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Abstract While the relationship between circulating osteoprotegerin (OPG) and cardiovascular events is well-established in the general population, its association with cardiovascular risks in chronic kidney disease (CKD) patients remains less robust. This study hypothesized that elevated circulating OPG levels might be associated with an increased risk of major adverse cardiac events (MACE) in CKD patients, a total of 2,109 patients with CKD stages 1 through pre-dialysis 5 from the KNOW-CKD cohort were categorized into quartiles based on serum OPG levels. The primary outcome of the study was 3-point MACE, defined as a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiac death. The median follow-up duration was 7.9 years. The cumulative incidence of 3-point MACE significantly varied across serum OPG levels in Kaplan–Meier curve analysis (P

Background: Osteoprotegerin (OPG) plays a role in preventing osteoclast formation and osteoclastic bone resorption by inhibiting the receptor activator nuclear factor-β and its ligand (RANK–RANKL) interaction that causes bone resorption. Pangasius djambal gelatin contains essential amino acids that may stimulate bone remodeling. Purpose: This study aimed to investigate the expressions of OPG, RANKL, and RANK following tooth extraction to ascertain whether OPG is associated with the RANKL and RANK ratios following gelatin induction. Methods: This study was a true experimental study with a simple, randomized post-test only control group design. Twenty-four albino rats (Rattus norvegicus) were divided into two groups (n = 4). The treatment group was treated with P. djambal gelatin following tooth extraction, while the control group was left untreated. Animal models undergoing tooth extraction were anesthetized intraperitoneally with ketamine (1,000 mg/10 ml up to 0.2 ml). The tooth was then extracted slowly so as not to break it. P. djambal gelatin was dripped (0.1 ml) into the socket after the extraction procedure. The association of OPG with RANKL and RANK immunohistochemistry expressions was evaluated after three, five, and seven days. Results: There was a significant increase in OPG expression on day 7 (P < 0.05) and a significant decrease in the expression of RANKL and RANK (P < 0.05) in the treatment group. Conclusion: The application of P. djambal gelatin could increase OPG expression, decrease RANKL and RANK expression in the socket following tooth extraction, and might be associated with the inhibition of bone resorption.

This article discusses a study on the effects of Pangasius djambal gelatin on the healing process of tooth extraction sockets in rats. The study found that the application of the gelatin increased the expression of osteoprotegerin (OPG), a key regulator in the bone remodeling process, and decreased the expression of receptor activator nuclear factor-ß ligand (RANKL), which can impair hard tissue healing. These findings suggest that P. djambal gelatin may have potential as a biomaterial for promoting healing after tooth extraction. [Extracted from the article]

Objective To investigate the role and mechanism of bone formation caused by the ratio of advanced platelet-rich fibrin (A-PRF) and β-tricalcium phosphate (β-TCP) in rabbit femur defect model, which provides a new idea for clinical treatment of bone defect. Methods Twenty-four New Zealand white rabbits were divided into model group, 1∶1 complex group (A-PRF∶β-TCP=1∶1), 2∶1 complex group (A-PRF∶β- TCP=2∶1) and 4∶1 complex group (A-PRF∶β- TCP=4∶1）, with 6 rabbits in each group. Femoral defect models were constructed in each group. In the composite group, the bone defect was filled with composite material, while in the model group, no material was filled. After 8 weeks, the animals were euthanized and specimens were collected. Bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.SP) and trabecular number (Tb.N) in femoral defect tissue were measured by micro-CT and photographed. Hematoxylin - eosin staining was used to detect the pathological changes of new bone tissue. The morphological changes of the new bone tissue were observed by scanning electron microscopy. Determination of phospho-mitogen activated protein kinase p38 (p-p38MAPK), CCAAT/enhancer binding protein homologous protein (CHOP) and phospho-cysteine aspartic protease-3 (p-Caspase3) in newborn femur by ELISA. The mRNA expressions of osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2), receptor activator of nuclear factor kappa-B ligand (RANKL) and p38MAPK were detected by real-time quantitative PCR. The expression of OPG, BMP-2, RANKL, p-p38MAPK and p-Caspase3 protein in the new bone tissue was observed by immunohistochemistry. Results In the model group, bone formation in the femoral defect area was slow and osteogenic quality was poor. Compared with the model group, the bone formation and neocapillaries of femoral defect area in the complex group was good, BMD, BV.TV, Tb.Th, Tb.N were increased, and Tb.Sp were decreased, the expressions of p-p38MAPK, CHOP and p-Caspase3 were decreased, and the mRNA and protein expressions of OPG and BMP-2 were increased. The mRNA expression of RANKL and p38MAPK was decreased. Apoptosis in new bone tissue of each group showed the lowest apoptosis rate in samples of the 2∶1 complex group (P

Aims: The aim of this study was to analyze the induction effect of a combination of N. sativa and bovine bone graft on the expression and ratio of receptor activator of nuclear factor kappa-B ligand expression (RANKL) and osteoprotegerin (OPG) on alveolar bone socket preservation on days 7 and 14. Settings and Design: The research incorporated a posttest-only control group design. A total of 56 Cavia cobaya were divided into four groups: a control group, an N. sativa group, a bovine bone graft group, and a combined N. sativa and bovine bone graft group. Materials and Methods: The lower incisors of the C. cobaya were extracted with material subsequently being applied to the resulting socket. After the 7th and 14th days, the experimental animals were terminated to enable observation of the socket. Following processing, the tissue was subjected to immunohistochemistry staining consisting of RANKL and OPG antibodies before being observed under a light microscope at × 400. Statistical Analysis Used: Statistical analysis was carried out using the one-way ANOVA and Tukey's honestly significant difference tests. Results: A combination of N. sativa and bovine bone graft reduced both RANKL expression and the RANKL/OPG ratio while increasing OPG expression in comparison to the other groups. In all the results obtained, the N. sativa and bovine bone graft combination was significant (P < 0.05) when compared to the control group on both the 7th and 14th days. Conclusion: A combination of N. sativa and bovine bone graft reduced both RANKL expression and the RANKL/OPG ratio while increasing OPG expression. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is among the most significant health problems, with the associated cardiovascular disease and bone metabolism disorders being the leading cause of morbidity and mortality in these patients. The aim of the study was to determine markers of bone turnover in patient sera (phosphates, calcium, alkaline phosphatase, parathyroid hormone and osteoprotegerin (OPG)) in all stages of kidney failure including kidney transplant recipients. We also wanted to determine whether dialysis vintage affects recovery of bone markers one year after transplantation. There were 164 study patients, whereas 30 healthy individuals served as a control group. Serum OPG progressively increased with decline of the glomerular filtration rate. The highest OPG concentration was recorded in dialysis group. We observed a statistically significant OPG increase in stage 2 CKD. In kidney transplant group, there was positive correlation between OPG and dialysis vintage. We also found that serum OPG was lower in patients treated with dialysis for less than 4 years prior to transplantation. We confirmed that CKD-mineral and bone disorder began in stage 3 CKD with parathyroid hormone and OPG elevation, and a statistically significant OPG increase in stage 2 CKD might be an early sign of CKD-mineral and bone disorder. Dialysis vintage longer than 4 years is associated with more significant disturbances in mineral and bone metabolism.

Periodontitis is a multifactorial chronic condition associated with the formation of a dysbiotic biofilm, leading to inflammation that can modulate cell signaling. R-spondins (Rspos) are cysteine-rich secreted glycoproteins which control a variety of functions which are essential for embryonic development and tissue homeostasis. Numerous studies have explained about their pivotal role in critical developmental regulators, the most important finding being Rspos synergise Wingless/Integration (Wnt) signaling. Novel receptors for Rspos, the Leucine-rich repeat containing G protein-coupled (LGR) receptors, proposed that Rspos potentiate canonical Wnt signaling via these receptors. Here, authors discussed about the Wnt signaling and outlined the biological role of Rspos in tissue development and homeostasis and explore the possibility that Rspos may be used as therapeutic targets. Wnt5a is important for promoting periodontal ligament remodeling and impairing regenerative responses modulated by the Wnt/β-catenin pathway, for alveolar bone formation.

Aim. To clarify the mechanisms of the effect of osteoprotegerin (OPG) and sclerostin on vascular calcification and the state of the cardiovascular system in chronic kidney disease (CKD). Materials and methods. A total of 110 patients aged 18 to 65 years with CKD stages 35D were examined. OPG, sclerostin, intact parathyroid hormone, and serum troponin I were determined using the commercial "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" from Cloude-Clone Corp. (USA) by enzyme-linked immunosorbent assay. Results. An increase in sclerostin and OPG levels was revealed, which significantly correlated with a decrease in glomerular filtration rate, as well as an increase in left ventricle myocardial mass index and peak systolic blood flow in the aortic arch. Conclusion. Changes in the regulation of bone-mineral metabolism, in which the proteins inhibitors of bone metabolism, OPG and sclerostin, as well as the interactive interaction between the vascular and skeletal systems, play a decisive role in the development of lesions of the cardiovascular system caused by vascular calcification in CKD.

Abstract Background and Aims Limitations of the conventional diagnostic techniques urged researchers to seek novel methods to predict, diagnose, and monitor periodontal disease. Use of the biomarkers available in oral fluids could be a revolutionary surrogate for the manual probing/diagnostic radiograph. Several salivary biomarkers have the potential to accurately discriminate periodontal health and disease. This study aimed to determine the diagnostic sensitivity and specificity of salivary interleukin (IL)‐17, receptor activator of nuclear factor‐κB ligand (RANKL), osteoprotegerin (OPG), RANKL/OPG for differentiating (1) periodontal health from disease and (2) stable and unstable periodontitis. Methods Participants with periodontitis (n = 50) and gingivitis (n = 25), both diseases represented the cases, and subjects with healthy periodontium (n = 15) as a control were recruited for this study. Periodontitis cases were further equally subdivided into stable and unstable. Whole unstimulated salivary sample were collected from all participants. Periodontal parameters including bleeding on probing, probing pocket depth, clinical attachment loss, and number of missing teeth were recorded. The protein levels of salivary IL‐17, RANKL, and OPG were determined by using enzyme‐linked immunosorbent assays technique. Results Salivary IL‐17, OPG, RANKL, and RANKL/OPG showed high sensitivity and specificity to differentiate periodontal health from gingivitis and periodontitis. Similar pattern was observed in discriminating stable and unstable periodontitis. Salivary IL‐17 and RANKL showed a good accuracy to differentiate gingivitis from periodontitis. However, OPG and RANKL/OPG did not exhibit enough sensitivity and specificity to differentiate the latter conditions. Conclusion Salivary IL‐17, RANKL, OPG, and RANKL/OPG system are potential candidates for differentiating periodontal health and disease and discriminate stable and unstable periodontitis.

Context: Osteoporosis occurs not only in the lumbar bone, femur, and radius but also occurs in the mandibular bone. Therefore, osteoporosis is a disease that required attention from the dentists. Aims: To determine the ratio of Receptor Activator of Nuclear Factor kB-Ligand:Osteoprotegerin (RANKL:OPG) expression and the ratio of osteoclasts:osteoblasts number in the mandibular bone of the osteoporosis rat models. Methods: The research subjects used were 20 Rattus novergicus, which were randomly divided into two groups, namely ovariectomy (OVX) and sham surgery (SHS). Twelve weeks after surgery, the animals were terminated and mandibular bone specimens were taken for histological examination of osteoclasts, osteoblasts, RANKL, and OPG expression. An examination of estrogen levels in the blood of the research subjects was also carried out. All data obtained were tested statistically using a t-test. Results: There was a decrease in the amount of estrogen in the OVX group rather than SHS (p = 0.005). In the SHS group, the RANKL:OPG expression value ratio was 0.51 ± 0.15, while in the OVX group was 0.86 ± 0.22 (p = 0.001). In the SHS group, the ratio of osteoclasts:osteoblasts number was 0.012 ± 0.004, while in the OVX group was 0.061 ± 0.023 (p = 0.001). Conclusions: A decrease in estrogen significantly induces the ratio of RANKL:OPG and osteoclast:osteoblasts in the mandibular bone.

The maintenance of thyroid hormone homeostasis is essential in the regulation of skeletal system development, bone tissue mineralization and fracture risk prevention. This study was carried out to evaluate the serum level of osteoprotegerin (OPG), sclerostin (SOST), and osteocalcin (OC) in hypo- and hyperthyroidism patients. A total number of examined patients was 90 individuals, 30 of them were normal as a control group, the rest 60 individuals were arranged in two groups: 30 patients with hypothyroidism and 30 patients with hyperthyroidism. Serum assay tests for OPG, SOST, OC, thyroid stimulating hormone (TSH), total triiodothyronine (T3), and total thyroxine (T4) were used. The present study reported high levels of SOST, T3, and T4 and low levels of OPG, OC, and TSH in patients with hyperthyroidism compared to control. Whereas in patients with hypothyroidism only SOST and TSH levels were increased, but OPG, OC, T3, and T4 levels were low compared to control. The data obtained indicate the correlation on osteoprotegerin, sclerostin, and osteocalcin levels with thyroid hormones disturbances.

In recent years, it has been proven that the formation of OA can occur against the background of impaired bone metabolism. Bone remodeling is considered as a continuous complex process aimed at eliminating microdamages and updating the bone matrix. A key link in the regulation of this process is the system RANK / RANKL / OPG (osteoprotegerin), which provides a balance of activity of osteoblasts and osteoclasts. It blocks the interaction between RANK and RANKL by intercepting the RANKL ligand, which inhibits osteoclast development and reduces bone resorption. Thus, these properties of OPG can be considered as one of the pathogenetic factors in patients with dystrophic joint lesions. Objective: to investigate the content and role of osteoprotegerin in young patients with osteoarthritis, which occurs against the background of changes in body weight. Materials and methods. The study involved 75 young patients (mean age - 30.92 ± 0.546 years) with overweight or obesity, who in the previous stages of the study was diagnosed with osteoarthritis (main group). The comparison group was represented by 50 patients with osteoarthritis and normal body weight. The age of patients was 30.95 ± 0.545 years; as in the previous group, men predominated - 64% and 36% respectively. Benchmarks of osteoprotegerin were obtained in a study of 37 relatively healthy individuals of the same age and sex. The level of osteoprotegerin was determined by enzyme-linked immunosorbent assay using the FineTest EH0247 reagent kit, China. The outcomes were processed by the methods of variation statistics using the computer program STATISTICA.Results and discussion. When determining the content of OPG in the serum of patients of the main group was found to increase to 124.03 pg / ml, against control - 65.64 pg / ml. In the group of patients with isolated OA, this value was 92.29 pg / ml. Meaning that, in OA, running on the background of altered BMI, the content of OPG is likely to increase, both in relation to the norm and the results of the comparison group (p

Background Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, is a tumor necrosis factor receptor superfamily component. There is an established relationship between OPG and cardiovascular disease. We hypothesized that plasma OPG levels are associated with functional outcomes in acute ischemic stroke patients who have undergone endovascular thrombectomy (EVT). Methods From April 2014 through December 2020, a total of 360 acute ischemic stroke patients who underwent EVT were prospectively included in this retrospective observational study. Plasma OPG was measured after fasting for 12 postoperative hours after EVT. A modified Rankin Scale (mRS) was used to assess functional outcomes 3 months after index stroke occurrence. Univariate and multivariate binary logistic regression and ordinal logistic regression analyses were performed to investigate the association of plasma OPG levels with poor functional outcomes. Results Overall, 145 (40.2%) patients had poor (mRS > 2) outcomes. The mean ± standard deviation plasma OPG level was 200.2 ± 74.4 pg/mL. Multivariate analysis after adjusting for sex, body mass index, and variables with p

Aim:In this study, we aimed to compare osteoprotegerin (OPG) levels in patients with and without polycystic ovary syndrome (PCOS) and to investigate the correlation between OPG levels and cardiovascular risk factors.Methods:A total of 49 patients with PCOS and 31 age- and body mass index-matched healthy controls were included in the study. Blood samples were collected and hormonal and metabolic parameters and OPG levels were analyzed. The carotid intima-media thickness (CIMT) was measured for each patient and control through ultrasonography.Results:The low-density lipoprotein and total cholesterol levels were higher and the Homeostasis Model Assessment-Insulin Index (HOMA-IR) values were higher in patients with PCOS (p=0.002, p=0.037, and p=0.028, respectively). The OPG levels were 4.29 pmol/L and 4.07 pmol/L in the patient and control groups, respectively, indicating no significant difference between the groups. The CIMT was 0.57 in both groups.Conclusion:Our study results suggest that OPG levels appear to be similar in patients with PCOS and healthy controls. Although OPG has been associated with endothelial dysfunction, atherosclerosis and coronary calcification in previous studies, currently not a useful marker for cardiovascular risk analysis in this patient population.

Osteoprotegerin (OPG) appears to be a very promising marker both in the diagnosis of abdominal aortic aneurysms (AAAs) and as a potential target in its treatment. This article presents an overview of the current literature that discusses the role of OPG in the pathogenesis of atherosclerosis and its potential value as a prognostic factor in AAA. Pharmacological modulation of OPG expression has been considered. In conclusion, it seems that further research designed to assess the relationship between OPG and AAA is needed as this may contribute to improved AAA monitoring and more effective treatment of patients with AAA.

Aim: We aimed to examine the association between several circulating bone turnover markers [ osteocalcin (OC), osteoprotegerin (OPG), beta-CrossLaps (β-CTx)], hip and spine bone mineral density (BMD) and abdominal aortic calcification (AAC) in patients with chondrocalcinosis (CC).

Background. СDC (USА) places yersiniosis in ten intestinal infections which are subject to close observation. Exposure to multiple agents is responsible for possible damages of the joints at infection diseases acting as rare forms however, as a pathognomonic syndrome it is found at yersiniosis infections, brucellosis, and Lyme borreliosis. Studies of fine mechanisms of infection arthritis development do gain their relevance. The purpose of the research was to study the TNFRSF11B gene’s Asn3Lys polymorphic marker distribution at patients suffering from generalized and arthritic form of yersiniosis, and to determine the connection of the polymorphism in question with development of yersiniosis arthritis (YA). Materials and methods 123 patients aged 16 to 68 years, with proven yersiniosis infection, were observed. The 1st group included 61 patients with secondary focal arthritic form of yersiniosis whereas the 2nd control group consisted of 62 patients with generalized form of yersiniosis without damaging of joints. 50 patients (82 %) had chronic form of YA. For genetic tests, SNP–express test system – 31Т>С of IL1β gene and Asn3Lys of TNFRSF11B gene was applied. Results. In 2 groups of examined persons, three genotypes being Asn/Asn, Asn/Lys and Lys/Lys were detected. The incidence for genotype Asn/Asn in group with YA made 19.7 %, being 1,7 times lower as compared with control group (33.9 %). The genotype Lys/Lys in group with YA was detected with incidence 31.1 %, which is 2.14 times higher than the value for control group. The genotype Lys/Lys was found prevailing for patients with YA. Genotype Lys/Lys relates to increased risk of development of YA (χ2 = 6.08, р = 0.49; OR = 2.66, confidence interval 1.09–6.49). Coclusions. Polymorphism of Asn3Lys of TNFRSF11B gene coding the osteoprotegerin relates to development of YA. Genotype Lys/Lys of TNFRSF11B gene is a marker of increased risk of development and progressing of YA. Study of genetic predisposition to occurrence of YA, аs well as possible genetically determined resistance to treatment performed based on molecular and genetic testing is an important predictor for YA treatment and prevention.

Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p

Background. Calcium pyrophosphate deposition disease is defined by deposition of calcium pyrophosphate crystals in hyaline cartilage, fibrocartilage and soft tissues. The study of bone markers is of great interest in different types of arthritis. In patients with calcium pyrophosphate deposition disease, bone turnover markers may yield additional information from many perspectives. Objectives. To measure synovial and serum levels of osteocalcin, osteoprotegerin and β-CrossLaps in patients with calcium pyrophosphate deposition disease. Material and methods. In this pilot, prospective study were enrolled eight patients with calcium pyrophosphate deposition disease. Osteocalcin, osteoprotegerin and β-CrossLaps were measured in serum and in the synovial fluid using ELISA kits. Results. Synovial fluid osteocalcin was significantly lower comparative with serum osteocalcin (2.1±0.6 versus 9.21 ±46, p=0.02). Synovial fluid osteoprotegerin was significantly higher than serum osteoprotegerin (55.5±284 versus 8.44±7; p=0.0001). Synovial fluid β-CrossLaps wasn’t statistically different from serum levels (6146±66818 versus 6077±12212; p=0.5). Ratios between synovial fluid and serum levels were 0.22 for osteocalcin, 6.57 for osteoprotegerin and 1.01 for β-CrossLaps. Conclusions. Osteocalcin was higher in serum than in the synovial fluid. β-CrossLaps had similar values in serum and synovial fluid. Osteoprotegerin was higher in synovial fluid than serum.

Introduction:We aimed to investigate the levels of receptor activator of nuclear factor kappa-b ligand (RANKL) and osteoprotegerin (OPG) in order to evaluate the negative effects of type 2 diabetes mellitus on bone health and their relationship to the severity of disease based on the treatment. We also evaluated the relationship between hemoglobin A1c (HbA1c), parathyroid hormone (PTH) and bone specific alkaline phosphatase (BAP) levels and RANKL and OPG levels.Methods:The study group consisted of 19 volunteers (15 females and 4 males) and 65 patients with type 2 diabetes mellitus (49 females and 16 males). In order to evaluate the relationship between the treatment and the disease severity, the patient group was divided into two subgroups: patients treated with oral anti-diabetics (OAD) (sulfonylurea and metformin) or insulin. The levels of glucose, calcium, phosphorus, HbA1c, BAP, PTH, RANKL and OPG were compared.Results:The RANKL and OPG levels of patients treated with insulin were significantly higher than the control group (p=0.008, p=0.033, respectively). However, there was no significant difference in the OAD group for both parameters (p=0.1, p=0.46, respectively). There was no significant difference between the groups in terms of PTH and BAP levels (p=0.97, p=0.66, respectively).Conclusion:We believe that RANKL and OPG levels are higher in patients with poor glycemic control and that they may be indicators of disease severity.

Background: Recent studies have reported that melatonin inhibits bone resorption through the regulation of Receptor Activator of Nuclear Factor Kappa-B Ligand (RANΚL): Osteoprotegerin (OPG) ratio in osteoblast. However, the role of melatonin in osteoblast derived from MSCs is unclear. Aim and Objectives: To determine the down-regulation of RANΚL:OPG ratio by melatonin supplementation in osteoblast culture in osteogenic medium derived from rat Bone-Marrow Mesenchymal Stem Cells (BMMSCs). Material and Methods: This research was an experimental research conducted in a laboratory in vitro making use of rat BM-MSCs in osteogenic medium with or without melatonin for a duration of 21 days. Characteristics of MSCs were explored with the use of immunocytochemistry staining (CD45 and CD105). Results: After 15 days, mineralisation assay was carried out by means of Alizarin Red staining and at 21 days the RANΚL and OPG levels were assessed with the use of sandwich ELISA. Conclusion: 150 nM or higher concentrations of melatonin could reduce RANΚL levels; the supplementation of melatonin had no influence on OPG levels, and melatonin could reduce the RANΚL:OPG ratio. The results of this study summarise that melatonin could reduce the RANΚL:OPG ratio in the osteoblast culture originated from rat BM-MSCs.

Abstract Objective Thalassemia intermedia (TI) describes a disease ranging in severity between β thalassemia major (TM) and β thalassemia trait. Osteoporosis is observed in TI and TM. The exact reason of osteoporosis in TI could be hypogonadism and/or an increase in erythropoietin (EPO) levels. The carboxy-terminal collagen cross links (CTX), a marker of bone resorption, and the N-terminal propeptide of type 1 collagen (P1NP), a marker of bone formation are serum markers of osteoporosis. The receptor activator of NF-kappaB ligand (RANKL)/receptor activator of NF-kappaB (RANK)/osteoprotegerin (OPG) axis plays an important role in metabolic bone diseases. Herein, we tested the relationship between the RANKL/RANK/OPG axis and the bone-turnover markers CTX and P1NP in TI. Results We recruited 44 TI patients and 33 non-thalassemic controls and measured the serum levels of hemoglobin, sex steroid hormones, CTX, P1NP, RANKL and OPG. We then used a general linear model to test the association of the above variables with CTX and P1NP as outcome variables. We showed that EPO levels were the strongest predictor of CTX change (P

Cardiovascular disease is one of the most frequent causes of mortality and morbidity worldwide. Several variables have been identified as risk factors for cardiovascular disease. Recently, the role of receptor activator of nuclear factor kappa B, receptor activator of nuclear factor kappa B ligand, and the osteoprotegerin system has been recognized as more important in the pathogenesis of cardiovascular disease. Besides their roles in the regulation of bone resorption, these molecules have been reported to be associated with the pathophysiology of cardiovascular disease. There are conflicting data regarding the impact of osteoprotegerin, a glycoprotein with a regulatory role in the cardiovascular system. The aim of this review is to discuss the current knowledge and the role of osteoprotegerin in cardiovascular disease.

Aim. To study changes in antimicrobial and osteotropic oral fluid mediators during pregnancy in women with chronic generalized periodontitis (CGР) of mild and moderate severity, taking into account the factor of steroid regulation by cortisol.Materials and methods. Among the 62 pregnant women (age 18 to 35 years), depending on the presence or absence of inflammatory periodontal diseases, the main group (n=31) with moderate and moderate CGР and control group (n=31) with no disease were formed. In addition, 32 healthy non-pregnant women (age 18 to 30 years) examined the oral fluid in the same diagnostic volume. In the oral liquid, the amount of catelicidin LL-37, osteoprotegerin and cortisol was determined using a solid-phase immunoassay method. Laboratory studies were conducted in I (8-12 weeks), II (13-27 weeks) and III (28-40 weeks) trimester of pregnancy.Results. In pregnant women with a physiologically pregnant pregnancy and in the absence of dental diseases in the oral fluid with a consequent increase in the concentration of cortisol, there was a decrease in the content of catelicidin LL-37 1 trimester followed by an increase in the 2nd and 3rd trimesters of the antimicrobial potential of the oral biological environment, an increase in the concentration of osteoprotegerin that inhibits the activity of osteoresorption in the alveolar bone. In pregnant women with CGR of mild and moderate severity, a marked increase in the concentration of cortisol in the oral fluid was accompanied in the first two terms by an increased content of cathelicidin LL-37 and activation of antimicrobial congenital mechanisms of resistance to pathogenic bacteria, followed by a decrease in the antimicrobial factor to the third trimester of the gestation period, a consistent decrease in the content of osteoprotegerin in mixed saliva.Conclusion. The presence of CGР of mild and moderate severity in pregnant women leads to a dissociation of the connection between cortisol mixed saliva and immune defense factors, osteotropic mediators in contrast to women who do not suffer from dental pathology during the gestational period.

Introduction: Oxygen is emerging as an important factor in the local regulation of bone remodeling. Some preclinical data suggest that hyperoxia may have deleterious effects on bone cells. However, its clinical relevance is unclear. Hence, we studied the effect of hyperbaric oxygen therapy (HBOT) on serum biomarkers reflecting the status of the Wnt and receptor activator of NF-κB ligand (RANKL) pathways, two core pathways for bone homeostasis. Materials and methods: This was a prospective study of 20 patients undergoing HBOT (mean age 58 yrs., range 35–82 yrs.) because of complications of radiotherapy or chronic anal fissure. Patients were subjected to HBOT (100% oxygen; 2.4 atmospheres absolute for 90 min). The average number of HBOT sessions was 20 ± 5 (range 8–31). Serum hypoxia-inducible factor 1-α (HIF1-α), osteoprotegerin (OPG), RANKL, and the Wnt inhibitors sclerostin and dickkopf-1 (DKK1) were measured at baseline and after HBOT by using specific immunoassays. Results: HIF-1α in eight patients with measurable serum levels increased from 0.084 (0.098) ng/mL at baseline to 0.146 (0.130) ng/mL after HBOT (p = 0.028). However, HBOT did not induce any significant changes in the serum levels of OPG, RANKL, sclerostin or DKK1. This was independent of the patients’ diagnosis, either neoplasia or benign. Conclusion: Despite the potential concerns about hyperoxia, we found no evidence that HBOT has any detrimental effect on bone homeostasis.

50% of the orthodontic treatments experience a relapse and the tendency of post-orthodontic treatment relapse is 33-90%. A retainer can prevent relapse, which is not effectively used and there are 19% relapse cases after that treatment. Meanwhile, Epigallocatechin-3-Gallate (EGCG) has the ability to inhibit osteoclastogenesis. Whereas, Stem-Cells from Human Exfoliated Deciduous-Teeth (SHEDs) are able to proliferate and differentiate as well. This study was aimed to explain the potential of freeze-dried EGCG and SHED scaffold as the biocompatible anti-relapse material during post-orthodontic treatment. Orthodontic relapse is the return of the tooth position due to osteoclast activity and lack of osteoblast activity. EGCG is one of the catechins which is most foundin green tea that may increase the expression of NF-kB, Runx2, BMP-2 and decrease the expression of RANKL. SHEDs may differentiate osteogenic better than DPSCs by expressing higher ALP. Freeze-drying is a method to form the 3D geometry and the strength to cross-link the scaffold. A relapse after any orthodontic treatment occurs due to the inadequate remodeling of alveolar bone. ALP expression in osteoprotegerin (OPG) is important in osteogenesis to prevent any relapse. EGCG may induce BMP2, RUNX2 and also ALP in osteogenesis process. Whereas, SHEDs may differentiate osteogenic with osteoblast markers expressions such as RUNX2, osteopontin, and osteocalcin. Furthermore, SHEDs form calcium matrix minerals for osteogenic formation. Freeze-dried EGCG and SHED scaffold may have the potential to induce osteogenesis as a biocompatible material for anti-relapse post-orthodontic treatment. [ABSTRACT FROM AUTHOR]

Background: In Indonesia, the incidence rate of tooth extraction as the main form of dental treatment reached as high as 79.6% in 2014. Teeth extraction leads to periodontal tissue defect whose treatment, incorporating the use of graft material Hydroxyapatite (HA) and Platelet Rich Fibrin (PRF) with stem cells, has become increasingly widespread. The stem cell potentially put to therapeutic use is the Hematopoetic Stem Cell (HSC). Aim and Objectives: to examine the effect of hematopoetic stem cell addition to HA graft and PRF post-tooth extraction on the number of osteoblasts and amount of Osteoprotegerin (OPG) in periodontal defect treatment. Material and Methods: This study constituted laboratory-based experimental research with a post test-only control group. Twenty four rats (Rattus novergicus) represented the animal study model in this research. Alveolar bone defect in the animal study model was induced by extracting the first molar of the mandible using sterile needle holder clamps. The sample population was divided into four groups: K0: the untreated control group; K1: socket filled with HA Graft and PRF. K2: socket filled with HSC 105 cells. K3: the socket filled with HA Graft and PRF with HSC 106 cells. Results: The K3 group had both the highest number of osteoblasts when compared with the control group (350.17 ± 33.42; P

Background: Decreasing of estrogen level can lead to alveolar bone loss. This bone loss reflects an imbalance between resorption and apposition. Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) is a key mediator in osteoclast activation, while Osteoprotegerin (OPG) is modulator of bone apposition. Aim and Objectives: To obtain the value of RANKL and OPG expressions in alveolar bone socket under condition of low plasma estrogen level. Materials and Methods: Sixteen female Wistar rats, aged 2-3 months divided into control and treatment group. Ovariectomy was done to treatment group. Seven days after ovariectomy, mandibular right incisor was extracted on each group. Fourteen days after extraction, immunohistochemical examination procedure was performed to determine expressions of RANKL and OPG level in alveolar bone socket. Results: The values of RANKL and OPG expressions in control group respectively were 5.13 ± 0.83 and 14.75 ± 1.39. In the treatment group, the values of RANKL and OPG expressions were 11.63 ± 1.6 and19.88 ± 0.40. Independent t-test showed that there was a significant difference between both groups (p < 0.05). Conclusion: Low plasma estrogen level condition can increase both RANKL and OPG expressions, but the increase was higher in RANKL expressions than in OPG expressions.

Aim. Pperform a comparative analysis of the content of markers of bone metabolism in the oral fluid in pregnant women without dental pathology and complications of the gestational period in comparison with healthy donors in the dynamics of the gestational period.Material and Methods. 31 pregnant women (clinical group) were examined. The control group consisted of 32 non-pregnant women. In the oral fluid and serum, the level of activity of alkaline phosphatase (AP), the content of osteoprotegerin (OPG) and receptors for the ligand of the nuclear factor kappa-B (sRANKL) was determined by an enzyme immunoassay.Results. The index evaluation of the hygienic state of the oral cavity, periodontal conditions, confirmed the absence of inflammatory changes and dental pathology in patients of the clinical group. In pregnant women with a physiologically pregnant pregnancy, OPG, AP (markers of restriction of osteoresorption) accumulated to the third trimester both systemically and in biological fluids of the oral cavity.Conclusion. The content of sRANKL during the gestational period in the oral fluid did not change. The study of the content of OPG and AP in the oral fluid in pregnant women is informative, reflecting the osteosynthetic processes of bone metabolism in the alveolar processes.

Osteoprotegerin (OPG) is a glycoprotein that is a representative of the tumor necrosis factor-α receptor superfamily. Information about the possible role of OPG in the development of cardiovascular diseases has begun to appear in the literature in recent years. This review discusses the role of increasing the level of OPG in the development and progression of atherosclerosis and as a consequence of coronary heart disease and chronic heart failure.

Introduction : Osteoprotegerin (OPG), the endogenous inhibitor of RANKL, prevents or reverses bone loss in a variety of preclinical models of bone disease. Preclinical studies indicate that osteoporosis significantly impairs implant fixation. This study aims to investigate the role of OPG in implant osseointegration in ovariectomized rats. Material and methods: Twelve weeks after bilateral ovariectomy, each rat accepted two titanium screws in the proximal tibiae. All animals were then randomly divided into two groups: the control (10 rats) and OPG group (10 rats). Subcutaneous injection of OPG (10 mg/kg) or vehicle was performed three times a week. Eight weeks later, tibiae with screws were harvested for micro-computed tomography (µCT), histological and biomechanical analysis. Results : Compared to control, OPG increased the percent bone volume by 124%, the percent osseointegration by 167%, the mean trabecular number by 111%, the mean trabecular thickness by 92% (p < 0.01), the mean connective density by 95% (p < 0.05); and decreased the mean trabecular separation by 64% in µCT analysis (p < 0.05). OPG also increased bone area density by 160% and bone-to-implant contact by 234% in histomorphometric evaluation (p < 0.01), and increased the maximal push-out force by 228% in biomechanical test (p < 0.01). Conclusions : Systemic administration of OPG improved implant osseointegration and fixation in ovariectomized rats, resulting from the increased peri-implant bone mass and improved trabecular microarchitecture.

Objective To investigate the role of osteoprotegerin (OPG) in implant osseointegration in ovariecto⁃ mized rats. Methods 12 weeks after bilateral ovariectomy, each rat accepted 2 titanium screws in the proximal tibiae. All animals were then randomly divided into 2 groups: control (10 rats) and OPG group (10 rats). Subcutaneous injection of OPG (10 mg/kg) or vehicle was performed 3 times a week. 8 weeks later, tibiae with screws were harvested for μCT, histological and biomechanical analysis. Results Compared to control, OPG increased the percent bone volume by 124%, the percent osseointegration by 167%, the mean trabecular number by 111%, the mean trabecular thickness by 92%, the mean connective density by 95%; and decreased the mean trabecular separation by 64% in μCT analysis. OPG also increased bone area density by 160% and bone⁃to⁃implant contact by 234% in histomorphometric evaluation, and increased the maximal push ⁃ out force by 228% in biomechanical test. Conclusion Systemic administration of OPG can improve implant osseointegration and fixation in ovariectomized rats, resulting from the increased peri⁃implant bone mass and improved trabecular microarchitecture.

Background: Biomechanical stress and inflammatory biomarkers relate to global contractility dysfunction; however, adding these biomarkers into a risk model constructed on clinical data does not improve its prediction value in chronic heart failure (CHF).

Adolescent idiopathic scoliosis is the most common form of spinal deformity in children. The aetiology of the condition has not been elucidated. Currently, the multifactorial theory seems to be the most probable. Certain authors propose that melatonin should be considered as a causative factor of adolescent idiopathic scoliosis. Their assumption is supported by a range of research studies conducted on animal models with removed pineal gland, which induced scoliosis. Melatonin has been proven to exert direct and indirect effects on the development of the skeletal system. The role of calmodulin or osteoprotegerin seems equally important. In patients with this condition, the levels of platelet calmodulin and calmodulin in the specimens of the paraspinal muscles on the convex side of the curve have been shown to rise. Osteoprotegerin, in turn, modifies osteoclastic and osteoblastic differentiation. These substances have a direct influence on the cellular calcium and phosphate metabolism and can be potentially responsible for spinal deformity in adolescents. The role of oestrogens is being investigated. Moreover, the role of growth factors or thrombospondins still remains obscure. Additionally, molecular tests have revealed a number of genes that can predispose to adolescent idiopathic scoliosis. It still needs to be determined which of the musculoskeletal disorders occur first in the development of scoliosis and which are secondary to the deformity. The identification of the aetiological factor and factors responsible for scoliosis progression determines the manner of treatment.

Objectives: Osteoprotegerin (OPG) has an important role in bone remodeling, and it has been proposed that the OPG gene might be a candidate gene for osteoporosis predisposition. Several studies have already assessed the connection between OPG gene polymorphism and bone mineral density (BMD). In this study we wanted to analyze the association of two polymorphisms in the OPG gene with BMD and bone turnover markers in women with and without osteoporosis. Material and methods: In 22 postmenopausal women with osteoporosis (aged 65.6 ±12.6) and 59 women without osteoporosis (aged 60.8 ±8.7) we analyzed the association of two polymorphisms in the OPG gene with BMD, measured by dual energy absorptiometry and with bone turnover markers (crosslaps and osteoprotegerin). A163G, G209A, T245G and G1181C polymorphisms were determined. Results: No significant differences in age, anthropometry, number of fractures, osteocalcin and cross-laps were found between women with and without osteoporosis. Women with osteoporosis were significantly longer in postmenopause. Significantly more women with osteoporosis had AG polymorphism (p = 0.038) compared to women without osteoporosis, while no significant difference was found in prevalence of TT and GG polymorphism between patients with and without osteoporosis. No relationship was found between investigated polymorphism and bone turnover markers. A significant negative correlation between total hip BMD and crosslaps (p = 0.046) as well as between total hip T score and crosslaps (p = 0.044) was found in women without osteoporosis Conclusions : Postmenopausal women with osteoporosis had AG polymorphism more frequently than women without osteoporosis. Our results indicate that A163G polymorphism could have an impact on higher bone loss in postmenopausal women.

Purpose: The aim of this study was to evaluate the serum levels of omentin, osteoprotegerin and malondialdehyde levels in patients with polycystic ovary syndrome (PCOS). Material and Methods: This prospective case-control study included 31 patients with the diagnosis of PCOS and 33 healthy cases as a control group. Both groups were compared according to demographic characteristics, antropometric measurements, levels of biochemical parameters and serum levels of omentin, osteoprotegerin and malondialdehyde. Results: When compared with control group, patients in PCOS group were found to have statistically significantly lower age but have higher hirsutism score, fasting glucose level, total testosteron level, free androgen index, LH level and LH/FSH ratio. There was no statistically significant difference among PCOS and control groups in terms of serum omentin, osteoprotegerin and malondialdehyde levels. Conclusion: No significant change was shown in the levels of serum omentin, osteoprotegerin and malondealdeheyde levels in women with PCOS. [Cukurova Med J 2016; 41(1.000): 1-7]

Background: Osteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-μ) with bone turnover in men with very severe COPD. Methods: Pulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using an independent t-test and Mann–Whitney U-test. The Pearson coefficient was used to assess the relationships between variables. Results: OPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum βCL, TNF-μ, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEV1) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01). In contrast, serum RANKL inversely associated with LS and FN T-score (r = −0.62, P < 0.001 and r = −0.48, P < 0.001) but directly correlated with βCL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = −0.39, P < 0.01), TNF-μ (r = −0.56, P < 0.001), and sTNFR-I (r = −0.40, P < 0.01). Conclusion: Our results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.

Background: Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats. Methods: Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis. Results: Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks. Conclusions: Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling.

Type 2 diabetes mellitus (DM) is caused by insulin resistance and/or impaired insulin secretion, thus causing hyperglycemia leading to endothelial dysfunction. Endothelial dysfunction is an early process of atherosclerosis and is one of the risk factors for coronary arterial disease (CAD). Currently, coronary angiography is used as the gold standard for diagnosing CAD. Examination of osteoprotegerin (OPG) is an alternative assay for endothelial dysfunction marker which is less invasive, has the ability to detect earlier, and less expensive. Osteoprotegerin is associated with the development of arterial plaque in patients with type 2 DM. The aim of this study was to determine the differences in serum OPG levels in patients with type 2 DM with and without CAD. The study was conducted in September–December 2012 in the Endocrine Clinic and Emergency Unit of Dr. Hasan Sadikin General Hospital Bandung on 102 patients aged between 35–75 years, with 51 subjects type 2 DM patients with CAD and 51 subjects with type 2 DM without CAD, both diagnosed by clinician. The method used was, OPG enzyme linked immunosorbent assay (ELISA) examination method. The study was an observational cross-sectional comparative study. Statistical analysis was performed using normality test with Shapiro Wilk’s, independent T and Mann Whitney test. The median value for patients with type 2 DM with CAD equaled to 6.1 pmol/L and the value for type 2 diabetic patients without CAD was 2.6 pmol/L. In this study, the OPG levels obtained in patients type 2 DM with CAD were higher than those without CAD. In conclusion, there is a significant difference in OPG levels between type 2 DM with and without CAD groups.