), smoking status, male gender, symptom duration, BMI, and baseline biomarker level (the latter only in models with biomarker change).Results:Of the 137 included AS patients, 72% were male, 79% HLAB27+; mean age at baseline was 42 years (SD 10.8), ASDAScrp 3.8 (0.8) and mSASSS 10.6 (16.1). After 2 years of follow-up, 33% showed mSASSS change ≥2 units and 24% had developed ≥1 new syndesmophyte. Serum levels of biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, whereas adipokine levels were not altered from baseline (Figure 1).Univariable logistic regression revealed a significant association of baseline visfatin (odds ratio OR [95% confidence interval] 1.106 [1.007-1.215]) and sclerostin serum levels (OR 1.006 [1.001-1.011]) with mSASSS progression after 2 years. Baseline sclerostin levels were also associated with syndesmophyte progression (OR 1.007 [1.001-1.013]). In multivariable logistic analysis, only baseline visfatin level remained significantly associated (OR 1.465 [1.137-1.889]) with mSASSS progression. Furthermore, baseline calprotectin showed a positive association with both, mSASSS (OR 1.195 [1.055-1.355]) and syndesmophyte progression (OR 1.107 [1.001-1.225]) when adjusting for known risk factors for radiographic progression.Univariable logistic regression showed that change of sclerostin after 3 months was associated with syndesmophytes progression (OR 1.007 [1.000-1.015), change of PINP level after 2 years was associated with mSASSS progression (OR 1.027 [1.003-1.052]) and change of visfatin after 2 years was associated with both measures of radiographic progression – mSASSS (OR 1.108 [1.004-1.224]) and syndesmophyte formation (OR 1.115; [1.002-1.24]). However, those associations were lost in multivariable analysis.Conclusion:Independent of known risk factors, baseline calprotectin and visfatin levels were associated with radiographic spinal progression after 2 years of TNFi. Although biomarkers of inflammation and bone formation showed significant changes under TNFi therapy, these changes were not significantly related to radiographic spinal progression in our cohort of AS patients.References:[1]Poddubnyy et al 2018[2]Maas et al 2019Acknowledgements:Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health.Disclosure of Interests:Judith Rademacher: None declared, Mark Siderius: None declared, Laura Gellert: None declared, Freke Wink Consultant of: AbbVie, Maryna Verba: None declared, Fiona Maas: None declared, Lorraine M Tietz: None declared, Denis Poddubnyy: None declared, Anneke Spoorenberg Consultant of: Abbvie, Pfizer, MSD, UCB, Lilly and Novartis, Grant/research support from: Abbvie, Pfizer, UCB, Novartis, Suzanne Arends Grant/research support from: Pfizer.

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The degenerative changes of the sacroiliac joint after S2 alar-iliac screw placement

Journal of Neurosurgery Spine ◽

10.3171/2021.4.spine202035 ◽

2021 ◽

pp. 1-7

Author(s):

Norimasa Ikeda ◽

Shunsuke Fujibayashi ◽

Bungo Otsuki ◽

Kazutaka Masamoto ◽

Takayoshi Shimizu ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Bone Formation ◽

Sacroiliac Joint ◽

Safe Procedure ◽

Multivariate Logistic Regression ◽

Age At Surgery ◽

Iliac Screw ◽

New Onset

OBJECTIVE The goal of this study was to investigate clinical outcomes and risk factors for the progression of sacroiliac joint (SIJ) degeneration and bone formation after S2 alar-iliac screw (S2AIS) insertion. METHODS Using preoperative and follow-up CT scan findings (median follow-up 26 months, range 16–43 months), the authors retrospectively studied 100 SIJs in 50 patients who underwent S2AIS placement. The authors measured the progression of SIJ degeneration and bone formation after S2AIS insertion, postoperative new-onset SIJ pain, S2AIS-related reoperation, and instrumentation failures. Stepwise multivariate logistic regression modeling was performed to clarify the risk factors associated with the progression of SIJ degeneration. RESULTS Significant progression of SIJ degeneration was observed in 10% of the group with preoperative SIJ degeneration (p = 0.01). Bone formation was observed in 6.9% of joints. None of the patients with these radiographic changes had new-onset SIJ pain or underwent reoperation related to instrumentation failures. Multivariate logistic regression analysis revealed that preoperative SIJ degeneration (p < 0.01) and a young age at surgery (p = 0.03) significantly affected the progression of SIJ degeneration. CONCLUSIONS The progression of SIJ degeneration and bone formation neither led to major screw-related complications nor affected the postoperative clinical course during the median follow-up period of 26 months. Although S2AIS insertion is a safe procedure for most patients, the results of this study suggested that preoperative degeneration and younger age at surgery affected SIJ degeneration after S2AIS insertion. Further long-term observation may reveal other effects of S2AIS insertion on SIJ degeneration.

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994. Risk for Viral Rebound in the Era of U=U; A CNICS Analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1180 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S525-S526

Author(s):

Blake Hansen ◽

Tao Liu ◽

Lauri Bazerman ◽

Mari-Lynn Drainoni ◽

Fizza S Gillani ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Regression Model ◽

Logistic Regression Model ◽

Viral Suppression ◽

Viral Rebound ◽

Research Support ◽

Multivariable Logistic Regression Model ◽

Multivariable Logistic Regression

Abstract Background The “Undetectable equals Untransmittable (U=U)” HIV prevention campaign is a cornerstone of HIV prevention. However, there are few recommendations to guide patients and providers in U=U implementation and limited data on risk factors for viral rebound among persons eligible for U=U. Methods We conducted a retrospective multi-center study using data from the CNICS HIV research network to identify risk factors for viral rebound among persons with established viral suppression [two viral loads (VL) and all VLs of < 200 copies/ul within a one-year period (U=U eligible)]. Demographics, patient-reported outcomes, and longitudinal clinical data from 21,359 persons with HIV were analyzed. To include missing data in the analysis, they were treated as a separate category. The primary outcome of viral rebound was defined as any VL > 200 copies/ul within two years after U=U eligibility. A univariable logistic regression model was conducted to identify predictors of viral rebound. Significant variables (p< 0.05) were included in a multivariable logistic regression model. Predictive values of individual variables were captured by adjusted odds ratios (aORs). Results From 2011-2019, 12,150 patients met criteria for U=U eligibility and had two years of follow up data. The median age was 46 (IQR: 38-53); 68% male; 51% were white, 39% black. 1544 (13%) experienced viral rebound during follow-up. Forest plot summaries of univariable and multivariable logistic regression models are in Figures 1&2. In multivariable analysis, Black race (aOR=1.56, p< 0.001); MSM-IDU risk (aOR=1.38, p=0.006); lower QoL score (aOR=1.49, p=0.005); poorer ART adherence (aOR=1.84, p< 0.001); duration of lifetime ART [aOR=1.47 (10+yrs), = 1.37 (5-10 yrs); and = 1.28 (2-5 yrs), p< 0.001]; use of InSTIs after eligibility (aOR=1.60, p< 0.001); current smoker (aOR=1.49, p< 0.001), current amphetamine (aOR=1.83, p< 0.001) or cocaine use (aOR=1.46, p=0.012), were associated with viral rebound. In both analyses, older age was protective against viral rebound. Figure 1. Summary of Univariate Logistic Regression Model Figure 2. Summary of Multivariable Logistic Regression Model Conclusion We identified multiple risk factors for viral rebound among PWH with viral suppression. Further research is needed to identify synergistic risk factors that increase probability of viral rebound to inform optimal implementation of U=U. Disclosures Edward Cachay, MD, MAS, Gilead (Consultant, Grant/Research Support)Merck Sciences (Grant/Research Support) Heidi Crane, MD, MPH, ViiV (Grant/Research Support) Benigno Rodriguez, MD, Gilead (Speaker’s Bureau)ViiV (Speaker’s Bureau)

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FRI0303 PERIPHERAL SYMPTOMS ARE ASSOCIATED WITH LESS SPINAL RADIOGRAPHIC PROGRESSION IN PATIENTS WITH EARLY AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3397 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 741-741

Author(s):

M. Torgutalp ◽

M. Protopopov ◽

F. Proft ◽

J. Sieper ◽

V. Rios Rodriguez ◽

...

Keyword(s):

Regression Analysis ◽

Ankylosing Spondylitis ◽

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Smoking Status ◽

Hla B27 ◽

Research Support ◽

Sum Score ◽

Multivariable Regression

Background:Peripheral symptoms (PS), such as arthritis, enthesitis, and dactylitis, are common in axial spondyloarthritis (axSpA); data showing the association of PS and spinal radiographic progression in axSpA are controversial.Objectives:To analyze the association of PS and spinal radiographic progression in patients with axSpA.Methods:A total of 210 patients with axSpA (115 with radiographic and 95 with non-radiographic axSpA) were selected for analysis. Spinal radiographs were scored by two readers in a random order according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Pelvic radiographs were scored according to the grading system of the modified New York criteria; a sacroiliitis sum score was calculated as a sum of the grades for both sacroiliac joints. Mann-Whitney and Fisher exact tests were performed for group comparisons. A multivariable regression analysis was performed to analyze the influence of PS on radiographic progression.Results:Of the 101 (48.1%) patients with PS, 78 had peripheral arthritis, 48 - enthesitis, 12 - dactylitis. 32 patients had ≤1 PS. Patients with PS were older, less frequently HLA-B27 positive, compared with patients with no PS (73 (73.0%) vs. 93 (85.3%), p=0.028), had higher disease activity (time-averaged ASDAS over 2 years 2.6 ± 0.9 vs. 2.3 ± 0.9; p=0.032), worse physical function (BASFI 3.5 ± 2.3 vs. 2.3 ± 2.2, p<0.001), higher exposure to disease modifying anti-rheumatic drugs (39 (38.6%) vs. 22 (20.2%), p=0.003) and lower baseline radiographic sacroiliitis sum score (3.8 ± 1.9 vs. 4.4 ± 2.1, p=0.026); other baseline characteristics were similar. Patients with PS had lower absolute progression in mSASSS after 2 years of follow-up than those without (0.28 ± 1.39 vs 1.15 ± 2.9, p=0.045); 7.9% of patients with PS had a progression of mSASSS by ≥2 points compared to 20.2% in patients without PS (p=0.011). Radiographic progression of sacroiliitis was similar in both groups. In a multivariable regression analysis, presence of PS was associated with a lower mSASSS progression and lower odds for the mSASSS progression by ≥2 points after 2 years of follow-up: β=-0.98 (95% -1.68 to -0.28) OR=0.33 (95% CI 0.12 to 0.91), respectively – Table 1.Table 1.Association of peripheral symptoms with radiographic progression in axial spondyloarthritis after 2 years of follow-up.Multivariable linear regression analysisOutcomeβ (95 %CI)mSASSS change score−0.98 (-1.68 to -0.28)*Change of the sacroiliitis sum score−0.06 (-0.32 to 0.20)**Multivariable logistic regression analysisOutcomeOdds ratio (95 %CI)Progression of mSASSS by ≥2 points0.33 (0.12 to 0.91)*Progression of sacroiliitis by at least 1 grade in opinion of both readers0.84 (0.33 to 2.09)**mSASSS - modified Stoke Ankylosing Spondylitis Spine Score.*Adjusted for the smoking status, HLA-B27 status, NSAIDs intake, baseline syndesmophytes, and time-averaged ASDAS.**Adjusted for the smoking status, HLA-B27 status, NSAIDs intake, sacroiliitis sum score at baseline, and time-averaged ASDAS.Conclusion:Presence of PS is associated with distinct characteristics of SpA including slower radiographic spinal progression which might be explained partly by the numerically lower mSASSS score at baseline.Acknowledgments:GESPIC has been financially supported by the German Federal Ministry of Education and Research (BMBF). As funding by BMBF was reduced in 2005 and stopped in 2007, financial support has been obtained from Abbott / Abbvie, Amgen, Centocor, Schering-Plough, and Wyeth. Since 2010 GESPIC is supported by Abbvie.Dr. Murat Torgutalp was supported by the Scientific and Technological Research Council of Turkey (TUBITAK).Disclosure of Interests:Murat Torgutalp: None declared, Mikhail Protopopov Consultant of: Novartis, Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB

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AB0119 SERUM LEVELS OF INTERLEUKIN-22 ARE HIGH IN ANKYLOSING SPONDYLITIS, PARTICULARLY IN SMOKERS, BUT DO NOT CORRELATE WITH RADIOGRAPHIC BONE FORMATION NOR WITH DISEASE ACTIVITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2961 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1359.1-1360

Author(s):

M. Sagiv ◽

G. Slobodin ◽

T. Khatib ◽

I. Rosner ◽

M. Rozenbaum ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Ankylosing Spondylitis ◽

Bone Formation ◽

Disease Activity ◽

Radiographic Progression ◽

Elevated Serum ◽

Serum Levels ◽

Interleukin 22 ◽

Activity Indices

Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing spondylitis (AS).[1]IL-22 was also reported to drive the osteogenic differentiation of mesenchymal stem cells.[2]Objectives:To confirm the fact that serum levels of IL-22 are elevated in AS patients and to examine the relationship between concentrations of IL-22 and degree of radiographic progression in AS patients.Methods:Seventeen male patients with established AS of more than 4 years duration signed the informed consent and donated 10 ml of peripheral blood. Demographic data was collected from patient’s charts. Disease activity indices were calculated for all patients and radiographic disease progression was calculated as mSASS. A control group included 6 healthy persons and 4 patients with advanced diffuse idiopathic skeletal hyperostosis (DISH). Serum levels of IL-22 were tested using enzyme-linked immunosorbent assay. Intergroup differences were examined using the Mann-Whitney test, while correlations were calculated using Pearson correlation coefficient.Results:Serum IL-22 levels were remarkably elevated in patients with AS, comparing to healthy individuals and patients with DISH (p=0.005). However, increased concentrations of IL-22 did not correlate with the degree of radiographic progression or AS disease activity indices, nor with disease duration or patient’s age. Presence of diarrhea, psoriasis, uveitis, or elevated levels of C-reactive protein did not influence the levels of IL-22 as well. More AS patients with elevated serum IL-22 were smokers (p=0.05).Fig. 1.Serum levels of interleukin 22 (pg/ml)Conclusion:The serum levels of IL-22 are elevated in patients with AS. It seems that smoking can be related to the elevated levels of serum IL-22 in AS. The significance of this data is unclear and further research is needed.References:[1]Zhang L, Li Y gang, Li Y hua, Qi L, Liu X guang, Yuan C zhong, et al. Increased frequencies of th22 cells as well as th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS One. 2012;7(4).[2]El-Zayadi AA, Jones E, Churchman S, Baboolal T, Cuthbert R, El-Jawhari J, et al. Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology. 2016 Dec 10;56.Disclosure of Interests:None declared

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Logistic regression analysis on risk factors of augmented vertebra recompression after percutaneous vertebral augmentation

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02480-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Zhongcheng An ◽

Chen Chen ◽

Junjie Wang ◽

Yuchen Zhu ◽

Liqiang Dong ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Bone Cement ◽

Vertebral Compression Fracture ◽

Univariate Analysis ◽

Compression Fracture ◽

Osteoporotic Vertebral Compression Fracture ◽

Vertebral Augmentation ◽

Surgical Methods

Abstract Objective To explore the high-risk factors of augmented vertebra recompression after percutaneous vertebral augmentation (PVA) in the treatment of osteoporotic vertebral compression fracture (OVCF) and analyze the correlation between these factors and augmented vertebra recompression after PVA. Methods A retrospective analysis was conducted on 353 patients who received PVA for a single-segment osteoporotic vertebral compression fracture from January 2017 to December 2018 in our department according to the inclusion criteria. All cases meeting the inclusion and exclusion criteria were divided into two groups: 82 patients in the recompression group and 175 patients in the non-compression group. The following covariates were reviewed: age, gender, body mass index (BMI), injured vertebral segment, bone mineral density (BMD) during follow-up, intravertebral cleft (IVC) before operation, selection of surgical methods, unilateral or bilateral puncture, volume of bone cement injected, postoperative leakage of bone cement, distribution of bone cement, contact between the bone cement and the upper or lower endplates, and anterior height of injured vertebrae before operation, after surgery, and at the last follow-up. Univariate analysis was performed on these factors, and the statistically significant factors were substituted into the logistic regression model to analyze their correlation with the augmented vertebra recompression after PVA. Results A total of 257 patients from 353 patients were included in this study. The follow-up time was 12–24 months, with an average of 13.5 ± 0.9 months. All the operations were successfully completed, and the pain of patients was relieved obviously after PVA. Univariate analysis showed that in the early stage after PVA, the augmented vertebra recompression was correlated with BMD, surgical methods, volume of bone cement injected, preoperative IVC, contact between bone cement and the upper or lower endplates, and recovery of anterior column height. The difference was statistically significant (P < 0.05). Among them, multiple factors logistic regression elucidated that more injected cement (P < 0.001, OR = 0.558) and high BMD (P = 0.028, OR = 0.583) were negatively correlated with the augmented vertebra recompression after PVA, which meant protective factors (B < 0). Preoperative IVC (P < 0.001, OR = 3.252) and bone cement not in contact with upper or lower endplates (P = 0.006, OR = 2.504) were risk factors for the augmented vertebra recompression after PVA. The augmented vertebra recompression after PVP was significantly less than that of PKP (P = 0.007, OR = 0.337). Conclusions The augmented vertebra recompression after PVA is due to the interaction of various factors, such as surgical methods, volume of bone cement injected, osteoporosis, preoperative IVC, and whether the bone cement is in contact with the upper or lower endplates.

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Serum levels of bone formation and resorption markers in relation to vitamin D status in professional gymnastics and physically active men during upper and lower body high-intensity exercise

Journal of the International Society of Sports Nutrition ◽

10.1186/s12970-021-00430-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Jan Mieszkowski ◽

Andrzej Kochanowicz ◽

Elżbieta Piskorska ◽

Bartłomiej Niespodziński ◽

Joanna Siódmiak ◽

...

Keyword(s):

Vitamin D ◽

Bone Formation ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Type I Collagen ◽

Serum Levels ◽

Type I ◽

Vitamin D Metabolites ◽

Physically Active ◽

Turnover Markers

Abstract Purpose/introduction To compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels. Methods Sixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption. Results UBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects. Conclusion Vitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.

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AB1087 DETECTING AXIAL AND PERIPHERAL NEW BONE FORMATION IN SPONDYLOARTHRITIS PATIENTS USING [18F]FLUORIDE PET-CT IMAGING

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4216 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1832.2-1833

Author(s):

J. De Jongh ◽

R. Hemke ◽

G. C. J. Zwezerijnen ◽

M. Yaqub ◽

I. Van der Horst-Bruinsma ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Bone Formation ◽

Ct Imaging ◽

Whole Body ◽

Therapeutic Effects ◽

New Bone Formation ◽

Research Support ◽

Patella Tendon ◽

Pet Ct ◽

18F Fluoride

Background:Bone formation in spondyloarthritis (SpA) is presumably related to local enthesitis/peri-articular inflammation and ultimately may lead to functional limitation (1,2). X-rays only allow long-term monitoring of bone formation (≥2 years) (3). Imaging techniques that can visualize bone formation at an early stage would therefore be valuable. Positron Emission Tomography (PET) using [18F]Fluoride can visualize and quantify (early changes in) bone formation at molecular level (4).Objectives:To investigate the feasibility of [18F]Fluoride to assess new bone formation at axial and peripheral enthesial sites in SpA patients.Methods:Thus far, 5 of the total of 15 patients with clinically active ankylosing spondylitis (AS) (according to modified New York criteria and BASDAI ≥4) and 8 of the 25 patients with active psoriatic arthritis (PsA) (according to CASPAR criteria and ≥1 clinically active enthesitis) were included. Of each patient, a whole body [18F]Fluoride PET-CT scan was performed. All scans were visually judged and scored dichotomously by one reader (blinded for clinical data) for PET-positive lesions in the spine, peripheral enthesis sites and joints. Low dose CT was used for anatomical reference.Results:The study is ongoing, with whole body [18F]Fluoride PET-CT scans available in five AS patients and eight PsA patients. In 4/5 AS scans, at least (≥1) PET positive lesions were found in the cervical, thoracic and/or lumbar vertebrae. These were mainly found in anterior corners of vertebrae and bridging syndesmophytes (Fig. 1A). In all eight PsA patients, at least 1 PET positive lesion was visualized, projected either at the site of a tendon attachment (fascia plantaris, achilles- and patella tendon (Fig 1B)) or peri-articularly (in the ankle or wrist).Fig 1.[18F]Fluoride uptake in the cervical, thoracic and lumbar spine in a clinically active AS patient (A) and in the patella tendon of the right knee in a clinically active PsA patient (B)Conclusion:[18F]Fluoride PET uptake, reflecting new bone formation, can be visualized at heterogeneously distributed enthesis and (peri-)articular sites in AS- and PsA patients. The technique therefore is sensitive to visualize new bone formation and may reflect local disease activity. Additional scans will be collected and analyzed quantitatively, also after anti-TNF or Secukinumab treatment, to further investigate the applicability of [18F]Fluoride PET for monitoring of therapeutic effects on bone formation in SpA.References: :[1]Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53.[2]Rezvani A, Bodur H, Ataman S, Kaya T, Bugdayci DS, Demir SE, et al. Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24(4):651-6.[3]Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52:1000-8..[4]Bruijnen ST, Verweij NJF, van Duivenvoorde L, Bravenboer N, Baeten D, van Denderen JC, et al. [18F]Fluoride PET-CT imaging of bone formation in ankylosing spondylitis before and after 12 weeks of anti-TNF treatment. 2017.Acknowledgments:We thank EULAR Foreum, Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of Interests:Jerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Marleen G.H. van de Sande Grant/research support from: Novartis, Eli lily, UCB, Jansen, Consultant of: Abbvie, Novartis, Eli lily, MSD, Arno Van Kuijk: None declared, Irene Bultink: None declared, Lot Burgemeister: None declared, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared

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FRI0416 COMBINATION OF SERUM ADIPOKINES/RELATED INFLAMMATORY FACTORS AND RATIOS AS PREDICTORS OF INFRAPATELLAR FAT PAD VOLUME IN KNEE OSTEOARTHRITIS PATIENTS: USAGE OF A COMPREHENSIVE MACHINE LEARNING APPROACH

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1447 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 806.1-807

Author(s):

H. Bonakdari ◽

G. Tardif ◽

F. Abram ◽

J. P. Pelletier ◽

J. Martel-Pelletier

Keyword(s):

Risk Factors ◽

Serum Levels ◽

Infrapatellar Fat Pad ◽

Inflammatory Factors ◽

Fat Pad ◽

Research Support ◽

Knee Oa ◽

Total Cohort ◽

Low Bmi ◽

The University

Background:One of the hurdles in osteoarthritis (OA) drug discovery and the improvement of therapeutic approaches is the early identification of patients who will progress. It is therefore crucial to find efficient and reliable means of screening OA progressors. Although the main risk factors, age, gender and body mass index (BMI), are important, they alone are poor predictors. However, serum factors could be potential biomarkers for early prediction of knee OA progression.Objectives:In a first step toward finding early reliable predictors of OA progressors, this study aimed to determine, in OA individuals, the optimum combination of serum levels of adipokines/related inflammatory factors, their ratios, and the three main OA risk factors for predicting knee OA infrapatellar fat pad (IPFP) volume, as this tissue has been associated with knee OA onset and progression.Methods:Serum and magnetic resonance images (MRI) were from the Osteoarthritis Initiative at baseline. Variables (48) comprised the 3 main OA risk factors (age, gender, BMI), 6 adipokines, 3 inflammatory factors, and their 36 ratios. IPFP volume was assessed on MRI with a neural network methodology. The best variables and models were identified in Total cohort (n=678), High-BMI (n=341) and Low-BMI (n=337), using an artificial intelligence selection approach: the adaptive neuro-fuzzy inference system embedded with fuzzy c-means clustering (ANFIS-FCM). Performance was validated using uncertainty analyses and statistical indices. Reproducibility was done using 80 OA patients from a clinical trial (female, n=57; male, n=23).Results:For the three groups, 8.44E+14 sub-variables were investigated and 48 models were selected. The best model for each group included five variables: the three risk factors and adipsin/C-reactive protein combined for Total cohort, adipsin/chemerin; High-BMI, chemerin/adiponectin high molecular weight; and Low-BMI, interleukin-8. Data also revealed that the main form of the ratio used for the model was justified, as the use of the inverse form slightly decreased the performance of the model in both training and testing stages. Further investigation indicated that gender improved (13-16%) the prediction results compared to the BMI-based models. For each gender, we then generated a pseudocode (an evolutionary computation equation) with the 5 variables for predicting IPFP volume. Reproducibility experiments were excellent (correlation coefficient: female 0.83, male 0.95).Conclusion:This study demonstrates, for the first time, that the combination of the serum levels of adipokines/inflammatory factors and the three main risk factors of OA could predict IPFP volume with high reproducibility, and superior performance with gender separation. By using the models for each gender and the pseudocodes for OA patients provided in this study, the next step will be to develop a predictive model for OA progressors.Acknowledgments:This work was funded by the Chair in Osteoarthritis of the University of Montreal, the Osteoarthritis Research Unit of the University of Montreal Hospital Research Centre, the Groupe de recherches des maladies rhumatismales du Québec and by ArthroLab Inc., all from Montreal, Quebec, Canada.Disclosure of Interests:Hossein Bonakdari: None declared, Ginette Tardif: None declared, François Abram Employee of: ArthroLab Inc., Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Johanne Martel-Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica

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Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01964-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Widet Gallo ◽

Filip Ottosson ◽

Cecilia Kennbäck ◽

Amra Jujic ◽

Jonathan Lou S. Esguerra ◽

...

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Cardiometabolic Risk ◽

Carotid Atherosclerosis ◽

Tissue Injury ◽

Control Sample ◽

Cardiometabolic Risk Factors ◽

Cardiometabolic Disease ◽

Micro Rnas

Abstract Background Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis. Methods We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound. Results In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007). Conclusion miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.

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Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2011-200357 ◽

2011 ◽

Vol 71 (1) ◽

pp. 71-74 ◽

Cited By ~ 38

Author(s):

L Senolt ◽

H Hulejova ◽

O Krystufkova ◽

S Forejtova ◽

L Andres Cerezo ◽

...

Keyword(s):

Bone Formation ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Diffuse Idiopathic Skeletal Hyperostosis ◽

Serum Levels ◽

Total Serum ◽

Mineral Density ◽

Spinal Involvement ◽

Turnover Markers ◽

Dickkopf 1

ObjectiveDickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH).MethodsSerum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH.ResultsThe levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1.ConclusionThese observations indicate that DKK-1 may play a significant role in bone formation during DISH.

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