Jovan Nedovic

Relation between bone density and certain parameters of lipid status in postmenopausal women

The aim of the paper was to examine the relation between bone density and certain parameters of lipid status in postmenopausal women. The research involved 300 women referred to densitometric examination as they belonged to the risk group of postmenopausal women. All the examinees had the following biochemical parameters determined: total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, glycemia, serum Ca and P. Univariate logistic regression analyses showed that each year of age, menopause duration, AH are significantly connected to risk increase for the appearance of osteopenia or osteoporosis. Increase in values of SBP, DBP, cholesterol, LDL and triglyceride are connected with significant risk increase for the appearance of osteopenia or osteoporosis. Patients with AH are connected to 11 times elevated risk for the appearance of osteopenia or osteoporosis, cigarette smoking increased the risk by seven times, physical inactivity even by 52 times, CVD in the family anamnesis by eight times, and osteoporosis in the family anamnesis is connected to the risk by four times. In our research, atherogenic lipoproteins negatively correlate with lumbar bone density. Disturbed lipide status is a risk factor for cardiovascular diseases, but also a risk factor for the appearance of osteoporosis.

Association of the A Allele of the TNF-Alpha-308 G/A Gene Polymorphism with Radiographic Progression in Rheumatoid Arthritis

Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with erosive arthritis and rapid radiological progression of the disease. The examined group included 131 patients with early RA. Using the PCR-RFLP method, the TNF-Alpha-308 G/A gene polymorphism was determined for all patients. In relation to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). Based on the presence of the destructive changes in joints found in the initial radiographs, the findings were classified as erosive and non-erosive RA. Radiological progression was assessed on the basis of the annual change in the Larsen score – LS (0-200). Group A comprised 62 (47.33%) patients, while group G comprised 69 (52.67%) patients. The presence of cysts and erosions in subgroups A and G was compared before the start of the methotrexate therapy. It was determined that erosions (erosive RA) were statistically significantly more frequent in group A (83.87% of patients) in comparison with group G (44.93% of patients), p < 0,001. Group A patients had a higher value of the Larsen score in relation to the group G both before and after methotrexate was administered for a year (before therapy, LS in group A: 48.58 ± 20.54; in group G 20.73 ± 12.31; p < 0.01; after MTX therapy, LS in group A: 58.32 ± 22.25; in group G 25.35 ± 14.57; p < 0.001). The average value of the annual LS change in group A was statistically significantly greater than the change in group G patients (9.98 ± 4.95 to 5.23 ± 2.72) (p < 0.05). The presence of the A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with the occurrence of early erosive joint changes and more rapid radiological progression of the disease.

SAT0378 Bone marrow oedema and synovitis on MRI of the hand are associate with digital ulcers, active disease and impaired functional capacity in systemic sclerosis

Background Hand inflammatory involvement is a major feature in patients with systemic sclerosis (SSc), responsible for major disability. Magnetic resonance imaging (MRI) can identify and characterize subclinical inflammation and joint damage on hand with much greater precision than clinical, radiographic and ultrasonography assessment in SSc. Objectives To determine the association of MR bone marrow oedema, synovitis and probability for the occurrence of listed inflammatory changes with clinical features and laboratory tests in SSc patients Methods 112 SSc patients were tested (mean age 54y). Contrast enhanced low field MRI of the wrist and MCP2–5 joints was performed to all the pts. MRI bone marrow oedema and synovitis were assessed and scored by OMERACT RAMRIS scoring system. Age, sex, SSc type, disease duration (date of first non Raynaud symptom), Raynaud phenomenon, articular or periarticular pain, joint swelling and contractures, digital ulceration, HAQ, acroosteolysis (by standard PA radiographs of hand and wrist) pulmonary arterial hypertension (PAP>40mmHg at rest on Doppler echocardiography), pulmonary fibrosis (by CT and pulmonary function tests) and laboratory tests (antibody profile, RF, CRP, Creatine phosphokinase) and disease activity (by Valentini index) were done. Results By multiple logistic regression analysis taking into account all clinical and laboratory variable, we found that MRI bone marrow oedema of the hand was associated and probability for the occurance of MRI bone marrow oedema was higher for the SSc pts with digital ulcers (OR=6.081;95%IP:1.295–28.550; p<0.05), HAQ>1.5 (OR=6.448; 95%IP: 1.714–24.257; p<0.01) and active disease (OR=3.377; 95%IP; 1.175–9.706; p<0.05). MRI synovitis of the hand was associated and probability for the occurance of MRI synovitis was higher, also, for the SSc pts with digital ulcers (OR=5.128; 95%IP: 1.085–24.243; p<0.05), HAQ>1.5 (OR=9.067; 95%IP: 1.925–42.708; p<0.01) and active disease (OR=3.565; 95%IP: 1.181–10.764; p<0.05). Conclusions MRI bone marrow oedema and synovitis on the hand in SSc are associate with digital ulcers, impaired functional capacity and active disease. Monitoring and treatment of clinical features and organ involvement are essential in all the pts with SSc, especially those with proven bone marrow oedema and synovitis on MRI of the hand. Disclosure of Interest None declared

AB0937 The Comparison of Synovial Degree Inflammation between Systemic Sclerosis and Rheumatoid Arthritis by Magnetic Resonance Imaging of Hands

Background MRI is a usefull tool for assessing subclinical synovial inflammation and joint damage in rheumatic diseases. There are no references clarifying the problem of distinguishing arthritis in systemic sclerosis (SSc) and rheumatoid arthritis (RA) so far Objectives The aim of our investigation is to compare the degree of inflamatory changes of the hand (bone edema, synovitis, bone erosion and tenosynovitis) in SSc and RA. Methods 82 SSc pts, mean age 54,5y and 35 RA pts (EULAR/ACR 2010 criteria), mean age 54,3y underwent low field MRI with gadolinium at the dominant hand including wrist and MCP joints 2–5. Assessment of bone marrow edema, synovitis, bone erosions and tenosynovitis was performed by the OMERACT RA MRI scoring system. Images were evaluated independently by two blinded readers. The mean scores of the two readers were analyzed. Results Anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) were found in 89% and 74,3% of RA pts and 13,4% and 14,6% of SSc pts. Synovitis was more frequently detected on MRI with significantly higher score in RA compared to SSc (wrist:4,37±1,31 vs 2,69±2,29,p<0,001; MCP joints:5,26±2,09 vs 3,15±2,95, p<0, 001). MRI erosion score in the wrist and MCP was significantly higher in RA compared to SSc (wrist:20,57±10,23 vs 6,58±10,89,p<0,001; MCP joints:10,51±7,90 vs 3,99±9,82, p<0,001). MRI bone edema score was also significantly higher in RA compared to SSc (wrist:18,60±5,01 vs 6,84±7,43, p<0,001; MCP joints:9,09±4,27 vs 4,04±4,76, p<0,001). Conclusions The present data suggest great frequency of inflammatory changes on the hands in SSc and RA using MRI. Inflammation scores were significantly higher in RA compared to SSc. MRI may be helpful in differentiating arthritis in RA and SSc, specially in subclinical inflammation. Disclosure of Interest None declared

AB0318 Does Concentration of Antibodies To Etanercept and Adalimumab Correlates with Parameters of Disease Activity in Patients with Rheumatoid Arthritis

Background Introduction of tumor necrosis factor alpha (TNF) inhibitors has revolutionized therapy of rheumatoid arthritis (RA). Immunogenicity with consequent formation of antidrug antibodies (ADAb) is most responsible factor for secondary resistance. Adalimumab (ADA) as a fully humanized monoclonal antibody and Etanercept (ETN) as a fusion protein, are considered less immunogenic compared to other TNF inhibitors. In spite of this, various studies detected ADAb to ETN from 0% to 18% and for ADA from 0.04% to 87%. Objectives Our objectives were to determine the prevalence of ADAb to ETN and ADA in patients with RA and to evaluate correlations of ADAb with concentration of ETN and ADA and with parameters of disease activity. Methods Consecutive patients with established RA treated with ETN (25 patients) and ADA (20 patients) were enrolled in our cross-sectional study. Patients treated with ETN were older compared to patients treated with ADA (53.09±13.20 versus 47.06±12.54 years), had longer duration of disease (13.78±6.88 versus 9.11±6.91 years) and had longer duration of treatment (58.76±22.53 versus 20.3±14.11 years). Drug levels and concentration of ADAb were measured with commercially available ELISA kits from blood samples taken before next injection (trough values), and these levels were correlated with parameters of disease activity and compared between two groups. Results Both drugs had comparable efficacy according to DAS 28 SE (3.32±0.93 for ETN and 3.86±1.43 for ADA). Mean trough concentration of both drugs was satisfactory with values sevenfold greater than referent values: 240.23±502.64 ng/mL for ETN (referent values 0.0–35 ng/mL) and fourfold greater for ADA: 94.86±25.56 ng/mL (referent values 0.0–24.0 ng/mL). In spite of this, a more than a double concentration of ADAb was recorded in both groups: 326.96±292.51 IU/mL for ETN (referent values 0.0–142.06 IU/mL) and 23.21±56.87 IU/mL for ADA (referent values 0.0–10.00 IU/mL). Eight from 25 patients (32.4%) in ETN group and 8/20 (40%) in ADA group had elevated concentration of ADAb and this difference was not significant. Pearson correlation coefficient (r) showed weak negative correlation (r=-0.338) between concentration of ADAb to ETN and concentration of ETN and no correlation between ADAb to ADA and concentration of ADA. There were positive correlation of ADAb to ETN and Erythrocyte Sedimentation Rate (r=+0.482) and CRP (r=+0.411) but not with DAS 28 SE nor with the levels of RF and CCP Ab. The concentration of ADAb to ADA shoved only weak correlation with CCP Ab (r=+0.366) but not with any other parameter of disease activity. Conclusions Our data suggest that formation of ADAb after prolonged time of therapy is common even in the patients treated with TNF inhibitors considered as less immunogenic. But, a weak or even absent correlation with disease activity also suggest that not all of these ADAb are neutralizing with clinical consequences. These results also suggest that methodological aspects are of even more significance. There is a need for assay standardization and validation and consensus on the interpretation of serum drug and ADAb cut-off values with evidence based treatment algorithm useful for clinical practice. Disclosure of Interest None declared

AB0291 An Analysis of The Relationship between Clinical Activity, Mode of Therapy and Depession in Rheumatoid Arthritis

Background An ever increasing body of research confirm that rheumatoid arthritis is associated wuth depression. Objectives Assessment of presence and severity of depression in patients suffering from RA. Determination of the connection between depression with the activity of the disease, functional status, and radiological stage of the disease. To examine the effect of therapy on the severity of depression. Methods The examination was conducted with 276 patients with RA (82.24% women and 17.76% men), with the average age of 5563±14.46 years. The average duration of the disease was 48.4±20.3 months. The control group comprised 145 healthy examinees homogenous with the examined group in age and sex distribution. The activity of the disease was determined using the DAS 28 SE index, the functional status was determined on the basis of an HAQ questionnaire, while the degree of radiological damage was determined using the Larsen score (0–200). The intensity of pain was determined by the examinees themselves on the visual-analog pain scale VAS (0–100mm). The degree of depressivity was determined through application of the Beck scale for depression. The statistical data processing was performed in the SPSS package, version 15.0. Results The symptoms of depression were registered in 73.19% of patients, significantly more than in CG (21.34%), p<0.01. Mild depressivity was registered in 37.62% of patients, moderate in 28.71%, pronounced in 14.76%, and major depression in 8.91% of patients. Out of the total number of examinees, 34.78% received combined therapy (MTX + biological therapy). 65.22% of patients were treated using monotherapy (MTX). The mean value of the Beck index of the patients receiving biological therapy was significantly lower than the value of the Beck index of the patients receiving monotherapy MTX (11.8±7.16 vs.16.86±8.09). The connection between the ages of patients, the duration of the disease, DAS 28 SE, VAS of pain, Larsen score and HAQ index with the Beck index of depressivity was studied. The results of the univariant logistic regression show that the degree of depression is separately affected by the duration of the disease and the functional status of the patient. The multivariant model of logistic regression emphasizes the functional status as the most dominant predictor of depressivity (coef. Beta 0.764), p<0.001. Conclusions Depression is a frequently present manifestation of RA which is most prominently influenced by the degree of functional disability of RA patients. Apart from the medication therapy, the treatment of RA requires an individual psychosocial approach and wider social support. References Margaretten M, Yelin E, Imboden J, et al. Predictors of depression in a multiethnic cohort of patients with rheumatoid arthritis. Arthritis Rheum. 2009;61(11):1586–1591 McNamara D. Depression interferes with anti-TNF therapy. Rheumatology News. 2007;6(6) Disclosure of Interest None declared

AB0072 Association of the a Allele of the TNF Alpha-308 G/A Gene Polymorphism with the Activity of MMP-9 in the Plasma and Synovial Fluid of Patients Suffering from Rheumatoid Arthritis

Background Proteolytic enzymes – Matrix Metalloproteinases (MMP), have a significant role in the process of bone and cartilage destruction in rheumatoid arthritis (RA). Objectives Examination of the influence of the TNF-α gene polymorphism on the production of MMP-9 in the plasma (PL) and synovial fluid (SF) of patients suffering from RA. Methods The examination included 72 patients with early RA and knee synovitis, receiving methotrexate therapy. RA diagnosis was established within 6 months from the onset of symptoms, based on the ACR/EULAR criteria from 2010. The control group comprised 25 examinees with knee osteoarthrosis (OA), who were comparable with the RA group according to their demographic characteristics (Table 1).Table 1 Group Age [year], X±SD N Sex, Male/Female N/% RA 60.59±11.29 72 27 (37.5%)/45 (62.5%) OA-CG 62.70±6.18 25 6 (24%)/19 (76%) The -308 G/A gene polymorphism for TNF alpha was determined for all patients using the PCR-RFLP method. With regards to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). The activity of MMP-9 was measured in PL and SF of all examinees using the sandwich enzyme-linked immunosorbent assay (ELISA) method, according to the instructions provided by the manufacturer (Amersham Biosciences, Little Chalfont, Great Britain). Statistical calculations were performed in the SPSS program, version 15.0 Results The activity of MMP-9 in PL and SF of the patients with RA is statistically significantly greater than the activity of this enzyme in PL and SF of the control group patients, with the statistically more significant difference (p<0.001) determined for the activity of MMP-9 in SF (15.07±13.24 to 0.65±0.41 ng/ml) in relation to the activity of this enzyme in PL (18.28±7.54 to 13.58±3.07 ng/ml), (p<0.01). Within the group of patients where the activity of MMP-9 in PL and SF was determined, 37 (51.39%) examinees belonged to Group A, while 35 (48.61%) belonged to Group G. A higher activity of MMP-9 both in PL and SF was registered in Group A than in Group G, with the statistical significance reached only for the activity of MMP-9 in SF (Table 2).Table 2. Activity of MMP-9 (ng/ml) in PL and SF in Groups A and G Group Group A (N=37) Group G (N=35) p Activity of MMP in PL, X±SD 18.83±8.04 17.66±7.16 n.s. Activity of MMP in SF, X±SD 19.38±14.61 10.18±9.81 <0.05 Conclusions The activity of MMP-9 in the plasma and synovial fluid of RA patients is greater than the activity of this enzyme in PL and SF of examinees with osteoarthrosis. The presence of the A allele of the TNF-α -308 G/A gene polymorphism is associated with the increased activity of MMP-9 enzyme in the synovial fluid of patients with early RA, and it can predict a faster radiological progression of the disease. Disclosure of Interest None declared

AB0622 Risk Factors for Organ Damage in Patients with Systemic Lupus Erythematosus

Background Adequate assessment of disease activity in patients with systemic lupus erythematosus (SLE) using disease activity index, evaluating the extent of organ damage and quality of life, contributes to better monitoring, treatment, and improved prognosis in SLE patients. Organ damage element of the index in SLE patients predicts further organ damage and is associated with increased risk of mortality. Objectives Our aim was to examine the correlation between organ damage and disease activity, quality of life, and severity of fatigue. Risk factors for organ damage in SLE patients were established. Methods The study enrolled 83 SLE patients with disease duration of over 6 months, hospitalized at the Institute “Niška Banja” in 2012, out of which 6 men (7.2%) and 77 women (92.8%), aged 45.8±9.2 years on the average, with average disease duration of 10.6±7.9 years. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physicians global assessment, and degree of damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE (SLICC/ACR Damage Index - SDI). Quality of life was assessed based on the standardized Medical Outcome Survey Short Form 36 (SF-36), and severity of fatigue using the Fatigue Severity Scale. Results Average SDI value was 1.8±1.9 (median 1, min. 0, max. 9), and average SLEDAI was 10.9±7.4. Our results demonstrated that SDI was positively correlated with SLEDAI, global physicians assessment, and severity of fatigue (r=0.359, p=0.001; r=0.357, p=0.001; r=0.296, p=0.007, respectively), being associated as well with poorer quality of life. Univariant analysis demonstrated that age, disease duration (especially if over 10 years- OR 3.368, CI95% 1.01-11.34, p=0.045), high disease activity at global physicians assessment, as well as the use of Azathioprine, were all independent risk factors for organ damage. Use of Chloroquine was an important protective factor regarding organ damage (OR 0.378, CI95% 0.14-0.99, p=0.048). Our results demonstrated that the levels of anti-dsDNA antibodies, anti-nucleosome, anti-C1q antibodies, as well as the level of monocyte chemoattractant protein-1 in the serum and urin, were not predictors of organ damage. Multivariant logistic regression showed that high disease activity at global physicians assessment (OR 31.839, 95CI% 2.33-435.58, p=0.01) and use of Azathioprine (OR 7.256, 95CI% 1.37-5.63, p=0.005) were the strongest predictors of organ damage. Conclusions Organ damage in SLE patients increases with advancing age and disease duration. The strongest predictors of organ damage are high disease activity at global physicians assessment and use of cytostatic agents. Use of Chloroquine can afford some protection against organ damage. Disclosure of Interest None declared

SAT0176 Arthritis Might BE Useful in the Future to Select High Risk Patients for Systemic Inflammation and More Severe Disease- A Low Field MRI Study in Systemic Sclerosis

Background Joint involvement is frequent finding and correlate with poor life quality in systemic sclerosis (SSc). MRI is a useful method for detection and quantification of inflammatory lesions of the hand (bone oedema, erosions, synovitis, tenosynovitis) in SSc patients. Objectives In order to clarify the reported association between joint involvement (synovitis, tendon friction rubs, joint contracture) and clinical and/or laboratory features, it was decided to evaluate a group of pts with SSc. Methods A total of 82 SSc pts (mean age 54y) were included in a study. All the patients were investigated for clinical and serological subset, disease duration, vascular, skin, joint, tendon, muscle, oesophagogastrointestinal, heart, lung and kidney involvement, diseaseactivity and HAQ-DI Index. MRI (contrast enhanced) low field MRI of the wrist the 2nd-5th metacarpophalangeal joints of the dominant hand were obtained. MRI were scored by 2 independent, blinded readers using the OMERACT RA scoring system for assessment bone marrow oedema, synovitis, bone erosions and tenosynovitis.Data were statistically analysed using Chi-square and the Students T test. A univariate step-wise logistic regression analysis was also performed for all variables identified with p<0,01. p<0,05 was considered statistically significant Results Of 82 SSc pts 17,1% had clinical arthritis (14/82). Inflammatory MR findings with synovitis we found in 64/82 (78%)pts, MRI erosions in 52 (62,4%) or tenosynovitis in 11/82 (14,1%). Synovitis was more frequently detected on MRI (78%) than clinically (17,1%, p<0,001.We found that clinical arthritis of the hand was associated with joint contracture (probability for the occurrence of joint contractures was higher for the SSc pts with clinical arthritis- OR=4.64;95%CI 1,37-15,64; p<0,01), with HAQ>1,5 (OR=4.03;95%CI 1,14-14,21,p<0,03), with elevated sPAP>40mmHg (OR=8.62;95%CI 1,23-60,03;p<0,04), muscle weakness (OR=9.00;95%CI 1,34-60,15, p<0,03).It was also associated with elevated acute-phase reactants (OR=39,0;95%CI;474-320,62,p<0,001). Conclusions Arthritis is a common finding in SSc even independent of clinical symptoms and signs. Our data show that arthritis is associated with a more severe disease and with systemic inflammation. This data support the use of MRI in clinical practice for early identification of SSc pts who will develop more severe disease with systemic inflammation Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5795

AB0390 Serum RANKL Activity is Suppressed by TNF Alpha Inhibition but not with MTX Alone

Background Bone is, together with cartilage a central target of rheumatoid arthritis (RA). Chronic synovitis attacks the juxtaarticular bone, where it causes bone erosions. Formation of bone erosions is a consequence of osteoclasts activity. Osteoclasts are generated from mononuclear precursor cells mediated by the receptor activator of NF-kappaB ligand (RANKL). Tumor necrosis factor alpha (TNF) is considered as a most important proinflammatory cytokine and also, a mediator of structural damage in RA. TNF is an important inducer of osteoclast formation by increasing production of RANKL and is thus a key molecular link between inflammation and bone damage. Objectives The aim of our study was to investigate whether the serum concentration of RANKL is influenced by therapy with and without TNF inhibitors or by disease activity itself. Methods 45 RA patients (86,7% female, mean age 55,09±11,61 years) who fulfilled 1987. ACR criteria for RA and 20 age-matched controls with osteoarthritis were enrolled in the study. Group of RA patients consisted from 25 patients treated with Methotrexate (MTX group), mean disease duration 6,83±4,78 years and from 20 patients treated with Methotrexte and Etanercept (TNF group), mean disease duration 9,8±5,59 years. The serum levels of RANKL was determined by commercially available ELISA kit, values expressed in pg/ml. Disease activity was measured by Erythrocyte Sedimentation Rate (ESR) in mm, concentration of hsCRP in mg/L and wit composite index DAS28. Results The mean values of serum concentrations of RANKL in MTX group, TNF group and in control group were: 246,81±226,06; 134,53±86,85 and 122,85±138,89 respectively. Patients in MTX group had statistically significantly higher values of RANKL compared with patients in TNF group and in control group, p<0,05. There were no significant differences between patients from TNF and control group. DAS28 was significantly higher in MTX group (6,08±1,16) compared to TNF group (3,18±1,04), p<0,001. Values of ESR were also higher in MTX group as compared to TNF group and control group: 41,44±18,68; 22,45±11,88 and 13,15±6,89 respectively, p<0,01 as well as the values of hsCRP: 9,91±14,45; 1,99±1,79 and 1,52±1,33, p<0,001. There were no significant differences between TNF and control group neither in level of ESR nor in hsCRP. Conclusions In our study we determined that concomitant treatment with TNF blocker and MTX significantly reduce the concentration and thus activity of RANKL as compared to treatment with MTX alone. Thus, it is possible that the bone protective effect of anti TNF agents is at least partly, mediated through the RANKL. We also find that concentration of RANKL was in correlation with disease activity as expected. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6016