Femoral neck osteopenia in patients with inflammatory bowel disease

Objective: The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients.
Methods: Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients.
Results: In the femoral neck 42% of the patients had osteopenia (−2.5 SD < BMD T score < −1 SD) and another 41% had osteoporosis (BMD T score < −2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration ( r =−0.36 , p < 0.05 ). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < −2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients.
Conclusions: There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.     

炎症性肠病治疗目标的演变

炎症性肠病(IBD)目前发病机制未明,可能与环境、遗传、感染、免疫等多种因素有关。IBD的治疗目标最初为临床缓解,随着基础研究进展及新型生物制剂的临床广泛实践,推荐黏膜愈合作为炎症性肠病的重要治疗目标,最近深度缓解作为一个新的治疗目标被提出,在国外已被广泛接受并应用于疾病评估,本文主要介绍炎症性肠病治疗目标的演变及黏膜愈合、深度缓解作为IBD治疗目标的重要意义。     

Small bowel length in inflammatory bowel disease

Small intestinal length has a particular significance in patients with inflammatory bowel disease (IBD). A determination of intestinal length by a standardised and simple technique is of interest for surgical decision making in primary and recurrent disease and in the evaluation and management of postoperative malabsorption. The aim of the present investigation was to analyse intestinal length in patients with IBD and define a standard method for this measurement. Material and methods: Two consecutive series of patients, Crohn's disease (n = 279) and ulcerative colitis (n = 315) and a control group (n = 77) underwent standardised intra-operative small intestinal length measurement. Results: Small intestinal length correlated to weight and height and was less in women than in men (P < 0.001) in both IBD groups and the controls. The small bowel in patients with Crohn's disease was significantly shorter than in patients with ulcerative colitis and in controls, P < 0.001. Also in Ulcerative Colitis small bowel length was significantly less than in controls, P < 0.001. In CD patients there was no difference in bowel length with regards to the anatomical extent of the disease. Original small bowel length in patients with CD and one or two bowel resections (n = 67) was not different from that in patients with three or more resections (n = 88). Conclusion: Small bowel length correlated to weight, height and sex. Patients with CD had a significantly shorter small intestine at first laparotomy, compared with U.C. patients and controls. In CD-patients there was no difference between the anatomical subgroups.

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Résumé. La longueur de l'intestin grêle a une signification tout à fait particulière chez les patients atteints de maladie inflammatoire de l'intestin (IBD). Une détermination de la longueur de l'intestin au moyen d'une technique standardisée et simple est utile lors d'une prise de décision chirurgicale chez des patients atteints de manière primaire ou récurrente de la maladie et dans l'évaluation et le management des troubles d'absorption postopératoire. Le but de la présente étude est d'analyser la longueur de l'intestin chez des patients atteints d'IBD et de définir une méthode standard de mesure. Materiel et methode: Deux séries consécutives de patients atteints de maladie de Crohn (n = 279) et de colite ulcéreuse (n = 315) ainsi qu'un groupe-contr?le (n = 77) ont fait l'objet d'une mesure standardisée per-opératoire de la longueur de l'intestin. Resultats: La longueur de l'intestin est corrélée au poids et à la taille et est plus petite chez les femmes que chez les hommes (P < 0,001) dans les deux groupes de maladie inflammatoire et dans le groupe-contr?le. L'intestin grêle des patients atteints de maladie de Crohn est significativement plus court que celui des patients atteints de colite ulcéreuse et que celui du groupe-contr?le (P < 0,001). De même que l'intestin grêle des patients atteints de colite ulcéreuse est significativement plus court que celui des groupes-contr?le (P < 0,001). Chez des patients atteints de maladie de Crohn, il n'y a pas de différence dans la longueur de l'intestin en relation avec l'étendue de la maladie anatomique. La longuer initiale de l'intestin chez les patients atteints de maladie de Crohn ayant fait l'objet d'une ou de deux résections segmentaires (n = 67) n'est pas significativement différente de celle mesurée chez les patients faisant l'objet de 3 ou plus résections (n = 88). Conclusion: La longueur de l'intestin grêle est corrélée au poids, à la taille et au sexe. Les patients porteurs d'une maladie de Crohn ont un intestin grêle significativement plus court à la première laparotomie que ceux atteints de colite ulcéreuse ou que les sujets-contr?le. Chez les patients porteurs de maladie de Crohn, il n'y a pas de différence significative entre les différents sous-groupes anatomiques.

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Accepted: 11 March 1997     

Hepatobiliary disease in inflammatory bowel disease

Many hepatobiliary diseases are seen in IBD. PSC is the most common, occurring in 7.5% of patients with UC. The cause of PSC is not well understood, but PSC seems to be associated with genetic susceptibility, sharing some immunologic abnormalities with UC. A characteristic cholangiogram in a patient with abnormal liver function tests usually establishes the diagnosis. Liver biopsy is not essential but can help make the diagnosis of small duct PSC in patients with a normal cholangiogram. There are no medications that treat PSC effectively. Endoscopic dilation of dominant strictures reduces the frequency of cholangitis and may improve survival. OLT remains the only proven treatment of advanced PSC. Cholangiocarcinoma is a feared complication of PSC that is difficult to diagnose. Cholelithiasis, PBC, portal vein thrombosis, and hepatic abscess are hepatobiliary disorders that occur less frequently in IBD patients.     

Functional bowel disorders in inflammatory bowel disease

Patients with IBD in remission often have ongoing gastrointestinal symptoms that are related to active inflammation. It is now apparent that functional gastrointestinal disorders may overlap with IBD and increase morbidity and diminish the quality of life of patients. Recognition and treatment of functional symptoms that may be the result of IBD are crucial in the appropriate medical management of these patients.     

Joint disease in inflammatory bowel disease

The joint disorders taxonomically included in the group of seronegative spondyloarthropathies under the generic name of enteropathic arthropathy represent the most frequent extra-intestinal manifestation of inflammatory bowel disease (IBD), affecting 33% of patients. Their frequency is similar to that of ulcerative colitis and Crohn's disease. Enteropathic arthropathy consists of two main joint alterations, peripheral and axial arthritis, as well as a variable group of other peri-articular disorders. Type 1, or pauciarticular, peripheral arthritis generally coincides with IBD exacerbations, while type 2, or polyarticular, peripheral arthritis follows an independent course from IBD. Axial involvement precedes and follows an independent course from IBD and can behave as ankylosing spondylitis or asymptomatic sacroiliitis. The treatment of these rheumatologic disorders is based on the application of general measures and the use of nonsteroidal anti-inflammatory agents; intraarticular corticosteroid administration may eventually become necessary. Sulphasalazine and/or infliximab, which are indicated when the previously mentioned measures fail, can be used to treat both the articular and intestinal diseases simultaneously.     

Emergencies in inflammatory bowel disease

A review of acute emergencies in inflammatory bowel disease is presented. Caveats include prompt surgical drainage of loculated abscesses and aggressive management of bleeding or perforation. Adequate nutritional and immunologic assessment of all patients prior to surgery is paramount and has resulted in the widespread use of total parenteral nutrition. Aggressive medical therapy, particularly steroids, may be useful in "cooling down" cases of acute inflammation prior to surgery. This is particularly useful in Crohn's disease, in which recurrences abound and surgery has a significant degree of complication and recurrence. When urgent operation is necessary for acute ulcerative colitis, abdominal colectomy with ileostomy and preservation of the rectum is generally indicated. This will allow subsequent mucosal proctectomy and ileoanal anastomosis. When urgent colectomy is indicated for Crohn's colitis without rectal involvement, ileorectal anastomosis can be considered either as a primary or secondary procedure. If toxic megacolon is present, an initial trial of medical therapy is warranted in order to allow a single-staged operation to be performed electively.     

Osteoporosis in inflammatory bowel disease

Half of all patients with inflammatory bowel disease show a significant reduction of their bone mass during the course of their chronic inflammatory disease. In contrast to women with postmenopausal osteoporosis these patients are much younger and a significant subgroup develops vertebral fractures which are mostly asymptomatic.The activity of the chronic inflammatory disease and the steroid treatment leads to bone loss predominantly through the TNFα-driven osteoprotegerin system. Clinical useful genetic markers to identify patients at risk for fractures have not been developed so far. Long-term clinical remission leads in most patients to normalisation of the bone density. Patients with reduced bone density should be substituted with calcium and vitamin D. Patients with vertebral fractures should receive bisphosphonates.     

Nutrition in inflammatory bowel disease

Nutrition is clearly disturbed by active intestinal inflammation. Appetite is reduced, yet energy substrates are diverted into the inflammatory process, and thus weight loss is characteristic. The nutritional disturbance represents part of a profound defect of somatic function. Linear growth and pubertal development in children are notably retarded, body composition is altered, and there may be significant psychosocial disturbance. Macrophage products such as tumour necrosis factor-alpha and interleukins-1 and 6 may be the central molecules that link the inflammatory process to this derangement of homeostasis. Intriguingly, there is also increasing evidence that an aggressive nutritional programme may in itself be sufficient to reduce the mucosal inflammatory response. Recent evidence suggests that enteral nutrition alone may reduce many pro-inflammatory cytokines to normal and allow mucosal healing. In addition, specific nutritional components, such as n-3 polyunsaturated fatty acids, may have an anti-inflammatory effect as they may alter the pattern of leukotrienes generated during the immune response. The recent discovery of the specific molecular mediators of appetite and body composition, such as leptin and myostatin, may allow increased therapeutic specificity and further improvement in the nutritional treatment of the inflammatory bowel diseases.     

Methotrexate in inflammatory bowel disease

Over the past decade methotrexate has emerged as a new treatment for chronically active Crohn's disease. Although controlled trials to compare the relative efficacy and safety of azathioprine and methotrexate in therapy-resistant patients are desirable, these studies will be difficult, if not impossible, to conduct because of the relatively small differences in potency and tolerability between these agents. A more productive area for future investigations is to explore the use of these drugs in combination with infliximab and other biologic treatments.     

Endoscopy in inflammatory bowel disease

With the heterogeneous clinical presentation of IBD, endoscopy plays an integral role in the initial diagnosis of ulcerative colitis and Crohn's disease. Although radiographic tests often are supplemental in the work-up of IBD, colonoscopy with biopsy is the test of choice if IBD is suspected and is more sensitive than radiographic tests. Endoscopic features can be helpful in differentiating ulcerative colitis and Crohn's disease. Currently the only mode for detecting dysplasia and stratifying the risk of developing colorectal cancer is through complete colonoscopy with multiple biopsy specimens. Complications of IBD can be managed effectively with endoscopic therapy. The role of endoscopic ultrasound and future developments in endoscopic therapy need to be defined by future studies.     

英夫利昔单抗在炎症性肠病治疗中的应用

克罗恩病(CD)和溃疡性结肠炎(UC)是两种特发性肠道炎性疾病。此文对新出现的生物制剂之一,英夫利昔单抗(infliximab)在这类疾病中实际应用方面的依据进行评论和回顾,包括剂量、疗效、注意事项和不良反应,并作一总结。     

Cholelithiasis in inflammatory bowel disease

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.     

Chromoendoscopy in inflammatory bowel disease

Chromoendoscopy with methylene blue or indigo carmine significantly increases the diagnostic yield of finding intraepithelial neoplasia in patients with longstanding colitis. The number needed to treat is 14 for panchromoendoscopy to identify 1 additional patient with dysplasia. Chromoendoscopy can greatly facilitate the identification of flat lesions harboring intraepithelial neoplasia. Chromoendoscopy can guide biopsies and clearly reduces the amount of biopsies that are needed per patient. Magnifying endoscopy or CLE are additional techniques, which can be used in conjunction with chromoendoscopy to further reduce the amount of biopsies and to further increase the diagnostic yield. Chromoendoscopy is an established clinical procedure and recommended by many gastroenterological societies for surveillance of patients with longstanding ulcerative colitis. Thus, intravital staining should be an essential part of the diagnostic armamentarium of every colonoscopist.     

MicroRNAs in inflammatory bowel disease

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene and protein expression. miRNAs are critical to a normal immune response and have altered expression in multiple immune-mediated disorders. This emerging role of miRNAs in the pathogenesis of multiple disease states has led to investigations into miRNA expression profiles in inflammatory bowel disease (IBD). The discovery of miRNAs in IBD is likely to contribute to our understanding of IBD pathogenesis and lead to clinical advances in IBD. This review focuses on miRNA expression in inflammation, autoimmune disorders, and inflammation-associated cancer, as well as their function in the biology and management of IBD.