Elhem Cheour

Bone mineral density in healthy Tunisian women

Interpretation of densitometric results requires a comparison with reference bone mineral density (BMD) values of normal age and sex-matched persons. Thus the aim of this study was to determine these values for healthy Tunisian women, to estimate the prevalence of osteoporosis and to compare our findings with other populations. A cross-sectional study of 1378 Tunisian women aged between 20 and 96 years was carried out using DXA (GE-Lunar Prodigy). Subjects with suspected conditions affecting bone metabolism were excluded. Measurements were taken at the lumbar spine and femoral neck. These values were expressed at T-scores, with reference to the mean BMD values of the group aged 20-40 years. The peak bone mass, estimated in this age group was 1.174+0.127 g/cm(2) at the lumbar spine and 1.016+/-0.118 g/cm(2) at the femoral site. It was attained respectively within the age of 25 years and 36 years. For both sites, the expected decline in BMD was shown when the successive age groups [40-49 years] and [50-59 years] were compared. Bone loss was rapid during the first 5 years after menopause. Thereafter BMD declined slowly but continually. The prevalence of osteoporosis in the women over 50 years of age, taking account of peak bone mass observed in our cohort, was 23.3% at the spine and 17.3% at the femoral neck with a combined prevalence of 23.4%. These rates attained respectively 30.4%, 11.8% and 32.9% when we considered the Italian values, which demonstrate the variability of osteodensitometric depending to the reference population adopted.

sFRP3 and DKK1 Regulate Fibroblast-Like Synoviocytes Markers and Wnt Elements Expression Depending on Cellular Context

ABSTRACT Context: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS. Materials and methods: RA and OA FLS were treated with sFRP3 and DKK1 for 6 days. Wnt signaling components (Wnt5a, LRP5 and β-catenin), Wnt target oncogenes (cyclin E1 and WISP1), and FLS markers (fibronectin and MMP3) were analyzed using western blotting and/or qRT-PCR. Results: Our data indicated that sFRP3 down-regulated the key gene β-catenin in RA FLS. sFRP3 decreased fibronectin, a well-known downstream effectors gene of Wnt/β-catenin pathway, and LRP5 expression in both RA and OA FLS. In OA FLS, sFRP3 induced increased expression of Wnt5a and MMP3 but did not affect their levels in RA FLS. On the other hand, DKK1 increased fibronectin expression in RA FLS and decreased its expression in OA FLS. Conclusion: Our results confirm the involvement of Wnt signaling in FLS transformation and show that two inhibitors of the same cascade can regulate differently the same elements and that a single inhibitor can initiate signaling depending on cellular context. Abbreviations: FLS: fibroblast-like synoviocytes; RA: rheumatoid arthritis; Wnt: Wingless; Fz: frizzled; LRP: Fz/low-density lipoprotein receptor protein; WISP1: Wnt1 inducible signaling pathway protein 1; sFRP: secreted Fz-related proteins; DKK: Dickkopf; OA: osteoarthritis; DMEM: Dulbecco’s modified Eagle’s medium; FBS: fetal bovine serum; PBS: phosphate buffered saline; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; ECL: enhanced chemiluminescence detection solution; MMP3: metaloproteinase 3; qRT-PCR: quantitative real-time polymerase chain reaction; S.D: standard deviation; CRD: cysteine-rich domain; MeCP2: methyl-CpG-binding protein; RANKL: nuclear factor-kappa B ligand.

Molecular basis of complement factor I deficiency in Tunisian atypical hemolytic and uremic syndrome Patients: CFI deficiency in Tunisian atypical hemolytic and uremic syndrome patients

The aim of the present study was to characterize the molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uremic syndrome patients with low factor I levels.

A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis

ABSTRACT The aim of our study was to assess the relationship between bone and cartilage remodeling biomarkers and joint damage in Rheumatoid Arthritis (RA), and to detect whether they have the capacity to predict the progression of joint disease assessment by computed tomography (CT) erosion score. We analyzed 65 female patients with established RA in our Rheumatology Department. Serum levels of bone and cartilage markers were measured: osteocalcin (OC), N-propeptide of type I collagen (PINP), collagen type I and II, C-telopeptide (CTX I, CTX-II) and cartilage oligomeric matrix protein (COMP). Radiography of both wrist and MCP joints were available. Two expert-readers independently scored articular damage and progression using the High-resolution low dose CT scan in a blinded fashion. 65 female patients with established RA with a median age of 44 years were included. The median disease-duration was two years and the median (Disease activity score) DAS 28 score at 4.46 [2.65–7.36]. The percentage of patient with low disease activity was 13.8%, while 55.4 and 30.8% for those with moderate and high disease activity respectively. The resorption bone markers were high in active versus non-active RA. Wrist and MCP erosion scores were also associated with RA activity. Our study shows that biomarkers of bone and cartilage collagen breakdown were related to specific joint erosion in RA and could predict subsequent radiographic damage in RA. Further larger scale longitudinal studies maybe needed to confirm our data.

Unusual Clinical Presentation of Stress Fracture

A 56 year old woman, presents with bilateral algic supra malleolar tumefaction. The tumefactions appeared spontaneously and at the same time three months before. The patient did not have a history of smoking. She has been menopaused for five years and was overweight with a BMI at 28. Standard x rays revealed a poorly limited opacity englobed by a discrete sclerocele. There was a unilamelleolar homogenous periostic reaction Figure 1a. This opacity was located in the malleolar Fibula and was more important on the left side.

AB0849 Spinal Brucellosis: A Study of 40 Cases in A Tunisian Hospital

Background Brucellosis is a major health problem in Mediterranean countries, including Tunisia. The clinical presentation of this zoonosis varies considerably, but osteoarticular involvement and spinal brucellosis particularly, is the commonest complication. Methods This study was carried out between 2006 and 2013. Forty patients with infectious spondylodiscitis hospitalized in the department of Rheumatology were analyzed. All patients were thoroughly interrogated, subjected to a rigorous clinical examination and a battery of investigations including: complete blood count, urine analysis, blood culture, erythrocyte sedimentation rate, C-reactive protein (CRP) and serology for brucellosis. The imaging ordered including: plain X-ray of the lumbosacral spine, bone scan and magnetic resonance imaging (MRI) with contrast enhancement of the spine. Results Ten of the forty patients (25%) proved to have spinal brucellosis. The mean age of this patients was 51 years (range 15 – 68 years) and female/male ratio: 1,5. The mean delay of diagnosis was 7 months. The following symptoms were observed: fever in 9 patients and back pain in all patients. Other symptoms were less frequently observed, such as splenomegaly (one patient), peripheral adenopathy (two patients) and diarrhoea (one patient). Laboratory exams showed elevated erythrocyte sedimentation rate in most of them (8 patients), high levels of CRP in all patients and leukocytosis in 7 cases. Wright serology was positive in all of them. Brucella melitensis was isolated in blood cultures in 2 cases. Standard X-rays were performed in all patients; they showed signs of spondylodiscitis in the lumbar spine in 5 cases, cervical in one case and dorsal in two cases. CT-scan and MRI confirms the diagnosis and showed associated epiduritis (3cases) or abscess (4 cases). Bone biopsy and histopathological examination were performed in three cases. A combination of cycline and rifampicin was given to all patients. The duration of therapy was between 6 and 8 weeks. Conclusions Brucellosis is present with various clinical signs in endemic areas and may simulate many diseases. The need for prompt diagnosis and treatment of spinal brucellosis is of the utmost importance to prevent serious bone destruction and severe neurologic sequelae. Disclosure of Interest None declared

AB0902 Risk Factors of Osteoporosis in Hemodialysis Patients

Background Low bone mass is common in patients undergoing hemodialysis. Osteoporosis can be associated with serious bone health problems, especially fragility fractures. Objectives The aim of the study was to determine the frequency of osteoporosis in hemodialysis Tunisian patients and to identify the risk factors of low bone mass in this population. Methods We conducted a cross-sectional study over a period of 4 years [2009-2012] including 90 hemodialysis. Blood samples were drawn before hemodialysis session from patients. We measured calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (PTH). Bone mass density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and total hip. Using WHO criteria as a cutoff point, osteopenia was defined as a T-score lower than -1 and osteoporosis was defined as a T-score lower than -2.5. All statistical analysis were performed using the Windows SPSS 19 package. Results Ninety patients were included: 58 male (64%) and 32 female (36%). The mean age was 53.01±14.60 years. The mean age of onset of hemodialysis was 50.06±14.82 years. Serum calcium and phosphorus levels were respectively at 2.084±0.32 mmol/L and 1.84±0.57 mmol/L. The average rates of PTH and ALP were respectively at 425.70±380.78 pg/mL and 88.35±72.56 UI/L. Fifty six percent of patients have PTH values between 2 and 9 times the upper normal limit of the assay as recommended by KDIGO (Kidney Disease: Improving Global Outcomes). However, 19% of patients have PTH values less than 2 times the upper normal limit of the assay. The mean of BMD was 0.854±0.152 g/cm2 in the hip and 1.155±0.218 g/cm2 in the lumbar spine. Twenty three percent of patients have osteoporosis and 45% have osteopenia. Osteoporosis affected the hip (20%) more than the spine (5.5%). Regarding risk factors, femoral BMD had significant negative correlations with the with the following parameters: age (r:-0.289; p:0.006), age of onset of hemodialysis (r:-0.359; p:0.001) and PTH level (r:-0.275; p:0.009). However, no correlations was found between lumbar spine BMD and the following parameters: age, age of onset of hemodialysis, calcium, phosphorus and PTH level. Conclusions Our study showed that osteoporosis is common in dialysis patient [1]. The most common region of bone loss was the hip. The decrease in cortical BMD was associated with advanced age, age of onset of hemodialysis and elevated levels of PTH [2]. References Nybo M, Jespersen B, Aarup M, Ejersted C, Hermann AP, Brixen K. Determinants of bone mineral density in patients on haemodialysis or peritoneal dialysis–across-sectional, longitudinal study. Biochem Med. 2013;23(3):342-50. Huang GS, Chu TS, Lou MF, Hwang SL, Yang RS. Factors associated with low bone mass in the hemodialysis patients–a cross-sectionalcorrelation study. BMC Musculoskelet Disord. 2009; 4;10:60. Disclosure of Interest None declared

AB0307 Assessment Asymptomatic Preclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease with High Resolution CT and Pulmonary Function Tests

Background Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. Objectives The objective of this study was to define high-resolution chest CT (HRCT) and pulmonary function test (PFT) abnormalities to identify asymptomatic, preclinical forms of RA-ILD that may represent precursors to more severe fibrotic lung disease. Methods Our study is prospective. We collect 20 RA patients with no respiratory functional sign. All patients met the 1987 diagnostic criteria of the American College of Rheumatology (ACR). We analyzed chest HRCTs in consecutively enrolled RA patients and subsequently classified these individuals as RA-ILD or RA-no ILD based on the presence/absence of ground glass opacification, septal thickening, reticulation, traction bronchiectasis, and/or honeycombing. Coexisting PFT abnormalities (reductions in percent predicted FEV1, FVC) were also used to further characterize occult respiratory defects. Results Twenty patients were included in the study. Their demographic and clinical characteristics are summerized in the table below. Variable Value Total number 20 Gender (F/M) 16/4 Mean age (years) 50±22 Mean disease duration (years) 2.8±2 Early RA 15/20 DAS28 3.86±1.25 RF(+) 18/20 Anti-CCP 4/20 In this study, all RA patients were treated with combinations of DMARDs and cortico steroids (7.5 mg per day) that included methotrexate (MTX), with a dose ranging from 10 to 15 mg (mean at 12.33 mg) per week; however, only 4.6% of RA patients used Leflunomide (20 mg per day). In terms of additional environmental risk factors, the prevalence of smoking was very low (1/20). Radiographic abnormalities are objectified in 4 cases 20% of cases. The most common abnormality is represented by interstitial syndrome found in 3 cases: diffuse reticulomicronodular images in 2 cases and pleural thickening in one case. The results of our study showed a restrictive syndrome in 5 cases (25%) and a mixed syndrome in 1 case (5%). Among the 13 patients with ILD on HRCT, only 4 have a restrictive syndrome. As regards the restrictive syndrome (CVF equal to 69% of the theoretical in both cases), corresponding HRCT was normal. In the case of mixed syndrome CT revealed centrolobular and para septal emphysema predominantly in the bi upper lobe. Conclusions HRCT represents an effective tool to detect occult/asymptomatic ILD that is highly prevalent in our unselected, university-based cohort of RA patients. Disclosure of Interest None declared

SAT0291 Clinical Relevance of FGF-23 in Dialysis Tunisian Patients

Background Fibroblast growth factor-23 (FGF23) is a bone-derived hormone. The association between FGF-23 levels and clinical outcome in hemodialysis patients suggests that FGF-23 can be considered as a cardiovascular risk in this population, Moreover, relationship between FGF-23 and osteoporosis remains unclear in dialysis patients. Objectives The aim of the study was to demonstrate the association between FGF-23 levels with either osteoporosis and cardiovascular risk factors in hemodialysis patients. Methods We conducted a transversal study over a period of 4 years [2009-2012] including 80 patients under hemodialysis therapy over one year period. Blood samples were drawn before hemodialysis session from patients. We measured calcium, phosphate, 25 OH-vitamin D and fibroblast growth factor (FGF23). Bone mass density (BMD) was measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and total hip. Lumbar spine X-rays were used to diagnose vascular calcification. All statistical analysis were performed using the Windows SPSS 19 package. Results Eighty patients were included: 51 male and 29 female. The mean age was 53.27 years [20; 89]. The mean age of onset of hemodialysis was 50.42±14.49 years. The mean body mass index (BMI) was 25.91±4.86 kg/m2 and the mean weight was 68.16±13.36 kg. Diabetes, hypertension and dyslipidemia were observed respectively in 45%, 66.3% and 15% of cases. Serum calcium and phosphorus levels were respectively 2.06±0.39 mmol/L and 1.83±0.57 mmol/L. The average rates of parathyroid hormone (PTH), vitamin D and FGF23 were respectively 422.60±382.8 pg/mL 15.92±11.39 ng/mL, and 248.96±221.87 pg/mL. Osteoporosis affected the hip in 20% of cases and the spine in 9% whereas osteopenia was observed in 44% of cases in the hip and 33% of cases in the spine lumbar. Vascular calcifications (CV) were found in 31.11% of cases. Negative correlation was observed between FGF23 and vitamin D (r: -0.245, p: 0.027). Patients with dyslipidemia had higher FGF23 levels than patients without dyslipidemia (239.28 pg/mL vs 123.19pg/mL). No correlation was found between FGF23 and following parameters: calcium and phosphorus levels, PTH levels, BMI and weight. FGF levels 23 tend to be higher in hemodialysis with CV but this difference was not significant (275.85 pg/mL vs 195.88 pg/mL, p:0.231). Lumbar osteoporosis was associated with high concentrations of FGF23. Conclusions Our study showed that FGF-23 levels are increased in hemodialysis patients. We demonstrate also that higher concentrations of FGF23 are associated with osteoporosis in lumbar spine. Given the association FGF23 and dyslipidemia, this factor can be considered as a cardiovascular risk in hemodialysis patients. Disclosure of Interest None declared

SAT0235 Assessment of Achilles Enthesitis in the Spondyloarthritis by Colour Doppler Ultrasound

Background Enthesitis is the inflammatory process marked by the insertions of tendons, ligaments and joint capsules on the bone and it is the cardinal feature and diagnostic criteria of spondyloarthritis (SpA). Although, it is usually revealed by clinical examination, the enthesitis can be asymptomatic, both in the axial and peripheral skeleta. Objectives Our objective is to investigate by colour Doppler ultrasound (CDU) the modality and the frequency of involvement of Achilles enthesitis, the main site of involvement in SpA after calcaneal entheses, to identify its characteristic features, and to correlate these findings with clinical complaints and radiographic evidence. Methods Our study is prospective. Thirty patients with SpA diagnosis were included. The diagnoses were ankylosing spondylitis in 18 patients, psoriatic arthritis in 8, SpA associated with inflammatory bowel diseases (IBD) in 3, and Reiters disease in one patient. All of them were clinically evaluated and underwent CDU examination of Achilles entheses. Particular attention was given to the detection of enthesis thickness, structure, cortical bone insertion, junction between tendon and entheses, body of tendon, calcifications, erosions, bursae, power Doppler signal and vascularization. Results Patients male/female ratio was 4 (24/6), mean age was 30 (range 16-53) years and mean disease duration was 8 (range 1-13)years. Mean (SD) BASDAI and BASFI scores were 33 and 64 respectively. Twenty-three of the 30 SpA patients (76%) showed at least one abnormal finding of the enthesitis on CDU examination, affecting 43 of 60 Achilles entheses examined (71%). Only 11 Achilles entheses (18%) showed vascular signals in the periosteal areas or in the area of enthesis fibrocartilage. Ultimate correlations were found between pain and tenderness with increased vascularity. In addition, 29 (48%) and 8 (14%) of 60 Achilles entheses examined showed, respectively, cortical bone irregularities and erosions. Fourteen (87%) of 16 clinically detected Achilles enthesitis and 4 (57%) of 7 Achilles entheses with swelling on clinical examination presented corresponding abnormalities on CDU examination. CDU revealed Achilles tendon calcifications in 30% without significant correlation between talalgia or sex of patients but with excellent agreement with radiography. Deep retrocalcaneal bursitis was found in 3 (13%) and there was a significantly correlation with talalgia. Conclusions This study demonstrates the characteristic features of Achilles enthesitis detectable by CDU in the SpA and shows a good correlation with clinical as well as with radiography findings. It may be useful and complementary to the clinical evaluation to track down this reach of Achilles tendon. Further researches are needed to improve the role of CDU in diagnosis and follow up of SpA course. References Li CA, Kim HO, Lee SY, Lee SI. Assessment of Achilles enthesitis in the spondyloarthropathies by colour Doppler energy ultrasound in the context of the “enthesis organ”. Scand J Rheumatol. 2010 Mar;39(2):141-7. Disclosure of Interest None declared