Bone health in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are prone to reduced bone mineral density and elevated overall fracture risk. Osteopenia affects up to 40% of patients with IBD (high regional variability). Besides disease activity, IBD specialists must consider possible side effects of medication and the presence of associated diseases and extraintestinal manifestations. Osteopenia and osteoporosis remain frequent problems in patients with IBD and are often underestimated because of widely differing screening and treatment practices. Malnutrition, chronic intestinal inflammation and corticosteroid intake are the major pathophysiological factors contributing to osteoporosis. Patients with IBD are screened for osteoporosis using dual-energy X-ray absorptiometry (DXA), which is recommended for all patients with a prolonged disease course of more than three months, with repeated corticosteroid administration, aged >40 years with a high FRAX risk score or aged <40 years with multiple risk factors. From a therapeutic perspective, besides good disease control, vitamin D supplementation and glucocorticoid sparing, several specific osteological options are available: bisphosphonates, receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (denosumab), parathyroid hormone (PTH) analogues and selective estrogen receptor modulators. This review provides an overview of the pathophysiology, diagnosis, prevention and treatment of IBD-associated bone loss

Dairy products, dietary calcium and the risk of inflammatory bowel disease: results from a European prospective cohort investigation

Background: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC). Methods: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. Results: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47). Conclusions: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect

Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management.

Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear. Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models. In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P &lt; 10 &lt;sup&gt;-15&lt;/sup&gt; ), examinations (P &lt; 10 &lt;sup&gt;-12&lt;/sup&gt; ), medical therapies (P = 0.023) and weeks of hospitalisation (P = 0.0013) in a multivariate model. We detected an association between maximal abdominal pain in UC patients and two IBS-associated SNPs. Abdominal pain levels had a pronounced impact on diagnostic and therapeutic procedures in CD but not in UC patients

Prevalence of Anemia in Inflammatory Bowel Diseases in European Countries: A Systematic Review and Individual Patient Data Meta-analysis.

The main objective is to determine the overall prevalence of anemia in inflammatory bowel diseases (IBD) in Europe

Predictors of temporary and permanent work disability in patients with inflammatory bowel disease: results of the swiss inflammatory bowel disease cohort study

BACKGROUND Inflammatory bowel disease can decrease the quality of life and induce work disability. We sought to (1) identify and quantify the predictors of disease-specific work disability in patients with inflammatory bowel disease and (2) assess the suitability of using cross-sectional data to predict future outcomes, using the Swiss Inflammatory Bowel Disease Cohort Study data. METHODS A total of 1187 patients were enrolled and followed up for an average of 13 months. Predictors included patient and disease characteristics and drug utilization. Potential predictors were identified through an expert panel and published literature. We estimated adjusted effect estimates with 95% confidence intervals using logistic and zero-inflated Poisson regression. RESULTS Overall, 699 (58.9%) experienced Crohn's disease and 488 (41.1%) had ulcerative colitis. Most important predictors for temporary work disability in patients with Crohn's disease included gender, disease duration, disease activity, C-reactive protein level, smoking, depressive symptoms, fistulas, extraintestinal manifestations, and the use of immunosuppressants/steroids. Temporary work disability in patients with ulcerative colitis was associated with age, disease duration, disease activity, and the use of steroids/antibiotics. In all patients, disease activity emerged as the only predictor of permanent work disability. Comparing data at enrollment versus follow-up yielded substantial differences regarding disability and predictors, with follow-up data showing greater predictor effects. CONCLUSIONS We identified predictors of work disability in patients with Crohn's disease and ulcerative colitis. Our findings can help in forecasting these disease courses and guide the choice of appropriate measures to prevent adverse outcomes. Comparing cross-sectional and longitudinal data showed that the conduction of cohort studies is inevitable for the examination of disability

UniFrac distance between samples and rarefaction curve of phylogenetic diversity.

<p>(A) Unweighted UniFrac distance. The higher a UniFrac distance value between two samples the more different the bacterial composition. The highest distance values were determined for subjects undergoing smoking cessation between t1 and t2 as well as between t1 and t3. All other distance values were substantially smaller (error bars indicate SEM; *: p<0.05; ns: not significant). (B) Rarefaction curves. These curves express the accumulation of phylogenetic richness that would be obtained with continuous sampling effort and hence minimize potential differences that would be a result of the variable number of sequences obtained per sample. For the control groups the three sampling time points were combined in a single curve, while for the intervention group separated curves for t1, t2 and t3 were depicted to visualize the increased phlyogenetic diversity (PD) in the samples 4 weeks after smoking cessation (I2) compared to I1 and I3 (additional indices of α-diversity are depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059260#pone.0059260.s009" target="_blank">Figure S9</a>).</p

Phylogeny-based Principal Component Analysis.

<p>Bacterial communities of the three different treatment groups were clustered using PCA and the unweighted UniFrac distance matrix as an input (weighted PCA is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059260#pone.0059260.s006" target="_blank">Figure S6</a>). With PCA, a multivariate statistical analyses, axes that reflect the largest part of sample variation are identified (Percentage values at the axes reflect the level of variation explained by each principal coordinate; the first axis indicates the largest fraction of difference). Separation of the different sample collectives in 3 dimensions is visualized. A separation of the samples from the intervention group (I), that is most predominant 4 weeks after smoking cessation, was revealed. In contrast, the samples from the non-smoking (N) and smoking (S) control groups clustered together closely, thus reflecting their overall similar microbial composition.</p

Comparison of the major phyla of the gut microbiota before and after smoking cessation.

<p>(A) Phyla Composition. The results for the intervention group (I) and the control groups (non-smoking  = N; smoking  = S) are given for samples taken one week prior to smoking cessation (t1) as well as four weeks (t2) and eight weeks (t3) thereafter. Whereas the intervention group revealed a significant increase in fractions of <i>Firmicutes</i> and <i>Actinobacteria</i> and a decrease in fractions of <i>Proteobacteria</i> and <i>Bacteroidetes</i>, the microbiota of the control groups remained rather stable. The phyla <i>Tenericutes</i>, <i>Verrucomicrobia</i>, <i>Synergistetes</i>, <i>Fusobacteria</i>, <i>Deinococcus-Thermus</i>, <i>TM7</i>, <i>Acidobacteria</i> and <i>OD1</i> are summarized under “other”. (B) Heat Map. The result of paired Student's t-test is shown on the phylum level with a color coded heat map. Significance levels are shown in different colors (shades of red, significant shifts in bacteria composition; shades of yellow, green and blue, non-significant shifts) and are indicated by the exact significance values within the colored squares of the graph. The major changes in the microbiota in the intervention group were observed between the time points before (t1) and after (t2, t3) smoking cessation. In contrast no significant changes were detected in the control groups and – with the exception of <i>Bacteroidetes</i> – after smoking cessation between t2 and t3 in the intervention group (an extended version of the heat map including all identified genera is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059260#pone.0059260.s005" target="_blank">Figure S5</a>, n/a =  not applicable).</p

Development of the Paris Definition of Early Crohnʼs Disease for Disease-Modification Trials: Results of an International Expert Opinion Process

peer reviewedWe report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD