Marine toxin C17-SAMT causes major structural damage to vital organs in mice following subchronic toxicity trials.

C17-sphinganine analog mycotoxin (C17-SAMT) has been characterized as the contaminant responsible for the atypical toxicity reported in mussels from the Bizerte lagoon (northern Tunisia) over the past decade. C17-SAMT exhibited common symptoms of toxicity in mice, including flaccid paralysis and severe respiratory distress, followed by rapid death. To determine the potential health risks of this neurotoxin, we assessed its subchronic toxicity according to the recommendations of OCDE n° 407. The body weight and the structural changes of vital organs were recorded. Biochemical and hematological parameters were also quantified. Macroscopic observations showed that mice treated with 0.9, 9, and 90 µg/kg C17-SAMT had significantly reduced stomach weights, swollen and fragile intestines, and signs of nephritis with renal abscesses. Transaminase assays pointed out that exposure to C17-SAMT can lead to transaminitis. Above-average lactate dehydrogenase values were recorded in both the treated and satellite groups. Hematology data showed a significant reduction in red blood cell counts in high-dose-treated group. Reductions in hemoglobin and hematocrit were also recorded. Mean leukocyte counts were significantly elevated in the high-, mid-dose treated and satellite groups. At the microscopic level, we noted myocardial atrophy and hyperemia. In the lungs, we noted necrosis associated with macrophages perivascular infiltration and congestion. The kidneys showed mild inflammation and glomerular atrophy. The stomach exhibited mucosal atrophy, while a thin colon and distended small intestine were observed in high-dose-treated group. The liver was affected by vascular congestion, inflammatory infiltration, and lobular necrosis that evolved into acute hepatitis. Lesions, such as inflammatory infiltration and mild necrosis of the liver, cortical abscess with central necrosis in the kidney, and mild congestion of cardiac tissue were recorded in the satellite group.

New Markers of Bone Fragility in Hemodialysis Patients: A Monocentric Study.

INTRODUCTION: Mechanisms underlying bone fragility in patients under dialysis are various. The assessment of bone disorder is not yet codified in these patients. Our study aimed to determine the relationship between the serum fibroblast growth factor 23 (FGF23) level and bone fragility. We also aimed to assess the bone alkaline phosphatase (bAP) to the C-terminal telopeptide of type I (CTX) ratio and the FGF23*bAP product to CTX ratio in patients under hemodialysis. METHODOLOGY: We conducted a cross-sectional study, including 76 patients under hemodialysis. To assess bone fragility, we measured bAP, CTX, and FGF 23. We calculated the bAP to the CTX ratio (bAP/CTX) and the FGF23*bAP product to the CTX ratio (FGF23*bAP/CTX). We defined bone fragility as the existence of osteoporosis or fragility fractures. Receiver operating characteristic (ROC) curves were evaluated for each biological using the existence of osteoporosis or fragility fracture as the gold standard for bone fragility. RESULTS: There were 51 men. The mean age was 53.36 ± 14.27 years. Bone fragility was noted in 25 cases. Patients with osteoporosis had higher FGF*bAP/CTX and bAP/CTX ratios. The ability of the ratio (bAP/CTX) to distinguish patients with osteoporosis from those without osteoporosis was good, with a ROC AUC of 0.707. The optimal ratio cut-off value with the highest accuracy was 9.72. The ability of the ratio (FGF23*bAP/CTX) to distinguish patients with bone fragility was good, with a ROC AUC of 0.701. The optimal ratio cut-off value with the highest accuracy was 1621.89 (sensitivity 60%, specificity 78.4%). CONCLUSION: Our study showed FGF23, FGF23*bAP product to CTX ratio, and the bAP to CTX ratio can be used as markers of bone fragility in hemodialysis patients. Therefore, these noninvasive and relatively inexpensive methods may serve to diagnose bone fragility in patients under hemodialysis.

Prevalence and risk factors for vitamin D deficiency in Crohn disease patients: A Tunisian study.

INTRODUCTION: Vitamin D plays a role in regulating the immune response through an immunomodulatory effect, and is probably involved in the pathophysiology of Crohn's disease (CD). AIM: to assess vitamin D status in patients with CD as well as in healthy controls and to determine associated factors of vitamin D deficiency in patients with CD. METHODS: We conducted a prospective study over 18 months, including CD patients with age and sex matched with healthy controls. Suboptimal vitamin D status was defined by vitamin D serum level < 30 ng/ml, vitamin insufficiency by vitamin D serum level between 10 and 30 ng/ml and vitamin deficiency serum level < 10 ng/ml. RESULTS: We included 77 subjects (52 patients with CD and 25 controls) with mean age of 38 years± 11. Most patients and controls had suboptimal levels of vitamin D (98% and 96% respectively) including vitamin D deficiency in 75% and 67%, respectively and vitamin D insufficiency in 25% and 33%, respectively. In univariate analysis, vitamin D deficiency was associated with disease flare-up (p=0.001), anemia (p=0.002), hypo-albuminemia (p=0.002), elevated C-reactive protein (CRP) (p=0.003), Crohn's Disease Activity Index (CDAI) (p<0.001), ileal location (p=0.04) and immunosuppressive therapy (p=0.01). In multivariate analysis, only CDAI was significantly associated with vitamin D deficiency (p=0.003, OR=9.33). CONCLUSION: Vitamin D deficiency is common in Tunisian CD patients as well as in controls and is associated with disease activity.

The first exome wide association study in Tunisia: identification of candidate loci and pathways with biological relevance for type 2 diabetes.

Introduction: Type 2 diabetes (T2D) is a multifactorial disease involving genetic and environmental components. Several genome-wide association studies (GWAS) have been conducted to decipher potential genetic aberrations promoting the onset of this metabolic disorder. These GWAS have identified over 400 associated variants, mostly in the intronic or intergenic regions. Recently, a growing number of exome genotyping or exome sequencing experiments have identified coding variants associated with T2D. Such studies were mainly conducted in European populations, and the few candidate-gene replication studies in North African populations revealed inconsistent results. In the present study, we aimed to discover the coding genetic etiology of T2D in the Tunisian population. Methods: We carried out a pilot Exome Wide Association Study (EWAS) on 50 Tunisian individuals. Single variant analysis was performed as implemented in PLINK on potentially deleterious coding variants. Subsequently, we applied gene-based and gene-set analyses using MAGMA software to identify genes and pathways associated with T2D. Potential signals were further replicated in an existing large in-silico dataset, involving up to 177116 European individuals. Results: Our analysis revealed, for the first time, promising associations between T2D and variations in MYORG gene, implicated in the skeletal muscle fiber development. Gene-set analysis identified two candidate pathways having nominal associations with T2D in our study samples, namely the positive regulation of neuron apoptotic process and the regulation of mucus secretion. These two pathways are implicated in the neurogenerative alterations and in the inflammatory mechanisms of metabolic diseases. In addition, replication analysis revealed nominal associations of the regulation of beta-cell development and the regulation of peptidase activity pathways with T2D, both in the Tunisian subjects and in the European in-silico dataset. Conclusions: The present study is the first EWAS to investigate the impact of single genetic variants and their aggregate effects on T2D risk in Africa. The promising disease markers, revealed by our pilot EWAS, will promote the understanding of the T2D pathophysiology in North Africa as well as the discovery of potential treatments.

Whole-exome sequencing reveals novel variants of monogenic diabetes in Tunisia: impact on diagnosis and healthcare management.

Introduction: Monogenic diabetes (MD) accounts for 3%-6% of all cases of diabetes. This prevalence is underestimated due to its overlapping clinical features with type 1 and type 2 diabetes. Hence, genetic testing is the most appropriate tool for obtaining an accurate diagnosis. In Tunisia, few cohorts of MD have been investigated until now. The aim of this study is to search for pathogenic variants among 11 patients suspected of having MD in Tunisia using whole-exome sequencing (WES). Materials and methods: WES was performed in 11 diabetic patients recruited from a collaborating medical center. The pathogenicity of genetic variation was assessed using combined filtering and bioinformatics prediction tools. The online ORVAL tool was used to predict the likelihood of combinations of pathogenic variations. Then, Sanger sequencing was carried out to confirm likely pathogenic predicted variants among patients and to check for familial segregation. Finally, for some variants, we performed structural modeling to study their impact on protein function. Results: We identified novel variants related to MD in Tunisia. Pathogenic variants are located in several MODY and non-MODY genes. We highlighted the presence of syndromic forms of diabetes, including the Bardet-Biedl syndrome, Alström syndrome, and severe insulin resistance, as well as the presence of isolated diabetes with significantly reduced penetrance for Wolfram syndrome-related features. Idiopathic type 1 diabetes was also identified in one patient. Conclusion: In this study, we emphasized the importance of genetic screening for MD in patients with a familial history of diabetes, mainly among admixed and under-represented populations living in low- and middle-income countries. An accurate diagnosis with molecular investigation of MD may improve the therapeutic choice for better management of patients and their families. Additional research and rigorous investigations are required to better understand the physiopathological mechanisms of MD and implement efficient therapies that take into account genomic context and other related factors.

Prevalence and risk factors of diabetes mellitus and hypertension in North East Tunisia calling for efficient and effective actions.

Diabetes and hypertension are a serious public health problem worldwide. In the last decades, prevalence of these two metabolic diseases has dramatically increased in the Middle East and North Africa region, especially in Tunisia. This study aimed to determine the prevalence of type 2 diabetes (T2D) and High Blood Pressure (HBP) in Zaghouan, a North-East region of Tunisia. To this end, an exploratory study with stratified random sampling of 420 participants has been carried out. Various data were collected. Blood samples and urine were drawn for biochemical assay. Then, all data were analyzed using the statistical R software. Results showed an alarming situation with an inter-regional difference in prevalence of obesity (50.0%, CI 95.0%), HBP (39.0%, CI 95.0%) and T2D (32.0%, CI 95.0%). This study allowed the discovery of 24, 17 and 2 new cases of T2D, HBP and T2D&HBP respectively. The association of some socio-economic factors and biochemical parameters with these chronic diseases has been highlighted. To conclude, the health situation in the governorate of Zaghouan requires urgent interventions to better manage the growing epidemic of non-communicable diseases (NCD) in the region. This study demonstrated the importance of engaging health policy makers in road mapping and implementing national NCD prevention programs.

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.

The Role of Dietary Intake in Type 2 Diabetes Mellitus: Importance of Macro and Micronutrients in Glucose Homeostasis.

The prevalence of Type 2 diabetes (T2D) is increasing worldwide. Genetics and lifestyle, especially diet, are contributing factors. Analyses of macro- and micronutrient intake across global populations may help to explain their impact on glucose homeostasis and disease development. To this end, 420 Tunisians were enrolled in a prospective cross-sectional study of daily food consumption. Various data were collected and blood samples were drawn for biochemical assay. A 24-h recall questionnaire was obtained from participants to evaluate dietary intake. Statistical analyses were conducted using Nutrilog and R software. Biochemical analyses stratified the studied population (n = 371) into three groups: diabetics (n = 106), prediabetics (n = 192) and controls (n = 73); 49 subjects were excluded. Our results showed that Tunisians had hypercaloric diets high in carbohydrates and fat with variability in the levels of some vitamins and minerals, including riboflavin and niacin, that were statistically different among groups. The lower intake of vitamin D was associated with a greater risk of T2D. Higher vitamin A and sodium intake were associated with poor glucose homeostasis, although protein intake may improve it. In perspective, nutrigenomic studies can provide insight into problematic diets and poor eating habits and offer opportunities to analyze the effects of behavioral changes that can mitigate T2D development and progression.

Vitamin D in healthy Tunisian population: Preliminary results.

Background: Vitamin D deficiency is one of the most common medical conditions worldwide. In Tunisia, several studies evaluated Vitamin D status, but this was concerning specific populations (pregnant women, obese or diabetic patients and children with asthma). The only study that evaluated Vitamin D status in a healthy Tunisian population was conducted by Meddeb and associeties in 2002. The update of data available, based on the currently recommended limits, is necessary. This study aimed to estimate the prevalence of hypovitaminosis D in a healthy Tunisian population, and correlate the values with potential risk factors. Methods: It was conducted on 209 Tunisian healthy subjects. Data collected included clinical characteristics and dietary intakes. We measured 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), glycemia, creatinine, calcium, phosphorus, and alkaline phosphatase concentrations. Hypovitaminosis D was retained for 25(OH)D concentrations <75 nmol/L. Vitamin D deficiency was defined by 25(OH)D concentrations <25 nmol/L. Results: The prevalence of hypovitaminosis D and vitamin D deficiency were respectively 92.3% and 47.6%. The main factors that were significantly associated with low vitamin D levels in our multivariate analysis were veiling, living in rural areas and sunscreen use. However, sex, age, socioeconomic level, phototype, solar exposure score, smoking and bone mass index, were not statistically associated with hypovitaminosis D. The study of relationship between vitamin D status and serum PTH levels showed a significative and negative correlation (P < 0.005). Conclusions: Given the high prevalence of vitamin D, an adapted health policy is essential. A widespread vitamin D supplementation and food fortification seems to be necessary in Tunisia.

Association of HNF1A gene variants and haplotypes with metabolic syndrome: a case-control study in the Tunisian population and a meta-analysis.

BACKGROUND: Variants in the Hepatocyte Nuclear Factor 1 Alpha gene (HNF1A) are associated with lipoproteins levels and type 2 diabetes. In this study, we aimed to assess the association of HNF1A gene and haplotypes with the metabolic syndrome (MetS) and its components through an association study in the Tunisian population as well as by a meta-analysis. METHODS: A total of 594 Tunisian individuals were genotyped for three variants (rs1169288, rs2464196 and rs735396) located in HNF1A gene using KASPar technology. Statistical analyses were performed with R software. The association was furthermore evaluated through a meta-analysis of our results with those obtained in a Moroccan population. RESULTS: Our results showed no association between HNF1A variants and MetS in the Tunisian population. However, a significant association was observed between the variant rs735396 and a higher waist circumference. The stratified analysis according to the sex highlighted a significant association between the variant rs1169288 and high cholesterol levels only in women. Similarly, Haplotype analysis showed an association between the HNF1A minor haplotype and high total cholesterol mainly in women. Finally, our meta-analysis showed no association between HNF1A variants and MetS. CONCLUSIONS: Our findings exclude the involvement of the three HNF1A variants rs1169288, rs2464196 and rs735396 in the susceptibility to MetS in our studied Tunisian population but emphasize the role of these variants in the cholesterol homeostasis with sex-specific differences, which may serve to rise clinical consideration to early statin therapy in women carrying these genetic variants.

Effects of Zinc supplementation on serum copper to Zinc and CRP to albumin ratios in hemodialysis patients.

BACKGROUND: Zinc (Zn) deficiency is a common condition and could contribute to poor outcomes in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of Zn supplementation on serum copper (Cu) to Zn and C-reactive protein (CRP) to albumin ratios (CAR) in HD patients. METHODS: Seventy-seven HD patients were enrolled in a multicentre simple-blind randomized clinical trial. Only 37 HD patients completed the study; they were randomly divided into two groups and supplemented with zinc sulphate (n=17) or placebo (n=20) for two months. Serum Zn and Cu were measured by atomic absorption spectrophotometry. Serum albumin and hypersensitive-CRP were assessed by colorimetric and immunoturbidimetric method, respectively. Determinations were performed before and after supplementation. RESULTS: After two months of supplementation, serum Zn significantly increased, and Cu to Zn ratio decreased in Zn supplemented group, but remained unchanged in the placebo group. In parallel, serum albumin concentrations significantly increased, and CAR decreased in Zn supplemented group only. CONCLUSIONS: Zn supplementation reduces Cu to Zn and CRP to albumin ratios in HD patients. These changes point towards an improvement in nutritional, oxidative and inflammatory status. The study findings suggest that correcting Zn deficiency reduces poor outcomes in HD patients.

Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report.

Juvenile-onset diabetes may occur in the context of a rare syndromic presentation, suggesting a monogenic etiology rather than a common multifactorial diabetes. In the present study, we report the case of a young diabetic Tunisian patient presenting learning problems, speech deficits, short stature, brachydactyly, and a normal weight. Whole exome sequencing analysis revealed five heterozygous genetic variants in BBS1, BBS4, BBS8, MKS1, and CEP290. These genes are involved in the regulation of cilium biogenesis and function. We analyzed variant combinations pathogenicity using the recently developed ORVAL tool, and we hypothesized that cumulative synergetic effects of these variants could explain the syndromic phenotype observed in our patient. Therefore, our investigation suggested a genetic diagnosis of Bardet-Biedl syndrome with an oligogenic inheritance pattern rather than a monogenic diabetes. Although there is no curative therapy for this ciliopathy at the moment, a genetic diagnosis may offer other supportive care options, including the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension, as well as the genetic counseling for family members.

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.

Mineral bone disorder and osteoporosis in hemodialysis patients.

BACKGROUND: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. METHODS: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. RESULTS: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. CONCLUSIONS: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.

Effects of risedronate on bone turnover markers in osteoporotic postmenopausal women: comparison of two protocols of treatment.

BACKGROUND: Bisphosphonates are powerful agents able to prevent bone loss. AIM: The objective of the study was to evaluate the efficacy and tolerability of risedronate once a week (35 mg) compared with risedronate 5 mg once daily in women with osteoporosis. METHODS: A randomized, double-blind, active-controlled study enrolled 102 postmenopausal women aged 66.5+/-7.5 years with osteoporotic fractures. All women received risedronate during 6 months. Group 1 (G1, n=51) received risedronate 5 mg once daily and group 2 (G2, n=51) received 35 mg once a week. Serum alkaline phosphatase (ALP), bone alkaline phosphatase (bone ALP), serum C-terminal telopeptide of type I collagen (CTX) were measured at baseline, 3 months and 6 months after treatment in the two groups. RESULTS: We noted no significant difference in markers between women of the 2 groups. After 3 months, bone ALP and CTX decreased (respectively -22.1% and -47.6%) in the 2 groups with no significant difference between them. After 6 months study, bone ALP and CTX decreased respectively by -46.5% and -62.9% with no statistically significant difference between study groups for bone markers. CONCLUSION: Our study found that treatment with once weekly risedronate 35 mg is able to decrease CTX and bone ALP compared with risedronate 5 mg once daily, in postmenopausal women with osteoporotic fractures. We didn't find adverse events with the 35 mg once-a-week dose group compared to the once-daily dose group. Based on these results, the effects of risedronate 35 mg once a week are similar in efficacy to daily dosing and may lead less adverse events than once-a-month dose. This therapeutic protocol may provide an alternative for patients who prefer once-a-week oral dosing.

Effects of risedronate on bone turnover markers in osteoporotic postmenopausal women: comparison of two protocols of treatment.

AIM: Bisphosphonates are powerful agents able to prevent bone loss. The objective of the study was to evaluate the efficacy and tolerability of risedronate once a week (35 mg) compared with risedronate 5 mg once daily in women with osteoporosis. METHODS: A randomized, double-blind, active-controlled study enrolled 102 postmenopausal women aged 66.5 + 7.5 years with osteoporotic fractures. All women received risedronate during 6 months. Group 1 (G1, n=51) received risedronate 5 mg once daily and group 2 (G2, n=51) received 35 mg once a week. Serum alkaline phosphatase (ALP), bone alkaline phosphatase (bone ALP), serum C-terminal telopeptide of type I collagen (CTX) were measured at baseline, 3 months and 6 months after treatment in the two groups. RESULTS: We noted no significant difference in markers between women of the 2 groups. After 3 months, bone ALP and CTX decreased (respectively -22.1% and -47.6%) in the 2 groups with no significant difference between them. After 6 months study, bone ALP and CTX decreased respectively by -46.5% and -62.9% with no statistically significant difference between study groups for bone markers. CONCLUSION: Our study found that treatment with once weekly risedronate 35 mg is able to decrease CTX and bone ALP compared with risedronate 5 mg once daily, in postmenopausal women with osteoporotic fractures. We didn't find adverse events with the 35 mg once-a-week dose group compared to the once-daily dose group. Based on these results, the effects of risedronate 35 mg once a week are similar in efficacy to daily dosing and may lead less adverse events than once-a-month dose. This therapeutic protocol may provide an alternative for patients who prefer once-a-week oral dosing.

[Soluble tranferrin receptor in the biological diagnosis of iron deficiency. Report of 24 cases]. / Apport du récepteur soluble de la transferrine dans le diagnostic biologique de la carence en fer chez l'homme. A propos de 24 cas.

BACKGROUND: In inflammatory diseases, classical parameters of iron status (serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation) are not very reliable. AIM: The purpose of this study is to investigate soluble transferrin receptor, its index and classical parameters of iron status [serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation] during iron-deficiency anemia and combined iron deficiency and inflammatory anemia. METHODS: Our study concerned 24 patients: 18 patients with iron-deficiency anemia and 6 patients with combined iron-deficiency and inflammatory anemia. 55 healthy subjects were included as controls. Both groups underwent classical parameters of iron status [serum iron, serum ferritin, total iron-binding capacity of transferrin and transferrin saturation] and measurement of soluble transferrin receptor with its index. RESULTS: In iron-deficiency anemia, total iron-binding capacity of transferrin, soluble transferrin receptor and its index were enhanced, whereas serum iron, ferritinemia and transferrin saturation were low compared to controls. Compared to patients with iron-deficiency anemia, those with combined iron-deficiency and inflammatory anemia showed higher levels of serum iron and ferritinemia. In contrast, soluble transferrin receptor and its index did not vary significantly between both groups. CONCLUSION: Our findings show the interest of soluble transferrin receptor and its index in the detection of iron deficiency during anemia of inflammatory states.

Hypovitaminosis D in Tunisian osteoporotic postmenopausal women and the relationship with bone fractures.

AIM: The purpose of this study is to evaluate the frequency of hypovitaminosis D in Tunisian osteoporotic women and to search an eventual association between vitamin D status and the fracture risk. METHODS: A transverse descriptive study enrolled 134 osteoporotic menopausal women aged 50 years or more. We measured calcium, phosphorus, albumin, alkaline phosphatase, creatinine and 25 hydroxyvitamin D [25 (OH) vit D]. Bone mineral density (BMD) was measured for all and osteoporotic women were defined for a T-score of -2,5 or less in the spine, hip or femoral neck. Two groups were defined: G1 with fracture and G2 without fracture. We used SPSS 10.5, chi-2 tests and a statistical significance level of p<0,05. RESULTS: Women in G1 (n= 102) were more aged than those in G2 (n= 32) and their menopause was more ancient. Hypovitaminosis D was found in 45,2% of all women, respectively in 50,98% of G1 and 25% of G2. The mean level of vitamin D was more important in G2 (27,5 + 15,1 vs 21,3 + 12,8 ng/ml; p=0,002). BMD in femoral and lumbar were statistically lower when fractures are present (p<0,001). CONCLUSION: Our study shows that women with hypovitaminosis D (vit D < 20 ng/ml) are prone to osteoporotic fractures. All fracture in community in menopausal women, should be assessed with BMD and screening for 25 (OH) vit D. Increasing life expectancy in our country suggests that this public health problem will grow in the years to come, pointing out the importance of better management of osteoporosis and hypovitaminosis D to prevent fractures.

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.