sRANKL Levels Research Articles

Gingival Crevicular Fluid, Serum Levels of Receptor Activator of Nuclear Factor‐κB Ligand, Osteoprotegerin, and Interleukin‐17 in Patients With Rheumatoid Arthritis and Osteoporosis and With Periodontal Disease

This study is performed to evaluate gingival crevicular fluid (GCF) and serum levels of soluble receptor activator of nuclear factor-κB ligand (sRANKL), interleukin (IL)-17A, IL-17E, IL-17F, IL-17A/F, and osteoprotegerin (OPG) in women with rheumatoid arthritis (RA), osteoporosis (OPR), and those who are systemically healthy (SH), all with periodontal disease. GCF and serum samples were obtained before any periodontal intervention from 17 women with RA, 19 with OPR, and 13 who were SH with periodontitis. Full-mouth clinical periodontal measurements were recorded. sRANKL, OPG, and IL-17 levels were determined by enzyme-linked immunosorbent assay. Clinical periodontal measurements were similar in the three study groups. Although the total amounts of GCF albumin, OPG, IL-17A, and IL-17A/F were similar in the study groups, there were statistically significant differences in GCF concentrations of sRANKL, OPG, IL-17A, IL-17E, IL-17F, and IL-17A/F. The sRANKL/OPG ratios were significantly higher in the RA group than in the OPR and SH groups (P <0.05). Serum sRANKL, sRANKL/OPG, and IL-17A/IL-17E ratios were significantly higher, whereas OPG concentrations were significantly lower in the RA group compared to other groups (P <0.05). Serum IL-17A concentrations were significantly higher in the RA and OPR groups than in the SH group (P <0.05). Increased inflammatory mediator levels in patients with RA, despite the long-term use of various anti-inflammatory drugs, suggest that these patients may have a propensity to overproduce these inflammatory mediators.

Effect of Breastfeeding on Serum Osteoprotegerin and Soluble Receptor Activator of Nuclear Factor-Kappa B Ligand in Full Term Neonates

BackgroundHuman breast milk, the sole source of nutrition during the early neonatal period, is rich in nutrients, hormones, growth factors, and immunoactive molecules, which influence the growth, development, and immune status of the newborn infant. It had long been thought that breast milk is an adequate source of anthracitic activity for the newborns and growing child.ObjectiveHuman milk is a complex biologic fluid which contains nutritional and protective factors such as Osteoprotegerin (OPG), at levels 1000-fold higher than normal human serum. Since OPG and Receptor activator of nuclear factor-kappa B ligand (RANKL) system are tightly involved in bone remodeling and immune activity, the study was designated to evaluate the effect of breastfeeding on serum soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) /OPG ratio in full term neonates in comparison with those of formula feeding full term neonates.Materials and MethodsIn this cross-sectional study serum levels of OPG and sRANKL in 45 breastfed infants were compared to those of 44 formula-fed full term infants. The levels of serum OPG, sRANKL, and Tumor necrosis factor alpha (TNFα) were determined by standard techniques using enzyme-linked immunosorbent assay kits.ResultsThe serum levels of OPG were significantly higher (P < 0.001), and the concentrations of TNFα was markedly lower (P = 0.024) in breastfed infants than those of formula-fed infants. No marked differences were observed between the serum levels of sRANKL in the two study groups (P = 0.8).ConclusionsHigh OPG and low TNFα levels in serum of breastfed infants are important factors involved in remodeling of bone, and immune activity may prove superiority of breastfeeding over formula feeding during infancy.

Serum sRANKL/OPG predict recurrence after radiofrequency catheter ablation of lone atrial fibrillation

BackgroundRadiofrequency catheter ablation (RFCA) is a widely accepted strategy for eliminating atrial fibrillation (AF). A considerable recurrence rate has partly been ascribed to atrial remodeling. Osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL) axis may contribute to the development and progression of AF by regulating atrial structural remodeling. This study aimed to determine the relationship between serum soluble RANKL (sRANKL)/OPG and the risk of recurrent arrhythmia after ablation of lone AF. MethodsWe enrolled 527 lone AF patients undergoing first-time RFCA with complete follow-up data. Pre-ablation venous blood samples were obtained for measurement of serum sRANKL and OPG. ResultsDuring the follow-up period of 15 (3–64)months, AF recurred in 187 patients (35.5%). Recurrence was associated with an elevation of serum sRANKL level and sRANKL/OPG ratio. In multivariate survival regression, persistent AF, AF duration, left atrial diameter, amiodarone after ablation, particularly serum sRANKL level and sRANKL/OPG ratio independently predicted AF recurrence. According to ROC curve analysis, the best diagnostic values of serum sRANKL level and sRANKL/OPG ratio for predicting recurrence were 4.89pmol/l and 0.76, respectively. ConclusionsBaseline serum high sRANKL level and sRANKL/OPG ratio are associated with AF recurrence after primary ablation procedure in lone AF patients, and may be used in the prediction of AF recurrence in these patients.

Serum osteoprotegerin and periodontal destruction in subjects with type 1 diabetes mellitus

Besides their role in bone metabolism, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are also known to be associated with inflammation. We explored associations between the extent/severity of periodontitis and circulating levels of sRANKL and OPG and their ratio using a cross-sectional study design. The extent of periodontal inflammation and tissue destruction and the serum levels of sRANKL (pg/ml) and OPG (pg/ml) were determined in 80 subjects with type 1 diabetes mellitus (T1DM). Plaque-, age-, gender-, smoking-, HbA1c- and body mass index-adjusted associations between periodontal parameters and serum sRANKL, OPG and their ratio were studied using multiple linear regression analysis. Adjusted regression analyses of all the subjects indicated a significant positive association between AL≥4mm and severity of periodontitis and the level of serum OPG. A major drop in the strength and statistical significance of the above association was observed when the analyses included only non-smokers. Serum sRANKL level and sRANKL/OPG ratio were not associated with periodontitis. Our observations suggest that serum OPG may be an indicator of periodontal tissue destruction in T1DM.

OPG and sRANKL serum levels and incident hip fracture in postmenopausal Caucasian women in the Women's Health Initiative Observational Study

PurposeThe osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture. MethodsA nested case–control study was conducted among postmenopausal, Caucasian women aged 50–79 at baseline (1993–1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with no prior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors. ResultsSerum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45–3.61) after adjusting for the matching variables (p-value for linear trend <0.001), and 1.87 (95% CI, 1.15–3.04; p for linear trend=0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed. ConclusionSerum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women.

AB0557 Effects of tocilizumab on bone homeostasis and DICKKOPF-1 in rheumatoid arthritis

BackgroundTocilizumab (TCZ) is a humanized monoclonal anti-IL-6 receptor antibody. TCZ has demonstrated efficacy in moderate to severe active rheumatoid arthritis (RA) with inadequate clinical response to disease-modifying anti-rheumatic drugs (DMARD)...

AB0123 Increase in serum levels of srankl and SRANKL/OPG but stable CTX-I in patients with infliximab-treated active ankylosing spondylitis

BackgroundAnkylosing spondylitis is characterised by an increased pathological bone formation in the spine in association with increased prevalence of osteoporosis. The effect of treatment with TNF-inhibitors on syndesmophyte formation is...

FRI0489 Haemophilic artropathy: from sonographic scoring to histopathological modifications

BackgroundHaemophilic arthropathy (HA) may involve mainly the larger joints (target joint) presenting a spontaneous bleeding, haemarthrosis. Repeated bleeding episodes lead to synovitis implying synovial changes, cartilage and bone damages resulting...

THU0388 Menatetrenone (Vitamin K2) Partially Restores the Suppression of Bone Formation by Glucocorticoid Therapy in Patients with Systemic Autoimmune Diseases

BackgroundOsteoporosis is a serious complication of systemic glucocorticoid (GC) therapy. Bisphosphonate is recommended, however insufficient result have been reported in some cases. Menatetrenone (vitamin K2;VK) is a stimulator of bone...

Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

It has been suggested that disturbances in melatonin (MEL) secretion might play a role in osteoporosis development in females with anorexia nervosa (AN). It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue. We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system. Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA), immunoradiometric assay (IRMA) or enzyme-linked immunosorbent assay (ELISA) methods. Our study participants with AN showed a significant reduction in body mass and body mass index (BMI), a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00) as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a significant and independent predictor of OPG, cortisol and FT3 were significant and independent predictors of sRANKL, while LH, E2, Δ MEL2.00/9.00 and FT3 were significant predictors of the OPG/sRANKL ratio. Alterations in OPG and sRANKL levels observed in girls with AN are associated with changes in nocturnal MEL secretion, the circadian rhythm of MEL, and LH, E2, FT3 and cortisol levels. Dysregulation of the relationships between MEL and LH, E2, FT3 and cortisol found in girls with AN might affect the balance of the OPG/sRANKL system. Low values of the OPG/sRANKL ratio associated with high OPG and sRANKL levels suggest some defect in the mechanism compensating for bone remodeling disturbances.

Multiparameter analysis of serum levels of C-telopeptide crosslaps, bone-specific alkaline phosphatase, cathepsin K, osteoprotegerin and receptor activator of nuclear factor κB ligand in the diagnosis of osteoporosis

ObjectivesC-telopeptide crosslaps (CTX) and bone-specific alkaline phosphatase (BAP) do not provide sufficient sensitivity and specificity for diagnosis of osteoporosis. Cathepsin K (CatK), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (total (t) and soluble (s) RANKL) play an important role in bone metabolism. Thus serum levels of biochemical markers, each or in combination, may be useful in diagnosis of osteoporosis. Study DesignIn total, 121 healthy women, 27 premenopausal women aged between 20 and 45 years, and 94 postmenopausal women aged 59–81 years, all free of known skeletal disorders were included. They underwent bone density measurement and measurement of biochemical markers. Main Outcome MeasuresBased on WHO criteria, women were stratified in four groups (premenopausal: healthy; postmenopausal: healthy, osteopenia, osteoporosis), and their levels of CatK, OPG, RANKL, CTX and BAP were analyzed. ResultsUsing WHO criteria 21 postmenopausal women had normal bone mineral density (BMD), 49 had osteopenia and 24 had osteoporosis. There were no significant correlations of CatK, OPG and RANKL with BMD (T-score) in age-adjusted analysis, but for BAP and CTX. ROC analyses resulted in poor diagnostic validity of all parameters. The best result – also confirmed by discriminant analysis – was yielded by BAP (AUC=0.646 [0.510; 0.781]). A combination of variables did not significantly improve the diagnostic power. ConclusionsBaseline serum levels of BAP, CTX, CatK, OPG, sRANKL or tRANKL alone or in combination are not suitable to distinguish osteoporotic from non-osteoporotic postmenopausal women with sufficient accuracy.

Serum receptor activator of nuclear factor κB ligand (RANKL) levels predict biochemical recurrence in patients undergoing radical prostatectomy

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There is increasing evidence that the receptor activator of nuclear factor κB ligand (RANKL) pathway not only contributes to the development of bone metastases, but also influences tumour biology in earlier stages of cancer. The study shows that preoperative serum levels of RANKL and its inhibitor osteoprotegerin (OPG) have a prognostic impact in patients undergoing radical prostatectomy for clinically localized prostate cancer. Both high levels of RANKL and a higher RANKL/OPG ratio are independent predictors of early biochemical recurrence in these patients. To assess the prognostic impact of proteins of the receptor activator of nuclear factor κB (RANKL) pathway in serum samples from patients undergoing radical prostatectomy. We retrospectively determined soluble RANKL (sRANKL) and osteoprotegerin (OPG) by ELISA in serum samples of 178 patients undergoing radical prostatectomy between 2004 and 2006. Clinical and patient follow-up data were analysed using the Wilcoxon-Mann-Whitney test, the Kaplan-Maier method, and single variable or multifactorial Cox proportional hazards analysis. Higher serum sRANKL levels (P = 0.01), lower serum OPG levels (P = 0.01) and a higher sRANKL/OPG ratio (P = 0.004) were significant risk factors for biochemical recurrence (BCR). In multifactorial analysis, adjusted for the common risk factors for BCR, sRANKL and sRANKL/OPG ratio were confirmed as independent prognostic factors. Neither sRANKL nor OPG showed a clear association with histopathological factors such as pT stage, pN Gleason score or resection margin status, nor were they associated with prostate-specific antigen level. Greater activity of the RANKL pathway in the serum of patients with prostate cancer undergoing radical prostatectomy is a risk factor for BCR. The RANKL pathway seems to contribute to the biological behaviour of prostate cancer even at the organ-confined stage of the disease.

Ghrelin levels in chronic periodontitis patients

Ghrelin is a peptide hormone that has modulatory effects on the immune system. This study was designed to evaluate plasma ghrelin levels in patients with chronic periodontitis and to investigate if a relationship exists between ghrelin and periodontal parameters, serum cytokines, and bone turnover markers. Thirty-five chronic periodontitis patients (CP) and periodontal healthy individuals (C) were included in this study. Periodontal parameters were recorded. Blood samples were obtained to determine the levels of total and acylated ghrelin, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), the soluble receptor activator nuclear factor kappaB ligand (sRANKL), alkaline phosphatase (ALP), and osteocalcin (OSC). Plasma levels of total and acylated ghrelin were significantly elevated in the CP group compared with the C group (p < 0.05). The difference was significant only between males in the two groups (groups were compared with respect to gender) (p < 0.05). There was no difference between the groups regarding the levels of serum sRANKL, TNF-α, and ALP. A relative increase in the serum levels of IL-1β and a decrease in the serum levels of OSC of the CP group were observed (p < 0.05). In addition, positive correlations between total ghrelin/ALP and total ghrelin/acylated ghrelin were discovered. We found no direct correlation between ghrelin levels and periodontal parameters. Our results indicate an increase of total and acylated ghrelin levels in patients with chronic periodontitis. Further, studies in larger populations (which could include ghrelin levels in gingival tissue, gingival crevicular fluid, and saliva) are needed in order to confirm the role of ghrelin in periodontal disease.

Circulating Levels of Soluble Receptor Activator of NF-κB Ligand and Matrix Metalloproteinase 3 (and Their Antagonists) in Asian Indian Patients with Ankylosing Spondylitis

Background. Bone loss in ankylosing spondylitis may be related to inflammation. Data from previous studies on circulating levels of sRANKL, OPG, MMP3, and TIMP is inconsistent; thus this study is planned to look at this aspect in Asian Indian patients. Methods. Cross-sectional study included patients with ankylosing spondylitis and age- and gender-similar controls. Serum levels of sRANKL, OPG, MMP-3, and TIMP-1 were measured by ELISA. Results. Included 85 patients (M : F = 82 : 3) having mean age (±SD) 33.0 ± 10.0 years and disease duration 11.3 ± 7.3 years. BASDAI, BASFI, BASMI, and ESR were 4.0 ± 2.2, 3.9 ± 2.8, 3.0 ± 2.8, and 59.2 ± 31.2, respectively. Patients had higher mean (±SD) OPG level (649.7 ± 286.8, 389.3 ± 244.8 pg/mL, P < 0.001). However, there was no difference in sRANKL (349.2 ± 872.0, 554.7 ± 1850.1, P = ns). Serum MMP-3 (91.4 ± 84.7, 55.9 ± 37.1 ng/mL, P < 0.01) and TIMP-1 (520.6 ± 450.7, 296.5 ± 114.2 ng/mL, P < 0.001) levels were higher in patients; however, there was no difference in MMP-3/TIMP-1 ratio. Conclusion. Circulating levels of OPG were higher; however, there was no difference in sRANKL in Asian Indian ankylosing spondylitis patients. Although both MMP-3 and TIMP-1 were raised, their ratio was not different from that of controls.

Salivary soluble receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio in periodontal disease and health

PurposeThe receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system plays a significant role in osteoclastogenesis, activation of osteoclasts, and regulation of bone resorption. This study aimed to evaluate the use of the salivary soluble RANKL (sRANKL)/OPG ratio as a diagnostic marker for periodontitis in nonsmokers.MethodsTwenty-five patients with chronic periodontitis and 25 individuals with a healthy periodontium were enrolled in this study. Samples containing 5 mL of unstimulated saliva were obtained from each subject. Salivary sRANKL and OPG concentrations were determined using a standard enzyme-linked immunosorbent assay. Statistical analysis was performed using SPSS ver. 18.0.ResultsThe levels of sRANKL and OPG were detectable in all of the samples. Positive relationships were found between the plaque index and clinical attachment level and both the salivary concentration of sRANKL and the salivary sRANKL/OPG ratio (P<0.05). The salivary concentration of sRANKL and the sRANKL/OPG ratio were significantly higher in the periodontitis group than in the healthy group (P=0.004 and P=0.001, respectively). In contrast, the OPG concentration showed no significant differences between the groups (P=0.455).ConclusionsThese findings suggest that the salivary sRANKL/OPG ratio may be helpful in the screening and diagnosis of periodontitis. However, longitudinal studies with larger populations are needed to confirm these results.

Osteoprotegerin, Soluble Receptor Activator of Nuclear Factor-κB Ligand, and Subclinical Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus

Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) system in type 1 diabetes (T1DM) children and adolescents and controls. Subjects and Methods. Fifty six T1DM patients (mean ± SD age: 12.0 ± 2.7 years, diabetes duration: 5.42 ± 2.87 years and HbA1c: 8.0 ± 1.5%) and 28 healthy matched controls, were studied with anthropometric and laboratory measurements, including serum OPG, soluble RANKL (sRANKL) and cIMT. Results. Anthropometric, laboratory, and cIMT measurements were similar between T1DM youngsters and controls. However patients with longer diabetes duration (>/7.0 years) had indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm, P 0.072) and triglyceride levels than the rest of the patients (93.7 vs 64.6 mg/dl, P 0.025). Both in the total study population (β 0.418, P 0.027) and among T1DM patients separately (β 0.604, P 0.013), BMI was the only factor associated with cIMT. BMI was further associated with OPG in both groups (β −0.335, P 0.003 and β −0.356, P 0.008 respectively), while sRANKL levels were not associated with any factor. Conclusions. BMI was the strongest independent predictor of cIMT among the whole population, and especially in diabetics, suggesting a possible synergistic effect of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly associated with circulating OPG, but the causes of this association remain unclear.

Time-related changes in salivary levels of the osteotropic factors sRANKL and OPG through orthodontic tooth movement

In this study, we aimed to determine whether the variations in salivary concentrations of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG), and their ratios, might be linked with the different phases of orthodontic tooth movement. Twenty healthy subjects who required fixed appliance therapy not involving tooth extractions or surgical procedures were selected. Unstimulated whole saliva samples were collected from each patient before fitting the orthodontic appliances, and at 24 to 48 hours, 2 weeks, 5 weeks, and 8 weeks after the activation. Salivary sRANKL and OPG concentrations were determined by enzyme-linked immunosorbent assays. The data were analyzed by using nonparametric statistics. Overall, median values of sRANKL showed significant increases, median OPG salivary values showed a significant downward trend, and the sRANKL/OPG ratio tended to increase significantly over time after the activation visit. However, clear fluctuations in the immunoenzymatic findings were noted at the different sampling times, indicating nonlinear trends in the levels of the biomarkers through time. Post-hoc pairwise comparisons showed significant differences between (1) all sRANKL values relative to those of the 8-week sampling time; (2) baseline/8-week OPG salivary levels; and (3) baseline, 24 to 48 hours, and 2-week sRANKL/OPG ratios compared with those of the 8-week test. The findings indicate that variations in salivary concentrations of sRANKL and OPG and their ratios might be linked to the different phases of orthodontic tooth movement. Hence, these analytes might serve in a panel of salivary functional biomarkers that could assist in the screening of orthodontic treatment in clinical practice.

Effect of Unfractionated and Low-Molecular-Weight Heparin on OPG, sRANKL, and von Willebrand Factor Concentrations During Hemodialysis

Endothelial dysfunction marker, von Willebrand factor (vWF), is physically connected with osteoprotegerin (OPG) in the Weibel-Palade bodies. We aimed to compare the effect of unfractionated (UFH) and low-molecular-weight (LMWH enoxaparin) heparin used as anticoagulants during hemodialysis (HD) on plasma levels and relationships of OPG, soluble receptor activator of nuclear factor κB Ligand (sRANKL), and vWF. Totally 21 clinically stable chronic HD patients were randomly assigned to either enoxaparin (n = 10) or UFH (n = 11) anticoagulation and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. The OPG, RANKL, and vWF levels were measured at T0, T10, and T180 of HD session after each period of evaluation. The baseline sRANKL level was higher under UFH treatment. Its over-HD level does not behave significantly different under enoxaparin and UFH treatment. Plasma OPG levels expressly changed during both enoxaparin (χ(2) analysis of variance [ANOVA] = 31.13, P < .016) and UFH (χ(2) ANOVA = 8.26, P = .016) anticoagulation, and its increment at T10 and T180 was significantly different between both the heparins. The main negative predictor of OPG concentration was the total cholesterol level (β = -.51, P = .025). von Willebrand factor concentration remained stable during UFH anticoagulation, whereas constant, no significant increments were noticed, under enoxaparin treatment. After 10 minutes of HD, especially under enoxaparin use, a positive correlation between OPG and vWF increase was noticed (P = .03, R = .45). Impact of heparin on endothelial cells and simultaneously on OPG/RANK/RANKL axis reinforces the presumption of the pathophysiological linkage between bone mineralization and endothelial dysfunction in end-stage renal disease.

Association of salivary levels of the bone remodelling regulators sRANKL and OPG with periodontal clinical status

To determine the variations in salivary concentrations of sRANKL, osteoprotegerin (OPG) and its ratio, regarding the periodontal status. Ninety-seven chronic periodontitis (CP) subjects and 43 healthy controls were selected. Periodontal status was assessed based on full-mouth clinical periodontal measurements. sRANKL and OPG salivary levels were analysed by ELISA. The association between these analytes and its ratio with CP was analysed individually and adjusted for confounding using a binary logistic regression model. sRANKL and sRANKL/OPG ratio were increased, whereas OPG was decreased in CP compared with healthy controls subjects. Although univariate analysis revealed a positive association of sRANKL salivary levels ≥6pg/ml, OPG salivary levels ≤131pg/ml and sRANKL/OPG ratio ≥0.062 with CP, after logistic regression analysis only the latter parameter was strongly and independently associated with disease status. Confounding and interaction effects of ageing and smoking habit on sRANKL and OPG levels could be noted. Although salivary concentrations of sRANKL, OPG and its ratio may act as indicators of the amount/extent of periodontal breakdown, the mutual confounding and synergistic biological interactive effects related to ageing and smoking habit of the susceptible host may also promote the tissue destruction in CP.

Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen.Methods55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied.ResultsThe levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents.ConclusionsIn this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.