Morbidity In Inflammatory Bowel Disease Research Articles

Transcriptomic profiling reveals a pronociceptive role for angiotensin II in inflammatory bowel disease.

Visceral pain is a leading cause of morbidity in inflammatory bowel disease (IBD), contributing significantly to reduced quality of life. Currently available analgesics often lack efficacy or have intolerable side effects, driving the need for a more complete understanding of the mechanisms causing pain. Whole transcriptome gene expression analysis was performed by bulk RNA sequencing of colonic biopsies from patients with ulcerative colitis (UC) and Crohn disease (CD) reporting abdominal pain and compared with noninflamed control biopsies. Putative pronociceptive mediators were identified based on analysis of differentially expressed genes in IBD biopsy tissue and single-cell gene expression in murine colonic sensory neurons. Pronociceptive activity of identified mediators was assessed in assays of sensory neuron and colonic afferent activity. RNA sequencing analysis highlighted a 7.6-fold increase in the expression of angiotensinogen transcripts, Agt, which encode the precursor to angiotensin II (Ang II), in samples from UC patients (P = 3.2 × 10-8). Consistent with the marked expression of the angiotensin AT1 receptor in colonic sensory neurons, Ang II elicited an increase in intracellular Ca2+ in capsaicin-sensitive, voltage-gated sodium channel subtype NaV1.8-positive sensory neurons. Ang II also evoked action potential discharge in high-threshold colonic nociceptors. These effects were inhibited by the AT1 receptor antagonist valsartan. Findings from our study identify AT1 receptor-mediated colonic nociceptor activation as a novel pathway of visceral nociception in patients with UC. This work highlights the potential utility of angiotensin receptor blockers, such as valsartan, as treatments for pain in IBD.

The Gut-Immune-Brain Axis: An Important Route for Neuropsychiatric Morbidity in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) comprises Crohn’s disease (CD) and ulcerative colitis (UC) and is associated with neuropsychiatric symptoms like anxiety and depression. Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression and anxiety in IBD. We present a stepwise cascade along a gut–immune–brain axis initiated by evasion of chronic intestinal inflammation to pass the epithelial and vascular barrier in the gut and cause systemic inflammation. We then summarize different anatomical transmission routes of gut-derived peripheral inflammation into the central nervous system (CNS) and highlight the current knowledge on neuroinflammatory changes in the CNS of preclinical IBD mouse models with a focus on microglia, the brain-resident macrophages. Subsequently, we discuss how neuroinflammation in IBD can alter neuronal circuitry to trigger symptoms like depression and anxiety. Finally, the role of intestinal microbiota in the gut–immune–brain axis in IBD will be reviewed. A more comprehensive understanding of the interaction between the gastrointestinal tract, the immune system and the CNS accounting for the similarities and differences between UC and CD will pave the path for improved prediction and treatment of neuropsychiatric comorbidities in IBD and other inflammatory diseases.

Effects of Milk-Derived Extracellular Vesicles on the Colonic Transcriptome and Proteome in Murine Model

Evidence shows that effective nutritional intervention can prevent or mitigate the risk and morbidity of inflammatory bowel disease (IBD). Bovine milk extracellular vesicles (mEVs), a major bioactive constituent of milk, play an important role in maintaining intestinal health. The aims of this study were to assess the effects of mEV pre-supplementation on the colonic transcriptome and proteome in dextran sulphate sodium (DSS)-induced acute colitis, in order to understand the underlying molecular mechanisms of mEV protection against acute colitis. Our results revealed that dietary mEV supplementation alleviated the severity of acute colitis, as evidenced by the reduced disease activity index scores, histological damage, and infiltration of inflammatory cells. In addition, transcriptome profiling analysis found that oral mEVs significantly reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17A and IL-33), chemokine ligands (CXCL1, CXCL2, CXCL3, CXCL5, CCL3 and CCL11) and chemokine receptors (CXCR2 and CCR3). Moreover, oral mEVs up-regulated 109 proteins and down-regulated 150 proteins in the DSS-induced murine model, which were involved in modulating amino acid metabolism and lipid metabolism. Collectively, this study might provide new insights for identifying potential targets for the therapeutic effects of mEVs on colitis.

Depression, anxiety, and stress among inflammatory bowel disease patients during COVID-19: A UK cohort study.

Background and AimPatients with chronic diseases are believed to be at increased risk of mental health conditions during the COVID‐19 pandemic. We aimed to assess the incidence of psychological morbidity in inflammatory bowel disease (IBD) patients during the COVID‐19 pandemic, explore for association with risk of severe COVID‐19 and other factors, and establish patients' interest in psychological support.MethodsA survey including the Patient Health Questionnaire‐9, General Anxiety Disorder‐7, and Perceived Stress Scale tools for depression, anxiety, and stress was administered to IBD patients from a tertiary center in London, United Kingdom, in June 2020.ResultsTwo hundred seventy‐four patients responded to the survey (57% response rate), with 271 (99%) completing it. Moderate–severe depression was observed in 61 (22.5%), while 49 (18%) had moderate–severe anxiety; 39 (14%) had both diagnoses. Mean (SD) stress score was 16.2 (7.4). There was no association between degree of severe COVID‐19 risk and psychological morbidity. Flare symptoms and fatigue were associated with worse psychological morbidity, while accessibility of information regarding COVID‐19 risk and reducing that risk was protective for depression (odds ratio [OR] 0.56 [0.33–0.94], P = 0.03), anxiety (OR 0.62 [0.4–0.96], P = 0.03), and stress (standardized β‐coefficient −0.15 [−0.28 to −0.03], P = 0.02). Seventy‐nine (30%) respondents were interested in receiving psychological support during the pandemic, while 200 (76%) expressed interest beyond the pandemic.ConclusionsAlthough depression, anxiety, and stress among IBD patients during the pandemic were common, their frequency was similar to pre‐pandemic rates and recent general population levels. Ensuring easy access to personalized risk information with targeted psychological support may mitigate psychological burden as patients reintegrate into society and deal with future COVID‐19 waves.

Quality assessment of clinical guidelines on probiotics therapy in children with IBD using the AGREE II instrument.

The morbidity of inflammatory bowel disease (IBD) in children has significantly increased in recent years. The diagnosis and treatment of IBD in children are progressing rapidly. Probiotics have been extensively studied in a variety of gastrointestinal diseases. However, the effectiveness of probiotics for IBD is inconsistent. This study summarized the recommendations on using probiotics from high-quality guidelines, and the recommendations may assist clinicians in the treatment of paediatric IBD. Guidelines were identified by searching PubMed, EMBASE, three Chinese literature databases and websites of relevant institutions. Guidelines that addressed the treatments of paediatric IBD in Chinese and English were included and evaluated with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument to assess methodological quality. The levels of recommendation were also evaluated, and finally, the recommendations of probiotics application in IBD were summarized. A total of 14 guidelines that met inclusion criteria were identified and evaluated, and 12 of them were evidence-based (EB) guidelines, and the other two guidelines were developed by consensus. The mean percentages for the AGREE II domain scores were as follows: "Scope and purpose" 97.22%, "Clarity of presentation" 93.78%, "Applicability" 55.85%, "Editorial independence" 59.92%, "Stakeholder involvement" 74.34%, and "Rigor of development" 71.58%. Three guidelines received the Grade A-"Strongly recommended," the rest of the guidelines received a B grade-"Recommended with modifications" in the overall assessment. The overall quality of the guidelines on IBD management in children was high. Conversely, the fundamental recommendations on the application of probiotics in the treatment of IBD varied. For instance, the recommendations of probiotics on Crohn's disease (CD) were not available by any of the analysed guidelines, the recommendations of utilizing probiotics in treating ulcerative colitis (UC) were not uniform as several guidelines considered using VSL#3 or Escherichia coli Nissle 1917 for the treatment.

P255 Predictors of postoperative morbidity in patients with inflammatory bowel disease

Abstract Background More than half of patients suffering from inflammatory bowel disease (IBD) requires surgery in their lifetime. However, predictors of post-operative morbidity and mortality are poorly investigated. Our aim was to assess the predictors of post-operative mortality and morbidity in IBD. Methods retrospective cohort study enrolling all IBD subjects followed-up and operated at our tertiary IBD Centre from 2015 to 2018. For each patient, we evaluated patient-dependent (comorbidities, smoking, drugs, nutritional status), disease-dependent (disease duration, location, behaviour, extension), surgery-dependent variables (duration, emergency/election, laparoscopy/laparotomy, bowel/colic resection, length of intestinal resection). Results 158 subjects were operated during the period study (males 53.8%, Crohn’s disease 75.3%, mean age 41.9 + 16.2, disease duration 109.5 + 98.3 months); the majority (83%) underwent an elective surgery. No patient died. About morbidity, 40 (25.3%) developed post-operative complications: wound infection (8.9%), respiratory complications (6.9%), prolonged ileum (5.1%), anastomotic leak (3.2%), urinary infections (3.2%), abdominal abscess (3.2%), anastomotic bleeding (3.2%), other infections (2.5%), abdominal bleeding (1.9%), obstruction (1.3%). Two subjects (1.3%) required re-operation within 30 days. A surgery-duration <142 min was predictive for a better post-operative outcome (sensitivity 80%, specificity 42%, PPV 32%, NPV 85.9%). At binary logistic regression, stricturing/fistulizing behaviour (OR 3.7, 95% CI 1.6–6.4, p = 0.02), need for total parenteral nutrition (OR 4.1, 95% CI 2.4–9.2, p = 0.01), pre-operative bowel cleansing (OR 0.6, 95% CI 0.4–0.8, p = 0.01), surgery duration <142 min (OR 0.2, 95% CI 0.08–0.7, p = 0.03), were the only predictors for post-operative morbidities. A pre-operative BMI<24 was also predictive for anastomotic leak (OR 4.3, 95% CI 1.8–8.6, p = 0.02); pre-operative hypoalbuminemia was predictive for urinary infections (OR 2.5, 95% CI 1.8–7.9, p = 0.04); pre-operative infliximab was predictive for pneumonia (OR 3.8, 95% CI 2.2–6.3, p = 0.01); diabetes (OR 5.7, 95% CI 2.3–9.8, p < 0.01) and pre-operative steroids (OR 6.1, 95% CI 1.8–11.4, p < 0.01) were predictors of wound infection; need for TPN predicted prolonged ileum (OR 6.1, 95% CI 2.3–15.3, p = 0.03). Conclusion about a quarter of IBD patients undergoing surgery develops a post-operative complication, especially infective. Several patient-related, disease-related and surgery-related factors are predictive for post-operative morbidity. The recognition of these factors, as well the multidisciplinary approach (gastroenterologists, surgeons and nutritionists), and intensive preoperative management could be able to minimise these complications.

A Decade of Varicella Screening Within a Paediatric Inflammatory Bowel Disease Population.

Increased risk of opportunistic infection-e.g., varicella zoster infection-secondary to therapies is a cause of morbidity in inflammatory bowel disease [IBD] patients. The UK vaccination schedule does not include varicella immunisation. We aimed to evaluate the varicella screening and immunisation programme in a paediatric IBD population. Data regarding IBD diagnosis, varicella status, and consequent immunisations/treatment interventions were collected retrospectively from the records of patients diagnosed with IBD over a 10-year period [2009-2018]. In all, 520 IBD patients were diagnosed; 505/520 [97%] had varicella testing; 46/505 [9%] were naïve. Of 501 patients, 391[78%] were tested before or within 7 days of diagnosis; this increased in the second 5-year period compared with the first (229/268 [85%] versus 162/233 [70%]; p <0.00001). Median diagnosis age of naïve patients was lower [8.3 years versus 12.8 years; p <0.00001]. Where vaccination was feasible, 21/31 [68%] had two and 7/31 [23%] one immunisation. Prednisolone induction led to lower rates of vaccination (5/13 [39%] versus 23/33 [70%] for other induction therapies; p =0.02). Of 28 vaccinated patients, 5 [18%] had suspected breakthrough varicella; and 6/18 [33%] unimmunised patients required post-exposure prophylaxis or treatment for varicella. Immunisation was associated with a decrease in patients requiring post-exposure prophylaxis (0/28 [0%] versus 5/18 [28%]; p =0.0006) and varicella-related hospital admission (1/28 [4%] versus 4/18 [22%]; p =0.01). High rates of varicella screening and immunisation within a PIBD population are possible, resulting in a reduction in hospital admissions for varicella treatment. Varicella immunisation may be of increasing importance within the PIBD population with the emergence of novel therapeutic strategies.

Improving morbidity in inflammatory bowel disease: An audit of compliance with the European Crohn’s and Colitis Organisation guidelines

Improving morbidity in inflammatory bowel disease: An audit of compliance with the European Crohn’s and Colitis Organisation guidelines

Sarcopenia is a Predictor of Surgical Morbidity in Inflammatory Bowel Disease.

Sarcopenia is associated with an increased risk of operative morbidity and mortality. The impact of sarcopenia in inflammatory bowel disease (IBD) has not been evaluated. This study assessed the role of sarcopenia on operative outcomes in IBD. A retrospective review of American College of Surgeons National Surgical Quality Improvement Program data of patients with IBD was completed. Records were abstracted for comorbidities and perioperative complications. The Hounsfield unit average calculation was used from preoperative computed tomography (CT). Criteria for sarcopenia were based on the lowest 25th percentile. Complications were graded using the Clavien-Dindo classification system. Statistical analysis was completed using SAS. There were 178 patients included. Sarcopenic patients were more likely to be older (P = 0.001), have hypertension (odds ratio = 2.23), and be diabetic (5.27). In those patients younger than 40 years, sarcopenia was an independent predictor of complications. This subset was significantly more likely to have a normal or elevated body mass index. In this population, the average age of sarcopenic patients is increased from those who do not meet criteria. Among patients younger than 40 years, sarcopenia affects surgical outcomes. Assessment of sarcopenia can be used to improve preoperative management and describe risks before surgery in patients with IBD.

Systematic review with meta-analysis: the impact of a depressive state on disease course in adult inflammatory bowel disease.

Despite a higher prevalence of psychosocial morbidity in Inflammatory Bowel Disease (IBD), the association between depressive state and disease course in IBD is poorly understood. To investigate the impact of depressive state on disease course in IBD. We conducted a systematic review in MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and PsychINFO for prospective studies evaluating the impact of baseline depressive state on subsequent disease course in adult IBD. Eleven studies matched our entry criteria, representing 3194 patients with IBD. Three reported on patients with ulcerative colitis (UC), four included patients with Crohn's disease (CD) exclusively, and four studies included both UC and CD. Five studies reported an association between depressive state and disease course. None of the UC-specific studies found any association. In three of four CD-specific studies, a relationship between depressive state and worsening disease course was found. In four of five studies including patients in remission at baseline, no association between depressive state and disease course was found. Pooled analysis of IBD studies with patients in clinical remission at baseline identified no association between depressive state and disease course (HR 1.04, 95%CI: 0.97-1.12). There is limited evidence to support an association between depressive state and subsequent deterioration in disease course in IBD, but what data that exist are more supportive of an association with CD than UC. Baseline disease activity may be an important factor in this relationship. Further studies are needed to understand the relationship between mental health and outcomes in IBD.

Current status and progress of the pediatric inflammatory bowel disease treatment

Inflammatory bowel disease, a type of intestinal chronic inflammatory disease caused by multi-factors, which include ulcerative colitis, Crohn′s disease and inflammatory bowel disease unclassified.The morbidity of inflammatory bowel disease has been increasing by years with a younger age trend.Nowadays the pediatric inflammatory bowel disease is prevalent.Pediatric inflammatory bowel disease is different from adult at many aspects such as clinical manifestation, disease type, treatment, complications etc.It is because children are in a special condition with fast growth and development.This article will elaborate the current status of treatment and progresses of inflammatory bowel disease especially pediatric inflammatory bowel disease. Key words: Inflammatory bowel disease; Children; Nutritional therapy; Biological agent

Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut-brain pathways.

The nature of depression has recently been reconceptualized, being conceived as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut-brain pathways. IO&NS pathways are similarly integral to the pathogenesis of inflammatory bowel disease (IBD). The increased depression prevalence in IBD associates with a lower quality of life and increased morbidity in IBD, highlighting the role of depression in modulating the pathophysiology of IBD.This review covers data within such a wider conceptualization that better explains the heightened co-occurrence of IBD and depression. Common IO&NS underpinning between both disorders is evidenced by increased pro-inflammatory cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-α, IL-6 trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2 receptor levels; positive acute phase reactants (haptoglobin and C-reactive protein); lowered levels of negative acute phase reactants (albumin, transferrin, zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor-β); increased O&NS with damage to lipids, proteinsm and DNA; increased production of nitric oxide (NO) and inducible NO synthase; lowered plasma tryptophan but increased TRYCAT levels; autoimmune responses; and increased bacterial translocation. As such, heightened IO&NS processes in depression overlap with the biological underpinnings of IBD, potentially explaining their increased co-occurrence. This supports the perspective that there is a spectrum of IO&NS disorders that includes depression, both as an emergent comorbidity and as a contributor to IO&NS processes. Such a frame of reference has treatment implications for IBD when "comorbid" with depression.

Remodeling of Tight Junctions and Enhancement of Barrier Integrity of the CACO-2 Intestinal Epithelial Cell Layer by Micronutrients.

The micronutrients zinc, quercetin, butyrate, indole and berberine were evaluated for their ability to induce remodeling of epithelial tight junctions (TJs) and enhance barrier integrity in the CACO-2 gastrointestinal epithelial cell culture model. All five of these chemically very diverse micronutrients increased transepithelial electrical resistance (Rt) significantly, but only berberine also improved barrier integrity to the non-electrolyte D-mannitol. Increases of Rt as much as 200% of untreated controls were observed. Each of the five micronutrients also induced unique, signature-like changes in TJ protein composition, suggesting multiple pathways (and TJ arrangements) by which TJ barrier function can be enhanced. Decreases in abundance by as much as 90% were observed for claudin-2, and increases of over 300% could be seen for claudins -5 and -7. The exact effects of the micronutrients on barrier integrity and TJ protein composition were found to be highly dependent on the degree of differentiation of the cell layer at the time it was exposed to the micronutrient. The substratum to which the epithelial layer adheres was also found to regulate the response of the cell layer to the micronutrient. The implications of these findings for therapeutically decreasing morbidity in Inflammatory Bowel Disease are discussed.

The impact of preoperative serum anti-TNFα therapy levels on early postoperative outcomes in inflammatory bowel disease surgery.

Assess the impact of preoperative serum antitumor necrosis factor-α (anti-TNFα) drug levels on 30-day postoperative morbidity in inflammatory bowel disease (IBD) patients. Studies on the association of anti-TNFα drugs and postoperative outcomes in IBD are conflicting due to variable pharmacokinetics of anti-TNFα drugs. It remains to be seen whether preoperative serum anti-TNFα drug levels correlate with postoperative morbidity. Thirty-day postoperative outcomes of consecutive IBD surgical patients with serum drawn within 7 days preoperatively were studied. The total serum level of 3 anti-TNFα drugs (infliximab, adalimumab, and certolizumab) was measured, with ≥ 0.98 μg/mL considered as detected. Data were also reviewed according to a clinical cutoff value of 3 μg/mL. A total of 217 patients [123 with Crohn disease (CD) and 94 with ulcerative colitis (UC)] were analyzed; 75 of 150 (50%) treated with anti-TNFα therapy did not have detected levels at the time of surgery. In the UC cohort, adverse postoperative outcome rates between the undetectable and detectable groups were similar when stratified according to type of UC surgery. In the CD cohort, there was a higher but statistically insignificant rate of adverse outcomes in the detectable versus undetectable groups. Using a cut off level of 3 μg/mL, postoperative morbidity (odds ratio [OR] = 2.5, P = 0.03) and infectious complications (OR = 3.0, P = 0.03) were significantly higher in the ≥ 3 μg/mL group. There were higher rates of postoperative morbidity (P = 0.047) and hospital readmissions (P = 0.04) in the ≥ 8 μg/mL compared with <3 μg/mL group. Increasing preoperative serum anti-TNFα drug levels are associated with adverse postoperative outcomes in CD but not UC patients.

Comprehensive study of cardiovascular morbidity in hospitalized inflammatory bowel disease patients

Background The full extent of cardiovascular morbidity in inflammatory bowel disease is not well understood. Objective To comprehensively study the association of different cardiovascular diseases in hospitalized patients with inflammatory bowel disease (IBD) using a large database. Methods We used the Nationwide Inpatient Sample (NIS) database to perform a cross-sectional study. The study group was defined as all hospitalized patients between ages 18–60 years included in the NIS 2006 database with a discharge diagnosis of IBD, as per the International Classification of Diseases - Clinical Modification, 9th revision (ICD-9-CM) codes. Individuals in the same age group whose hospital discharge records did not note IBD were identified as the control group. Cardiovascular diseases, identified by the ICD-9-CM codes, were studied comprehensively for their association with IBD using multivariate logistic regression analysis. Odds ratios were calculated adjusting for relevant patient comorbidities. Results IBD was found to be strongly associated with mesenteric ischemia (adjusted odds ratio (aOR), 3.4; 95% confidence interval (CI), 2.9–4.0) and venous thrombotic diseases (aOR, 1.38; 95% CI, 1.25–1.53). Age and gender stratified analysis revealed that IBD is positively associated with dysrhythmias in females aged 18–39 years (aOR, 2.05; 95% CI, 1.72–2.44). We did not find an increased risk of other cardiovascular diseases in IBD patients. Conclusions Our study substantiates the previously reported associations of mesenteric ischemia and venous thrombotic disorders with IBD. Our study also suggests that young females with IBD might have an increased risk for dysrhythmias.

Neoplasia in inflammatory bowel disease: Surveillance and management strategies

Dysplasia surveillance remains the standard approach to minimize colorectal cancer (CRC) risk and morbidity in inflammatory bowel disease. Approaches to treatment in Crohn's disease are generally similar to those for ulcerative colitis. Recently the addition of dye spraying onto the colon to facilitate targeted biopsy has become increasingly associated with enhanced dysplasia surveillance; however, random biopsies are mostly still undertaken, even by those endoscopists who use chromoendoscopy. The prevailing literature continues to support colectomy for any degree of dysplasia. However, for those with adenoma-like masses, ongoing surveillance after polypectomy could still be considered appropriate. Certain endoscopic features are associated with increased incidence of neoplasia. These include not only strictures but also pseudopolyps. Past corticosteroid use and more than one screening colonoscopy were associated in two large case-control studies with reduced incidence of CRC. Although great interest has been expressed in the possible effectiveness of 5-aminosalicylic acid, it has not been proved to be an effective chemopreventive agent.

Skeletal morbidity in inflammatory bowel disease

Patients with Crohn's disease are at increased risk of developing disturbances in bone and mineral metabolism because of several factors, including the cytokine-mediated nature of the inflammatory bowel disease, the intestinal malabsorption resulting from disease activity or from extensive intestinal resection and the use of glucucorticoids to control disease activity. Inability to achieve peak bone mass when the disease starts in childhood, malnutrition, immobilization, low BMI, smoking and hypogonadism may also play a contributing role in the pathogenesis of bone loss. The relationship between long-term use of glucocorticoids for any disease indication and increased risk for osteoporosis and fractures is well established. However, the relationship between Crohn's disease and ulcerative colitis and bone loss remains controversial. Depending on the population studied the prevalence of osteoporosis has thus been variably reported to range from 12 to 42% in patients with inflammatory bowel disease (IBD). In IBD most studies demonstrate a negative correlation between bone mineral density (BMD) and glucocorticoid use, but not all authors agree on the relationship between long-term glucocorticoid use and continuing bone loss. Whereas prospective studies do suggest sustained bone loss at both trabecular and cortical sites in long-term glucocorticoid users with inflammatory bowel disease, a decrease in bone mass is also observed in patients with active Crohn's disease not using glucocorticoids, and bone loss is not universally observed in patients with Crohn's disease using orally or rectally administered glucocorticoids. Data on vertebral fractures are scarce and there is no agreement about the risk of non-vertebral fractures in patients with Crohn's disease, although it has been suggested that non-vertebral fracture risk may be increased by up to 60% in patients with IBD. A recent publication reports an increased risk of hip fractures in Crohn's disease related to current and cumulative corticosteroid use and use of opiates, although these fractures could not be related to the severity of osteoporosis. The issue of the magnitude of the problem of osteoporosis has become particularly relevant in Crohn's disease, since the ability of therapeutic interventions to beneficially influence skeletal morbidity has been clearly established in patients with osteoporosis, whether post-menopausal women, men or glucocorticoid users. The main question that arises is whether all patients with Crohn's disease should be treated with bone protective agents on the assumption that they all have the potential to develop osteoporosis or whether the use of these agents should be restricted to patients clearly at risk of osteoporosis and fractures, providing these can be identified. We recommend, based on the available literature and our own experience, that all patients with Crohn's disease should be screened for osteoporosis by means of a bone mineral density measurement in addition to full correction of any potential calcium and vitamin D deficiency, to allow timely therapeutic intervention of the patient at risk while sparing the vast majority unnecessary medical treatment.