Osteoprotegerin Concentrations Research Articles

Alterations of the RANKL pathway in blood and bone marrow samples of prostate cancer patients without bone metastases

The receptor activator of the NF-kB ligand (RANKL) pathway is a key mediator of prostate cancer (PC)-induced bone disease. However, little is known about this pathway in patients with non-metastatic PC. We aimed to investigate whether changes of RANKL, its inhibitor osteoprotegerin (OPG) and bone marrow-mesenchymal stromal cells (BM-MSCs) occur in PC patients without manifest bone metastases. We determined OPG and soluble RANKL (sRANKL) in serum and corresponding bone marrow (BM) samples of 140 patients before radical prostatectomy by enzyme-linked immunosorbent assay (ELISA). As control serum samples of 50 patients with benign prostate hyperplasia were analyzed. BM mononuclear cells (BMNCs) of 16 PC patients were analyzed for expression of RANKL and CD271 (as marker for MSCs) by flow cytometry. PC patients had significantly lower serum levels of OPG compared to BPH patients (P = 0.007), whereas no differences were observed for serum sRANKL (P = 0.74). Both OPG and sRANKL concentrations of serum and corresponding BM samples correlated significantly (P < 0.0001 each). Interestingly, in PC patients, lower serum and BM OPG levels were associated with a higher proportion of BM-MSCs (P = 0.04 and 0.0016, respectively). No correlations were observed for sRANKL, OPG, BM-MSCs, and established risk parameters of PC. The results of the study indicate that localized PC is associated with early specific changes of the RANKL pathway in serum and bone marrow (BM). These changes might be part of the pre-metastatic niche of PC and implicate a potential benefit of RANKL inhibition in patients with localized PC.

Biochemical markers of bone metabolism in gingival crevicular fluid during early orthodontic tooth movement

To evaluate the expression of an activator of nuclear factor-kappa (RANK), osteoprotegerin (OPG), osteopontin (OPN), and transforming growth factor ß1 (TGF-ß1) in gingival crevicular fluid (GCF) of teeth subjected to orthodontic forces. A randomized, pilot clinical trial including 10 healthy volunteers was conducted using a split-mouth design. Orthodontic elastic separators were placed between the second premolar and first molar, with the contralateral quadrant serving as a control. The GCF samples were collected from the tension and compression sites at baseline, 24 hours, and 7 days after the placement of separators. The GCF sample volumes were measured using a Periotron 8000, and total protein concentrations were determined. Levels of RANK, OPG, OPN, and TGF-ß1 were also analyzed using a multiplex enzyme-linked immunosorbent assay. The control sites remained unchanged throughout the study. In contrast, the concentration of OPG significantly decreased at the compression site by 24 hours, and the amount and concentration of RANK differed significantly between the control, compression, and tension sites after 7 days. A significant increase in absolute TGF-ß1 levels was also detected at the compression site versus the control and tension sites after 7 days. Bone metabolism is affected by application of force to the teeth by elastic separators. Both increased expression of bone resorptive mediators (eg, RANK and TGF-ß1) and decreased expression of a bone-forming mediator (eg, OPG) on the compression side were detected.

Serum osteoprotegerin concentration is associated with carotid atherosclerotic plaque in patients with rheumatoid arthritis

Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients. Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined. Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA (P = 0.038). RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque.

Abstract 396: Serum Osteoprotegerin (OPG) Differs Significantly in Patients with Calcified Aortic Valve Stenosis in Relation to the Presence of Coronary Atherosclerosis

Background. We concentrated on OPG/RANKL in patients with symptomatic calcified AoS of the trileaflet valve, who were being considered for aortic valve replacement (AVR). Methods. Serum levels of cytokines were measured in: Group A (N = 101) patients with AoS and normal coronary arteries (assessed using coronary angiography), Group B (N = 105) patients with AoS and significant (stenosis &gt; 50%) coronary atherosclerosis. Control groups consisted of patients without AoS and with normal coronary arteries (group C, N = 39) or with significant coronary atherosclerosis (Group D, N = 30). Results. Values of OPG were significantly higher in patients with AoS and normal coronary arteries compared to controls with normal coronary arteries and without AoS. No difference was observed between levels of OPG in patients with AoS and CAD and control group of patients with CAD and without AoS. Multivariable analyses underscored these results (table). Serum levels of RANKL did not differ significantly between groups A vs. C. Serum OPG did not change significantly in patients after AVR (Group A). The difference in serum concentration of OPG in patients after AVR and CABG (Group B) was significant (p&lt;0.001). Conclusion. Serum OPG differs significantly in patients with calcified aortic stenosis in relation to the presence of significant coronary atherosclerosis. Our results suggest that OPG plays and important role in pathomechanism of calcified aortic valve disease in patients without coronary atherosclerosis

RANK, RANKL and OPG Expression in Breast Cancer - Influence on Osseous Metastasis.

In women, malignant breast tumours are among the most common malignant diseases in Europe. In advanced breast cancer, the risk of bone metastasis increases to 65-75 %. The discovery of the physiological bone metabolism parameters RANK (receptor activator of nuclear factor-κB), RANKL (receptor activator of nuclear factor-κB ligand) and OPG (osteoprotegerin) as well as their pathophysiological involvement in bone-related diseases is the subject of new therapeutic strategies. The formation of osteolytic bone metastasis requires increased osteoclast activity. Activation of osteoclasts by excessive direct RANKL or reduced OPG expression of osseous metastatic tumour cells remains to be elucidated. More than 50 % of primary breast cancer cells express OPG and RANK, while RANKL could be detected only in 14-60 %. Increased OPG concentrations in the serum of patients with bone metastases have been shown in several studies, whereas the RANKL results are described in an opposite manner. The use of OPG as a biomarker for the detection of osteolytic bone metastases is not consistent and needs to be proved in further studies. Increased RANKL activity was found in diseases characterised by excessive bone loss and formed the basis of new therapeutic options. In several studies, a human monoclonal antibody to RANKL (denosumab) was investigated for the treatment of bone diseases. Denosumab is a promising therapeutic option due to its bone-protective effects.

Osteoprotegerin Is Associated With Aneurysm Diameter and Proteolysis in Abdominal Aortic Aneurysm Disease

Serum osteoprotegerin (OPG) concentrations have previously been associated with growth of abdominal aortic aneurysms (AAAs). In vitro experiments showed that OPG promotes matrix metalloprotease (MMP) release from monocytes and vascular smooth muscle cells. We hypothesized that OPG expression is increased in human AAAs and is associated with proteolysis. AAA biopsies were collected from 329 patients. We assessed the concentrations of OPG, cathepsins A, B, and S as well as the activity of MMP-2 and MMP-9. The AAA wall infiltration by macrophages, lymphocytes, and plasma cells was estimated by immunohistochemistry. The concentration of OPG correlated positively with aortic diameter (<55 mm: 16.1 [5.8-28.7], 55-70 mm: 21.9 [10.2-36.0], >70 mm: 24.0 [13.5-52.9] ng OPG/mg total amount of protein, P=0.020), cathepsin A (r=0.221, P=0.005), B (r=0.384, P<0.001), and S (r=0.467, P<0.001), MMP-2 (r=0.180, P<0.001), MMP-9 (r=0.178, P<0.001), and the number of lymphocytes (P<0.001) and plasma cells (P=0.001). OPG immunostaining was predominantly demonstrated in plasma cells. The concentration of aortic wall OPG is positively associated with established markers of AAA severity and pathogenesis. OPG appeared to be associated with lymphocytes and plasma cells. These human data support previous experimental data suggesting a role for OPG in AAA pathogenesis.

Osteoprotegerin, leptin and IL-6: Association with silent myocardial ischemia in type 2 diabetes mellitus

Diabetic patients often exhibit severe, asymptomatic coronary artery disease (CAD). The relationship between osteoprotegerin (OPG), inflammatory markers and silent myocardial ischemia remains to be elucidated. We recruited 45 type 2 diabetic patients and 33 healthy controls and assessed them for silent myocardial ischemia (SMI) by myocardial perfusion imaging. Patient blood was tested for OPG, IL-6 and leptin concentrations. OPG, leptin and IL-6 levels were found significantly elevated in diabetic patients (p < 0.001, p < 0.01, p < 0.05). Based on our classification of presence/absence of SMI in our diabetic group, we found that there was a significant association between SMI and the biomarkers IL-6 (p < 0.001), leptin (p < 0.001) and OPG (p < 0.05). In multivariate regression analyses, OPG was found to be significantly related to diabetes mellitus and to SMI. Age, sex and smoking increased the association between OPG and SMI. High OPG, leptin and IL-6 levels are associated with the presence and severity of SMI in type 2 diabetic patients.

Role of the OPG/RANK/RANKL triad in calcifications of the atheromatous plaques: Comparison between carotid and femoral beds

Recent works demonstrated the difference of calcification genesis between carotid and femoral plaques, femoral plaques being more calcified. It has been clearly demonstrated that the molecular triad osteoprotegerin (OPG)/Receptor Activator of NFkB (RANK)/RANK Ligand (RANKL) exerts its activities in the osteoimmunology and vascular system. The aim of this study was to determine their expression and their potential role in calcifications of the atheromatous plaques located in two different peripheral arterial beds, carotid and femoral. The expression of OPG, RANK and RANKL was analyzed by immunochemistry in 40 carotid and femoral samples. Blood OPG and RANKL were quantified using specific ELISA assays. OPG staining was more frequently observed in carotid than in femoral plaques, especially in lipid core. Its expression correlated with macrophage infiltration more abundantly observed in carotid specimens. Surprisingly, serum OPG concentration was significantly lower in carotid population compared to femoral population while RANK and RANKL were equally expressed in both arterial beds. Carotid plaques that are less rich in calcium than femoral specimens, express more frequently OPG, this expression being correlated with the abundance of macrophages in the lesions. These data strengthen the key role played by OPG in the differential calcification in carotid and femoral plaques.

Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes

ObjectiveTo assess the relationship between osteoprotegerin (OPG) and cardiovascular death, and the pathobiological mechanisms contributing to the association, in acute coronary syndromes (ACS).DesignProspective observational.SettingBiomarker substudy of MERLIN-TIMI 36, a randomised,...

Serum Level of the Phosphaturic Factor FGF23 Is Associated with Abdominal Aortic Calcification in Men: The STRAMBO Study

Calcification inhibitor deficiencies, mineral imbalance, and phenotypic transformation of vascular cells to osteogenic cells initiate and sustain vascular calcification. Fibroblast growth factor-23 (FGF23) is a key molecule regulating mineral homeostasis. Our objective was to assess the association of serum FGF23 levels with mineral metabolism parameters and abdominal aortic calcification (AAC) in men. This was a cross-sectional analysis in the STRAMBO cohort. Men holding a private health insurance cover with Mutuelle de Travailleurs de la Région Lyonnaise were included in the study. Participants included male volunteers aged 20-87 (n = 1130). Nonfasting blood collection was done. AAC was semiquantitatively assessed from vertebral fracture assessment scans obtained using dual-energy x-ray absorptiometry. We evaluated the association between FGF23 concentration and AAC severity in men. In 350 men aged 60 yr or younger, FGF23 levels decreased with age (r = -0.21; P < 0.001) but were not associated with any other parameter. In 780 men aged over 60 yr, serum FGF23 correlated with age (r = 0.37; P < 0.001) and, after adjustment for confounders, with glomerular filtration rate (r = -0.31; P < 0.001) and PTH levels (r = 0.25; P < 0.001). After adjustment for confounders, self-reported ischemic heart disease, diabetes mellitus as well as higher concentrations of C-reactive protein and osteoprotegerin were all associated with higher FGF23 levels. After adjustment for confounders, subjects in the highest FGF23 quartile had higher prevalence of severe AAC compared with the three lower quartiles combined (odds ratio = 1.88; 95% confidence interval = 1.22-2.85; P < 0.005). In healthy older men, circulating FGF23 is associated with parameters of mineral metabolism, including bone metabolism-regulating cytokines, and with severe AAC independent of traditional risk factors.

Osteoprotegerin, but not osteopontin, as a potential predictor of vascular calcification in normotensive subjects

We conducted a cross-sectional observation study that included 500 asymptomatic subjects to investigate the relationship between bone metabolism and coronary artery calcification (CAC) in hypertensive conditions. Osteoprotegerin (OPG) and osteopontin (OPN) levels and their associations with hypertension were analyzed to predict CAC in 316 subjects. Multislice computed tomography was used to quantify CAC. Multivariate analysis of variance was used to test the non-interactive effects of hypertension, CAC severity and biomarker levels, and the logistic regression model was applied to predict the risk of CAC. OPG and OPN concentrations were significantly higher in the hypertensive than the normotensive subjects, at 3.0 (2.3-4.0) pmol l(-1) and 51 (21-136) ng ml(-1) vs. 2.4 (2.0-3.0) pmol l(-1) and 41 (13-63) ng ml(-1), respectively. The OPG level, but not OPN level, increased with age (r = 0.29; P = 0.0001). Zero or minimal CAC (<10 Agatston units (AU)) was observed in 63% of the subjects, mild (11-100 AU) in 17%, moderate (101-400 AU) in 12% and severe (401-1000 AU)-to-extensive (>1000 AU) in 8%. In hypertensive subjects, only glomerular filtration rate (GFR) (β = -0.67) and gender (β = 0.52) were significant predictors for CAC (R = 0.68). In normotensive patients, GFR (β = -0.81), gender (β = 0.48) and log-transformed OPG levels (β = 0.15) were significant predictors for CAC. OPG levels were associated with an increased risk of CAC in normotensive subjects only (odds ratio: 3.37; 95% confidence interval (1.63-6.57); P = 0.0002). OPG predicted a premature state of vascular calcification in asymptomatic normotensive individuals, and renal function significantly contributed to this process in both hypertensive and normotensive subjects.

Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: Novel involvement of glutathione S-transferases in bone remodeling process

Objectives Osteoporosis (OP) is an age-related disease associated with increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense system, such as low activity of glutathione S-transferase (GST) family. The enzyme activity of the member of GSTs, GSTP1, depends on gene polymorphisms such as: Ala114Val and Ile105Val. The aim of this study was to evaluate the association between genetic polymorphisms of the GSTP1 gene and BMD variation and biochemical bone remodeling markers in 523 Slovenian pre- and post-menopausal women. Study design Observational pilot study in a representative cohort of Slovenian patients with adjustment for potential confounders (age, height, weight, years since menopause, smoking status and glucocorticoid use) using univariate one-way and two-way analyses. Main outcome measures Ala114Val and Ile105Val polymorphisms genotypes of GSTP1 gene, bone mineral density (BMD) values of total hip (_th), femoral neck (_fn) and lumbar spine (_ls), plasma osteocalcin (OC), serum bone alkaline phosphatase (BALP), free soluble RANKL and serum osteoprotegerin (sOPG) concentrations were determined. Results Our results show that the Ala114Val heterozygotes are (borderline) significantly associated with higher concentrations of pOC ( p = 0.052) and decreased BMD_fn values ( p = 0.053) and the same trend is shown for BMD_th and BMD_ls values in osteopenic postmenopausal women. Furthermore, significantly higher concentrations of pOC were determined among Val allele carriers of Ile105Val gene polymorphism ( p = 0.037) and in carriers with the absent 114Ala–105Ile haplotype combination, again in osteopenic post-menopausal women. In addition, in pre-menopausal women the significant associations between sOPG and Ala114Val genotypes subgroups and between sBALP and Ile105Val genotypes subgroups, alone or in combination with Ala114Val, were determined (0.032, 0.026 and 0.008, respectively). Conclusions Since significant associations existed in Ala114Val genotype and 114Ala–105Ile haplotype subgroups, these variations can be useful for determining low BMD and high pOC risk in postmenopausal women.

Correlation of plasma osteoprotegerin (OPG) and receptor activator of the nuclear factor κB ligand (RANKL) levels with clinical risk factors in patients with advanced carotid atherosclerosis

SummaryBackgroundOsteoprotegerin (OPG) is considered to be a crucial regulatory mediator of bone metabolism by acting as a decoy receptor of the receptor activator of nuclear factor κB ligand (RANKL). OPG and RANKL have further become the subject of intense interest for their potential role in cardiovascular disease. The present study aimed to assess the clinical implication of plasma OPG and RANKL levels in patients with advanced carotid atherosclerosisMaterial/MethodsPlasma OPG and RANKL concentrations measured by solid-phase enzyme-linked immunosorbent assay (ELISA) were correlated with medical history, risk factors and medication intake in 131 patients who underwent carotid endarterectomy for vascular repair.ResultsPlasma OPG concentrations were associated with patients’ age (p=0.0258), homocysteine levels (p<0.00001), eGFR (p=0.0254), history of diabetes (p=0.0324), statins therapy (p=0.0044), hyperlipidemia (p=0.0407), smoking (p=0.0226) and CAD (p=0.0377). Plasma RANKL concentrations were associated with patients’ age (p=0.0191), homocysteine levels (p<0.00001), history of smoking (p=0.0185) and statins therapy (p=0.0004). Diabetes, CAD, smoking status, statins therapy and homocysteine were identified as independent predictors of OPG concentrations (p=0.0157, p=0.0030, p=0.0249, p=0.0047 and p=0.0072, respectively), whereas smoking showed an independent effect for RANKL (p=0.0010).ConclusionsThe present data reinforce the clinical utility of OPG in carotid atherosclerosis, whereas the clinical implication of RANKL seems uncertain.

Serum Osteoprotegerin is Increased and Predicts Survival in Idiopathic Pulmonary Arterial Hypertension

We previously reported that osteoprotegerin (OPG) is regulated by pathways associated with pulmonary arterial hypertension (PAH), and is present at elevated levels within pulmonary vascular lesions and sera from patients with idiopathic PAH (IPAH). Since OPG is a naturally secreted protein, we investigated the relationship between serum OPG and disease severity and outcome in patients with IPAH and animal models. OPG mRNA expression was measured in pulmonary artery smooth muscle cells (PASMC) from pulmonary arteries of patients with and without IPAH. Serum concentrations of OPG were measured in a retrospective and prospective group of patients. OPG levels were compared with phenotypic data and other putative PAH biomarkers. Prognostic significance was assessed and levels compared with healthy controls. Correlation of OPG and pulmonary vascular remodeling was also performed in rodent models of PAH. OPG mRNA was significantly increased 2-fold in PASMC isolated from explanted PAH lungs compared with control. Serum OPG concentrations were markedly elevated in IPAH compared with controls. In Cohort 1 OPG levels significantly correlated with mean right atrial pressure and cardiac index, while in Cohort 2 significant correlations existed between age-adjusted OPG levels and gas transfer. In both cohorts an OPG concentration above a ROC-derived threshold of 4728 pg/ml predicted poorer survival. In two rodent models, OPG correlated with the degree of pulmonary vascular remodeling. OPG levels are significantly elevated in patients with idiopathic PAH and are of prognostic significance. The role of OPG as a potential biomarker and therapeutic target merits further investigation.

OPG inhibits gene expression of RANK and CAII in mouse osteoclast-like cell

This study was designed to determine the effects of the osteoprotegerin (OPG) on the mRNA expression of carbonic anhydrase II (CAII) and the receptor activator of NF-κB (RANK) in mouse osteoclast-like cells. Marrow cells were harvested from femora and tibiae of mouse and cultured in 6-well chamber slides. After 1 day of incubation, the marrow cells were exposed to M-CSF (25 ng/ml), RANKL (50 ng/ml), and different concentrations of OPG (50, 75, and 100 ng/ml, respectively) for 3 days. Osteoclast-like cells were confirmed by both tartrate-resistant acid phosphatase (TRAP) stain and bone resorption assay. The expression of RANK and CAIImRNA was determined with real-time fluorescent quantitative polymerase chain reaction. The numbers of multinucleated, TRAP-positive osteoclast-like cells, and resorption pits formed were observed. Compared with the M-CSF + RANKL group, RANKmRNA expression was statistically decreased in the M-CSF and M-CSF + RANKL + OPG (100 ng/ml) groups (P = 0.004, P = 0.024, respectively); Compared with the M-CSF, M-CSF + RANKL, and M-CSF + RANKL + OPG (100 ng/ml) group, CAIImRNA expression in the M-CSF + RANKL + OPG (75 ng/ml) groups was statistically decreased (P = 0.001, P = 0.008, and P = 0.036, respectively). These data suggest that OPG could regulate the expression of RANK and CA II mRNA in the marrow culture system.

S69 Serum osteoprotegerin predicts mortality in a prospective study on incident cases of pulmonary arterial hypertension

Background and ObjectivesDespite improvements in the overall management of Pulmonary Arterial Hypertension (PAH) the disorder still causes significant morbidity and mortality. Current treatments fail to reverse the disease, and clinical...

Comparison of Osteoprotegerin to Traditional Atherosclerotic Risk Factors and High-Sensitivity C-Reactive Protein for Diagnosis of Atherosclerosis

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic stroke, and compared to controls, this group with clinical atherosclerosis had higher mean OPG (1,773 vs 1,337 ng/L, p <0.001) and high-sensitivity C-reactive protein (2.3 vs 1.6 mg/L, p <0.001). In a multivariate model with age, gender, body mass index, hypertension, diabetes, hypercholesterolemia, smoking status, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and OPG, OPG remained significantly associated with clinical atherosclerosis (p <0.01); high-sensitivity C-reactive protein, in contrast, did not (p = 0.74). In the control group without clinical atherosclerosis, OPG was independently associated with hypertension, diabetes, hypercholesterolemia, smoking, and subclinical peripheral atherosclerosis as measured by ankle brachial index. For each doubling of the plasma OPG concentration, the risk for subclinical peripheral atherosclerosis increased by 50% (p <0.001) after multivariate adjustment. In conclusion, OPG appears to be a promising biomarker of atherosclerosis that is independently associated with traditional risk factors of atherosclerosis, subclinical peripheral atherosclerosis, and clinical atherosclerotic disease such as ischemic heart disease and ischemic stroke.

Osteocalcin and glucose metabolism in postmenopausal women subjected to aerobic training program for 8 weeks

Results of animal studies suggest that osteocalcin (OC) plays an important role in the regulation of carbohydrate metabolism. The aim of the present study was to assess the relationship between biochemical indices of bone turnover and carbohydrate metabolism in postmenopausal women subjected to aerobic training for 8 weeks. The study was conducted on 44 postmenopausal women: 27 of them participated in the training program, and 17 did not undertake any additional physical activity during the study period (control group). Subjects performed a cycle-ergometer physical workout at a level of 70% to 80% of ventilatory threshold intensity for 8 weeks (40-minute sessions, 3 times per week). Serum concentrations of OC, C-terminal telopeptide of type I collagen, osteoprotegerin (OPG), insulin, and glucose were measured; and the homeostasis model assessment of insulin resistance index (HOMA-IR) was calculated before and after the 8-week training program. The training program caused significant decrease in levels of OC (P < .05), HOMA-IR (P < .05), and waist-to-hip ratio (P < .05). No significant changes were observed in C-terminal telopeptide of type I collagen, OPG, insulin, and glucose concentrations. Pretraining OC levels inversely correlated with concentrations of OPG (P < .05), glucose (P < .05), and insulin (P < .05) and with HOMA-IR values (P < .05). Our study revealed an association between serum OC concentrations and metabolic markers in postmenopausal women. Regular physical activity was associated with decrease in central adiposity and OC levels and slight reduction of insulin resistance. However, no direct relationships between training-related changes in OC concentrations and metabolic markers were observed.

Osteoprotegerin in pregnant adolescents differs by race and is related to infant birth weight z-score.

Osteoprotegerin (OPG) is involved in the regulation of bone turnover, but little is known about this protein during pregnancy or among neonates. We undertook a prospective longitudinal study to identify relationships between OPG, markers of bone turnover and birth outcomes in 155 pregnant adolescents (13-18 years) and their newborns. Maternal blood samples were collected at mid-gestation and at delivery. Cord blood was obtained at delivery. Serum OPG, estradiol and markers of bone formation (osteocalcin) and resorption (N-telopeptide) were assessed in all samples. Placental OPG expression was assessed in placental tissue obtained at delivery. Bone markers and OPG increased significantly from mid-gestation (26.0 ± 3.4 weeks) to delivery (39.3 ± 2.6 weeks). Neonatal OPG was significantly lower, but bone turnover markers were significantly higher than maternal values at mid-gestation and at parturition (P < 0.001). African-American adolescents had higher concentrations of OPG than Caucasian adolescents at mid-gestation (P = 0.01) and delivery (P = 0.04). Gestational age and estradiol were also predictors of maternal OPG at mid-gestation and delivery. OPG concentrations in cord blood were correlated with maternal OPG concentrations and were negatively associated with infant birth weight z-score (P = 0.02) and ponderal index (P = 0.02). In conclusion, maternal OPG concentrations increased across gestation and were significantly higher than neonatal OPG concentrations. Maternal and neonatal OPG concentrations were not associated with markers of bone turnover or placental OPG expression, but neonatal OPG was inversely associated with neonatal anthropometric measures. Additional research is needed to identify roles of OPG during pregnancy.

Assessment of the Genetic Effects of Polymorphisms in the Osteoprotegerin Gene, TNFRSF11B, on Serum Osteoprotegerin Levels and Carotid Plaque Vulnerability

Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. Various mechanisms have been suggested by which calcification might alter atherosclerotic plaque stability, but the significance of this intimal calcification is controversial. High concentrations of OPG have been associated with the presence of vascular and cardiovascular diseases. This study was designed to assess the association between gene polymorphisms of the OPG gene (TNFRSF11B), the serum OPG level, and plaque stability in patients with carotid atherosclerosis. We studied 177 patients with internal carotid artery stenosis who underwent carotid endarterectomy and also 303 controls. Carotid endarterectomy samples removed from patients were assessed by immunohistochemistry. Concentrations of OPG were measured and gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis and were compared, initially between patients with carotid atherosclerosis and controls, and subsequently between stable and unstable carotid plaques. We found that the GG genotype of the T245G polymorphism, the CC genotype of the T950C polymorphism, and the CC genotype of the G1181C polymorphism were significantly higher in patients with carotid plaque than in controls (21.5% versus 10.9% , P<0.01; 15.8% versus 7.6%, P<0.01; and 20.3% versus 10.9%, P<0.01, respectively) and that these polymorphisms were associated with high serum OPG levels (4.02 [3.07] versus 2.94 [1.81] pmol/L; P<0.01), which were significantly higher in patients with unstable atherosclerotic plaques (5.86 [4.02] versus 3.53 [1.87] pmol/L; P<0.01). The TNFRSF11B gene polymorphisms studied are associated with high serum OPG levels and might be potential markers for plaque instability.