Didem Kozaci

Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen.Methods55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied.ResultsThe levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents.ConclusionsIn this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.

The BTA stat test is nonspecific for hematuria: an experimental hematuria model.

PURPOSE An experimental hematuria model was designed to determine whether the bladder tumor antigen (BTA) stat test (Bion Diagnostics, Redmond, Washington) is influenced by microscopic or macroscopic hematuria. MATERIALS AND METHODS A total of 25 healthy subjects provided urine and blood samples for the study. All subjects had a negative BTA stat test initially. Normal urine was mixed with autologous blood to cause hematuria of 3 degrees of severity. The test was performed in each sample after the creation of hematuria. RESULTS BTA stat assay specificity in the presence of microscopic and gross hematuria was 80% and 24%, respectively. Results varied depending on the severity of hematuria, that is 20% for microscopic and 76% for gross hematuria. CONCLUSIONS The results of the BTA stat test in the presence of microscopic hematuria must be interpreted in regard to the degree of hematuria. The test is not reliable in urine samples with gross hematuria due to a high false-positive rate.

Fetuin-A and interleukin-18 levels in ankylosing spondylitis.

Aim:  Interleukin‐18 (IL‐18) and fetuin‐A have been implicated in atherosclerosis. Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased risk of atherosclerosis. The aim of the present study was to investigate possible abnormalities in IL‐18 and fetuin‐A levels in AS.

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

IntroductionThe current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA.MethodsThis study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerrs criteria, disease extent index-Takayasu, physicians global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay.ResultsUnacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity.ConclusionsThis study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity.

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis.

Effects of tibolone on abdominal subcutaneous fat, serum leptin levels, and anthropometric indices: a 6-month, prospective, randomized, placebo-controlled, double-blind study.

This study was undertaken to evaluate the effects of tibolone on abdominal subcutaneous fat, serum leptin levels (SLLs), and anthropometric indices, and to investigate potential relationships between SLLs, subcutaneous abdominal fat thickness, and anthropometric indices in postmenopausal women. In a 6-mo, prospective, randomized, double-blind, placebo-controlled study, 40 healthy postmenopausal women aged 42 to 67 y (mean: 50±4.7 y) were randomly assigned to 1 of 2 groups; during a 6-mo treatment period, the first group received tibolone (Livial® tablet; Organon, The Netherlands; 2.5 mg/d; n=19) and the other group was given placebo (n=21). Fasting SLLs determined by enzyme-linked immunosorbent assay, subcutaneous abdominal fat thickness assessed by ultrasound, and anthropometric indices of body weight, body mass index, waist and hip circumference, and waist-to-hip ratio (WHR) were recorded at the beginning and the end of the study. Statistical analyses were performed with Mann-Whitney, Wilcoxon, and Spearman tests.P values < .05 were considered significant. No significant differences between the 2 groups were reported in terms of all baseline characteristics. After 6 mo, body weight (+0.77±0.43 kg) and SLLs (+14.7±6.4 ng/mL) increased in the placebo control group, whereas waist circumference (-2.6±3.0 cm), hip circumference (-3.6±3.5 cm), and subcutaneous abdominal fat thickness (-4.3±4.8 cm) decreased significantly in the tibolone group (P < .05). At the end of the study, group comparisons revealed significant differences in waist and hip circumference and subcutaneous abdominal fat thickness (P < .05). At baseline, SLLs were correlated with subcutaneous abdominal fat thickness and all anthropometric indices except WHR (P < .05). Subcutaneous abdominal fat thickness was also highly correlated with all indices except WHR (P < .0001). Tibolone was found to decrease waist and hip circumference, as well as subcutaneous abdominal fat thickness. Also, tibolone appeared to attenuate weight gain and leptin increase. SLLs and subcutaneous abdominal fat thickness were positively correlated with all anthropometric indices except WHR.

Evaluation of various endothelial biomarkers in ankylosing spondylitis

Atherosclerosis has been shown to be increased in chronic inflammatory diseases including ankylosing spondylitis (AS). Impaired endothelial function, the first step in atherosclerosis, may be reflected by changes in various endothelial biomarkers of hemostasis and the release of several cellular adhesion molecules or cytokines. In this study, we investigated changes in the levels of various possible markers with regard to disease activity and treatment regimen with/without anti-TNF-α drugs. Fifty-six AS patients (44 males) and 27 controls (19 males) with no known cardiovascular risk factors were included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index, and patients were evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Cytokines and various endothelial biomarkers were measured in serum samples using commercially available ELISA kits. Age, sex, BMI, waist circumference, fasting glucose, MAP, lipids are all similar between patients and controls. von Willebrand factor (vWF), soluble thrombomodulin (sTM), and urotensin (UT-II) were found to be significantly higher in the sera of the patients compared to the controls. Treatment with anti-TNF-α compared to conventional therapy and disease activity in AS patients seemed to have no effect on the blood levels of UT-II, sTM, CD146, vWF, plasminogen activator inhibitor-1, tissue plasminogen activator, or the thrombin–antithrombin complex. The increased UT-II, sTM, and vWF in AS patient sera regardless of treatment and disease activity suggest an increased tendency for atherosclerosis.

Biocompatibility of MG-63 cells on collagen, poly-L-lactic acid, hydroxyapatite scaffolds with different parameters

Purpose In this study, osteoblast-like MG-63 cells were cultured on 3 different scaffold types composed of (a) collagen + poly-L-lactic acid (PLLA), (b) collagen + hydroxyapatite (HA; 30°C) or (c) collagen + hydroxyapatite (HA; 37°C) and produced with different porosities. Methods Biomechanical properties of the scaffolds were characterized by tensile strength measurements. Properties of the cell-seeded scaffolds were evaluated with scanning electron microscopy (SEM). Cell adhesion and proliferation capacities were evaluated. Alkaline phosphatase (ALP) levels in media were measured. Transmission electron microscopy (TEM) and histological analyses were used to assess morphological characteristics. Results Our results showed that collagen-based PLLA and HA scaffolds have good cell biocompatibility. MTT test showed that the scaffolds exhibited no cytotoxicity. According to the force and displacement data, collagen + HA at 37°C showed the highest mechanical strength and displacement. Conclusion The results suggest that collagen-based PLLA and HA scaffolds might improve osteoblastic growth in vitro and have biomaterial integration potential in possible therapeutic approaches for future clinical studies.

Evaluation of periostin and factors associated with new bone formation in ankylosing spondylitis: Periostin may be associated with the Wnt pathway

Periostin has been shown to be involved in bone anabolism through the regulation of Wnt‐β‐catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes.

AB0744 There is NO Relationship between Glucagon like Peptide-1 and Inflammation in Psoriasis and Psoriatic Arthritis: Table 1.

Background Several studies have found a higher prevalence of type 2 diabetes mellitus in patients with psoriasis and psoriatic arthritis (PsA). Interestingly, a complete remission of psoriasis has been observed following immediately after the gastric bypass surgery in obese diabetic patients before any weight loss could have occurred, most likely due to the increased levels of GLP-1. There have been also diabetic cases who have showed improvements in psoriasis under the treatment with GLP-1 receptor agonists and with dipeptidyl peptidase-IV (DPP-IV) inhibitors.GLP-1 was suggested to have anti-inflammatory effects in addition to its effects on glucose homeostasis. Objectives To investigate the GLP-1 level and its relationship with inflammation in patients with psoriasis and PsA. Methods This study included non-diabetic PsA patients and healthy controls. Disease activity was assessed in the patients by using “Composite Psoriatic Disease Activity Index (CPDAI)” which assessed five domains of disease: peripheral arthritis, dactylitis, enthesitis, axial involvement and skin findings. High-sensitive C-reactive protein (hs-CRP) levels were also investigated for the assessment of the disease activity. Fasting blood GLP-1 levels were measured in PsA patients by using ELISA method and compared with those measured in the controls. Results There were 97 PsA patients who fulfilled the CASPAR criteria. Fifty-seven healthy sex, age- and –body mass index (BMI) matched hospital workers were evaluated as controls (Table 1).14 patients had predominantly axial and 52 had predominantly peripheral disease. 22 (17.5%) were receiving corticosteroids. 12 patients (7.8%) were on anti-TNF treatment, 78 (%80.4) were on methotrexate.There was no statistically significant difference in the GLP-1 levels between PsA patients and healthy controls. GLP-1 levels in patients with active disease were also not different from inactive patients and controls. No difference was determined in GLP-1 levels between patients with predominantly axial and predominantly peripheral disease and healthy controls. GLP-1 levels in patients with psoriasis and PsA were not correlated with the other disease activity scores including BASDAI, DAS28, PASI and hsCRP levels. There was also no correlation between GLP-1 level and functional disease index (BASFI) and also health assessment parameters (HAQ, ASQoL). The subgroup analysis in patients who were not taking glucocorticoid treatment (n:27) revealed the similar results. Table 1. Demographic, clinical and laboratory features of the patients and controls Psoriatic arthritis, n=97 Healthy controls, n=57 P value Median age (yrs) 48 (25–65) 43 (31–57) 0.09 Sex, M/F 32/65 24/33 0.29 Median disease duration (yrs) 4 (0–43) Smoking status, % 28.9 40.4 0.15 GLP-1 (pmol/L) 15.2 (3.6–58.6) 15.3 (3–56.3) 0.77 Insulin (μIU/ml) 7.4 (2–24.7) 5.7 (2.5–14.2) 0.02 HOMA-IR 1.6 (0.4–5.6) 1.3 (0.4–3.3) 0.054 ESR (mm/h) 26 (2–100) 12 (3–35) <0.001 hs-CRP (mg/L) 4.9 (0.7–65.2) 1.5 (0.2–6.8) <0.001 * GLP-1: glucagon like polipeptid-1; HOMA-IR: insulin resistance; ESR: erythrocyte sedimentation rate; hs-CRP: high sensitive C-reactive protein. Conclusions The results of this study suggests that there is no significant relationship between GLP-1 and inflammatory process in patients with psoriasis and PsA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4514