Serum Osteoprotegerin Research Articles

Abstract 601: Early pregnancy serum sRANKL, OPG, and TRAIL and maternal breast cancer risk: Results from the Finnish Maternity Cohort

Abstract The Receptor Activator of Nuclear Factor kappa-B (RANK)-axis mediates structural changes in the breast during pregnancy in preparation for lactation, but is also implicated in breast tumor development. The RANK-axis includes RANK, its ligand (RANKL) and osteoprotegerin (OPG). OPG is the decoy receptor for RANKL and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL). Based results from experimental and epidemiologic studies, we hypothesized that relatively high serum concentrations of RANK-axis members in early pregnancy would be associated with higher risk of breast cancer in the mother, with differential effects in estrogen (ER)+ and progesterone receptor (PR)+ and ER-/PR- disease. A case-control study including 288 case-control sets (165 ER+/PR+, 79 ER-/PR-) was nested in the Finnish Maternity Cohort. Women eligible for this study donated a blood sample at age ≤40 years and ≤140 days gestation age (GA) in a primiparous term pregnancy; cases were diagnosed within 10 years of this pregnancy. Serum OPG and TRAIL were measured using an electrochemiluminescence assay, and sRANKL (soluble RANKL) using an enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals [CI] were calculated using conditional logistic regression adjusted for GA at blood collection. Relatively high sRANKL concentrations were associated with higher risk of ER+/PR+ breast cancer (Tertile3vs.1, OR=2.08 [1.25-3.44]) (Table); this association was similar after adjustment for OPG levels. sRANKL concentrations were not associated with ER-/PR- disease, and we observed no associations for OPG and TRAIL. In line with previous studies in non-pregnant women, we provide the first evidence for an association between early pregnancy sRANKL and risk of breast cancer in the decade following pregnancy. Relatively high circulating sRANKL concentrations in early pregnancy may identify women at increased risk of breast cancer subsequent to pregnancy. Table.Serum concentrations of sRANKL, OPG and TRAIL in early pregnancy and breast cancer risk by ER/PR subtype: results from the Finnish Maternity Cohort.Tertiles123ptrendaORlog2phetbsRANKL, cut points (pmol/L)≤ .00050.005 - 0.09> 0.09Full populationCases/Controls86/18199/181103/180288/542OR (95% CI)Ref.1.27 (0.88-1.83)1.42 (0.99-2.06)0.051.14 (1.00-1.29)0.36ER+/PR+Cases/Controls43/11461/10361/93165/310OR (95% CI)Ref.1.76 (1.08-2.88)2.08 (1.25-3.44)0.031.21 (1.02-1.44)ER-/PR-Cases/Controls27/4624/5228/5379/151OR (95% CI)Ref.0.89 (0.45-1.76)1.03 (0.52-2.06)0.451.09 (0.87-1.36)OPG, cut points (pmol/L)≤ 6.946.94 - 8.62> 8.62Full populationCases/Controls c83/16773/166104/166260/499OR (95% CI)Ref.0.85 (0.57-1.26)1.21 (0.82-1.79)0.641.10 (0.73-1.65)0.99ER+/PR+Cases/Controls53/9842/9756/94151/289OR (95% CI)Ref.0.77 (0.46-1.28)1.08 (0.65-1.82)0.991.00 (0.58-1.70)ER-/PR-Cases/Controls19/4523/4129/5171/137OR (95% CI)Ref.1.36 (0.61-3.03)1.29 (0.60-2.77)0.950.98 (0.45-2.12)TRAIL, cut points (pmol/L)≤ 0.400.40 - 1.07> 1.07Full populationCases/Controls c93/16679/16688/166258/492OR (95% CI)Ref.0.86 (0.59-1.26)0.93 (0.65-1.34)0.620.93 (0.71-1.22)0.74ER+/PR+Cases/Controls54/9542/9655/98150/285OR (95% CI)Ref.0.73 (0.44-1.21)0.94 (0.59-1.51)0.930.99 (0.70-1.40)ER-/PR-Cases/Controls24/4727/4720/4270/134OR (95% CI)Ref.1.09 (0.55-2.16)0.91 (0.45-1.84)0.690.90 (0.55-1.53)a ptrend based on log2-transformed sRANKL and OPG concentrations; b pheterogeneity comparing ER+/PR+ to ER-/PR- subtypes, based on log2-transformed sRANKL concentrations (244 case-sets); c 28 case sets (OPG) and 30 case sets (TRAIL) missing concentrations due to equipment failure. Citation Format: Danja Sarink, Theron Johnson, Helja-Marja Surcel, Rudolf Kaaks, Renée Turzanski Fortner. Early pregnancy serum sRANKL, OPG, and TRAIL and maternal breast cancer risk: Results from the Finnish Maternity Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 601.

Alterations of Inflammatory and Matrix Production Indices in Celiac Disease With Low Bone Mass on Long-term Gluten-free Diet

A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD. In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured. Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide. The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients.

Heamatococcus pluvialis ameliorates bone loss in experimentally-induced osteoporosis in rats via the regulation of OPG/RANKL pathway

BackgroundsOsteoporosis prevailing in elderly involves a marked increase in bone resorption showing an initial fall in bone mineral density leading to a significant reduction in bone formation. AimThe present study aimed to investigate the effect of Heamatococcus pluvialis microalgae on osteoporosis in D-galactose-treated rats. The underlying mechanism was tracked targeting the osteoprotegerin (OPG)/ nuclear factor-κβ ligand (RANKL) pathway using micro-computed tomography scanning. MethodsOsteoporosis was induced in rats by intraperitoneal injection of D-galactose (200 mg/kg/day) for eight consecutive weeks. Osteoporotic rats were orally treated with H. pluvialis biomass (BHP; 450 mg/kg), its polar (PHP; 30 mg/kg) and carotenoid (CHP; 30 mg/kg) fractions for the last 2 weeks of D-Gal injection. Twenty four hours after the last dose of the treatments, tibia bones of the rats were scanned using micro-computed tomography scanning for bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness/separation/number (Tb.Th, Tb.Sp, Tb.N) evaluation, blood samples were withdrawn and sera were used for biochemical assessment. Moreover, femur bones were examined histopathologically using several stains. ResultsInduction of osteoporosis was associated with a marked reduction in BMD, BV/TV, Tb.Th, Tb.Sp, Tb.N and in serum levels of phosphorus and catalase. On the other hand, a significant elevation in serum levels of calcium, bone alkaline phosphatase (BALP) and interleukin-6 was observed. Moreover, up-regulation of OPG was detected in osteoporotic rats. Oral treatment with BHP, and PHP incremented tibia BMD and serum phosphorus level along with the decrease in serum levels of calcium, BALP, interleukin-6, OPG and RANKL. However, treatment with CHP almost restored all the fore mentioned parameters to normal values. Furthermore, the histopathological evaluation emphasized the biochemical outcomes. ConclusionH. pluvialis fractions rich in astaxanthin ameliorated bone loss in experimentally-induced osteoporosis in rats probably through the down-regulation of serum OPG in concurrence with up-regulation of serum RANKL.

Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease

BackgroundEndothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. Patients80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. ResultsAfter adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1–3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. ConclusionAmong novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

Serum osteoprotegerin is an independent marker of central arterial stiffness as assessed using carotid\u2013femoral pulse wave velocity in hemodialysis patients: a cross sectional study

BackgroundCardiovascular morbidity and mortality are highly prevalent in patients with end-stage renal disease, and osteoprotegerin (OPG) may be an important link between bone loss and vascular calcification. This study was conducted to evaluate the relationship between central arterial stiffness and serum OPG levels in hemodialysis (HD) patients.MethodsBlood samples were collected from 120 HD patients, and the carotid–femoral pulse wave velocity (cfPWV) value was measured using a validated tonometry system. The cfPWV value of > 10 m/s was used to define the high artery stiffness group. Serum OPG levels were analyzed categorically into tertiles.ResultsOf the 120 HD patients, 53 (44.2%) were defined as the high arterial stiffness group, who had higher values of systolic blood pressure (p = 0.038), serum calcium (p = 0.007), and OPG (p < 0.001) levels and a higher prevalence of diabetes mellitus (DM, p = 0.001). Increasing tertiles of serum OPG levels were significantly associated with greater height (p = 0.011), male gender (p = 0.008), higher cfPWV values (p = 0.020), and lower intact parathyroid hormone (iPTH, p = 0.049) levels. Multivariable linear regression analysis showed that cfPWV value was independently associated with DM (β = 1.83, p = 0.008) and increasing tertiles of serum OPG levels (β = 0.89 and 1.63 for tertile 2 and tertile 3, respectively, p for trend = 0.035) in HD patients. Multivariable logistic regression analysis revealed that, in addition to age, DM, low iPTH levels, and high serum calcium levels, increasing tertiles of serum OPG levels (OR = 5.34 for tertile 2; OR = 7.06 for tertile 3; p for trend = 0.002) were an independent predictor of high arterial stiffness in HD patients. Serum calcium levels positively correlated with cfPWV value only in the highest OPG tertile group (r = 0.408, p = 0.009).ConclusionA positive association was detected between serum OPG levels and central arterial stiffness in HD patients, and patients with high serum OPG levels may have greater influence of calcium load on central arterial stiffening.

Inverse regulation of serum osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand levels in patients with leg lesional vascular calcification: An observational study.

We hypothesized that circulating osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels could be associated with vascular calcification, which is predominant in diabetes.The study included 71 Korean participants (36 with diabetes and 35 without diabetes), who were sub-grouped according to the results of the ankle–brachial index (ABI) and/or X-ray computed tomography scan (CT scan). Serum OPG and TRAIL levels were assayed using the respective enzyme-linked immunosorbent assay kits. Statistical significance was analyzed using Student's t test between the 2 groups or analysis of variance (ANOVA) among the 4 groups.Serum OPG was up-regulated in the participants with diabetes, with peripheral arterial disease (PAD), and/or with vascular calcification. TRAIL down-regulation was more strictly controlled than OPG up-regulation; it was significantly downregulated in the participants with PAD and vascular calcification, but not in the participants with diabetes. Serum OPG and TRAIL were regulated in the participants with femoral, popliteal, and peroneal artery calcification but not in the participants with aortic calcification.OPG up-regulation and TRAIL down-regulation were found to be associated with leg lesional vascular calcification; therefore, the average OPG/TRAIL ratio was significantly increased by 3.2-fold in the leg lesional vascular calcification group.

Polymorphisms of T149C and T950C genes in osteoprotegerin promoter sites and the relationship between serum osteoprotegerin levels and coronary heart disease

To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD). 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD. All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD. The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.

Serum Levels of OPG, RANKL, and RANKL/OPG Ratio in Patients with Ankylosing Spondylitis: A Systematic Review and Meta-analysis

ABSTRACTObjectives: To investigate the role of osteoprotegerin (OPG), receptor activator of nuclear factor-kB ligand (RANKL), and RANKL/OPG ratio in the pathogenesis of ankylosing spondylitis (AS).Methods: Studies that compared serum levels of OPG, RANKL, and RANKL/OPG ratio between AS patients and healthy controls were gathered. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by the random-effects model.Results: Twenty studies containing 1592 AS patients and 1064 healthy controls were included in this meta-analysis. Serum levels of OPG, RANKL, and RANKL/OPG ratio in AS patients were significantly higher than that in normal controls (OPG: SMD = 0.401, 95%CI = 0.026–0.777, p = 0.036; RANKL: SMD = 1.116, 95%CI = 0.510–1.723, p < 0.001; RANKL/OPG ratio: SMD = 0.691, 95%CI = 0.084–1.299, p = 0.026, respectively). Subgroup analysis suggested that Asian AS patients and patients with elevated ESR (ESR >20 mm/h) had higher serum OPG levels compared to normal controls. Asian patients, CRP >10 mg/L, ESR >20 mm/h, duration of disease ≤8 years, and BASDAI score >4 points subgroups showed increased RANKL levels compared to controls.Conclusions: Serum levels of OPG, RANKL, and RANKL/OPG ratio may be used as potential susceptible biomarkers for AS, but they could be influenced by race, inflammatory factors, and disease activity of AS patients.

Osteoprotegerin Assessment Improves Prediction of Mortality in Stroke Patients

Background: Elevated circulating osteoprotegerin (OPG) level is associated with an increased risk of hospitalization for ischemic stroke and coronary artery disease. The aim of the present study was to analyze whether OPG assessment may improve the prediction of mortality in patients with stroke. Patients and Methods: Serum OPG, fetuin A, 25-OH-D3, intact parathyroid hormone levels were assessed in serum samples which were left over after routine tests in a hospital laboratory. This assessment was conducted in 240 consecutive patients with acute ischemic stroke, admitted within 24hours after the onset of symptoms to the Stroke Unit. Mortality data were obtained from the local registry office. Results: The mean OPG serum level was 14.6 ± 6.0pmol/L (range: 3.7-43.4). There were no significant differences in the OPG values between men and women (13.9 ± 5.0 versus 15.1 ± 6.7 pmol/L; P = .12). Therefore, tertiles were calculated for the whole group. During the follow-up, 85 (35.4%) patients died and 92 (38.3%) died or had recurrent stroke. OPG level appeared a significant predictors of death and composite end-point (death/recurrent stroke), in addition to the well-established once (age, atrial fibrillation, diabetes RANKIN at admission and discharge, severity of stroke). In multivariable stepwise backward analyses, the OPG level persisted as a significant and independent predictor of death (hazard ratio [HR] = 1.084 (95% confidence intervals: 1.036-1.134)] and composite and point (HR = 1.082 [1.037-1.129]). Conclusions: OPG level may be considered as a predictor of mortality in stroke patients.

Risk Factors Associated With Altered Circulating Micro RNA -125b andTheir Influences on Uremic Vascular Calcification Among PatientsWith End-Stage Renal Disease.

BackgroundMicroRNA‐125b (miR‐125b) has been shown to regulate vascular calcification (VC), and serum miR‐125b levels are a potential biomarker for estimating the risk of uremic VC status. However, it is unknown whether clinical features, including chronic kidney disease–mineral bone disorder molecules, affect serum miR‐125b levels.Methods and ResultsPatients receiving chronic dialysis for ≥3 months were recruited from different institutes. Serum miR‐125b and chronic kidney disease–mineral bone disorder effectors, including intact parathyroid hormone, 25‐OH‐D, fibroblast growth factor‐23, osteoprotegerin, and fetuin‐A, were quantified. We used multivariate regression analyses to identify factors associated with low serum miR‐125b levels and an area under receiver operating characteristic curve curve to derive optimal cutoffs for factors exhibiting close associations. Further regression analyses evaluated the influence of miR‐125b on VC risk. Among 223 patients receiving chronic dialysis (mean age, 67.3 years; mean years of dialysis, 5.2), 54 (24.2%) had high serum miR‐125b levels. Osteoprotegerin (P=0.013), fibroblast growth factor‐23 (P=0.006), and fetuin‐A (P=0.036) were linearly associated with serum miR‐125b levels. High osteoprotegerin levels independently correlated with high serum miR‐125 levels. Adding serum miR‐125b levels and serum osteoprotegerin levels (≥400 pg/mL) into models estimating the risk of uremic VC increased the area under receiver operating characteristic curve values (for models without miR‐125b/osteoprotegerin, with miR‐125b, and both: 0.74, 0.79, and 0.81, respectively).ConclusionsSerum osteoprotegerin levels ≥400 pg/mL and serum miR‐125b levels synergistically increased the accuracy of estimating VC risk among patients receiving chronic dialysis. Taking miR‐125b and osteoprotegerin levels into consideration when estimating VC risk may be recommended.

Effect of estrogen receptor-α gene polymorphism on serum osteoprotegerin and calcaneus bone density in postmenopausal women in Guangxi Zhuang nationality

Objective To investigate the effect of estrogen receptor-α gene polymorphism on osteoprotegerin(OPG)and calcaneus bone density in early and late postmenopausal women in Guangxi Zhuang nationality, in order to provide the theoretical basis for the early prevention and treatment of postmenopausal osteoporosis caused by estrogen receptor gene-induced osteoprotegerin reduction. Methods The broadband ultrasound attenuation in the right heel bone was measured by quantitative ultrasound bone densitometry in 621 postmenopausal women of Guangxi Zhuang nationality.Peripheral blood mononuclear cells and their DNA were extracted.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was used to detect the estrogen receptor-α gene polymorphism.Serum osteoprotegerin level was determined by enzyme-linked immunosorbent assay.The differences of data distribution of OPG and calcaneus bone density were compared between five items of 3 genotypes and 2 alleles at the same age group of 40-, 45-, 50-, 55-, 60-, 65-, 70-, 75-80 years. Results Women aged 60 years and over versus those aged 40-59 years showed that serum osteoprotegerin(OPG)and bone mineral density(BMD)were decreased(P 0.05). Women aged 60 years and over showed that ER-α Puv Ⅱ polymorphism of allele big P versus p, Pp, pp, PP in the same age groups had significantly decreased serum osteoprotegerin and bone mineral density.Women aged 65 years and over showed that ER-α XbaⅠpolymorphism of heterozygote Xx versus xx, XX, X, x in the same age groups had a significantly increased serum osteoprotegerin and bone mineral density(P<0.05). Conclusions Women with big P allele of ER-α PvuⅡpolymorphism have low serum osteoprotegerin level and a decreased bone mineral density, who are prone to postmenopausal osteoporosis.Thus, P allele of ER-α PvuⅡpolymorphism is a causative agent.More attention should be paid to early prevention and treatment.But, women with the Xx heterozygote of ER-α XbaⅠpolymorphism have high serum osteoprotegerin level and an increased bone mineral density, who are not easy to suffer from postmenopausal osteoporosis.Therefore, Xx heterozygote of ER-α XbaⅠpolymorphism is a protective agent.The prevention and treatment of postmenopausal osteoporosis should be individualized based on estrogen receptor-α gene polymorphism. Key words: Zhuang nationality; Receptors, estrogen; Polymorphism, single nucleotide; Osteoprotegerin

Role of Serum Osteopontin and Osteoprotegerin Levels in Diagnosis of Acute coronary Syndrome and Its Subtypes

Role of Serum Osteopontin and Osteoprotegerin Levels in Diagnosis of Acute coronary Syndrome and Its Subtypes

Effects of 12-months treatment with zoledronate or teriparatide on intima-media thickness of carotid artery in women with postmenopausal osteoporosis: A pilot study.

Atherosclerosis and osteoporosis are interrelated entities and share similar pathogenic mechanisms. Recent studies showed that key proteins of bone metabolism, such as osteoprotegerin (OPG) and osteopontin (OPN), are also involved in vascular atherosclerosis and calcifications. The carotid intima-media thickness (CA-IMT) is an early quantitative marker of generalized atherosclerosis. Aim of study was to investigate whether 12-months treatment with zoledronate (ZLN) or teriparatide (TPT) affects CA-IMT and circulating OPG and OPN levels. In this study, 11 postmenopausal osteoporotic women (aged 73, 70.5–74.5 years; median, range interquartile) treated with 5 mg/year iv ZLN; 9 postmenopausal osteoporotic women (aged 70, 62.5–73.5 years) treated with 20 µg/day sc TPT; and 10 aged-, body mass index (BMI)-, glycemic, and lipid profiles-matched, free from anti-osteoporotic and hypocholesterolemic drugs, controls were prospectively investigated at baseline and after 12 months. At baseline, median CA-IMT was similar in the three groups and increased after 12 months. CA-IMT increased significantly in TPT-treated patients (1.0, 0.8–1.2 vs 1.1, 0.9–15 mm, P = 0.04), though the change was minimal. After 12 months of treatment, CA-IMT positively correlated with alkaline phosphatase (ALP) levels (r = 0.767, P = 0.008) and negatively with high-density lipoprotein (HDL) cholesterol levels (r = −0.65, P = 0.03), suggesting interplay between active bone remodeling and lipid profile. At baseline and after 12 months, median serum OPG and OPN levels did not differ among the groups and did not correlate with changes in CA-IMT. In conclusion, ZLN and TPT treatments are safe on carotid walls in osteoporotic women with subclinical atherosclerosis; circulating OPG and OPN are not affected by long-term anti-osteoporotic treatments and do not correlate with CA-IMT.

Osteoprotegerin is a new independent predictor of the progression of cardiovascular pathology: chronic heart failure associated with type 2 diabetes and osteoporosis

Aim.To study the link of increased serum concentrations of osteoprotegerin (OPG) in patients with chronic heart failure (CHF) associated with type 2 diabetes mellitus (DM 2), osteoporosis or osteopenia with the development of cardiovascular events (primarily, decompensation of CHF, including those requiring hospitalization, death from cardiovascular disease, acute coronary syndrome or acute ischemic stroke) to determine the possibility of using this biomarker as a predictor of a severe course of cardiovascular disease in these patients.Materials and methods.In a 12-month cohort observational study included 75 patients (mean age 57.4 ± 5.4 years) with CHF associated with DM 2, osteoporosis or osteopenia. Cardiovascular events were analyzed in three groups of patients formed based terteling ranges of concentration of the OPG level in serum: in the 1st group (n= 25) included patients with serum OPG concentration is less than 5.0 pmol/l; in the 2nd group (n= 25) OPG level of 5.0–7.2 pmol/l; in the 3rd group (n= 25) - with the content of OPG more than 7.2 pmol/L. The serum OPG, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) serum levels were determined by ELISA. Assessment of bone mineral density (BMD) was performed by a densitometric method using dual-energy X-ray absorptiometry.Results.Highly reliable increased expression of OPG in 2 and 3th tertiles was found in patients with CHF associated with type 2 diabetes in comparison with the control group. The frequency of adverse events gradually increased from the 1st tertile to the 3rd tertile OPG. With the median for OPG more than 5.2 pmol/L and BMD less than -2.5 standard deviations, the highest frequency (60.9%) of adverse cardiovascular events was identified. A close correlation of OPG with the values of pro-inflammatory cytokines-TNF-α (r= 0.46;p= 0.019) and IL-1β (r= 0.4;p= 0.01), glycated hemoglobin (r= 0.55;p= 0.009) and the severity of CHF (r= 0.49;p= 0.013).Conclusions.Osteoprotegerin is an independent risk factor for the development of comorbid cardiovascular pathology: CHF associated with DM 2 and osteoporosis. It seems clinically justified to use OPG to stratify the risk of progression of cardiovascular pathology.

Effect of Resistance Exercise on Serum Osteoprotegerin Levels and Insulin Resistance in Middle-Aged Women with Metabolic Syndrome.

BackgroundOsteoprotegerin (OPG) is a soluble glycoprotein that belongs to the tumor necrosis factor (TNF) receptor superfamily. OPG is mainly secreted by bone. The relationship between acute resistance training, serum OPG levels and metabolic syndrome, including insulin resistance, remains unclear. The purpose of this study was to determine the effect of resistance exercise on serum OPG levels and insulin resistance in middle-aged women with metabolic syndrome.Material/MethodsTwenty-four middle-aged women were divided into those with metabolic syndrome (n=12) and a normal control group without metabolic syndrome or insulin resistance (n=12). Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The quantitative insulin-sensitivity check index (QUICKI) and the homeostatic model assessment (HOMA) index for assessing beta-cell function and insulin resistance were used. The intensity of the resistance exercise was 60–70% of the repetition maximum, for 40 minutes with 10–12 repetitions, performed three times per week. Venous blood samples were tested using standard laboratory procedures.ResultsBefore exercise, the metabolic syndrome group showed a significant increase in waist circumference (P=0.030) and serum triglyceride (TG) (P=0.014), and lower high-density lipoprotein-cholesterol (HDL-C) (P=0.010) compared with the control group. After the eight-week resistance exercise program, waist circumference, and the QUICKI decreased and OPG levels were significantly increased in the metabolic syndrome group compared with the normal control group.ConclusionsA resistance exercise program was effective in reducing factors associated with metabolic syndrome including insulin resistance and increases serum levels of OPG in middle-aged women.

Circulating miR-103a-3p and miR-660-5p are associated with bone parameters in patients with controlled acromegaly.

BackgroundBiochemical control of GH/IGF-I excess in acromegaly (ACRO) is associated with persistent impairment of trabecular microstructure leading to increased risk of vertebral fractures. Circulating miRNAs modulate the activity of osteoblasts and osteoclasts, and may be potential biomarkers of osteoporosis.AimsIdentify differentially expressed miRNAs in the serum of patients with controlled ACRO vs controls and correlate miRNA levels with both biochemical and structural bone parameters.Patients and methodsTwenty-seven patients with controlled ACRO (11 males, 16 females; mean age, 48 ± 5 years; BMI, 28 ± 4 kg/m2) and 27 age-, gender- and BMI-matched controls were recruited. Areal BMD at lumbar spine and femur, and trabecular bone score were assessed; volumetric BMD was measured by quantitative computed tomography QCT-Pro (Mindways). Twenty miRNAs, chosen by their putative role in bone, were quantified in serum using real-time qPCR.ResultsIn ACRO patients, miR-103a-3p and miR-191-5p were found overexpressed, whereas miR-660-5p was underexpressed (P < 0.001). miR-103a-3p levels were negatively associated with both trabecular vBMD at trochanter and serum osteoprotegerin concentrations (P < 0.05) and positively with vitamin D concentrations (P < 0.01) and total cross-sectional area of the femoral neck (P < 0.05). miR-660-5p levels were correlated with both trabecular vBMD at trochanter and OPG concentrations (P < 0.05), but were negatively associated with vitamin D levels (P < 0.05). A negative correlation between miR-103-a-3p and miR-660-5p was found in both groups (P < 0.001).ConclusionsCirculating miR-103a-3p and miR-660-5p are differentially expressed in controlled ACRO patients and associated with bone structural parameters. miRNAs may be one of the mechanisms involved in the pathogenesis of bone disease and could be used as biomarkers in ACRO patients.

Gossypol Promotes Bone Formation in Ovariectomy-Induced Osteoporosis through Regulating Cell Apoptosis.

Osteoporosis is among the most common forms of age-related diseases, especially for females, which has been a grave public health problem. Drug therapies have shown promising outcomes to promote bone formation and bone density. This study identified a novel potential drug, gossypol, for the treatment of osteoporosis. Treatments of ovariectomy-induced osteoporosis mice with gossypol significantly increased serum osteocalcin and osteoprotegerin (OPG) levels; meanwhile they decreased serum RANKL levels. Microcomputed tomography (microCT) analysis showed that treatment of gossypol improved bone density and strength and decreased bone postyield displacement for both medullar and cortical bones. In vitro experiments also showed that gossypol increased cell viability in a time- and dose-dependent manner. Furthermore, incubation of the osteoblast MC3T3-E1 cells with gossypol inhibited cell apoptosis through intrinsic apoptotic pathway as evidenced by the Annexin V/PI assay, TUNEL assay, biochemical analysis, and western blot assays. Moreover, the classical Wnt/β-catenin signaling pathway was found to be regulated by gossypol treatments. Inhibition of Wnt/β-catenin signaling reversed the prevention effects of gossypol in osteoporosis. Our findings provided novel clues for the treatment of osteoporosis in clinic.

Effects of Aldosterone, Osteoprotegerin and Fibroblast Growth Factor-23 and Some Biochemical Markers in Chronic Kidney Disease Patients (Stage II-IV) among Patients with or without Cardiovascular Events

Chronic Kidney Disease (CKD) is a public health problem and many studies support the link between kidney dysfunction and cardiovascular events. Aldosterone has been shown for decades that a plasma aldosterone concentration is elevated in CKD. Whilst, Osteoprotegerin (OPG), after its capacity to protect bone, also osteoprotegerin is elevated in patients with chronic kidney disease (CKD), where it could predict the deterioration of kidney function, cardiovascular, vascular events and all-cause mortality. On the other hand, fibroblast growth factors (FGFs), in patients with CKD, its levels seem to increase progressively as kidney function worsens. The aim of the present study is to assess the correlations between serum osteoprotegerin, aldosterone and fibroblast growth factor-23 levels in patients with chronic kidney disease stage (II-IV) with and without cardiovascular events.&#x0D; The study includes fifty-nine patients with chronic kidney disease(CKD) and according to CKD-EPI /Creatinine/ 2009 equation to be allocated as stage II-IV, patients were divided into three groups: Group1 (29 patients) with chronic kidney disease(CKD) stage (II-IV) with cardiovascular events. Group2 (30 patients) with chronic kidney disease stage (II-IV) without cardiovascular event, to be compared with Group 3(23 apparently healthy subjects), age and sex matched to that of patients. Serum obtained from their blood specimens to measure; glucose, urea, creatinine, calcium, phosphate, sodium, potassium, aldosterone, FGF-23, Osteoprotergen.&#x0D; Data analysis showed that fasting serum glucose levels of CKD patients (with and without CV disorder) had significantly higher values as compared to the controls (76.5% and 29% respectively).&#x0D; Serum Aldosterone, FGF-23, OPG levels were presented with no significant variation among studied groups with CV events or those without CV events.

Correlation between expressions of stromal cell-derived factor 1α and osteoprotegerin and bone disease in multiple myeloma

Objective To understand the correlation of expression levels of serum stromal cell-derived factor 1α (SDF-1α), osteoprotegerin (OPG) and β2 microglobulin (β2-MG) in patients with multiple myeloma (MM) with or without myeloma bone disease (MBD). Methods Eighty patients with MM who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2017 were selected; all of the patients met the international diagnostic criteria for MM. According to the symptoms such as bone pain, the patients were divided into group with MBD (45 cases) and group without MBD (35 cases). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of SDF-1α and OPG, and radioimmunoassay was used to detect the expression of MM major prognostic indicator β2-MG. The MBD score was evaluated in 45 patients selected by random number table after sacroiliac joint X-ray and three-dimensional bone reconstruction. The χ 2 test was used to compare the categorical variables; the two independent sample t-test was used to compare the continuous variables that conformed to the normal distribution between two groups, and the Pearson method was used for the correlation analysis. Results The expression level of serum SDF-1α in the group with MBD was significantly higher than that in the group without MBD [0.31±0.17) pg/ml vs. (0.18±0.06) pg/ml], and the difference was statistically significant (t=-4.21, P < 0.001). The expression level of serum OPG in the group with MBD was significantly lower than that in the group without MBD [(0.73±0.50) pg/ml vs. (1.08±0.31) pg/ml], and the difference was statistically significant (t= 3.62, P < 0.001). Pearson analysis showed that β2-MG level in the group was positively correlated with SDF-1α level (r= 0.84, P < 0.001), and negatively correlated with OPG level (r=-0.48, P < 0.001). The β2-MG level in the group without MBD did not show a correlation with the SDF-1α and OPG levels. Conclusions In the serum of patients with MBD, the expression levels of β2-MG and SDF-1α are increased, and the expression level of OPG is decreased. SDF-1α and OPG may be new clinical biochemical indicators for diagnosis, treatment and prognosis assessment in MBD. Key words: Multiple myeloma; Myeloma bone disease; Stromal cell-derived factor; Osteoprotegerin; β2 microglobulin

The effect of colostrum intake on osteoprotegerin and bone metabolic markers in the blood of newborn calves during the first week of life.

The aim of this study was to elucidate the bone metabolic status after taking colostrum in newborn calves. Fourteen neonatal calves were randomly allocated to two groups fed either unheated or heated (60°C, 30 min) colostrum three times on the first day (2 l every 10 hr; 6 l in total). Heat treatment on colostrum was to reduce the bone metabolic markers assumed as heat-sensitive. The concentrations of four bone metabolic markers (the enzymes from bone cells or the bone collagen fragments) and a bone protective protein, osteoprotegerin (OPG), were measured in the blood of calves during a week after the birth and in the colostrum. The colostral concentrations of four bone metabolic markers were reduced by heating. Then those circulatory markers peaked after colostrum intake in the calves fed unheated colostrum; whereas those fed heated colostrum did not show such changes. However, the plasma tartrate resistant acid phosphatase 5b (TRAP5b) activity was transiently increased after taking colostrum in both groups. Meanwhile, heating did not decrease colostral OPG and there was no significant rise in the serum OPG concentrations after the first colostrum intake in both groups. The study revealed that the blood concentrations of studied bone metabolic markers depended on those colostral values except for TRAP5b. Based on the plasma TRAP5b changes, accelerated formation of premature osteoclast cells may be induced by colostrum intake. Meanwhile, colostral OPG absorption is less likely to impact on its circulating levels.