Aleksandar Dimic

Validation of the osteoporosis quality of life questionnaire QUALEFFO-41 for the Serbian population

BackgroundVertebral fractures could lead to reduced physical, social and mental functioning, and loss of personal independence. Therefore, during the treatment of osteoporosis, it has become necessary to examine the changes in everyday functioning, well-being and health related quality of life (HRQOL). To that effect, this study aims to translate, culturally adapt, and validate the Serbian version of Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) for patients with vertebral fractures.MethodsNine female patients with osteoporosis participated in the pre-validation study. A validation, case–control study included two groups of female patients: one that consisted of 50 female patients with osteoporosis, and with at least one vertebral fracture, and another one that consisted of 50 control patients with osteoporosis but without fractures. They completed the QUALEFFO-41 and the EuroQol group questionnaire with five dimensions (EQ-5D) twice within a month. The validation study examined internal consistency, concurrent validity, test-retest reliability, sensitivity and specificity.ResultsDuring the pre-validation study, three of the items in the QUALEFFO-41 were slightly changed. Afterwards, during the validation study, the statistically significant differences (adjusted for: age, duration of menopause, current employment and marital status) in the mean values of all domains and total scores between the groups were noted. For the case group, the internal consistency of the QUALEFFO-41 domains and of total questionnaire was above 0.70. The test-retest reliability was tested by the intraclass correlation coefficients (ICC) that were in range 0.87 – 0.96 for the case, and 0.15 – 0.83 for the control group. Correlations between the total scores of the QUALEFFO-41 and the EQ-5D health state value, for both groups were negative and statistically significant (r = -0.78, p<0.001 and r = -0.73, p<0.001, respectively). The QUALEFFO-41 had a better prediction of the value of HRQOL of cases compared to the generic questionnaire EQ-5D (the AUC difference was 0.099, p = 0.013).ConclusionsThe Serbian QUALEFFO-41 version is reliable, valid, sensitive and predictive for examinations of HRQOL in patients with prevalent vertebral fractures and can be used in further studies.

The effect of vitamin C on amiodarone-induced toxicity in rat thymocytes

Although, the antiarrhythmic effect of amiodarone (AMD) is well characterized, the mechanism of its toxicity on extracardiac tissues is still poorly understood. Several antioxidants have been shown to prevent AMD-induced toxicity by antioxidant and/or non-antioxidant mechanisms. In the current study, we evaluated the possible protective effect, in vitro, of vitamin C on AMD-induced toxicity in rat thymocytes. Rat thymocytes were cultured with increasing AMD concentrations (1–20 μM) with or without vitamin C (1000 μg/ml), for 24 hours. Cells treatment with AMD resulted in a concentration-dependent increase of hypodiploid cells and a significant decrease in cellular glutathione content. Vitamin C combined with AMD significantly decreased the proportion of hypodiploid cells and markedly increased the cellular glutathione content, compared with AMD treatment alone. These results suggest that treatment with vitamin C may prevent AMD-induced toxicity in rat thymocytes by restoring cellular glutathione content.

The effects of one-year simvastatin therapy on women’s bone mineral density

Only few studies have reported that bone fracture risk is decreased in hypercholesterolemic postmenopausal women treated with statin therapy. Because of a lack of longitudinal studies on the effect of statins on bones, the aim of our investigation was to estimate the simvastatin therapy effects on bone mineral density in hypercholesterolemic postmenopausal women. Our investigation was carried out on 53 postmenopausal women with hypercholesterolemia. The women included in the study were divided into two groups. Group 1 was comprised of women with two or more (n=32) atherosclerosis risk factors, whereas group 2 had women with less than two (n=21) of these risk factors. All the women included in the study were placed on a hypocholesterolemic diet and the women in group 1 were additionally treated with 20 mg of simvastatin daily. The parameters of lipid status, body mass index, and L2–L4 densitometry were determined at baseline and then after one year. The simvastatin-treated group showed significant improvement of lipid parameters and increased bone mineral density. Finally, changes in bone mineral density between the groups showed significant differences (p<0.05). Although our investigation was carried out on a small group, our results showed a positive effect of the simvastatin therapy on the bone mineral density of postmenopausal women.

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.

Correlation between total cardiovascular risk and bone density in postmenopausal women

The aim of the paper was to examine the correlation between the total risk of cardiovascular events, determined by the SCORE (Systematic Coronary Risk Evaluation) system, and bone density in postmenopausal women. Examinees and method: The research involved 300 postmenopausal women. On the basis of bone density measurements, the participants were divided into three groups: group I — 84 examinees had osteoporosis, group II — 115 examinees had osteopenia, and group III — 101 examinees had normal bone mineral density (BMD). Results: Participants with high SCORE risk were statistically significantly older compared to low-risk women (60±3 vs. 55±5; p<0.001). They had significantly lower BMD and T scores (−1.09±0.94 vs. −2.86±0.63; p<0.001). Elevation of the SCORE risk by 1% caused a BMD decrease of 0.033 g/cm2(0.029 to 0.036 gr/cm2). Multivariate logistic regression analysis showed that the following factors caused a significant increase in the risk of decreasing BMD: every year of life by 20%, menopause duration by 26%, increase in systolic blood pressure (BP) by 1 mm Hg by 7%, increase in SCORE risk by 1% by 5.31 times, physical inactivity by 5.96 times, and osteoporosis in the family history by 3.91 times. Conclusion: Postmenopausal women who are at high risk for cardiovascular diseases have a lower BMD than those who are not at high risk for cardiovascular diseases.

Relation between bone mineral density and IL-17 serum levels in Serbian patients with early Rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and destruction of joint cartilage and bone. Different cytokines play important role in the processes that cause articular destruction and extra-articular manifestations in RA. The contribution of cytokines representing the Th1 (INF-γ), Th2 (IL-4) and IL-17A to the pathogenesis of early RA and bone mineral density (BMD) loss in still poorly understood. Serum samples of 38 early RA patients were evaluated for erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP) and for the tested cytokines (IL-17A, IL-4 and INF-γ). BMD was evaluated by dualenergyX-ray absorptiometry (DXA). Disease activity score (DAS28) calculation was assessed for all patients. Control serum samples were obtained from 34 healthy volunteers. The levels of tested cytokines were significantly higher (IL-17A, p<0.001; INF-γ, P<0.001; IL-4, P<0.01) in patients with early RA, compared to the healthy controls. In early RA patients, strong correlation of serum IL-17A was found with DAS28, ESR and CRP. Also, a significant negative correlation was found between serum INF-γ levels and the DAS28 score. Significantly positive correlation of BMD values and CRP, DAS28 IL-17A were also demonstrated. DXA analysis revealed that the most common site for osteoporosis was the lumbar spine followed by the femoral neck. BMD values significantly correlated with CRP, DAS28 score and IL-17A serum levels. The mean serum IL-17A levels, in patients with early RA, corresponded with disease activity, severity and BMD loss, indicating the potential usefulness of serum IL-17A in defining the disease activity and bone remodeling.

Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits

Background/Aim The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008). Conclusion In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft. [Projekat Ministarstva nauke Republike Srbije, br. 175021].

THU0116 Safety and efficacy of courses of rituximab in patients with rheumatoid arthritis - ritam study

Background Rituximab (RTX) is monoclonal antibody that selectively targets CD20+ B cells. The combination of RTX with MTX significantly improves disease symptoms in rheumathodi arthritis (RA) patients who have had an inadequate response to conventional DMARD therapy, and has been shown to improve quality of life in those patients. This is the only study that assessed efficacy and safety of RTX in daily practice in Serbia Objectives To determine the safety and efficacy of additional courses of RTX in patients with RA. Methods This is interim analysis of prospective noninterventional trial that enrolled 130 RA patients with inadequate response to previous biologic and/or synthetic DMARDs treated with RTX (age 50.37±11.59 years; 85.3% females and 14.7% males; disease duration 8.4±6.5 years). Patients were eligible for additional RTX courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited disease reactivation measeured by DAS28. Efficacy was assessed by DAS28 (number of tender and swollen joints, VAS-GH, sedimentation) and the disability index of the Health Assessment Questionnaire at baseline and 24 weeks after first, second and third course. Safety was assessed by the number and severity of registered adverse events (AE). Results 114 patients received >1 course of RTX (58 received 2 courses and 10 received 3 courses). Mean DAS28 scores decreased significantly from 6.41±0.97 at baseline to 4.91±1.65/4.33±1.23 and 3.86±1.43, 24 weeks after first/second/third RTX courses; p<0.001. The proportions of patients with low disease activity (DAS28<3.2) and in remission (DAS28<2.6), increased following third RTX course (4.3% and 17.4%) compared to baseline. Proportion of patients with moderate disease activity (DAS28, 3.2-5.1) increased after 3 RTX course from 7.8% to 60.9%. Total HAD-DI score, before and after third RTX course was 2,25 (1,19) and 1,37 (1,78), respectively; p<0,004. During the first/second/third courses AE were reported in 8/2/1 patients. No SAEs were reported. Conclusions During 3 courses of treatment, rituximab showed significant decrease of DAS28 and and increased quality of life measured by HAQ-DI questionnaire after each following rituximab course. Disclosure of Interest None Declared

FRI0479 Comparison of low field mri inflammatory findings on the hand in patients with rheumatoid arthritis and systemic sclerosis

Background Qualitative MRI assessment of hand inflammation in scleroderma (SSc) has been reported in only few MRI studies. However, there are no studies with quantitative assessment and differentiation of arthritis in SSc from other arthritides Objectives To compare low field MRI features- synovitis, bone marrow oedema (BME) and bone erosions, among patients with inflammatory hand pain in rheumatoid arthritis (RA) and systemic sclerosis (SSc). Methods 35 RA (EULAR/ACR 2010 criteria) and 82 SSc pts with clinical involvement of hand joints were consecutively included in the study. The 0.2T extremity contrast MRI was performed on the wrist and MCP joints of the more painful hand in all the pts. The inflammatory changes (synovitis, BME and bone erosions) were scored by two independent musculoskeletal radiologists who followed the recommendations of the OMERACT RAMRIS. Total scores were compared between SSc and RA groups of patients. Results 35 RA pts (mean age 54.3) and 82 SSc patients (mean age 54.5) with painful hands underwent 0.2T extremity MRI. Rheumatoid factor (RF) and anti-ciltrullinated protein antibodies (ACPA) were found in 74.3% and 89% RA pts, respectively, and in 14.6% and 13.4% SSc pts. Higher frequency of synovitis with statistically higher MRI score was observed in RA compared to SSc pts (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 erosions scored on the wrist and MCP joints were statistically higher in RA pts compared to SSc pts (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 BME scores were, also, statistically higher in RA pts compared to SSc on the wrist (18.60±5.01 vs. 6.84±7.43, p<0.001) and on MCP joints (9.09±4.27 vs. 4.04±4.76, p<0.001) Conclusions Our results suggest that painful hand in RA and SSc pts is associated with inflammatory changes on MRI: synovitis, erosions and bone marrow oedema. MRI scores of inflammation are much higher in RA than in SSc pts. MRI might help the physician to differentiate RA and SSc in pts with painful hand. Disclosure of Interest None Declared

AB0622 Significance of body mass index for the effect of bisphosphonate therapy in women with postmenopausal osteoporosis

Background Osteoporosis is generalized bone disease characterized by disturbed bone strength, consequently fracture predisposition increases. One of the risk factors for osteoporotic fractures is the Body Mass Index (BMI) and it is evaluated according to the following criteria: malnutrition- to 18 kg/m2, normal body weight - 20-25 kg/m2, overweight - 25-30 kg/m2 and obesity - over 30 kg/m2. Objectives To determine the significance of Body Mass Index for the effect of bisphosphonate therapy in women with newly diagnosed postmenopausal osteoporosis Methods 92 women, with newly diagnosed postmenopausal osteoporosis, were included in this research. According to BMI values, the patients were divided into groups of under 18, 18 to 25, 25 to 30 and over 30 kg/m2. The groups were homogenous in relation to other risk factors for the appearance of osteoporosis. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA) on the Hologic Discovery machine before the therapy, as well as, 12 months after the bisphosphonate therapy. Results T-score values and BMD during 12 month therapy with bisphosphonate the most increased in examinees whose BMI values were in the range of 25 to 30 kg/m2 (0,330±0,275), and the least in women with BMI below 18 (0,190±0,223), but ANOVA and Dante’s test did not confirm the existence of significant differences between all compared groups. Conclusions Statistically significant difference in the effect of the bisphosphonate therapy was not found in postmenopausal women with newly diagnosed osteoporosis nor with different body mass index. References Kanis JA. Diagnosis of osteoporosis and assessmentof fracture risk. Lancet 2002;359:1929-1936 Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Oden A. Assessment of fracture risk. Osteoporosis Int 2005;16(6):581-589 S. Ilić. Poremećaji ishrane. Interna medicina 2004;2:386-389 Epstein S. Update of current therapeutic options for the treatment of postmenopausal osteoporosis. Clin Ther. 2006; 28(2):151-173 Delmas PD. The use of bisphosphonates in the treatment of osteoporosis. Curr Opin Rheumatolog 2005;17(4):462-466 Asche S, Nelson R, McAdam-Marx C, Jhaveri M and Ye X. Predictors of oral bisphosphonate prescriptions in post-menopausal women with osteoporosis in a real-world setting in the USA. Osteoporosis international 2009; 1427-1436, 2009 Asomaning K, Bertone-Johnson E, Nasca P, Hooven F, Pekow P. Women with low BMI are at increased risk of osteoporosis. Journal of Women’s Health 2006; 15(9): 1028-1034 De Laet C, Kanis JA, Oden E, Johanson E. Body mass index as a predictor of fracture risk: A meta-analysis. International Osteoporosis Foundation and National Osteoporosis Foundation 2005 Ravn P, Cizza G, Bjarnason NH. Low Body Mass Index Is an Important Risk Factor for Low Bone Mass and Increased Bone Loss in Early Postmenopausal Women. Journal of Bone and Mineral Research 1999;14(9):1622–1627 Disclosure of Interest None Declared