osteoprotegerin and Colitis--Ulcerative

Osteoprotegerin (OPG) is increased in inflamed colonic mucosa and has a role in immune regulation and apoptosis resistance. Fecal OPG may be useful in predicting corticosteroid resistance in hospitalized children with severe ulcerative colitis (UC). We aimed to determine whether fecal OPG predicts the need for second-line therapies in children hospitalized for UC.. We included 83 children with UC admitted for intravenous corticosteroid treatment. Children were classified as responders/nonresponders based on the need for therapy escalation. Fecal OPG results were compared with those of four other fecal markers.. Of the enrolled children, seven had day 1 samples only, 53 children had day 3 samples only, and 23 had both. Twenty-two children failed corticosteroid therapy and required infliximab (n = 20) or colectomy (n = 2). On the third treatment day the median fecal OPG levels were significantly higher in the nonresponders group compared with the responders: 77 pmol/L (interquartile range [IQR] 27-137) versus 13 pmol/L (3-109); P = 0.007. The best day 3 fecal OPG cutoff to predict second-line therapy was >50 pmol/L with a sensitivity of 71% and specificity of 69% (area under the receiver operator curve [ROC] of 0.70%-95% confidence interval [CI] 0.57-0.82). Fecal OPG was superior to day 3 fecal calprotectin, lactoferrin, and S100A12 as a predictor of corticosteroid nonresponse, but equivalent to the less commonly used M2-pyruvate kinase.. Day 3 fecal OPG may guide the decision to institute second-line therapy in children with severe UC. The role of OPG in the inflammatory response in pediatric UC deserves further study.

Topics: Adolescent; Adrenal Cortex Hormones; Biomarkers; Child; Child, Preschool; Colectomy; Colitis, Ulcerative; Feces; Female; Hospitalization; Humans; Male; Osteoprotegerin; Predictive Value of Tests; ROC Curve; Severity of Illness Index; Time Factors; Treatment Failure

To investigate the effect of sequential. Three groups of patients were involved in this observational cross-sectional study: IBD (n = 83),. Serum osteoprotegerin levels were significantly correlated with the simple endoscopic score for Crohn's disease and Mayo score for ulcerative colitis. The receiver operating characteristic analysis of osteoprotegerin revealed high values for the area under the curve, sensitivity, and specificity. Discriminant analysis illustrated that osteoprotegerin levels significantly differentiated patients with IBD from healthy controls. Osteoprotegerin and FC levels distinguished the IBD and HP + IBD groups from the NC and HP groups.. Sequential eradication therapy did not affect serum osteoprotegerin levels in patients with

Topics: Colitis, Ulcerative; Helicobacter Infections; Helicobacter pylori; Humans; Inflammatory Bowel Diseases; Osteoprotegerin

Cytokines are mediators of inflammatory processes in the course of inflammatory bowel disease (IBD) and participate in the bone metabolism. Interleukin 6 (IL-6) initiates osteoclastogenesis by modulating the activity of soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin.. The aim of the study was to evaluate bone mineral density (BMD) by densitometry and the concentration of interleukin 6, osteoprotegerin (OPG) and sRANKL protein (sRANKL) by ELISA in patients with IBD in relation to the control group; to assess the relationship between IL-6, OPG, sRANKL and BMD; and to assess the impact of disease duration and number hospitalization on BMD.. The studied group included 37 patients with Crohn's disease (I - CD), 37 patients with ulcerative colitis (II - UC) and 37 healthy subjects - control group (III - CG).. The prevalence of osteoporosis and osteopenia was as follows: in I - CD, 18.92% and 32.43% in L2-L4; 13.51% and 35.13% in the neck, and in II - UC, 2.7% and 37.84% in L2-L4; 2.7%, and 29.73% in the femoral neck. The concentration of IL-6 correlated negatively with T-scores in the neck for the whole group, and in group I - CD, there was a significant positive correlation between serum OPG and IL-6.. The incidence of osteopenia and osteoporosis in patients with IBD is high and increases with the duration of the disease and the number of hospitalizations. Patients with CD are at a higher risk of skeletal pathology than patients with UC. IL-6 can modulate bone mineral density in the femoral neck especially in the course of CD.

Topics: Absorptiometry, Photon; Adult; Bone Density; Bone Diseases, Metabolic; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Female; Humans; Incidence; Inflammatory Bowel Diseases; Interleukin-6; Male; Middle Aged; Osteoporosis; Osteoprotegerin; RANK Ligand

Ulcerative colitis (UC) is a chronic disease with periods of remission and recurrences. Dysfunction of the local immune response leads to chronic inflammation within the large intestine which triggers morphological changes in the intestinal wall as well as induces the synthesis of numerous factors that have an adverse impact on the bone metabolism. The aim of the study was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC patients with long disease duration as well as serum level of these cytokines in the context of bone density and bone metabolism.. The UC group consisted of 56 patients with average disease duration of 16y. The control group comprised 37 healthy individuals. Local expression of cytokines was assessed in the biopsies of colonic mucosa by the real-time PCR and immunohistochemistry (IHC), and their serum concentration was measured by ELISA.. The increased bone resorption observed in patients with UC was reflected by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal RANKL expression and serum concentration were similar in UC group and healthy subjects, however, UC patients had higher local expression of OPG and serum OPG concentration. Increased IL-33 gene expression was observed only in UC at the mRNA level. We propose that bone resorption in UC patients despite OPG up-regulation could be caused by IL-33-induced mucosal synthesis of a potent proinflammatory cytokine, such as TNF-α, known as a possible inducer of osteoclastogenesis in the way independent of RANKL.

Topics: Adult; Bone and Bones; Bone Density; Case-Control Studies; Colitis, Ulcerative; Female; Humans; Interleukin-33; Interleukins; Intestinal Mucosa; Male; Middle Aged; Osteoprotegerin; RANK Ligand

To investigate the correlation between decoy receptor (DcR)1, DcR2 and osteoprotegerin (OPG) gene polymorphisms with the susceptibility to ulcerative colitis (UC) in Chinese population.. A total of 352 patients with UC as well as 463 sex- and age-matched healthy controls were recruited in the study. The genetic polymorphisms of DcR1 (rs12549481), DcR2 (rs1133782) and OPG (rs3102735) were determined using a mini-sequencing technique method.. In the autosomal dominant model, the rates of mutant allele (A) and genotype (GA+AA) of DcR2 (rs1133782) were lower in UC patients compared to the controls [6.25% (44/704) vs 8.96% (83/926), P = 0.043; 11.36% (40/352) vs 17.28% (80/463), P = 0.018, respectively]. In the recessive model, moreover, we found that the rates of mutant allele (T) and homozygote (TT) of OPG(rs3102735) were significantly increased in UC patients in contrast with the controls [86.36% (608/704) vs 81.53% (755/926), P = 0.009; 75.28% (265/352) vs 66.95% (310/463), P = 0.010, respectively]. By means of unconditional Logistic regression analysis, the rate of mutant allele (T) of OPG (rs3102735) was shown to be significantly decreased in patients with severe UC compared to the other UC patients [76.67% (69/90) vs 87.79% (539/614), OR = 0.457, 95%CI 0.265-0.788, P = 0.004]. Nevertheless, the genetic polymorphism of DcR2(rs1133782) was not significantly related to the clinical features in UC patients. In addition, the genotypic distribution of DcR1 (rs12549481) in control group did not conform to the Hardy-Weinberg equilibrium rule, thus a further statistical analysis was not performed in our study.. The genetic polymorphism of DcR2(rs1133782) might be associated with the susceptibility to UC. Not only is the mutation of OPG (rs3102735) gene correlated to the development of UC, but also to the severity of disease.

Topics: Alleles; Asian People; China; Colitis, Ulcerative; Gene Frequency; Genotype; Homozygote; Humans; Osteoprotegerin; Polymorphism, Genetic

There is a potential interface between osteoporosis and the chronic inflammation of inflammatory bowel disease (IBD), and the osteoprotegerin (OPG)/receptor for activated nuclear factor-kappaB (RANK)/RANK ligand (RANKL) signaling pathway may be an important mediator, although data are limited.. We conducted a population-based case-control seroassay study to look for alterations in serum OPG and soluble RANKL (sRANKL). The study population included IBD patients who were 18 to 50 years old with Crohn's disease (CD; n = 287) or ulcerative colitis (UC; n = 166), age-matched healthy controls (n = 368), and nonaffected siblings of IBD patients (n = 146). Serum OPG and sRANKL were measured by enzyme-linked immunoassay. Sex-specific reference ranges were derived from the healthy controls.. Analysis of variance (ANOVA) confirmed significant group differences in women for mean serum OPG (P = 0.018). CD women had higher values of OPG than UC women (P = 0.028) or healthy controls (P = 0.045), whereas the other groups were similar. OPG levels were above the reference range in 13/173 (8%) of CD women, exceeding the expected proportion (P = 0.032). In contrast, no differences in OPG were seen in men between controls, CD, or UC. Estrogen use in women (P = 0.000002) and corticosteroid use in men (P = 0.026) were associated with higher OPG levels. In multivariate analysis, CD diagnosis (P = 0.031) and estrogen use (P = 0.000002) were independently associated with higher OPG levels. No group differences were seen in mean serum sRANKL measurements.. An OPG:sRANKL imbalance with OPG exceeding sRANKL should inhibit osteoclastogenesis and promote bone formation. CD is associated with increased fracture risk, and possibly, the paradoxically higher OPG is a counterregulatory response to factors such as inflammatory cytokines, promoting high bone turnover. Alternatively, elevated OPG in CD may reflect T-cell activation.

Topics: Adult; Carrier Proteins; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Estrogen Replacement Therapy; Female; Glucocorticoids; Glycoproteins; Humans; Male; Membrane Glycoproteins; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sex Factors; Smoking

Osteoporosis is a significant complication of a multifactoral etiology associated with inflammatory bowel disease. The aim of study was to evaluate the relationships between bone mineral density as well as bone turnover markers and inflammatory activity modulators (i.e., PGE2 and TGFbeta1) in ulcerative colitis (UC). Twenty-one active ulcerative colitis subjects and 14 healthy individuals were included into the study. We observed no significant differences in serum concentrations of osteoprotegerin and osteocalcin, as well as bone mineral density between UC patients and healthy individuals. Plasma concentrations of PGE2, TGFbeta1 and TNF-alpha were significantly higher in UC patients than in controls. Serum osteocalcin demonstrated a positive correlation with both serum PGE2 and plasma TGFbeta1. Moreover there was significant correlation between osteoprotegerin and TGFbeta1 as well as serum TNF-alpha concentrations. In conclusion a positive association between PGE2 and TGFbeta1 and bone formation markers-osteoprotegerin and osteocalcin, as well as a comparable BMD in UC patients and healthy individuals was shown. Our results may indicate that increase of PGE2 as well as TGFbeta1 concentrations may play a protective role against bone loss in ulcerative colitis patients.

Topics: Absorptiometry, Photon; Adult; Bone Density; Bone Remodeling; Colitis, Ulcerative; Dinoprostone; Female; Glycoproteins; Humans; Magnetic Resonance Imaging; Male; Osteocalcin; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Transforming Growth Factor beta; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha