Correlation of Fgf23 and Balp with Bone Mineral Density in Hemodialysis Patients.

BACKGROUND: Chronic kidney disease (CKD) is associated with numerous complications such as bone mineral disorder. The aim of our study was to analyze the correlation of bone turnover markers with Bone Mineral Density (BMD) measurements in Tunisian end stage renal diseases (ESRD) patients. METHODS: This study included 100 ESRD Tunisian patients. Their estimated glomerular filtration rate (eGFR) was < 15 mL × min-1 × (1.73 m2)-1, which requires hemodialysis. Bone-specific alkaline phosphatase (BALP) serum concentration was determined with a chemiluminescence immunoassay. Fibroblast Growth Factor 23 (FGF23) serum was assessed by Enzyme-Linked Immunosorbent Assay method. The serum levels of 25-Hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH) and Beta cross-laps (CTX) was measured by Electrochemiluminescence Technology. DEXA (dual-energy x-ray absorptiometry) technique was used to evaluate BMD. RESULTS: We observed a statistically significant negative correlation between BALP levels and total body BMD (r = -0.268; P = 0.015) particularly in femoral neck (FN) (r = -0.219; P = 0.037). BALP concentrations were negatively associated with total BMD especially in FN for patients with BMI < 30, FGF23 concentrations were also negatively correlated with BMD in lumbar spine site (LS) (r = -0.209; P = 0.046). For osteopenic patients we found an inverse correlation between 25(OH)D concentrations and BMD in LS position (r = -0.336; P = 0.038). In men group, we have also found a negative correlation between iPTH and total BMD (r = -0.326; P = 0.015). However we found a positive correlation between calcium expression and BMD in LS site (r = 0.270; P = 0.031). CONCLUSIONS: FGF23 and BALP can predict bone loss in ESRD through their strong correlation with BMD in LS and FN sites respectively.

[The role of type II collagen fragments and X-ray progression of knee osteoarthritis]. / Rôle des marqueurs de dégradation du collagène de type II au cours de la progression de l'arthrose du genou.

AIMS: To investigate the association between type II collagen fragments and the presence of knee osteoarthritis (OA) in the Tunisian population and to determine whether this biomarker can predict X-ray progression of this disease. METHODS: Type II collagen C-telopeptide (uCTX-II) and helical peptide (sHelix-II) were assessed in 125 female patients with knee osteoarthritis aged 54 ± 8 years over 2 years and 57 female age-matched controls. The markers were measured at baseline, 1 and 2 yrs' follow-up corresponding to x-ray time points. RESULTS: Only urinary CTX-II values were significantly 48% higher in knee OA patients compared with controls (p=0.001). The longitudinal changes over 2 yrs in Helix-II were also significantly associated with Joint Space Narrowing: JSN (p=0.03). Over the 2-yr study period average CTX-II levels were not significantly higher in progressor compared with non-progressor (339.96 vs 256.00; NS). CONCLUSION: The data presented here suggest that CTX-II may be useful to identify patients with knee OA. These results demonstrate significantly association between progression of this disease and alterations levels of Helix-II.

Prevalence of hemoglobin variants in a diabetic population at high risk of hemoglobinopathies and optimization of HbA1c monitoring by incorporating HPLC in the laboratory workup.

BACKGROUND: In Tunisia, diabetes mellitus and hemoglobinopathies are major public health problems. Glycated hemoglobin (HbA1c) is recommended for long-term monitoring of diabetes mellitus, but the presence of hemoglobin variants may interfere with HbA1c measurement. The aim was to determine the prevalence of hemoglobin variants in Tunisian diabetics and optimize the monitoring of diabetics using HbA1c. METHODS: The study enrolled 9,792 Tunisian diabetic patients. HbA1c was measured by cation-exchange high-pressure liquid chromatography (HPLC). All the chromatograms were analyzed for the presence of Hb variants. RESULTS: We identified 228 cases (2.33%) of Hb variants with D-10 HPLC (Bio-Rad): 191 with HbA/S trait, 27 with HbA/C trait, and 10 hemoglobin variants with the mention 'Variant-Window' on the chromatograms and subsequently identified as HbA/S on Variant I HPLC (Bio-Rad). Thus, the prevalence of HbS was 2.05%. We did not find any homozygous variant. All HbA1c results were reported to the treating physician. CONCLUSIONS: To evaluate glycated hemoglobin in populations with a high prevalence of hemoglobinopathies, we should use the HPLC method, which is easy, economical, and reliable. Based on an algorithm, hemoglobin variants visualized on HPLC should be reported to the physician to improve the management of patients.

Advantage of HbA1c assay by HPLC D-10 versus cobas integra 400 in a population carrier for HbS and HbC.

BACKGROUND: Several studies demonstrate significant bias in analytical methods used to measure glycohemoglobin. The clinical importance of that fact is evident when HbA1c overestimation leads to aggressive glucose management, resulting in more frequent hypoglycaemic episodes. Our study was aimed to compare two automated instruments (Integra 400 and D-10) in the evaluation of HbA1c in the Tunisian population. METHODS: Samples of 205 Tunisian diabetic patients were collected. The HbA1c assay was done simultaneously with a first generation immunoturbidimetric assay on an INTEGRA 400 (ROCHE) and using ionic exchange high pressure liquid chromatography (HPLC) on a D-10 system (BIO-RAD). RESULTS: Correlation is determined by linear regression analysis: D-10 = 0.921*(Integra 400) +1.125; coefficient of correlation (r) = 0.946. This r increases to 0.973 when samples of carriers for HbS and HbC (n = 9) are filtered out. For the carrier patients, significant differences in the percentage of HbA1c were observed relating to the methodology used. CONCLUSIONS: Laboratories must be aware of hemoglobin variant interferences on their methods of assessment of glycated hemoglobin. Using ion-exchange HPLC to control glycated hemoglobin seems to be essential to prevent mis-management in diabetic patients and to permit the diagnosis of the presence of HbS in patients.

Association of serum levels of aggrecan ARGS, NITEGE fragments and radiologic knee osteoarthritis in Tunisian patients.

OBJECTIVES: Proteolytic degradation of aggrecan is a hallmark of the pathology of osteoarthritis. The aim of this study was to develop enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of specific aggrecan fragments generated by aggrecanases-mediated cleavage. We investigated the relationships between these two aggrecan degradations fragments and urinary CTX-II levels. METHODS: The competitive ELISAs employ a polyclonal antibody raised against the aggrecan fragments containing two neoepitopes NITEGE(373)and (374)ARGSVI. We measured serum levels of ARGSV and NITEGE in 125 women with knee osteoarthritis (mean±SD age of 53.6±7.6 years, mean±SD disease duration of 3.6±3.8 years), and 57 women age-matched controls. RESULTS: Aggrecan neoepitopes assays showed an intra- and inter-assay imprecision (CV) lower than 20% for both tests and good linearity. Median serum ARGSVI (by 18%; P=0.002), and NITEGE (36.4%; P<0.001) levels were significantly decreased in patients with knee osteoarthritis compared with controls. Minimal joint space width was negatively correlated with ARGSVI (r=-0.368, P=0.04) and NITEGE (r=-0.274, P=0.038) in knee osteoarthritis patients. Median urinary CTX-II levels were significantly increased by 39.5% (P=0.001) in knee OA patients compared with controls. CONCLUSION: Markers of degradation aggrecan were analyzed for the first time in an African osteoarthritis population. These markers can be used to monitor aggrecanase activity in human joint disease. Their combination with CTX-II can improve clinical investigation of patients with osteoarthritis patients.

C-telopeptides of type I collagen in postmenopausal women: an experience in a Tunisian clinical laboratory.

AIM: The purpose of study was to evaluate the interest of C-telopeptides of type I collagen (CTX) in the diagnosis of osteoporosis in postmenopausal women and to define its cut-off value. METHODS: A transverse descriptive study enrolled postmenopausal women: 139 osteoporotic (G1) and 39 non osteoporotic (G2). The 2 groups were defined by bone density measurement. The following markers were measured: serum alkaline phosphatase (ALP), bone alkaline phosphatase (bone ALP), serum C-terminal telopeptide of type I collagen (CTX). Statistical analyses were performed using SPSS 10.5. The corresponding estimation of sensitivity and specificity of CTX have been presented as 'receiver Operating Curve' (ROC). RESULTS: There was no difference in the measurement of ALP and bone ALP in the 2 groups but CTX was statistically higher in G1 compared to G2 (p <0.001). The percentage of osteoporotic women (G1) with CTX values > 0.500 ng/ml was higher than that of non osteoporotic women (G2). We have established a ROC curve to find the cut-off value of CTX that enables the distinction between osteoporotic women with high level of bone remodelling, and non osteoporotic women. The cut-off value of CTX 0.55 pg/ml was the best; it associated best sensitivity and specificity. CONCLUSION: The total increase and significance for CTX was greater in the group of osteoporotic women and appeared therefore to be a good bone turnover marker in the diagnosis of osteoporosis in comparison with ALP and bone ALP. The cut-off value of CTX 0.55 pg/ml may improve the sensitivity and specificity of prediction of future fractures.

[The interest of biochemical markers of bone turnover for monitoring treatment of postmenopausal osteoporosis]. / Intérêt des marqueurs biochimiques du remodelage osseux dans le suivi du traitement de l'ostéoporose post-ménopausique.

BACKGROUND: Postmenopausal osteoporosis is especially female pathology, whose incidence increases with age. AIM: The purposes of this study are to evaluate the level of bone turnover by the determination of markers of bone formation (PAL, BAP) and marker of bone resorption (CTX) in the osteoporotic women, to study the correlations between bone biochemical markers, clinical parameters and radiological measurements and to assess the interest of biochemical markers therapeutic monitoring after 6 months of antiresorptive treatment. METHODS: The authors report a prospective study of 134 osteoporotic women classified in two groups according to the presence of osteoporotic fracture. Patients of the first group G1 (n=102) with fractures, were treated by the bisphosphonates (risedronate), whereas the ones of the second group G2 (n=32) without fractures, were submited to calcic supplementation and vitamin D. RESULTS: The analyses showed that the femoral and lumbar BMD were statistically lower in the presence of osteoporotic fractures. However, the values of CTX were statistically higher in the patients of G1 group compared to those of the G2 group (0,708 +/- 0,332 ng/ml versus 0,514 +/- 0,225 ng/ml). The CTX were statistically correlated with the femoral and lumbar BMD (r = -0,21, p<0,05 and r= -0,348, p<0,001). The hypovitminosis were observed in 50,98% (52/102) of women with ostéoporotic fractures, whereas it was only 25% (8/32) in women without fractures. After 6 months of treatment by the bisphosphonates, the PAL, the BAP and the CTX have decreased with an average of, respectively, 19%, 46,5% and 62,9%. These variations were significantly more important in G1 group. CONCLUSION: The biochemical markers of bone turnover, in particular those of the resorption (CTX), can predict the postmenopausal woman's bone loss evaluated by BMD, the risk of fractures and the efficiency of the bone treatments.

[Biochemical markers of bone remodeling: recent data of their applications in managing postmenopausal osteoporosis]. / Marqueurs biochimiques du remodelage osseux: données actuelles sur leurs applications dans l'exploration de l'ostéoporose post-ménopausique.

The recent development of new biochemical markers has considerably improved the non invasive exploration of bone turnover. Currently, the most sensitive markers to access bone formation are osteocalcin, bone alkaline phosphatase and N-terminal propeptide of type I procollagen. Blood or urinary immunoassays of pyridinoline, deoxy-pyridinoline and terminal telopeptides type I of collagen are currently the best indices to evaluate the bone resorption. The principal application fields of biochemical markers in postmenopausal osteoporosis, in combination with the measurement of the bone mineral mass, are primarily the monitoring of anti-resorptive therapy response and prediction of bone loss and risk of fractures. In fact, treatment with anti-resorptive drugs is followed by rapid decrease of bone markers levels (3 months for the markers of resorption and 6 months for those of osteo-formation ), whereas the bone mineral density measurements requires at least two years to change significantly.