Association Of Osteoprotegerin Research Articles

Association of osteoprotegerin and rankl levels with insulin resistance in pubertal obese children

Abstract Osteoprotegerin (OPG)/“receptor activator of nuclear factor kappa B-ligand” (RANKL) system has an important role in the remodeling of bone through regulation of osteoclastogenesis. We aimed to detect OPG and RANKL levels, particularly in obese children in the pubertal period and to investigate whether these parameters correlate with insulin resistance in childhood. Our study included 66 obese children ranging in age from 9.1 to 16 years, and 22 non-obese children ranging in age from 10.5 to 16 years. Blood glucose, insulin, total cholesterol, HDL cholesterol, and LDL cholesterol levels were measured for all cases; HOMA-IR, Quicki index and atherogenic index were calculated. Serum OPG and RANKL levels were also measured. OPG and RANKL levels did not show any difference between obese and non-obese children (P>.05). No difference in these 2 parameters were observed among the children with and without insulin resistance (P>.05). No correlation could be established between the OPG, the HOMA-IR, Quick and atherogenic indices. Obesity and insulin resistance are believed to show their effect in the later period of life to become able to change some of the parameters.

Association of Osteoprotegerin With Aortic Stiffness in Patients With Symptomatic Peripheral Artery Disease and in Healthy Subjects

Arterial stiffening is an independent predictor for cardiovascular mortality. Preliminary studies have shown that arterial calcification may have an impact on increased vascular stiffness. However, there are limited data about the role of calcification inhibitor osteoprotegerin (OPG) as an independent predictor for arterial stiffness in patients with peripheral arterial disease (PAD) and in healthy subjects. The aim of this study was to evaluate the association between OPG and arterial stiffness parameters in patients with PAD and in healthy subjects. We studied 69 men with PAD (age 63 + or - 7 years) and 68 healthy subjects (age 54 + or - 8 years). Serum OPG and oxidized low-density lipoprotein (oxLDL) were measured using the enzyme-linked immunosorbent assay method. Radial and aortic pulse wave velocity (aPWV) and augmentation index (AIx) were determined by applanation tonometry. The OPG (5.4 + or - 1.7 vs. 4.4 + or - 1.1 pmol/l; P < 0.001) and aPWV (10.1 + or - 2.5 vs. 7.6 + or - 1.6 m/s; P < 0.001) were different for the patients and for the controls. There was a linear relationship between OPG and aPWV in patients with PAD (R = 0.37; P = 0.003) and in healthy individuals (R = 0.40; P = 0.001). In multiple regression models after adjustment for potential confounders, OPG was independently associated with aPWV in the patients (R(2) = 0.47; P < 0.0001) and in the controls (R(2) = 0.44; P < 0.0001). The AIx or radial PWV was not correlated with OPG for either group. The independent association between OPG and aPWV in patients with PAD and in controls suggests that the calcification inhibitor OPG may influence aortic stiffening in atherosclerosis and in clinically healthy subjects.

Does osteoprotegerin relate to micro- and macrovascular complications in long-term type 1 diabetes?

Purpose. Markers of micro- and macrovascular disease are needed in type 1 diabetes in order to identify patients at risk of severe complications. Osteoprotegerin (OPG) is expressed in vascular myocytes, and increasing levels have been reported in type 1 diabetes. Consequently, we investigated OPG as a non-invasive marker of micro- and macrovascular complications in long-term type 1 diabetic patients. Methods. This was a cross-sectional study of 200 type 1 diabetic patients with long diabetes duration from a population-based cohort from Fyn County, Denmark. Patients were examined in 2007–2008, and OPG was measured and correlated to diabetes-associated complications: retinopathy, nephropathy, neuropathy and macrovascular disease. Results. Median age and duration of diabetes was 58.7 years (range 37.7–84.4 years) and 43 years (range 34–70 years), respectively. Median level of OPG was 1257 pg/ml (range 379–5706 pg/ml). In univariate analyses, OPG was related to age, duration of diabetes, female gender, nephropathy and inversely to diastolic blood pressure. In an age- and sex-adjusted model, higher levels of OPG were associated with a higher risk of nephropathy (OR 2.54, 95% confidence interval 1.09–5.90 for third vs. first tertile). Statistical significance was, however, lost in a multivariate model, and proliferative diabetic retinopathy, neuropathy and macrovascular disease was not associated with OPG in either model. Conclusions. Some associations of OPG and nephropathy were found in a long-term type 1 diabetic cohort. Prospective studies are needed in order to determine whether OPG can be used to predict nephropathy.

Osteoprotegerin: A Novel Independent Marker for Silent Myocardial Ischemia in Asymptomatic Diabetic Patients

We sought to evaluate osteoprotegerin, an inhibitor of osteoclastogenesis involved in atherosclerosis, and other novel risk factors as predictive markers of silent myocardial ischemia (SMI). A total of 465 consecutive diabetic patients with more than one additional risk factor were evaluated for SMI using stress myocardial perfusion imaging (MPI). We studied the association of SMI (positive stress electrocardiogram and/or abnormal MPI) with osteoprotegerin, other novel risk factors (lipoprotein[a], homocysteine, adiponectin, C-reactive protein, and fibrinogen), and conventional risk factors (total, LDL, and HDL cholesterol and triglycerides). A total of 92 patients were diagnosed with SMI. Of the six novel markers, osteoprotegerin was the only one associated with SMI; the relative risk (RR) of SMI in patients with osteoprotegerin values above the 75th percentile was 3.19 (95% CI 1.99-5.18; P < 0.001) in comparison with those with osteoprotegerin below the 75th percentile. In univariate analyses, the other plasma markers significantly associated with SMI were higher triglycerides (P = 0.04) and lower HDL cholesterol (P = 0.02). The association of osteoprotegerin with SMI remained significant after correcting for other variables associated with SMI at P < 0.15 in univariate analysis (RR 3.95 [95% CI 2.21-7.06]; P < 0.0001). The association of osteoprotegerin with SMI was observed in male (P < 0.0001) and female (P = 0.03) patients, in type 1 (P = 0.002) and type 2 (P = 0.0004) diabetic patients, in patients with (P = 0.0004) or without (P = 0.03) nephropathy, and in patients without (P < 0.0001) but not with (P = 0.2) peripheral arterial disease. Osteoprotegerin measurement, together with other conventional factors, can help to better define the diabetic population with an increased likelihood for SMI.

The Association of Osteoprotegerin with Cardiovascular Disease and the New York Heart Association Classification

Background and Objectives:Recent studies have suggested that there is a significant correlation between elevated serum Osteoprotegerin (OPG) levels and cardiovascular diseases. We investigated whether the serum OPG levels were associated with heart failure (HF), acute myocardial infarction (AMI) and unstable angina (UA), and whether the serum OPG levels were correlated with the NYHA classifications. Subjects and Methods:The serum OPG levels were measured in 127 patients suffering with HF, AMI and UA and they were hospitalized in the cardiology department, and these values were compared to 63 healthy controls. The NYHA classification was used to define the clinical disease severity. The serum OPG level was measured by performing ELISA. Results:The serum OPG levels were significantly higher in the patients with HF and AMI than those in the control subjects (p=0.003, p=0.002, respectively). The mean OPG levels were 555, 683, 774 and 856 pg/mL for the subjects and controls, according to the NYHA classifications II, III and IV, respectively. Multiple regression analysis revealed that the serum OPG levels were significantly associated with HF and AMI, and when all subjects were regrouped according to NYHA classification, the serum OPG levels were also significantly associated with the NYHA classification. Conclusion:The serum OPG levels were increased in Asian patients suffering with cardiovascular disease such as HF and AMI, and they were also increased with the NYHA classification. The serum OPG level could be a marker for different stages of cardiovascular disease. (Korean Circulation J 2007;37:353-358)

Assessment of a Serum Assay for Quantification of Abdominal Aortic Calcification

Intimal vascular calcification is an important marker of atherosclerosis, and its severity is an independent risk factor for cardiovascular events. Measurement of coronary or aortic calcification requires CT-based imaging and elaborate data analysis to ensure accuracy. A blood assay which could quantify the severity of vascular calcification would be less expensive, avoid exposure to radiation, and be more accessible than present imaging based methods. Osteoprotegerin (OPG) and osteopontin (OPN) are present in human serum and have been implicated in vascular calcification. In this prospective study we assessed the value of a number of serum assays for OPG and OPN in determining abdominal aortic calcification. Firstly, we investigated the assay characteristics and reproducibility of 5 ELISAs using a subset of patients. Based on the findings of these assessments, we selected 3 assays for full evaluation in the entire cohort.

Plasma Osteoprotegerin Is Associated with Mortality in Hemodialysis Patients

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients.