Search results for: osteoprotegerin

Authors: Marek Kuźniewski, Magdalena B. Kaziuk , Danuta Fedak, Paulina Dumnicka, Ewa Stępień, Beata Kuśnierz-Cabala, Władysław Sułowicz

Abstract:

Background: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CaSc) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration. Cardiovascular and overall mortality data were collected during a 7-years follow-up. Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

Keywords: osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, receptor activator of nuclear factor kappa-B ligand, hemodialysis, chronic kidney disease, cardiovascular disease

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Authors: Oluwabori Emmanuel Olukoyejo, Ogra Victor Ogra, Bosede Amodu, Tewogbade Adeoye Adedeji

Abstract:

Background: Disorders of thyroid function are the second most common endocrine disorders worldwide, with a direct relationship with metabolic bone diseases. These metabolic bone complications are often subtle but manifest as bone pains and an increased risk of fractures. The gold standard for diagnosis, Dual Energy X-ray Absorptiometry (DEXA), is limited in this environment due to unavailability, cumbersomeness and cost. However, bone biomarkers have shown prospects in assessing alterations in bone remodeling, which has not been studied in this environment. Aim: This study evaluates serum levels of bone-specific alkaline phosphatase (bone-specific ALP), osteopontin and osteoprotegerin biomarkers of bone turnover in patients with disorders of thyroid function. Methods: This is a cross-sectional study carried out over a period of one and a half years. Forty patients with thyroid dysfunctions, aged 20 to 50 years, and thirty-eight age and sex-matched healthy euthyroid controls were included in this study. Patients were further stratified into hyperthyroid and hypothyroid groups. Bone-specific ALP, osteopontin, and osteoprotegerin, alongside serum total calcium, ionized calcium and inorganic phosphate, were assayed for all patients and controls. A self-administered questionnaire was used to obtain data on sociodemographic and medical history. Then, 5 ml of blood was collected in a plain bottle and serum was harvested following clotting and centrifugation. Serum samples were assayed for B-ALP, osteopontin, and osteoprotegerin using the ELISA technique. Total calcium and ionized calcium were assayed using an ion-selective electrode, while the inorganic phosphate was assayed with automated photometry. Results: The hyperthyroid and hypothyroid patient groups had significantly increased median serum B-ALP (30.40 and 26.50) ng/ml and significantly lower median OPG (0.80 and 0.80) ng/ml than the controls (10.81 and 1.30) ng/ml respectively, p < 0.05. However, serum osteopontin in the hyperthyroid group was significantly higher and significantly lower in the hypothyroid group when compared with the controls (11.00 and 2.10 vs 3.70) ng/ml, respectively, p < 0.05. Both hyperthyroid and hypothyroid groups had significantly higher mean serum total calcium, ionized calcium and inorganic phosphate than the controls (2.49 ± 0.28, 1.27 ± 0.14 and 1.33 ± 0.33) mmol/l and (2.41 ± 0.04, 1.20 ± 0.04 and 1.15 ± 0.16) mmol/l vs (2.27 ± 0.11, 1.17 ± 0.06 and 1.08 ± 0.16) mmol/l respectively, p < 0.05. Conclusion: Patients with disorders of thyroid function have metabolic imbalances of all the studied bone markers, suggesting a higher bone turnover. The routine bone markers will be an invaluable tool for monitoring bone health in patients with thyroid dysfunctions, while the less readily available markers can be introduced as supplementary tools. Moreover, bone-specific ALP, osteopontin and osteoprotegerin were found to be the strongest independent predictors of metabolic bone markers’ derangements in patients with thyroid dysfunctions.

Keywords: metabolic bone diseases, biomarker, bone turnover, hyperthyroid, hypothyroid, euthyroid

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Authors: I. Boroňová, J.Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, D. Gabriková, S. Mačeková

Abstract:

Osteoporosis is a complex health disease characterized by low bone mineral density, which is determined by an interaction of genetics with metabolic and environmental factors. Current research in genetics of osteoporosis is focused on identification of responsible genes and polymorphisms. TNFRSF11B gene plays a key role in bone remodeling. The aim of this study was to investigate the genotype and allele distribution of A163G (rs3102735) osteoprotegerin gene promoter and G1181C (rs2073618) osteoprotegerin first exon polymorphisms in the group of 180 unrelated postmenopausal women with diagnosed osteoporosis and 180 normal controls. Genomic DNA was isolated from peripheral blood leukocytes using standard methodology. Genotyping for presence of different polymorphisms was performed using the Custom Taqman®SNP Genotyping assays. Hardy-Weinberg equilibrium was tested for each SNP in the groups of participants using the chi-square (χ2) test. The distribution of investigated genotypes in the group of patients with osteoporosis were as follows: AA (66.7%), AG (32.2%), GG (1.1%) for A163G polymorphism; GG (19.4%), CG (44.4%), CC (36.1%) for G1181C polymorphism. The distribution of genotypes in normal controls were follows: AA (71.1%), AG (26.1%), GG (2.8%) for A163G polymorphism; GG (22.2%), CG (48.9%), CC (28.9%) for G1181C polymorphism. In A163G polymorphism the variant G allele was more common among patients with osteoporosis: 17.2% versus 15.8% in normal controls. Also, in G1181C polymorphism the phenomenon of more frequent occurrence of C allele in the group of patients with osteoporosis was observed (58.3% versus 53.3%). Genotype and allele distributions showed no significant differences (A163G: χ2=0.270, p=0.605; χ2=0.250, p=0.616; G1181C: χ2= 1.730, p=0.188; χ2=1.820, p=0.177). Our results represents an initial study, further studies of more numerous file and associations studies will be carried out. Knowing the distribution of genotypes is important for assessing the impact of these polymorphisms on various parameters associated with osteoporosis. Screening for identification of “at-risk” women likely to develop osteoporosis and initiating subsequent early intervention appears to be most effective strategy to substantially reduce the risks of osteoporosis.

Keywords: osteoporosis, real-time PCR method, SNP polymorphisms

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Authors: Najeeb Ullah Khan

Abstract:

Background: The receptor activator NF-κβ ligand (RANKL) and Osteoprotegerin (OPG) polymorphisms have been associated with the progression of breast cancer to bone metastasis. Here, we aimed to investigate the association of RANKL and OPG gene polymorphism with breast to bone metastasis in the Pashtun population, Pakistan. Methods: Genomic DNA was obtained from all the study subjects (106 breast cancer, 58 breast to bone metastasis, and 51 healthy controls). RANKL (rs9533156) and OPG (rs2073618, rs3102735) polymorphisms were genotyped using Tetra-ARMS PCR. Results: Our results indicated that the frequencies of OPG (rs3102735) risk allele and genotypes carrying risk allele in breast cancer vs healthy control (C- p=0.005; CC- p=0.0208; TC- p=0.0181), bone metastasis vs healthy control (C- p=0.0211; CC- p=0.0153; TC- p=0.0775), and breast cancer vs breast to bone metastasis (C- p=0.0001; CC- p=0.0001; TC- p=0.001) were found significantly associated with disease risk. However, there was no significant association observed for OPG (rs2073618) risk allele and risk allele containing genotypes in all study groups. Similarly, RANKL (rs9533156) risk alleles and corresponding genotypes in breast cancer vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.0084), bone metastasis vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.5593), and breast cancer vs breast to bone metastasis (C- p=0.0185; CC- p=0.6077; TC- p=0.1436) showed significant association except for the risk allele carrying genotypes in breast cancer to bone metastasis (TC, p=0.1436; CC, p=0.6077). Conclusion: OPG (rs3102735) and RANKL (rs9533156) showed significant association with breast to bone metastasis, while OPG (rs2073618) didn’t show a significant association with breast to bone metastasis in Pashtun population of Pakistan. However, more investigation will be required to disseminate the results while gene sequencing or whole-exome sequencing.

Keywords: breast cancer, bone metastasis, OPG, RANKL, polymorphism

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