Serum Osteoprotegerin Concentrations Research Articles

Mining Candidate Genes and Identifying Risk Factors for Leg Disease in Broilers: A Mendelian Randomization Study.

Clinical investigations have highlighted disruptions in bone metabolic processes and abnormal fluctuations in serum indicator levels during the onset of leg disease (LD) in broilers. However, the presence of a genetic causal relationship for this association remains undetermined. Therefore, the aim of this study is to discern the risk factors underlying LD development using 1235 sequenced white-feathered broilers. We employed Mendelian randomization (MR) analysis to assess the associations of bone strength (BS), bone mineral density (BMD), tibial bone weight (TBW), tibial bone length (TBL), tibial bone diameter (TBD), bone ash (BA), ash calcium (Ash Ca), ash phosphorus (Ash P), serum calcium (Ca), serum phosphorus (P), serum alkaline phosphatase (ALP), and serum osteoprotegerin (OPG) with the incidence of LD. Compelling evidence underscores a causal link between the risk of developing LD and decreased BMD (odds ratio (OR) = 0.998; 95% CI: 0.983, 0.993; P < 0.001) and narrower TBD (OR = 0.985, 95% CI: 0.975, 0.994, P = 0.002). Additionally, serum OPG concentrations (OR: 0.995, 95% CI: 0.992, 0.999, P = 0.008) were associated with BMD (OR = 0.0078, 95% CI = 0.0043 to 0.0140, P < 0.001), indicating a robust genetic relationship between ALP concentrations (OR: 0.988, 95% CI: 0.984, 0.993, P < 0.001) and TBD (OR = 0.0046, 95% CI = 0.0026, 0.0083, P < 0.001). Moreover, elevated serum Ca (OR: 0.564, 95% CI: 0.487, 0.655, P < 0.001) and P (OR: 0.614, 95% CI: 0.539, 0.699, P < 0.001) levels were associated with a narrower TBD. Elevated serum levels of Ca, P, ALP, and OPG contribute to disturbances in bone metabolism, while decreased BMD and narrower TBD are associated with a greater risk of developing LD in broilers. This discovery elucidates the metabolic risk factors for LD in broilers and could provide information on LDs, such as osteoporosis, in humans.

Serum levels of soluble receptor activator for nuclear factor kB ligand play a crucial role in the association of osteoprotegerin with coronary artery disease.

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of nuclear factor kB ligand (RANKL), and is implicated in the pathogenesis of atherosclerosis. The aim of the present study was to examine the hypothesis that serum OPG concentrations are increased in patients with stable coronary artery disease (CAD) at different serum levels of soluble RANKL (sRANKL). The study used a case-control design in which consecutively hospitalized individuals were recruited. Fasting blood samples were taken upon admission for serum testing. Participants with previously diagnosed CAD that was asymptomatic or had controlled symptoms constituted the stable CAD group, whereas patients with negative coronary computed tomography angiography results constituted the control non-CAD group. Exclusion criteria included recent acute coronary syndrome, severe heart failure, CAD-complicating autoimmune, blood or thyroid diseases, cancer, elevated temperature with or without infection, severe liver or kidney dysfunction, abnormal calcium metabolism, recent surgery and trauma history. A total of 118 individuals were included in the study. Smoothed plots generated using the recursive method and multivariate models showed that the incidence of stable CAD increased with serum OPG level up to the turning point of 18 pg/ml. This trend was observed at both high [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.04-2.50; P=0.032) and low sRANKL concentrations (OR, 1.52; 95% CI, 1.06-2.17; P=0.022) after adjustment for cardiovascular risk factors. In conclusion, serum OPG levels ≤18 pg/ml are positively associated with stable CAD, regardless of sRANKL levels. In addition, at the same serum OPG level, higher sRANKL levels are associated with a greater incidence of stable CAD compared with lower sRANKL levels. This study identified the relationship between OPG, sRANKL, and stable CAD, and established the reference range for future clinical use.

Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations.

Association of Serum Osteoprotegerin With Vascular Calcification, and Cardiovascular and Graft Outcomes in Kidney Transplant Patients: Results From the KNOW-KT.

Vascular calcification and stiffness contribute to increased cardiovascular morbidity in patients with chronic kidney disease. This study investigated associations between serum osteoprotegerin (OPG) levels and vascular calcification or stiffness to assess cardiovascular and graft outcomes in kidney transplant patients. The KoreaN cohort study for Outcome in patients With Kidney Transplantation was a prospective multicenter cohort study. Serum OPG levels were measured at baseline and 3 y after transplantation in 1018 patients. Patients were classified into high and low OPG groups according to median serum OPG levels. The median follow-up duration was 93.5 mo. The mean age was 45.8 ± 11.7 y and 62.9% were men. Patients with high OPG had significantly higher coronary artery calcium scores, abdominal aortic calcification scores, and brachial-ankle pulse wave velocities than those with lower OPG; these parameters remained significant for 5 y after transplantation. The 3-y OPG levels were lower than baseline values ( P < 0.001) and were positively correlated ( r = 0.42, P < 0.001). Multivariate Cox regression analysis showed that high OPG levels were significantly associated with posttransplant cardiovascular events ( P = 0.008) and death-censored graft loss ( P = 0.004). Similar findings regarding posttransplant cardiovascular events ( P = 0.012) and death-censored graft loss ( P = 0.037) were noted in patients with high OPG at the 3-y follow-up. Mediation analyses revealed that coronary artery calcium scores, abdominal aortic calcification scores, and brachial-ankle pulse wave velocities could act as mediators between serum OPG levels and posttransplant cardiovascular events. Serum OPG concentration is associated with vascular calcification and stiffness and could be a significant risk factor for cardiovascular outcomes and graft loss in patients undergoing kidney transplantation.

Peroxisome proliferator-activated receptor gamma and osteoprotegerin levels as an indicator and diagnostic predictor of endothelial dysfunction

Abstract Objectives Peroxisome proliferator-activated receptor gamma (PPAR-γ) modifies many cellular processes that contribute to atherosclerosis. The increased concentrations of osteoprotegerin (OPG) are related with coronary artery disease, calcification in vascular tissue, advanced atherosclerosis, and diabetic complications has been informed. The aim of our study was to define the relation among PPAR-γ Pro12Ala and, OPG and PPAR-γ in Peripheral Vascular Disease (PVD) and hypertension (HT). Also, it was aim to investigate the relationship between flow-mediated dilatation (FMD) in HT and ankle brachial index (ABI) in PVD in terms of endothelial dysfunction (ED). Methods Fifty-four patients with HT, 47 with PVD, and 52 healthy for the controls were included. Blood samples were used for analyzing PPAR-γ and OPG by Enzyme-Linked Immunosorbent Assay (ELISA), and biochemical assays. The PPAR-γ Pro12Ala was examined using TaqMan with PrimerProbMix. p value less than 0.05 was accepted as the limit of significance. Results The PPAR-γ was significantly decreased in both HT and PVD (p&lt;0.001). The serum concentrations of OPG were higher in HT (p&lt;0.001) and increased in diabetic ones (p&lt;0.05). CG genotype of PPAR-γ Pro12Ala was more frequent in HT patients (p&lt;0.001). In the HT patients, increased OPG and decreased PPAR-γ were found in CC (p&lt;0.001). In the PVD patients, PPAR-γ levels decreased in carrying with CC (p&lt;0.05). Conclusions It may be significant that increased OPG, as a marker of endothelial dysfunction, is found in HT. Moreover, decreased PPAR-γ in those who have to carry CC may be protective in both HT and PVD.

Clinical significance of Osteoprotegerin, Vitamin D, Obestatin and some biochemical variables in Kidney failure Patients

Chronic kidney disease (CKD) is described as an abnormalities of renal function, existing for a long period of time. By reason of the early grades of Chronic kidney disease can be experiences no symptoms, its premature identification is strenuous. initial stage CRD can cause various complications, such as anemia, matabolyic disorders of bone mineral. The study was done to assess the effect the chronic renal disease stage on the Osteoprotegerin, 1,25 dihydroxyvitamin D, Obestatin levels and some biochemical parameters in patients not undertaken dialysis therapy. In this case-control study fifty-five patients with Kidney failure and fourty healthy people were examined. Circulating concentrations of Osteoprotegerin, 1,25 dihydroxyvitamin D and Obestatin were estimated by ELIZA technique, serum urea, uric acid, total protein and total calciumu were estimated enzymatically using spectrophotometer.&#x0D; Serum concentration of Osteoprotegerin, Obestatin, renal function markers in patients group were higher (328.3±41.68 pg/mL; 15.52±4.28pg/mL; 183.2±10.35 mg/dL; 8.88±0.54 mg/dL; 6.57±0.22 mg/dL) respectively in comparison to the control group (172.6±55.48 pg/mL; 11.64±3.26 pg/mL; 33.45±1.08 mg/dL; 0.95±0.03 mg/dL; 4.35±0.22 mg/dL) respectively. Vitamin D, Total Calcium and Total Proteins level in patients group were lower(24.49±2.53 ng/mL; 8.06±0.18 mg/dL; 6.49±0.12 g/dL) respectively as compared to controls (57.11±12.39 ng/mL; 10.15±0.23 mg/dL; 6.82±0.10 g/dL) respectively. The current study reveals that circulating levels of Osteoprotegerin Obestatin are remarkably linked with the existence of renal failure, the current data identify a high prevalence deficiency and insufficiency of 1,25 dihydroxyvitamin D in patients with moderate and severe Chronic nephropathy.

Promotion of longitudinal bone growth by the intake of oat and green onion root water extracts in weaning rats through stimulating growth hormone secretion and elevating gut microbiota related to nervous system-related pathway

We determined whether oral oat and green onion water extracts (GOO) supplementation could stimulate longitudinal bone growth in weaning rats. Fistuloside A, B, and C in the green onions and 26-desglucoavenacoside A and B and avenacoside A in the oats lowered the binding energy of growth differentiation factor-5 (GDF5) and insulin-like growth factor-1 receptor (IGF1R). After a 4-week treatment, serum growth hormone (GH) and osteoprotegerin concentrations in the High-GOO group (500 mg/kg body weight) were similar to those of the Positive-control. The femur and tibia lengths promoting the proliferative and hypertrophic zones of the growth plate in the High-GOO were also similar to Positive-control. Along with increasing serum propionate and butyrate concentrations, cecal bacteria in the High-GOO were higher in virus infection, steroid and sesquiterpenoid biosynthesis, and nervous system-related pathways than the Control in the metagenome function. It suggested that gut bacteria potentially enhanced bone growth by improving immunity and neurological activity. In conclusion, GOO increased leg length by enhancing the proliferation of the growth plate as much as GH treatment by preventing gut dysbiosis.

Ganoderic acid A improves osteoarthritis by regulating RANKL/OPG ratio.

Ganoderma mushrooms have been used to treat rheumatoid arthritis (RA) in East Asia. Whether Ganoderic acid A (GAA), the natural product extracted from Ganoderma, could be utilized to alleviate osteoarthritis (OA) is investigated in this study. Destabilization of the medial meniscus (DMM) model was constructed to reveal the in vivo effect of GAA. We found that GAA could significantly alleviate the pathology of DMM, as confirmed by the diminished maximum histologic scores. On the contrary, GAA could down-regulate the relative expression of osteoprotegerin (OPG) and up-regulate the relative expression of nuclear factor kappa-B ligand (RANKL) in DMM cartilage and human articular chondrocytes (HC-A) cells with diminished matrix metallopeptidase 13 (MMP-13) secretion in the synovial fluid. It was further demonstrated that the serum concentration of OPG was correlated with the severity of osteoarthritis. All these data reveal that GAA could improve OA by regulating the RANKL/OPG ratio to inhibit the secretion of MMP-13.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Effects of Long-Term Treatment with Different Types of Anti-Epileptic Drugs on Vitamin D2 and Osteoprotegrin Serum Levels in Iraqi Patients

Epilepsy is a chronic neurological illness had been described as repeated seizures associated with abnormal neurological activities in the brain. Epilepsy affects nearly fifty million people worldwide, with 85 percent of them living in developing countries. Vitamin D2 (VD2) is ergocalciferol (made from ergosterol). Genetic disorders related to vitamin D metabolism are dysfunction of generally loss osteoid mineralization the leading cause to bone disorders including: rickets or osteomalacia. Osteoprotegerin (OPG) is an osteoclastogenesis inhibitory factor (OCIF), OPG has essential role in bone metabolism and bone mass level. The aim of the present study is to investigate the effects of long-term treatment with anti-epileptic drugs (old Vs new antiepileptics) on vitamin D2 and osteoprotegrin levels among Iraqi epileptic patients. The study included fifty-one epileptic outpatients, whom attending the Consultant Clinic of Baghdad Teaching Hospital at the Medical City –Complex for the period from October/2021 to December/2021. The selected patients were on antiepileptic drugs for more than 2years, hence were grouped according to their antiepileptic therapy into: Group-1: 24 epileptic patients on old antiepileptic drugs (Carbamazepine or Valproate). Group-2: 27 epileptic patients on new antiepileptic drugs (Levetiracetam), to be compared with Group-3: 28 apparently healthy control subjects, with age and sex matching to that of patients. Serum was obtained from their blood specimens to measure: serum VD2 and OPG concentrations among the study groups participants, using specific ELISA Kits. Data analysis revealed that the mean vitamin D2 levels were not significantly different between group -1 (old antiepileptic drugs) and group-2 (new antiepileptic drugs), whereas, both of the patients groups expressed significantly lower values than the control group. However, serum osteoprotegrin levels were significantly elevated in group-1 compared to group-2. Furthermore, both of the epileptic patients groups had significantly higher values compared to the healthy subjects group. Keywords: Osteomalacia, antiepileptic drugs, Vitamin D2, Osteoprotegrin.

Protection against Osteoporosis by Fermented Mulberry Vinegar Supplementation via Inhibiting Osteoclastic Activity in Ovariectomized Rats and Osteoclastic Cells

Menopause increases the osteoporosis risk, to which phytoestrogen intake can be beneficial. This study hypothesized that mulberry vinegar had a preventive effect on osteoporosis by decreasing osteoclastic activity. The hypothesis was tested in ovariectomized (OVX) rats and RANKL-differentiated osteoclast cells. OVX rats were given 0(OVX-CON), 0.5(OVX-MVL), 1(OVX-MVM), and 2(OVX-MVH) fermented mulberry vinegar (MV) mL/kg body weight (BW) daily for 12 weeks. Sham-operated rats had no MV supplementation (Normal-CON). The osteoporosis-related biomarkers were measured, and Micro-CT determined the bone mass of the femur. RANKL-differentiated Raw 264.7 cells were treated with MV (0–100 μg/mL). The cell viability, osteoporosis-related mRNA expression, and protein contents were measured. MV contained Acetobacter pasteurianus (7.31 log CFU/mL), citric acid (106 mg/mL), lactic acid (19.2 mg/mL), acetic acid (15.0 mg/mL), and rutin (0.36 mg/mL). OVX-MVM elevated the serum 17β-estradiol concentration similar to the Normal-CON group, but it did not prevent the decrease in uterine weight. OVX-MVM prevented the increase in osteoclastic-related parameters, including cathepsin K(CtsK), receptor activator of NF-κB ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) in the circulation. OVX-MVH also lowered C-telopeptide of type Ⅰ collagen as much as the Normal-CON group (p &lt; 0.05). By contrast, OVX-MVH increased the serum osteoprotegerin concentration, an inhibitor of osteoclasts, better than the Normal-CON group (p &lt; 0.05). These changes were integrated to alter the bone mineral density (BMD) in Micro-CT analysis: OVX-MVM and OVX-MVH prevented BMD decrease after OVX as much as the Normal-CON. In RANKL-differentiated osteoclast cells, the MV treatment for 24 and 48 h decreased RANKL-induced differentiation in osteoclast cells dose-dependently up to 100 µg/mL. Its decrease was related to inhibiting the TRAP activity and reducing TRAP-positive multinucleated cells during the five-day administration of RANKL. MV treatments also decreased mRNA expression of osteoclast-related genes (TRAP, Ctsk, OSCAR, and NFATc1). MV suppressed the protein contents of NFATc1 and c-FOS-related osteoclast. In conclusion, MV intake (1 mg/kg bw) protected against BMD loss mainly by inhibiting the osteoclastic activity (RANKL/RANK/TRAP) in OVX rats. MV may develop as a functional food for anti-osteoporosis in menopausal women.

Serum concentrations of osteoprotegerin, brain-derived nerve factor, angiotensin II, and endothelin-1 in aging dogs.

Gerontology is a major research topic in veterinary medicine; however, there are few reports on changes in biomarker levels in aged dogs. The purpose of this preliminary study was to evaluate the differences in serum biomarker levels between young (less than 36 months) and old (over 108 months) companion dogs. We measured the serum concentrations of brain-derived neurotrophic factor (BDNF), osteoprotegerin (OPG), angiotensin II (ANGII), and endothelin-1 (ET-1) in both groups (young: n = 16, 19.8 ± 9.3 months old; old: n = 16, 155.8 ± 22.8 months old). Although the concentrations of BDNF did not differ between the two groups, the OPG, ANGII, and ET-1 levels were significantly higher in the old companion dogs than in the young dogs (p < 0.05). OPG, ANGII, and ET-1 concentrations may increase in dogs during aging.

The role of calcification biomarkers in the formation of aortic stenosis

Abstract Background The main mechanism of aortic valve (AV) calcification is not yet known. One of the possibility pathway responsible for AV calcification (AVC) includes osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL) – the parts of the RANKL-RANK-OPG system and fetuin-A: cysteine protease inhibitors. Aim Evaluation of OPG, sRANKL, fetuin-A in blood serum and tissues in patients with varying severity of aortic stenosis (AS) to establish potential methods of estimation AVC depending on the presence of congenital heart disease: bicuspid AV (BAV) or its absence. Materials and methods The study involved 285 patients with AS (59.06±6.95 years, m:f – 1.1:1): 163 with (BAV) and 122 with tricuspid AV (TAV). The control group 53 patients (48.31±9.04 years, m:f-1:1) without valvular pathology, connective tissue dysplasia and coronary heart disease. ECHO (Vivid 7, GE, USA) was performed in all patients. The expression of OPG, RANKL, fetuin-A in homogenates of aortic valve were determined by immunoblotting. Serum concentration of OPG, RANKL, fetuin were performed in all pts by enzyme-linked immunosorbent assay. Results In the control group the concentration of fetuin-A in the blood serum was significantly higher than in TAV and BAV subgroups (446.66 [293.63; 619.19] vs 319.9 [239.6; 400.2] vs 315.6 [245.6; 385.6] pmol/l, p=0.ehab724.1560001). In all groups of patients with AS an increased level of sRANKL in the blood serum was revealed compared to the control group (TAV=0.39 [0.25; 0.53] vs BAV=0.38 [0.21; 0.55] vs control group 0.31 [0.18; 0.44] pmol/l; p&amp;lt;0.005). OPG level in serum was increased in patients with TAV: 8.1 [4.3; 11.9] pmol/l compared to BAV: 6.8 [3.9; 9.7] pmol/l, p=0.003, as well as the control group: 6.15 [3.41; 8.89] pmol/L, p=0.001. RANKL expression in AV tissue was significantly lower in patients in the control group: 2119,06 [1990.94; 2554.11] as compared with AS pts: 4273.03 [2887.620; 4956], p=0.001, and in subgroups with TAV: 4273.08 [2887.620; 5285], p=0.002 or BAV: 4272.99 [2884.430; 4847], p&amp;lt;0.01. In addition, a positive correlation of moderate strength was found between the RANKL in the blood serum and the expression of RANKL in the AV tissue in patients with BAV (r=0.357, p=0.04). OPG expression in the AV tissue was higher in patients in the control group: 3949,953 [1931.88; 6447.67], while significant only in comparison with the BAV subgroup: 2599.28 [1066.38; 4132.18], p=0.02. A positive correlation of moderate strength was found between the OPG in the blood serum and the expression of OPG in the AV tissue in TAV subgroup (r=0.423, p=0.03). Conclusion Different pathogenic mechanisms of AV calcification are accompanied by an increase in various markers of the OPG / RANK / RANKL system: in patients with TAV calcification marker is OPG, in patients with BAV it is RANKL. Funding Acknowledgement Type of funding sources: None.

Prognostic Value of Serum Osteoprotegerin Level in Patients With Hepatocellular Carcinoma Following Surgical Resection.

BackgroundMultiple studies have reported that tissue or serum osteoprotegerin (OPG) level is a prognostic factor for patients with cancer. However, little is known about the role of serum OPG in hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether serum OPG concentration has an effect on HCC patients’ prognosis.MethodsA total of 386 eligible HCC patients undergoing radical hepatectomy were enrolled from Shanghai Ninth People’s Hospital and Zhongshan Hospital between 2010 and 2018. Kaplan-Meier curves, Cox regression model, and the restricted mean survival time (RMST) were used to estimate the association of OPG and HCC patients’ survival outcome. In addition, sensitivity analyses were carried out including subgroup analysis and propensity score matching (PSM).ResultsPatients were separated into two groups according to the cut-off value of OPG calculated by X-tile. Multivariate Cox analysis showed that patients with high OPG level had worse overall survival (OS) (HR: 1.93; 95% CI: 1.40–2.66, p<0.001) and disease-free survival (DFS) (HR: 1.85; 95% CI: 1.39–2.47, p<0.001) before matching. On average, RMST ratio between high and low OPG turned out to be 0.797 (95% CI: 0.716–0.887, p<0.001). In the matched population, we found that OPG level was negatively associated with OS (HR: 1.85; 95% CI: 1.25–2.74, p=0.002) and DFS (HR: 1.71; 95% CI: 1.20–2.44, p=0.003). In addition, a similar trend was further confirmed by subgroup analyses.ConclusionIn a word, HCC patients with high OPG level had poorer survival rates compared with HCC patients with low OPG level. This factor could act as a potential prognostic predictor for HCC patients who underwent radical resection in the future.

Intestinal fatty acid-binding protein and osteoprotegerin in anthracycline-induced rabbit models of dilated cardiomyopathy

Anthracyclines are used for chemotherapy in small animal cancer patients. However, cardiotoxic complications are very common with anthracycline use and induce multi-organ complications. The purpose of this study was to investigate the associations between multi-organ complications, focusing on the liver and intestine, and the serum concentrations of intestinal fatty acid-binding protein (I-FABP) and osteoprotegerin (OPG) in rabbits with daunorubicin-induced dilated cardiomyopathy (DCM). Sixteen New Zealand white male rabbits (16–20 weeks old), weighing 2.4–3.65 kg, were randomly divided into the control (n = 8) and daunorubicin-induced DCM (n = 8) groups. The concentration of serum I-FABP was significantly elevated in the DCM group (201.9 ± 16.6 pg/mL) compared to the control group (152.2 ± 19.9 g/mL). Additionally, the concentration of serum lactate was markedly increased in the DCM group (0.16 ± 0.01 mM) compared to that in the control group (0.02 ± 0.01 mmol/mL). In addition, the OPG concentration was significantly higher in the DCM group (2.44 ± 0.14 ng/mL) than in the control group (0.1 ± 0.08 ng/mL). Although the histopathology of the ileum did not significantly differ between groups, pathological changes were observed in the livers of the DCM group animals. In conclusion, multi-organ complications were recognized in DCM models and were accompanied by elevated serum I-FABP and OPG concentrations.

Serum osteoprotegerin and cardiometabolic risk factors in overweight and obese children

IntroductionOsteoprotegerin has been shown to play a role in vascular calcification, atherosclerosis and the pathogenesis of cardiovascular diseases. We aimed to evaluate whether excess fat mass affects serum osteoprotegerin concentrations and to evaluate its associations with chosen cardiometabolic risk factors in overweight and obese children.Material and methodsWe enrolled 105 children ranging from 7.0 to 17.8 years of age. Among them 70 individuals were overweight and obese, and 35 were healthy with normal physical parameters. In all patients, anthropometric measurements and laboratory tests were performed. Atherogenic and insulin resistance indices were calculated.ResultsWe did not find any differences in serum osteoprotegerin concentrations between overweight and obese children and their lean peers. In all studied patients, together with elevated quartiles of osteoprotegerin concentration, insulin resistance status decreased, and low-density lipoprotein cholesterol concentration increased. In the group of overweight and obese children osteoprotegerin was associated with low-density lipoprotein cholesterol, total cholesterol, and non high-density lipoprotein cholesterol. In the multiple linear regression analysis osteoprotegerin correlated only with low-density lipoprotein cholesterol (β = 0.140, p = 0.005).ConclusionsInsulin resistance and lipid profile seem to influence circulating osteoprotegerin levels, but most likely needs more time to change its concentration in overweight and obese patients. The association of osteoprotegerin with low-density lipoprotein cholesterol may suggest its link with atherogenesis.

Association between Osteoprotegerin and Charcot Neuroarthropathy: a systematic review.

Osteoprotegerin (OPG) has been associated with Charcot Neuroarthropathy (CN); however, three studied OPG polymorphisms (1181C > G, 245A > C and 950T > C) have yielded conflicting results. Therefore, this meta-analysis was conducted to determine the difference in serum OPG concentrations between healthy controls and diabetics with and without CN and the effect OPG polymorphisms have on CN development. PubMed, LILAC, SCOPUS, and EBSCO databases and retrieved publications' bibliographies were searched for studies that examined for OPG and CN. Depending on the heterogeneity, fixed or random effects were used to calculate the pooled odds ratio (OR) or standard difference in means (SDM) with 95% confidence intervals (95%CI) for 5 genetic models (heterozygous, homozygous, dominant, recessive, and allelic) and serum concentrations, respectively. Seven publications (12 studies) demonstrated that serum OPG concentrations were more elevated in subjects with CN (SDM = 0.719, 95%CI = 0.555-0.883, p < 0.001). When CN was compared to healthy controls or diabetics, the difference was more prominent for healthy controls (SDM = 1.043, 95%CI = 0.676-1.409, p < 0.001) than diabetics (SDM = 0.639, 95%CI = 0.456-0.821, p < 0.001) and the SDM difference was significant (p = 0.013). Using 6 publications (9 studies), neither the 1181C > G or the 950T > C polymorphisms showed any significant associations for any genetic model. For the 245A > C polymorphism, only the homozygous genetic model showed a significant association between the polymorphism and CN (OR = 2.850, 95%CI: 1.051-7.729, p = 0.040). Here, we determined a potential correlation between the CN and serum OPG concentrations and that only the CC genotype of the 245A > C polymorphism showed an increased risk of developing CN.

P1421SERUM OSTEOPROTEGERIN LEVEL IS NEGATIVELY ASSOCIATED WITH BONE MINERAL DENSITY IN PATIENTS UNDERGOING HEMODIALYSIS

Abstract Background and Aims Osteoprotegerin, a potent osteoclast activation inhibitor, decreases bone resorption and positively affects bone mineral density (BMD). Our aim was to evaluate the relationship between BMD and fasting serum osteoprotegerin concentration in hemodialysis patients. Method Fasting blood samples were obtained from 75 chronic hemodialysis patients. BMD was measured by dual energy X-ray absorptiometry in lumbar vertebrae (L2-L4). Serum osteoprotegerin levels were measured using a commercial enzyme-linked immunosorbent assay. Results A total of 7 patients (9.3%) had osteoporosis and 20 patients (26.7%) had osteopenia in hemodialysis patients. Older age (p = 0.023), increased serum osteoprotegerin (p &amp;lt; 0.001), urea reduction rate (URR, p = 0.021), Kt/V (p = 0.027), while decreased height (p &amp;lt; 0.001), body weight (p &amp;lt; 0.001), body mass index (BMI; p &amp;lt; 0.001), and logarithmically transformed triglyceride (log-triglyceride, p = 0.020) was significantly correlated with low lumbar T-score cut-off points between groups (normal, osteopenia, and osteoporosis) in hemodialysis patients. Female patients had lower lumbar BMD than male hemodialysis patients (p = 0.002). Univariate linear regression analysis indicated lumbar BMD were positively correlated with height (p &amp;lt; 0.001), body weight (p &amp;lt; 0.001), BMI (p &amp;lt; 0.001), log-triglyceride (p = 0.004), creatinine (p = 0.016), while negatively correlated with age (p = 0.001), alkaline phosphatase (p = 0.016), URR (p = 0.012), Kt/V (p = 0.013), and osteoprotegerin (p &amp;lt; 0.001) among the hemodialysis patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that female hemodialysis patient (adjusted R2 change = 0.040; p = 0.003), body weight (adjusted R2 change = 0.126; p = 0.001), kt/V (adjusted R2 change = 0.024; p = 0.034) and osteoprotegerin (adjusted R2 change = 0.332; p &amp;lt; 0.001) were the independent predictors of lumbar BMD values in the hemodialysis patients. Conclusion Our study results revealed that increased serum osteoprotegerin levels were independently associated with decreased BMD in the lumbar spine, and with increased risk of osteoporosis in hemodialysis patients.

Inhibitors of canonical Wnt signaling pathway and inorganic phosphate imbalance in experimental chronic kidney disease

BACKGROUND. The molecular mechanisms of the initial stages of inorganic phosphate (Pi) metabolic disorders in chronic kidney disease (CKD) remain poorly understood.THE AIM. To test the hypothesis about changes in canonical Wnt signaling pathway inhibitors biosynthesis and a concomitant decrease in bone turnover as one of early mechanisms of Pi imbalance in CKD.MATERIAL AND METHODS. Creatinine (Cr), inorganic phosphate (Pi), serum parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), sclerostin (SOST) and Dickkopf-1 (DKK), renal SOST and DKK mRNA expression, albuminuria (Alb), proteinuria (uTP) levels, fractional (FEPi) and daily (uPi24) Pi excretion were analyzed in SHR rats (N = 52) with 3/4 nephrectomy (NE) or sham operation (SO) and observation periods of 2, 4, and 6 months.RESULTS. Experimental model was comparable with 1-2 stages of CKD. In groups NE4 and NE6, the concentration of sPi and renal Pi excretion (FEPi and uPi24) were significantly higher vs corresponding controls SO4 (p = 0.006, p &lt;0.010) and SO6 (p = 0.002, p = 0.028). Serum concentrations of FGF23 and PTH in NE and SO animals did not change significantly. In NE4 and NE6 groups, serum SOST and DKK concentrations were significantly higher vs controls (p &lt;0.049, p &lt;0.043), while the kidney expression SOST and DKK mRNA in NE rats did not change significantly or decreased (p = 0.002, p &lt;0.011). The serum concentration of OPG was higher in the NE6 vs SO6 control (p = 0.028).CONCLUSION. The initial stages of experimental CKD are characterized by an increase in serum concentrations of Dikkopf-1, sclerostin and osteoprotegerin. The obtained data suggest the possible role of canonical Wnt signaling inhibition and reduction of bone turnover in the pathogenesis of Pi metabolic disorders in early stages of CKD.

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.