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Attauabi M, Madsen GR, Holm JP, Bendtsen F, Møller S, Seidelin JB, Burisch J. Incidence of Osteoporosis and Osteopenia in Newly Diagnosed Inflammatory Bowel Disease: A Population-Based Cohort Study. Inflamm Bowel Dis 2025:izaf063. [PMID: 40198007 DOI: 10.1093/ibd/izaf063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Indexed: 04/10/2025]
Abstract
BACKGROUND Individuals with Crohn's disease (CD) and ulcerative colitis (UC) are at risk of developing osteoporosis. In Denmark, osteoporosis has been observed in 12.0% of postmenopausal women and 2.6% in men aged ≥ 50 years in the general population. We aimed to conduct a population-based analysis determining bone mineral density (BMD) at diagnosis of UC and CD. METHODS All adult patients diagnosed with UC or CD between May 2021 and May 2023 in an area covering 20% (1.2 million inhabitants) of the Danish population were invited for dual-energy X-ray absorptiometry at inflammatory bowel disease (IBD) diagnosis. RESULTS In total, 209 and 141 patients with UC and CD, respectively, were included. Among postmenopausal women (age ≥ 52 years) with UC, 15/42 (35.7%) had osteoporosis and 17/42 (40.5%) had osteopenia, while rates among patients with CD were 6/21 (28.6%, P = .57) and 8/21 (38.1%, P = .86), respectively. Among males aged ≥ 50 years, the rates were 5/38 (13.2%) and 17/38 (44.7%) in UC, respectively, and 3/24 (12.5%, P = 1.00) and 12/24 (50.0%, P = .69) in CD, respectively. Among younger patients, BMD below the expected range for age was observed in 3/69 (4.3%) and 3/60 (5.0%) of females and males with UC, and in 1/42 (2.4%) and 8/54 (14.8%) with CD, respectively. No nutritional or inflammatory marker, including C-reactive protein, fecal calprotectin, Mayo Endoscopic Score, or Simple Endoscopic Score for CD correlated with the T-score. CONCLUSIONS This population-based study demonstrated high rates of osteoporosis among postmenopausal women and males aged ≥ 50 years at IBD diagnosis, highlighting the need for systematic evaluation in these patients.
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Affiliation(s)
- Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
| | - Gorm Roager Madsen
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
| | - Jakob Præst Holm
- Department of Endocrinology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Centre for Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | - Jakob Benedict Seidelin
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Digestive Diseases, Transplantation and General Surgery, IBD Section, Rigshospitalet, Copenhagen, Denmark
| | - Johan Burisch
- Gastrounit, Medical Section, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents, and Adults, Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Gisbert JP, Chaparro M. Common Mistakes in Managing Patients with Inflammatory Bowel Disease. J Clin Med 2024; 13:4795. [PMID: 39200937 PMCID: PMC11355176 DOI: 10.3390/jcm13164795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain;
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Dai Z, Xu W, Ding R, Peng X, Shen X, Song J, Du P, Wang Z, Liu Y. Two-sample Mendelian randomization analysis evaluates causal associations between inflammatory bowel disease and osteoporosis. Front Public Health 2023; 11:1151837. [PMID: 37304119 PMCID: PMC10250718 DOI: 10.3389/fpubh.2023.1151837] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 05/15/2023] [Indexed: 06/13/2023] Open
Abstract
Introduction Over the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them. Methods We validated the association between IBD and reduced bone mineral density in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and osteoporosis, we performed a two-sample Mendelian randomization study using training and validation sets. Genetic variation data for IBD, CD, UC, and osteoporosis were derived from published genome-wide association studies in individuals of European ancestry. After a series of robust quality control steps, we included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). We adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, and Weighted mode, to infer the causal association between IBD and osteoporosis. In addition, we evaluated the robustness of Mendelian randomization analysis by heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate Mendelian randomization. Results Genetically predicted CD was positively associated with osteoporosis risk, with ORs of 1.060 (95% CIs 1.016, 1.106; p = 0.007) and 1.044 (95% CIs 1.002, 1.088; p = 0.039) for CD in the training and validation sets, respectively. However, Mendelian randomization analysis did not reveal a significant causal relationship between UC and osteoporosis (p > 0.05). Furthermore, we found that overall IBD was associated with osteoporosis prediction, with ORs of 1.050 (95% CIs 0.999, 1.103; p = 0.055) and 1.063 (95% CIs 1.019, 1.109; p = 0.005) in the training and validation sets, respectively. Conclusion We demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease.
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Affiliation(s)
- Zhujiang Dai
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Weimin Xu
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Rui Ding
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Xiang Peng
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Xia Shen
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Jinglue Song
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Peng Du
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Zhongchuan Wang
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
| | - Yun Liu
- Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Shanghai Colorectal Cancer Research Center, Shanghai, China
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Steell L, Gray SR, Russell RK, MacDonald J, Seenan JP, Wong SC, Gaya DR. Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease. Nutrients 2021; 13:nu13082899. [PMID: 34445056 PMCID: PMC8398806 DOI: 10.3390/nu13082899] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 08/18/2021] [Accepted: 08/20/2021] [Indexed: 12/11/2022] Open
Abstract
Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn’s disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.
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Affiliation(s)
- Lewis Steell
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK; (L.S.); (S.R.G.)
| | - Stuart R. Gray
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK; (L.S.); (S.R.G.)
| | - Richard K. Russell
- Department of Paediatric Gastroenterology, Royal Hospital for Sick Children, Edinburgh EH16 4TJ, UK;
| | - Jonathan MacDonald
- Department of Gastroenterology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; (J.M.); (J.P.S.)
| | - John Paul Seenan
- Department of Gastroenterology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK; (J.M.); (J.P.S.)
| | - Sze Choong Wong
- Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow G51 4TF, UK;
| | - Daniel R. Gaya
- Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK
- Correspondence:
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Lee JS, Lee HS, Jang BI, Kim ES, Kim SK, Kim KO, Lee YJ, Lee HJ, Kim EY, Jung YJ, Yang CH. Low Bone Mineral Density in Young Patients Newly Diagnosed with Inflammatory Bowel Disease. Dig Dis Sci 2021; 66:605-611. [PMID: 32222926 DOI: 10.1007/s10620-020-06220-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 03/18/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND The prevalence and risk factors of low bone mineral density (BMD) in Asian patients newly diagnosed with inflammatory bowel disease (IBD) have not been fully suggested. AIMS We aimed to examine the prevalence and risk factors of low BMD in young Korean patients newly diagnosed with IBD. METHODS We prospectively enrolled 132 patients aged less than 50 years and newly diagnosed with IBD from six tertiary referral centers in Korea between November 2014 and April 2017. BMD was measured by dual-energy X-ray absorptiometry, and then the Z-score was determined. We defined low BMD as a Z-score ≤ - 1.0. RESULTS Of 68 patients with ulcerative colitis (UC), 22 (32.4%) had low BMD. Also, of 64 patients with Crohn's disease (CD), 24 (37.5%) showed low BMD. Results from multivariate regression analysis identified the risk factors for low BMD as a high level of alkaline phosphatase (ALP) (≥ 140 U/L) (P = 0.010) in UC patients, and being underweight (body mass index ≤ 18.5 kg/m2) (P = 0.017) in CD patients. CONCLUSIONS Our study showed that about one-third of newly diagnosed IBD Asian patients had low BMD. The clinical factors associated with low BMD were a high level of ALP in UC patients, and being underweight, in CD patients. Therefore, measurements of BMD in young patients should be considered at the diagnosis of IBD.
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Affiliation(s)
- Joon Seop Lee
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 807 Hokuk-ro, Buk-gu, Daegu, 41404, Korea
| | - Hyun Seok Lee
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 807 Hokuk-ro, Buk-gu, Daegu, 41404, Korea.
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 807 Hokuk-ro, Buk-gu, Daegu, 41404, Korea
| | - Sung Kook Kim
- Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, 807 Hokuk-ro, Buk-gu, Daegu, 41404, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Hyun Jik Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Eun Young Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Yun Jin Jung
- Department of Internal Medicine, Fatima Hospital of Daegu, Daegu, Korea
| | - Chang Heon Yang
- Department of Internal Medicine, Dongguk University School of Medicine, Gyeongju, Korea
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Wu F, Huang Y, Hu J, Shao Z. Mendelian randomization study of inflammatory bowel disease and bone mineral density. BMC Med 2020; 18:312. [PMID: 33167994 PMCID: PMC7654011 DOI: 10.1186/s12916-020-01778-5] [Citation(s) in RCA: 224] [Impact Index Per Article: 44.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 09/08/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Recently, the association between inflammatory bowel disease (including ulcerative colitis and Crohn's disease) and BMD has attracted great interest in the research community. However, the results of the published epidemiological observational studies on the relationship between inflammatory bowel disease and BMD are still inconclusive. Here, we performed a two-sample Mendelian randomization analysis to investigate the causal link between inflammatory bowel disease and level of BMD using publically available GWAS summary statistics. METHODS A series of quality control steps were taken in our analysis to select eligible instrumental SNPs which were strongly associated with exposure. To make the conclusions more robust and reliable, we utilized several robust analytical methods (inverse-variance weighting, MR-PRESSO method, mode-based estimate method, weighted median, MR-Egger regression, and MR.RAPS method) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on BMD. Outlier variants identified by the MR-PRESSO outlier test were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy. RESULTS Our two-sample Mendelian randomization analysis with two groups of exposure GWAS summary statistics and four groups of outcome GWAS summary statistics suggested a definitively causal effect of genetically predicted ulcerative colitis on TB-BMD and FA-BMD but not on FN-BMD or LS-BMD (after Bonferroni correction), and we merely determined a causal effect of Crohn's disease on FN-BMD but not on the others, which was somewhat inconsistent with many published observational researches. The causal effect of inflammatory bowel disease on TB-BMD was significant and robust but not on FA-BMD, FN-BMD, and LS-BMD, which might result from the cumulative effect of ulcerative colitis and Crohn's disease on BMDs. CONCLUSIONS Our Mendelian randomization analysis supported the causal effect of ulcerative colitis on TB-BMD and FA-BMD. As to Crohn's disease, only the definitively causal effect of it on decreased FN-BMD was observed. Updated MR analysis is warranted to confirm our findings when a more advanced method to get less biased estimates and better precision or GWAS summary data with more ulcerative colitis and Crohn's disease patients was available.
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Affiliation(s)
- Fashuai Wu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Yu Huang
- Department of Otorhinolaryngology, The Third Hospital of Wuhan City, Wuhan, 430070, China
| | - Jialu Hu
- School of Computer Science, Northwestern Polytechnical University, West Youyi Road 127, Xi'an, 710072, China.
| | - Zengwu Shao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Khan ZAW, Shetty S, Pai GC, Acharya KKV, Nagaraja R. Prevalence of low bone mineral density in inflammatory bowel disease and factors associated with it. Indian J Gastroenterol 2020; 39:346-353. [PMID: 32940845 DOI: 10.1007/s12664-020-01048-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 04/29/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) have numerous risk factors for low bone mineral density (BMD). We aimed to study the prevalence of low BMD in IBD and the factors associated with it. METHODS BMD was measured by radial quantitative ultrasound, and clinical and biochemical characteristics were compared in prospectively enrolled patients and healthy age and gender-matched controls. Chi-square test, t test for independent samples, analysis of variance (ANOVA), Mann-Whitney U test and Kruskal-Wallis H tests were used as appropriate for univariate analysis to compare the characteristics between patients with and without abnormal BMD. Binary logistic regression analysis was done to determine the factors associated with low BMD in IBD patients. RESULTS One hundred and six patients (Crohn's disease [CD] = 35, ulcerative colitis [UC] = 71) and 55 controls were included. Low BMD was equally prevalent in CD, UC and controls (42.9%, 36.6%, 36.4% respectively, p = 0.791). Serum calcium and vitamin D were significantly lower in IBD patients compared to controls (p < 0.001 and p = 0.003, respectively) but not between patients with low and normal BMD. Older age (Odds ratio [OR] = 66.12 [9.299-470.243], p < 0.001), late onset of disease (OR = 4.795 [1.067-21.543], p = 0.041) and absence of steroid usage (OR = 0.272 [0.089-0.832], p = 0.022) were significantly associated with low BMD. CONCLUSIONS The prevalence of low BMD in patients with IBD was similar to controls and this was associated with increasing age, late onset of disease, and absence of steroid usage. Judicious use of steroids can help preserve bone health in IBD.
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Affiliation(s)
- Zohaib A W Khan
- Department of Gastroenterology and Hepatology, Kasturba Hospital, Manipal Academy of Higher Education, Manipal, Udupi, 576 104, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Hospital, Manipal Academy of Higher Education, Manipal, Udupi, 576 104, India
| | - Ganesh C Pai
- Department of Gastroenterology and Hepatology, Kasturba Hospital, Manipal Academy of Higher Education, Manipal, Udupi, 576 104, India.
| | - Kiran K V Acharya
- Department of Orthopedics, Kasturba Hospital, Manipal Academy of Higher Education, Manipal, Udupi, 576 104, India
| | - Ravishankar Nagaraja
- Department of Statistics, Manipal Academy of Higher Education, Manipal, Udupi, 576 104, India
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Zhou T, Pan J, Lai B, Cen L, Jiang W, Yu C, Shen Z. Bone mineral density is negatively correlated with ulcerative colitis: a systematic review and meta-analysis. Clin Transl Med 2020; 9:18. [PMID: 32072320 PMCID: PMC7028885 DOI: 10.1186/s40169-020-00270-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 02/09/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Newer epidemiological studies suggest that the incidence of ulcerative colitis might be increasing rapidly. Furthermore, osteoporosis in ulcerative colitis patients has gained great attention, but the epidemiologic evidence remains controversial. Therefore, a meta-analysis was performed to explore the association between bone density and ulcerative colitis. METHODS Two investigators used PubMed, EMBASE and the Cochrane Library databases to identify all studies published before August 2019. Depending on the outcomes, investigators divided these studies into four groups (OR, SMD [BMD], SMD [z-score] and SMD [t-score]). To address the use of steroids, which is a major confounding factor in this analysis, another subgroup analysis of studies of steroid-free patients was conducted. Additionally, heterogeneity, sensitivity and stratified analyses were also performed. RESULTS A total of 13 cross-sectional studies that involved 1154 participants were included in the present meta-analysis, and three of them were included in the steroid-free subgroup analysis. The pooled OR was 6.41 (95% CI 2.59-15.87) and the pooled SMD (BMD), SMD (t-score) and SMD (z-score) were - 0.24 (95% CI - 0.44 to - 0.04), - 0.55 (95% CI - 0.72 to - 0.37), and - 0.38 (95% CI - 0.56 and - 0.19), respectively. Since steroids are a significant confounder, the pooled SMD of the steroid-free subgroup was - 0.55 (- 0.85 to - 0.25), which revealed a strong negative relationship between bone density and ulcerative colitis in steroid-free patients. Additionally, other subgroup analyses also revealed a strong relationship. CONCLUSIONS This meta-analysis provides evidence for the potential association between ulcerative colitis and decreased bone density. It is essential for clinicians to consider bone mineral density in ulcerative colitis patients regardless of steroid-therapy.
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Affiliation(s)
- Tianyu Zhou
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiaqi Pan
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Bin Lai
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- People's Hospital of Jianggan District, Hangzhou, China
| | - Li Cen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wenxi Jiang
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhe Shen
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
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Ben Jemaa S, Chtourou L, Akrout R, Chaabouni K, Chaabouni T, Fourati HM, Amouri A, Tahri N, Ayedi F, Baklouti S. Bone Mineral Density and Bone Remodeling in Tunisian Patients with Inflammatory Bowel Disease. Open Rheumatol J 2019. [DOI: 10.2174/1874312901913010022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background:A high prevalence of osteopenia and osteoporosis is observed in patients with Inflammatory Bowel Disease (IBD).Objective:The aim of our study was to investigate the prevalence of bone loss, bone remodeling and risk factors in Tunisian patient with IBD.Patients and Methods:The study included 40 patients with IBD and 32 age- and sex-matched healthy controls subjects. All participants underwent bone densitometry by dual energy X-ray absorptiometry at the femoral neck and lumbar spine. Serum levels of 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), osteocalcin(OC), and urinary degradation products of C-terminal telopeptide of type I collagen (CTXI) were measured in all participants to assess the bone metabolism status.Results:Twelve (30%) patients were normal, 32.5% were osteopenic and 37.5% were osteoporotic. Osteoporosis was more frequent in IBD patients than controls (p=0.0001). Age and inflammation were associated with low bone mineral density (BMD). Mean calcium, phosphorus and alkaline phosphatase levels were similar in both groups. Median 25(OH) D levels were significantly lower in IBD patients compared with controls (p=0.0001). Median urinary CTXI levels were significantly higher in IBD patients compared with healthy controls (p=0.007). No significant differences between IBD patients and controls concerning the median serum OC and PTH levels were found.Conclusion:In our study, there is a high prevalence of low BMD in IBD patients and an increase in bone resorption without a change of bone formation. Low BMI and hypovitaminoses D were identified as risk factors for low BMD.
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Szafors P, Che H, Barnetche T, Morel J, Gaujoux-Viala C, Combe B, Lukas C. Risk of fracture and low bone mineral density in adults with inflammatory bowel diseases. A systematic literature review with meta-analysis. Osteoporos Int 2018; 29:2389-2397. [PMID: 29909470 DOI: 10.1007/s00198-018-4586-6] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 05/22/2018] [Indexed: 12/20/2022]
Abstract
Inflammatory bowel diseases (IBDs) are associated with a decreased bone mineral density, but the impact on fractures is unknown. In our study, global risk of fracture is increased for patients with IBDs versus controls. This result will help to determine the appropriate assessment with early screening and management of osteoporosis. Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), are associated with a decreased bone mineral density (BMD). However, the impact on fracture risk is unknown and data are contradictory across studies. In this systematic review and meta-analysis, we aimed to assess the risk of fracture and presence of low BMD in patients with IBDs compared to healthy controls. A systematic search of literature was conducted of MEDLINE, EMBASE, the Cochrane library and abstracts from appropriate scientific congresses. Studies were selected if they compared the incidence of fractures and/or BMD measurement by dual-energy X-ray absorptiometry in patients with IBDs and healthy sex- and age-matched controls. Data were extracted by two independent investigators. Meta-analysis was performed with the inverse variance approach to estimate pooled odds ratios (ORs) and risk ratios (RRs) with their 95% confidence intervals (CIs). Twenty-four studies met the inclusion criteria. On the basis of nine studies, global risk of fracture was increased for patients with IBDs versus controls (RR = 1.38, 95% CI 1.11-1.73; p = 0.005). Fracture risk with IBDs was significantly increased for vertebral fractures (OR = 2.26, 95% CI 1.04-4.90; p < 0.001), but not for any other site. The analysis of 16 studies evaluating BMD showed a significant decrease in mean BMD and Z-scores for IBD patients versus controls at all sites. In our meta-analysis, patients with IBDs have an increased risk of fractures, especially in the spine, and significant decreased BMD at all sites, which suggests the need for identifying high-risk individuals among this population.
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Affiliation(s)
- P Szafors
- Department of Rheumatology, Lapeyronie Hospital and University of Montpellier, Montpellier, France
| | - H Che
- Department of Rheumatology, Lapeyronie Hospital and University of Montpellier, Montpellier, France
| | - T Barnetche
- Department of Rheumatology, Lapeyronie Hospital and EA2415, University of Montpellier, Montpellier, France
| | - J Morel
- Department of Rheumatology, Lapeyronie Hospital and University of Montpellier, Montpellier, France
| | - C Gaujoux-Viala
- Department of Rheumatology, FHU ACRONIM, Pellegrin University Hospital, Bordeaux, France
| | - B Combe
- Department of Rheumatology, Lapeyronie Hospital and University of Montpellier, Montpellier, France
| | - C Lukas
- Department of Rheumatology, Nîmes University Hospital and EA2415, University of Montpellier, Nimes, France.
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Abstract
Inflammatory bowel diseases (IBDs), including both Crohn's disease (CD) and ulcerative colitis (UC), are chronic autoimmune diseases. Both CD and UC have relapsing and remitting courses. Although effective medical treatments exist for these chronic conditions, some patients do not respond to these traditional therapies. Patients are often left frustrated with incomplete resolution of symptoms and seek alternative or complementary forms of therapy. Patients often search for modifiable factors that could improve their symptoms or help them to maintain periods of remission. In this review, we examine both the published evidence on the benefits of exercise clinically and the pathophysiological changes associated with exercise. We then describe data on exercise patterns in patients with IBDs, potential barriers to exercise in IBDs, and the role of exercise in the development and course of IBDs. While some data support physical activity as having a protective role in the development of IBDs, the findings have not been robust. Importantly, studies of exercise in patients with mild-to-moderate IBD activity show no danger of disease or symptom exacerbation. Exercise has theoretical benefits on the immune response, and the limited available data suggest that exercise may improve disease activity, quality of life, bone mineral density, and fatigue levels in patients with IBDs. Overall, exercise is safe and probably beneficial in patients with IBDs. Evidence supporting specific exercise recommendations, including aspects such as duration and heart rate targets, is needed in order to better counsel patients with IBDs.
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Affiliation(s)
- Michael Engels
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond K Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Millie D Long
- Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, NC, USA
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12
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Lima C, Lyra A, Mendes C, Lopes M, Coqueiro F, Rocha R, Santana G. Bone mineral density and inflammatory bowel disease severity. Braz J Med Biol Res 2017; 50:e6374. [PMID: 29069227 PMCID: PMC5649869 DOI: 10.1590/1414-431x20176374] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 07/27/2017] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is associated with low bone mineral density (BMD). In this study, the association between disease severity and BMD in patients with IBD was evaluated. Associations between BMD and the Montreal classification, disease activity and drug therapy were also tested. A cross-sectional prevalence study with a comparison group was conducted. One hundred and twenty-eight patients were evaluated: 68 patients with ulcerative colitis (UC), and 60 with Crohn's disease (CD). The control group consisted of 67 healthy subjects. All patients and controls had BMD measured and in IBD patients, current medications, hospitalization, and disease location, extent and phenotype, according to the Montreal classification, were recorded. Multiple correspondence analysis was applied to evaluate categorical variables. In the CD group, most patients were diagnosed between 17-40 years of age. Ileocolonic and non-stricturing non-penetrating disease were the most frequent disease location and behavior, respectively. In UC patients, extensive colitis was the most frequent disease location. UC and CD patients were more likely to have osteopenia than controls (OR=14.93/OR=24.38, respectively). In the CD group, male patients, perianal disease, penetrating behavior and age at diagnosis >40 years were associated with low BMD. Taking azathioprine and infliximab also seemed to be associated with osteopenia. In the UC group, we observed an association between low BMD and male patients, left colitis, corticosteroid use and hospitalization. Disease activity was not associated with osteopenia or osteoporosis in CD and UC patients. Disease severity seems to be associated with osteopenia in IBD patients.
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Affiliation(s)
- C.A. Lima
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - A.C. Lyra
- Departamento de Gastroenterologia e Hepatologia, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - C.M.C. Mendes
- Instituto de Ciências e Saúde, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - M.B. Lopes
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - F.G. Coqueiro
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - R. Rocha
- Escola de Nutrição, Universidade Federal da Bahia, Salvador, BA, Brasil
| | - G.O. Santana
- Programa de Pós-Graduação em Medicina e Saúde, Universidade Federal da Bahia, Salvador, BA, Brasil
- Departamento de Ciências da Saúde, Universidade do Estado da Bahia, Salvador, BA, Brasil
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13
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Gandhi D, Naoghare PK, Bafana A, Kannan K, Sivanesan S. Fluoride-Induced Oxidative and Inflammatory Stress in Osteosarcoma Cells: Does It Affect Bone Development Pathway? Biol Trace Elem Res 2017; 175:103-111. [PMID: 27234253 DOI: 10.1007/s12011-016-0756-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 05/20/2016] [Indexed: 12/30/2022]
Abstract
Oxidative stress is reported to negatively affect osteoblast cells. Present study reports oxidative and inflammatory signatures in fluoride-exposed human osteosarcoma (HOS) cells, and their possible association with the genes involved in osteoblastic differentiation and bone development pathways. HOS cells were challenged with sublethal concentration (8 mg/L) of sodium fluoride for 30 days and analyzed for transcriptomic expression. In total, 2632 transcripts associated with several biological processes were found to be differentially expressed. Specifically, genes involved in oxidative stress, inflammation, osteoblastic differentiation, and bone development pathways were found to be significantly altered. Variation in expression of key genes involved in the abovementioned pathways was validated through qPCR. Expression of serum amyloid A1 protein, a key regulator of stress and inflammatory pathways, was validated through western blot analysis. This study provides evidence that chronic oxidative and inflammatory stress may be associated with the fluoride-induced impediment in osteoblast differentiation and bone development.
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Affiliation(s)
- Deepa Gandhi
- Environmental Health Division, CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, India
| | - Pravin K Naoghare
- Environmental Health Division, CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, India
| | - Amit Bafana
- Environmental Health Division, CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, India
| | - Krishnamurthi Kannan
- Environmental Health Division, CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, India
| | - Saravanadevi Sivanesan
- Environmental Health Division, CSIR-National Environmental Engineering Research Institute (NEERI), Nagpur, India.
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14
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Beattie RM. Enteral Nutrition as Primary Therapy in Childhood Crohn's Disease: Control of Intestinal Inflammation and Anabolic Response. JPEN J Parenter Enteral Nutr 2016; 29:S151-5; discussion S155-9, S184-8. [PMID: 15980277 DOI: 10.1177/01486071050290s4s151] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Crohn's disease in childhood is a chronic relapsing and remitting condition that can significantly impact normal growth and development. This influences choice of both initial and ongoing management. The goal of therapy is to induce and maintain remission with minimal side effects. Enteral nutrition is effective in active disease and will induce disease remission in most cases avoiding corticosteroid use. The high frequency of relapse means additional immunosuppressive therapies are usually required but nutrition remains a key priority as part of the subsequent management strategy.
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Affiliation(s)
- Robert M Beattie
- Pediatric Medical Unit, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
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15
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Veerappan SG, Healy M, Walsh B, O'Morain CA, Daly JS, Ryan BM. A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients. Eur J Gastroenterol Hepatol 2016; 28:1335-1344. [PMID: 27508327 DOI: 10.1097/meg.0000000000000719] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVES Infliximab (IFX) treatment has shown potentially beneficial effects on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to prospectively evaluate the impact of IFX treatment on bone metabolism in antitumour necrosis factor (TNF)-α-naive IBD patients using established bone metabolism markers and an in-vitro osteoblast model. MATERIALS AND METHODS A total of 37 anti-TNFα-naive IBD patients and 20 healthy controls were included. All measurements were performed at baseline and repeated in IBD patients following IFX therapy. Bone mineral density was measured by dual-energy X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble receptor activator of nuclear factor B ligand and proinflammatory and anti-inflammatory cytokines were measured. Bone formation was measured using osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was measured using serum type 1 collage c-telopeptide. The effect of control and IBD patient sera on human osteoblast viability and differentiation was analysed. RESULTS OC level was higher in controls than IBD patients (P=0.018). After IFX, OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011) and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX therapy, proinflammatory cytokines TNF-α, interleukin-6 and interleukin-13 decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6), respectively. Sera from IBD patients before IFX showed increased osteoblast viability compared with the controls (P=0.003 to P<0.005), but induced reduced osteoblast differentiation. After IFX, viability reduced to control levels, but osteoblast differentiation increased (P=0.041). CONCLUSION IFX treatment induced beneficial effects on bone metabolism. Osteoblast culture results suggest that IBD patients may have increased osteoblast viability, but reduced differentiation, which has implications for bone strength.
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Affiliation(s)
- Sundaram G Veerappan
- aDeparment of Gastroenterology, Adelaide & Meath Hospital, Tallaght, Dublin 24 Departments of bBiochemistry cGerontology, St James's Hospital, Dublin 8 dDepartment of Anatomy, Divison of Biology, Royal College of Surgeons in Ireland, Dublin 2, Republic of Ireland
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Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res 2016; 41:435-443. [PMID: 29021688 PMCID: PMC5628327 DOI: 10.1016/j.jgr.2016.08.004] [Citation(s) in RCA: 363] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Accepted: 08/09/2016] [Indexed: 01/06/2023] Open
Abstract
Panax ginseng is one of the most universally used herbal medicines in Asian and Western countries. Most of the biological activities of ginseng are derived from its main constituents, ginsenosides. Interestingly, a number of studies have reported that ginsenosides and their metabolites/derivatives—including ginsenoside (G)-Rb1, compound K, G-Rb2, G-Rd, G-Re, G-Rg1, G-Rg3, G-Rg5, G-Rh1, G-Rh2, and G-Rp1—exert anti-inflammatory activities in inflammatory responses by suppressing the production of proinflammatory cytokines and regulating the activities of inflammatory signaling pathways, such as nuclear factor-κB and activator protein-1. This review discusses recent studies regarding molecular mechanisms by which ginsenosides play critical roles in inflammatory responses and diseases, and provides evidence showing their potential to prevent and treat inflammatory diseases.
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Affiliation(s)
- Ji Hye Kim
- Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea
| | - Young-Su Yi
- Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea
| | - Mi-Yeon Kim
- School of Systems Biomedical Science, Soongsil University, Seoul, Republic of Korea
| | - Jae Youl Cho
- Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea
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17
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Setty-Shah N, Maranda L, Nwosu BU. Adiposity is associated with early reduction in bone mass in pediatric inflammatory bowel disease. Nutrition 2016; 32:761-6. [DOI: 10.1016/j.nut.2016.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 12/29/2015] [Accepted: 01/05/2016] [Indexed: 12/24/2022]
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18
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Lima CA, Lyra AC, Rocha R, Santana GO. Risk factors for osteoporosis in inflammatory bowel disease patients. World J Gastrointest Pathophysiol 2015; 6:210-218. [PMID: 26600979 PMCID: PMC4644885 DOI: 10.4291/wjgp.v6.i4.210] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2015] [Revised: 08/22/2015] [Accepted: 09/18/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) patients exhibit higher risk for bone loss than the general population. The chronic inflammation causes a reduction in bone mineral density (BMD), which leads to osteopenia and osteoporosis. This article reviewed each risk factor for osteoporosis in IBD patients. Inflammation is one of the factors that contribute to osteoporosis in IBD patients, and the main system that is involved in bone loss is likely RANK/RANKL/osteoprotegerin. Smoking is a risk factor for bone loss and fractures, and many mechanisms have been proposed to explain this loss. Body composition also interferes in bone metabolism and increasing muscle mass may positively affect BMD. IBD patients frequently use corticosteroids, which stimulates osteoclastogenesis. IBD patients are also associated with vitamin D deficiency, which contributes to bone loss. However, infliximab therapy is associated with improvements in bone metabolism, but it is not clear whether the effects are because of inflammation improvement or infliximab use. Ulcerative colitis patients with proctocolectomy and ileal pouches and Crohn’s disease patients with ostomy are also at risk for bone loss, and these patients should be closely monitored.
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19
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Kim JY, Park SH, Baek JM, Erkhembaatar M, Kim MS, Yoon KH, Oh J, Lee MS. Harpagoside Inhibits RANKL-Induced Osteoclastogenesis via Syk-Btk-PLCγ2-Ca(2+) Signaling Pathway and Prevents Inflammation-Mediated Bone Loss. JOURNAL OF NATURAL PRODUCTS 2015; 78:2167-2174. [PMID: 26308264 DOI: 10.1021/acs.jnatprod.5b00233] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Harpagoside (HAR) is a natural compound isolated from Harpagophytum procumbens (devil's claw) that is reported to have anti-inflammatory effects; however, these effects have not been investigated in the context of bone development. The current study describes for the first time that HAR inhibits receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in vitro and suppresses inflammation-induced bone loss in a mouse model. HAR also inhibited the formation of osteoclasts from mouse bone marrow macrophages (BMMs) in a dose-dependent manner as well as the activity of mature osteoclasts, including filamentous actin (F-actin) ring formation and bone matrix breakdown. This involved a HAR-induced decrease in extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation, leading to the inhibition of Syk-Btk-PLCγ2-Ca(2+) in RANKL-dependent early signaling, as well as the activation of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), which resulted in the down-regulation of various target genes. Consistent with these in vitro results, HAR blocked lipopolysaccharide (LPS)-induced bone loss in an inflammatory osteoporosis model. However, HAR did not prevent ovariectomy-mediated bone erosion in a postmenopausal osteoporosis model. These results suggest that HAR is a valuable agent against inflammation-related bone disorders but not osteoporosis induced by hormonal abnormalities.
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Affiliation(s)
- Ju-Young Kim
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Sun-Hyang Park
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Jong Min Baek
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Munkhsoyol Erkhembaatar
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Min Seuk Kim
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Kwon-Ha Yoon
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Jaemin Oh
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
| | - Myeung Su Lee
- Imaging Science-Based Lung and Bone Diseases Research Center, ‡Department of Anatomy, School of Medicine, §Department of Oral Physiology, School of Dentistry, ⊥Department of Radiology, School of Medicine, ∥Institute for Skeletal Disease, and ▽Division of Rheumatology, Department of Internal Medicine, Wonkwang University , Iksan, Jeonbuk 570-749, Korea
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van den Heuvel TRA, Jonkers DM, Jeuring SFG, Romberg-Camps MJL, Oostenbrug LE, Zeegers MP, Masclee AA, Pierik MJ. Cohort Profile: The Inflammatory Bowel Disease South Limburg Cohort (IBDSL). Int J Epidemiol 2015; 46:e7. [DOI: 10.1093/ije/dyv088] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Schlundt C, Schell H, Goodman SB, Vunjak-Novakovic G, Duda GN, Schmidt-Bleek K. Immune modulation as a therapeutic strategy in bone regeneration. J Exp Orthop 2015; 2:1. [PMID: 26914869 PMCID: PMC4545842 DOI: 10.1186/s40634-014-0017-6] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 12/08/2014] [Indexed: 12/31/2022] Open
Abstract
We summarize research approaches and findings on bone healing and regeneration that were presented at a workshop at the 60th annual meeting of the Orthopedic Research Society (ORS) in New Orleans in 2014. The workshop was designed to discuss the role of inflammation in bone regeneration in the context of fundamental biology, and to develop therapeutic strategies that involve immune modulation. Delayed or non-healing of bone is a major clinical problem, with around 10% of fracture patients suffering from unsatisfying healing outcomes. Inflammation is traditionally seen as a defense mechanism, but was recently found essential in supporting and modulating regenerative cascades. In bone healing, macrophages and T- and B-cells interact with progenitor cells, bone forming osteoblasts and remodeling osteoclasts. Among the cells of the innate immunity, macrophages are promising candidates for targets in immune-modulatory interventions that would overcome complications in bone healing and bone-related diseases. Among the cells of the adaptive immune system, CD8+ T cells have been shown to have a negative impact on bone fracture healing outcome, whereas regulatory T cells could be promising candidates that have a positive, modulating effect on bone fracture healing. This workshop addressed recent advances and key challenges in this exciting interdisciplinary research field.
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Affiliation(s)
- Claudia Schlundt
- Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. .,Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
| | - Hanna Schell
- Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
| | - Stuart B Goodman
- Department of Orthopaedic Surgery and (by courtesy) Bioengineering, Stanford University Medical Center Outpatient Center, 450 Broadway St., M/C 6342, 94063, Redwood City, CA, USA.
| | - Gordana Vunjak-Novakovic
- Department of Biomedical Engineering and Department of Medicine, Columbia University, 622 west 168th Street, VC12-234, 10032, New York, NY, USA.
| | - Georg N Duda
- Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. .,Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
| | - Katharina Schmidt-Bleek
- Julius Wolff Institut and Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. .,Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
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22
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Grover Z, Biron R, Carman N, Lewindon P. Predictors of response to Infliximab in children with luminal Crohn's disease. J Crohns Colitis 2014; 8:739-46. [PMID: 24445015 DOI: 10.1016/j.crohns.2013.12.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2013] [Revised: 12/19/2013] [Accepted: 12/19/2013] [Indexed: 02/06/2023]
Abstract
OBJECTIVE A significant proportion of patients with initial response to Inflximab (IFX), subsequently lose response (LOR). Multicentre paediatric studies report LOR in 33% to 50% with 3-5year follow-up. Our retrospective study examined durability of response and predictors of LOR. METHODS From our IBD database of 185 children with CD, 65 received IFX maintenance therapy for luminal or fistulising Crohn's disease between January, 2006 and April, 2013. 47 with luminal CD ≥1year follow-up after commencing IFX were included. We evaluated variables associated with response and describe outcomes on those remaining on IFX at four time points; before IFX, after induction, at 1year and at the last follow-up. Response was divided into sustained primary, recovered, durable (combined sustained primary and recovered) and complete LOR (discontinuation from LOR or intolerance). RESULTS Overall, 28/47 (60%) children sustained primary response over a median duration of 2.83years (1.6-4.4, IQR). 19/47 (40%) developed LOR (including 2 intolerant) at a median of 11months (9-19, IQR). Of 17 with LOR, 7 were successfully re-induced giving durable response (35/47, 74%); 6 failed dose intensification needing surgery (n=2), second anti-TNF (n=2) or both (n=2). 4 had surgery without dose intensification. LOR was associated with low BMI at diagnosis, lower height Z scores prior to induction, elevated CRP following induction (p=0.007) and failure to use concomitant IM (p=0.02). CONCLUSION The cumulative probability of durable response to IFX in luminal CD was 83%, 74% and 70% after 1, 2, and 3years on IFX maintenance therapy.
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Affiliation(s)
- Zubin Grover
- Queensland Children Medical Research Institute, Brisbane, QLD, Australia; Queensland Paediatric Gastroenterology Hepatology, Royal Children's Hospital, Brisbane, QLD, Australia.
| | - Rebecca Biron
- Queensland Paediatric Gastroenterology Hepatology, Royal Children's Hospital, Brisbane, QLD, Australia
| | - Nicholas Carman
- Queensland Paediatric Gastroenterology Hepatology, Royal Children's Hospital, Brisbane, QLD, Australia
| | - Peter Lewindon
- Queensland Children Medical Research Institute, Brisbane, QLD, Australia; University Of Queensland, Department of Paediatrics & Child Health, Brisbane, QLD, Australia
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Abraham BP, Prasad P, Malaty HM. Vitamin D deficiency and corticosteroid use are risk factors for low bone mineral density in inflammatory bowel disease patients. Dig Dis Sci 2014; 59:1878-84. [PMID: 24619280 DOI: 10.1007/s10620-014-3102-x] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Accepted: 02/27/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND As several factors can contribute to low bone mineral density (BMD), we investigated the role of vitamin D in low BMD while controlling for other risk factors in inflammatory bowel diseases (IBD) patients. METHODS We conducted a prospective cross-sectional study between 2008 and 2012 in adult IBD patients. Demographic data including age, gender, ethnicity, BMI, along with disease type and location, vitamin D levels, prior corticosteroid use, and anti-TNF use were recorded and evaluated with DEXA results. RESULTS A total of 166 patients [105 Crohn's disease (CD), 61 ulcerative colitis (UC)] qualified for the study. Low BMD was found in 40%, twice as frequently in CD than in UC (p = 0.048). Higher prevalence of low BMD was associated with those of male gender (p = 0.05), Asian ethnicity (p = 0.02), and history of corticosteroid use (p = 0.001). Age, body mass index, or disease location did not increase the risk of low BMD. The overall prevalence of low vitamin D was 60%, with insufficiency (25-hydroxy levels between 20 and 30 ng/mL) found in 37% and deficiency (levels <20 ng/mL) found in 23% of the patients. Vitamin D insufficient and deficient patients were two times (p = 0.049) and almost 3 times (p = 0.02) as likely to have low BMD, respectively. CONCLUSIONS Low vitamin D, male gender, Asian ethnicity, CD, and corticosteroid use significantly increased the risk of having low BMD, while age and disease location did not affect BMD in our IBD population. It remains important to evaluate for vitamin D nutritional deficiency and limit corticosteroid use to help prevent low BMD in IBD patients.
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Affiliation(s)
- Bincy P Abraham
- Houston Methodist, 6550 Fannin St. Smith Tower, Suite 1001, Houston, TX, 77030, USA,
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Grover Z, Muir R, Lewindon P. Exclusive enteral nutrition induces early clinical, mucosal and transmural remission in paediatric Crohn's disease. J Gastroenterol 2014; 49:638-45. [PMID: 23636735 DOI: 10.1007/s00535-013-0815-0] [Citation(s) in RCA: 146] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2013] [Accepted: 04/07/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Exclusive enteral nutrition (EEN) induces clinical and mucosal healing (MH) in Crohn's disease (CD), with MH the best determinant of future outcome. We investigated efficacy of EEN for inducing early clinical, biochemical, mucosal and transmural remission of CD and related early endoscopic response to outcomes at 1 year. METHODS In a prospective, open label study 34 children (mean 13.1 years; 21 males) with new diagnosis CD were offered EEN, 26 completed a minimum 6 weeks EEN and underwent paired clinical, biochemical and endoscopic assessment at start and completion using PCDAI, BMI, CRP and Simple Endoscopic Score for CD (SES-CD). A subset, 16/26, had paired MR enterography scored. Early good endoscopic response (complete MH, or near complete, SES-CD 0-3) was related to outcome at 1 year. RESULTS EEN improved mean PCDAI (37.88-7.01, p < 0.001; BMI Z scores (-1.54 to -0.54, p < 0.01); weight Z score (-0.79 to -0.08, p < 0.03); CRP (44.86-5.5, p < 0.001); endoscopy (SES-CD 14.28-3.88, p < 0.001) and MRE (5.14-2.79, p = 0.01). Of 26 children, 22 (84 %) achieved clinical remission; 20 (76 %) biochemical remission. Fifteen (58 %) had early good endoscopic response (11 complete, 4 near complete MH) and 3/14 (21 %) had complete transmural remission of ileal CD (MRE-CD: 0-1). Early good endoscopic response was associated with reduced endoscopic confirmed relapse (53 vs. 100 %, p = 0.02), anti-TNF use (33 vs. 88 %, p = 0.01) and hospitalisation (40 vs. 88 %) at 1 year. CONCLUSIONS EEN is effective for inducing early clinical, biochemical, mucosal and transmural remission. Early endoscopic remission improves outcomes at 1 year.
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Affiliation(s)
- Zubin Grover
- Queensland Children Medical Research Institute, Brisbane, QLD, Australia,
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Dumitrescu G, Mihai C, Dranga M, Prelipcean CC. Serum 25-hydroxyvitamin D concentration and inflammatory bowel disease characteristics in Romania. World J Gastroenterol 2014; 20:2392-2396. [PMID: 24605037 PMCID: PMC3942843 DOI: 10.3748/wjg.v20.i9.2392] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Revised: 11/19/2013] [Accepted: 01/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To describe the relationship between vitamin D levels and inflammatory bowel disease (IBD) characteristics in northeastern Romanian patients.
METHODS: This was a prospective study of 47 consecutive IBD patients admitted to The Institute of Gastroenterology and Hepatology in Iasi, Romania between March 2011 and June 2012. The diagnosis of IBD was established based on endoscopic, histologic and radiologic findings. Demographic data, disease characteristics, ongoing treatments and biological parameters of patients (including markers of inflammation: C-reactive protein level, fibrinogen level, and erythrocyte sedimentation rate) were recorded. Serum vitamin D levels were measured and compared with age- and sex-matched healthy volunteers from the same geographic area. Vitamin D levels were defined as sufficient (> 30 ng/mL), insufficient (20-30 ng/mL), or severely deficient (< 20 ng/mL).
RESULTS: Thirty-three of the IBD patients included in this study had ulcerative colitis (UC) and 14 had Crohn’s disease (CD). Only 24% of the UC patients and 21% of the CD patients had sufficient vitamin D levels. The vitamin D levels were significantly lower in the CD patients with moderate to severe disease activity compared to the CD patients in remission or with mild disease activity (16 ± 6 ng/mL vs 26 ± 7 ng/mL; 16 ± 6 ng/mL vs 31 ± 9 ng/mL, respectively, P < 0.05). Vitamin D levels in the UC patients were not influenced by disease activity and no correlation was observed with the inflammation markers tested (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate). No association was observed between vitamin D levels and smoking status or ongoing medication (5ASA, steroids, and anti-TNFα). Newly diagnosed IBD patients had lower vitamin D levels than patients with established cases, though these differences were not significant (UC: 22 ± 9 ng/mL vs 26 ± 12 ng/mL; CD: 18 ± 6 ng/mL vs 27 ± 11 ng/mL, respectively). Although no association was found between the season during which the visit was scheduled and vitamin D levels, the UC patients assessed during the winter tended to have lower levels than those assessed during the summer (22 ± 9 ng/mL vs 28 ± 13 ng/mL, respectively).
CONCLUSION: Vitamin D levels are significantly reduced in IBD patients in northeastern Romania, with the lowest levels occurring in CD patients with moderate to severe disease activity.
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Scorei ID, Scorei RI. Calcium fructoborate helps control inflammation associated with diminished bone health. Biol Trace Elem Res 2013; 155:315-21. [PMID: 23982445 DOI: 10.1007/s12011-013-9800-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Accepted: 08/01/2013] [Indexed: 10/26/2022]
Abstract
Inflammation has been identified as a possible contributory factor to disruption of the normal bone remodeling process, a process essential to healthy bone mineral density. Several large population-based clinical studies have specifically shown that levels of C-reactive protein, an immune recognition protein that is a sensitive marker of inflammation, are inversely and independently associated with total bone mineral density. The evidence suggests that control of C-reactive protein levels may contribute to bone health by protecting against inflammation's disruption of the equilibrium between bone resorption and bone deposition. Calcium fructoborate, a patented complex of calcium, fructose, and boron found naturally in fresh and dried fruits, vegetables and herbs, and wine, is a sugar-borate ester. A growing body of peer-reviewed, published clinical research indicates that the calcium fructoborate significantly reduces serum levels of the C-reactive protein in humans, suggesting that this unique plant-mineral complex may contribute to bone health by controlling the inflammation associated with loss of bone mineral density.
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Middleton JP, Bhagavathula AP, Gaye B, Alvarez JA, Huang CS, Sauer CG, Tenjarla G, Schoen BT, Kumar A, Prasad M, Okou DT, Ifeadike WC, Dhere TA, Conneely KN, Ziegler TR, Tangpricha V, Kugathasan S. Vitamin D status and bone mineral density in African American children with Crohn disease. J Pediatr Gastroenterol Nutr 2013; 57:587-93. [PMID: 23760229 PMCID: PMC3845217 DOI: 10.1097/mpg.0b013e31829e0b89] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD). METHODS We compared serum 25OHD concentrations of African American children with CD (n = 52) to white children with CD (n = 64) and healthy African American controls (n = 40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population. RESULTS African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5-17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2-24.6] ng/mL; P < 0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5-17.9] vs 16.3 [95% CI 14.4-18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P = 0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8-13.5] ng/mL). BMD was comparable between African American and white children with CD (z score -0.4 ± 0.9 vs -0.7 ± 1.2; NS). CONCLUSIONS African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.
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Affiliation(s)
- Jeremy P. Middleton
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Anita P. Bhagavathula
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Bilkisu Gaye
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Jessica A. Alvarez
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Clifton S. Huang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Cary G. Sauer
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Gayathri Tenjarla
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Bess T. Schoen
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Archana Kumar
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Mahadev Prasad
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - David T. Okou
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Walter C. Ifeadike
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Tanvi A. Dhere
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
| | - Karen N. Conneely
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA
| | - Thomas R. Ziegler
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Vin Tangpricha
- Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | - Subra Kugathasan
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory School of Medicine and Children’s Healthcare of Atlanta
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Blanck S, Aberra F. Vitamin d deficiency is associated with ulcerative colitis disease activity. Dig Dis Sci 2013; 58:1698-702. [PMID: 23334382 DOI: 10.1007/s10620-012-2531-7] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2012] [Accepted: 12/11/2012] [Indexed: 02/06/2023]
Abstract
PURPOSE Previous studies on experimental mouse models have suggested a role of vitamin D in immune system regulation and IBD disease severity. In this study, we examine the relationship between vitamin D levels and clinical disease activity in human subjects with ulcerative colitis (UC). We hypothesized that patients with vitamin D deficiency will display increased UC disease activity as compared to patients with normal vitamin D levels. METHODS A cross-sectional study was performed by querying the outpatient electronic medical record of our health system for patients seen in the gastroenterology clinic from January 2007 to October 2009 who carried both a diagnosis of UC and a documented 25-OH vitamin D level within 30 days of their clinic visit. Demographic and clinical variables were collected. Clinical disease activity was calculated using the six-point partial Mayo index. Active disease was defined as a six-point index score of ≥ 1. Vitamin D deficiency was defined as a 25-OH D level below 30 ng/ml. Data were analyzed using the chi-square distribution test. RESULTS Thirty-four patients met inclusion criteria (53 % female, mean age 45.7 ± 24.7 years). Fifteen patients had normal vitamin D levels and 19 patients were vitamin D deficient. Twelve patients had vitamin D levels <20 ng/ml. Vitamin D deficient patients were statistically more likely to have increased disease activity than patients with normal vitamin D levels (p = 0.04), with 68 % of deficient patients displaying active disease compared with 33 % in the sufficient group. There was also a statistically significant association between vitamin D status and need for treatment with steroids, with a higher percentage of vitamin D deficient patients (47 %) requiring such treatment compared with 7 % in the sufficient group (p = 0.02). There was no association between season of visit and disease activity. CONCLUSION Vitamin D deficiency is common among patients with active UC, particularly those requiring corticosteroids. Further investigation is needed to determine the clinical utility of vitamin D monitoring in patients with UC and whether there is a role for vitamin D as a treatment for UC.
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Affiliation(s)
- Stacey Blanck
- Department of Medicine, Hospital of University of Pennsylvania, Philadelphia, PA 19104, USA.
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Azzopardi N, Ellul P. Risk factors for osteoporosis in Crohn's disease: infliximab, corticosteroids, body mass index, and age of onset. Inflamm Bowel Dis 2013; 19:1173-8. [PMID: 23511037 DOI: 10.1097/mib.0b013e31828075a7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND We analyzed the characteristics associated with increased risk of osteoporosis in patients with Crohn's disease in Malta. METHOD Eighty-three patients with histologically and endoscopically confirmed Crohn's disease underwent a DEXA bone density scan and their phenotypic characteristics were analyzed. RESULTS There was a significant association between body mass index and bone mineral density (P = 0.004) and a significant difference in the T scores of patients according to age at diagnosis (Montreal Classification: P = 0.0006) with patients diagnosed <17 years (n = 13) having lower T scores than those diagnosed at older age groups (n = 70). There was a significant difference between the T scores of patients on infliximab (n = 33) and those not on biological therapy (n = 50, P = 0.0058). Patients with high cumulative corticosteroid doses (>10 mg/d for >3 mo, n = 18) had lower bone mineral densities than patients who received smaller corticosteroid doses (P = 0.013). There was however no significant difference in the T scores of patients according to disease location (P = 0.18), disease type (P = 0.64), gender (P = 0.30), and history of ileal resection (P = 0.68). There was also no significant correlation between disease duration and T scores (hip) (P = 0.61). CONCLUSIONS Low body mass index, early disease onset, high corticosteroid doses and, anti-tumor necrosis factor α therapy are associated with increased risk of osteoporosis. Lower T scores in patients on infliximab occur as patients receiving this therapy have more severe inflammation, which is associated with elevated osteoclastogenic factors, rather than as a side-effect of the anti-tumor necrosis factor-α therapy.
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Affiliation(s)
- Neville Azzopardi
- Division of Gastroenterology, Mater Dei Hospital (Malta), Mellieha, Malta.
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Shirazi KM, Somi MH, Rezaeifar P, Fattahi I, Khoshbaten M, Ahmadzadeh M. Bone density and bone metabolism in patients with inflammatory bowel disease. Saudi J Gastroenterol 2012; 18:241-7. [PMID: 22824766 PMCID: PMC3409884 DOI: 10.4103/1319-3767.98428] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/AIMS Patients with inflammatory bowel disease (IBD) are at high risk for low bone mineral density (BMD). This study aimed to evaluate BMD in IBD patients and its relationship with bone metabolism in a group of Iranian patients. PATIENTS AND METHODS A cross-sectional study was conducted on patients with IBD to assess BMD status and serum biochemical factors. After getting the demographic data from 200 patients, they were screened using dual-energy X-ray absorptiometry of the lumbar spine (L2-L4) and femoral neck for BMD status. Serum levels of calcium, phosphate, alkaline phosphatase (ALP), and 25-hydroxyvitamin D (25-OH vitamin D) were measured to assess the bone metabolism status. RESULTS Two hundred patients with IBD were enrolled in the study. One hundred and eighty three (91.5%) patients were identified as having ulcerative colitis (UC) and 17 (8.5%) as having Crohn's disease (CD). Based on the lumbar and femoral neck bone mass densitometry, 148 (74.4%) patients had low BMD at either lumbar spine or femoral neck. Of these, 100 patients (50.3%) were osteopenic and 48 patients (24.1%) were osteoporotic. A 58.6% and 61% of patients with UC had low BMD in the lumbar and femoral neck, respectively. These results for those with CD were 76.5% and 70.6%, respectively. The mean of femoral neck and lumbar T-scores in patients with UC were -1.14 and -1.38, and in patients with CD were -1.24 and -1.47, respectively (P > 0.05). The mean (±SD) levels for calcium (Ca) in UC and CD were in the normal range. The mean (±SD) levels of ALP and 25-OH vitamin D in both the groups were in the normal range, and in comparison between groups (UC and CD), no significant differences were observed (P = 0.20 for ALP and P = 0.44 for 25-OH vitamin D). In the assessment of correlation between biochemical markers and BMD, an inverse correlation between lumbar T-score and ALP or 25-OH vitamin D only in patients with UC was observed. CONCLUSIONS The high prevalence of low BMD in the Iranian population with IBD needs attention. The subclinical vitamin D deficiency may contribute to bone loss in IBD patients, which is more pronounced in patients with UC in this study because of the small population of patients with CD.
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Affiliation(s)
- Kourosh M. Shirazi
- Liver and Gastrointestinal Disease Research Center (LGDRC), Tabriz University of Medical Science Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad H. Somi
- Liver and Gastrointestinal Disease Research Center (LGDRC), Tabriz University of Medical Science Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parisa Rezaeifar
- Liver and Gastrointestinal Disease Research Center (LGDRC), Tabriz University of Medical Science Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran,Address for correspondence: Dr. Parisa Rezaeifar, The Internal Medicine Resident of Tabriz University of Medical Sciences, Liver and Gastrointestinal Diseases Research Center, Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran. E-mail:
| | - Ibrahim Fattahi
- Liver and Gastrointestinal Disease Research Center (LGDRC), Tabriz University of Medical Science Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manuchehr Khoshbaten
- Liver and Gastrointestinal Disease Research Center (LGDRC), Tabriz University of Medical Science Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoumeh Ahmadzadeh
- Liver and Gastrointestinal Disease Research Center (LGDRC), Tabriz University of Medical Science Imam Reza Hospital-Tabriz University of Medical Sciences, Tabriz, Iran
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Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG, Issa M. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr 2011; 35:308-16. [PMID: 21527593 DOI: 10.1177/0148607110381267] [Citation(s) in RCA: 228] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL). METHODS This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL. RESULTS The study included 504 IBD patients (403 Crohn's disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). CONCLUSIONS Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.
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Affiliation(s)
- Alex Ulitsky
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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Etzel JP, Larson MF, Anawalt BD, Collins J, Dominitz JA. Assessment and management of low bone density in inflammatory bowel disease and performance of professional society guidelines. Inflamm Bowel Dis 2011; 17:2122-9. [PMID: 21910174 DOI: 10.1002/ibd.21601] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2010] [Accepted: 11/05/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients have increased prevalence of osteoporosis, leading to guideline recommendations for bone mineral density (BMD) testing. The study aim was to identify predictors of BMD testing and treatment and assess guideline effectiveness to identify IBD patients with osteoporosis. METHODS Records of all IBD patients at seven medical facilities were reviewed for clinical data and BMD testing from January 1996 through October 2006. RESULTS A total of 2035 patients had 317 bone density tests performed. Osteopenia was found in 48% of patients, osteoporosis in 26%. Among patients meeting guideline criteria for BMD testing and ≥1 year of follow-up, 23.3% underwent testing. The strongest predictors of testing were menopause (adjusted hazard ratio [AHR] 3.02) and receiving care at a tertiary center (AHR 2.56). Testing rates were low in patients with age ≥60 years, ulcerative colitis, and a history of inpatient IBD treatment. Osteoporotic patients received calcium/vitamin D and bisphosphonates in 59% and 75% of cases, respectively. Osteoporotic males had a 37% rate of hypogonadism. Guideline criteria do not distinguish patients with osteoporosis. The criteria had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 23%, 27%, and 81% for osteoporosis in the tested population, respectively. CONCLUSIONS Osteoporosis is highly prevalent in the IBD population, but BMD testing and osteoporosis treatments are underutilized. Male hypogonadism is common in osteoporotic IBD patients. Guidelines do not identify IBD patients with osteoporosis.
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Affiliation(s)
- Jason P Etzel
- Division of Gastroenterology, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA
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Alteraciones del metabolismo óseo en 100 pacientes con enfermedad inflamatoria intestinal. GASTROENTEROLOGIA Y HEPATOLOGIA 2011; 34:379-84. [DOI: 10.1016/j.gastrohep.2011.03.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Revised: 03/05/2011] [Accepted: 03/09/2011] [Indexed: 01/05/2023]
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Gerasimidis K, McGrogan P, Edwards CA. The aetiology and impact of malnutrition in paediatric inflammatory bowel disease. J Hum Nutr Diet 2011; 24:313-26. [PMID: 21564345 DOI: 10.1111/j.1365-277x.2011.01171.x] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Disease-associated undernutrition of all types is very common in paediatric inflammatory bowel disease (IBD). Recent weight loss remains one of the triad of clinical manifestations and a cornerstone for the diagnosis of Crohn's disease (CD), although significantly fewer patients now present as being underweight. Recent evidence suggests that the introduction of medical treatment will quickly restore body weight, although this does not reflect concomitant changes in body composition. CD children present with features of nutritional cachexia with normal fat stores but depleted lean mass. Poor bone health, delayed puberty and growth failure are additional features that further complicate clinical management. Suboptimal nutritional intake is a main determinant of undernutrition, although activation of the immune system and secretion of pro-inflammatory cytokines exert additional independent effects. Biochemically low concentrations of plasma micronutrients are commonly reported in IBD patients, although their interpretation is difficult in the presence of an acute phase response and other indices of body stores adequacy are needed. Anaemia is a common extraintestinal manifestation of the IBD child. Iron-deficient anaemia is the predominant type, with anaemia of chronic disease second. Decreased dietary intake, as a result of decreased appetite and food aversion, is the major cause of undernutrition in paediatric IBD. Altered energy and nutrient requirements, malabsorption and increased gastrointestinal losses are additional factors, although their contribution to undernutrition in paediatric CD needs to be studied further.
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Affiliation(s)
- K Gerasimidis
- Human Nutrition Section, Developmental Medicine, University of Glasgow, Royal Hospital for Sick Children, UK.
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Peyrin-Biroulet L, Loftus EV, Colombel JF, Sandborn WJ. Long-term complications, extraintestinal manifestations, and mortality in adult Crohn's disease in population-based cohorts. Inflamm Bowel Dis 2011; 17:471-8. [PMID: 20725943 DOI: 10.1002/ibd.21417] [Citation(s) in RCA: 147] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2010] [Accepted: 06/10/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND Crohn's disease (CD) is a chronic, progressive, destructive disease. Numerous intestinal and extraintestinal complications and manifestations can occur during its clinical course. This literature review summarizes our current knowledge of the long-term complications, extraintestinal complications, and mortality in CD in adults as reported in population-based studies that include long-term follow-up results. METHODS A literature search of English and non-English language publications listed in the electronic databases of Medline (source PubMed, 1935 to July, 2009). RESULTS The relative risk of incident fractures is increased in CD patients by ≈30%-40%. These patients have also have a 3-fold increased risk of deep venous thrombosis and pulmonary embolism. A variety of extraintestinal manifestations (primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, erythema nodosum) and diseases (asthma, bronchitis, pericarditis, psoriasis, rheumatoid arthritis, and multiple sclerosis) are associated with CD. The risks of colorectal and small bowel cancers relative to the general population are 1.4-1.9 and 21.1-27.1, respectively. A slightly increased risk of lymphoma, irrespective of medication use, has been reported in a recent meta-analysis of population-based studies. Overall mortality is slightly increased in CD, with a standardized mortality ratio of 1.4. CONCLUSIONS CD is frequently associated with disease complications and extraintestinal conditions. Whether the impact of changing treatment paradigms with increased use of immunosuppressives and biologic agents can reduce disease complications and associated conditions is unknown.
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Hébuterne X, Filippi J, Al-Jaouni R, Schneider S. Nutritional consequences and nutrition therapy in Crohn's disease. ACTA ACUST UNITED AC 2010; 33 Suppl 3:S235-44. [PMID: 20117347 DOI: 10.1016/s0399-8320(09)73159-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
75% of hospital patients with Crohn's disease (CD) suffer from malnutrition and one third of CD patients have a body mass index below 20. Inflammatory bowel diseases (IBD) patients have many vitamin and nutrient deficiencies which can lead to important consequences such as hyperhomocysteinemia which is associated with a higher risk of thromboembolic disease. Nutritional deficiencies in IBD patients are the result of insufficient intake, malabsorption and protein-losing enteropathy as well as the metabolic distubances directly induced by the chronic disease and its treatments, in particular corticosteroids. Screening for nutritional deficiencies in chronic disease patients is warranted. Managing the deficiencies involves simple nutritional guidelines, vitamin supplements, and nutritional support in the worst cases, in particular in children in order to limit the impact of IBD on growth. In active CD, enteral nutrition is the first line therapy in children and should be used as sole therapy in adults mainly when treatment with corticosteroids is not feasible.
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Affiliation(s)
- X Hébuterne
- Centre Hospitalier Universitaire de Nice, Pôle Digestif, Service de Gastro-entérologie et Nutrition Clinique, Hôpital de l'Archet 2, CHU de Nice, 06202 Nice cedex 03, France.
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Ezzat Y, Hamdy K. The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseases. Int J Rheum Dis 2010; 13:259-65. [PMID: 20704624 DOI: 10.1111/j.1756-185x.2010.01542.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE To detect the frequency and the predictive factors of low bone mineral density in inflammatory bowel disease (IBD) patients, so as to optimize bone mineral density (BMD) monitoring and treatment for those at risk. SUBJECTS AND METHODS Thirty Asian patients were included in this study and were divided into 18 patients with ulcerative colitis (UC), and 12 patients with Crohn's disease (CD). All patients were diagnosed by colonoscopy and histopathological biopsy and were subjected to routine laboratory investigations in addition to 25 hydroxy vitamin D levels as well as serum calcium, phosphorus and alkaline phosphatise. BMD was measured by using dual-energy X-ray absorptiometry (DEXA) scan at lumbar spine and femoral neck; predictive factors for BMD were analyzed by group comparison and step-wise regression analysis. RESULTS There was increased frequency of osteoporosis and osteopenia involving the lumbar spine in patients with IBD being more common among CD patients than in the UC group. Positive correlations were found between low BMD measurements and vitamin D levels, body mass index (BMI) (P < 0.001) as well as steroid cumulative dose and duration of therapy (P < 0.001); stepwise regression analysis showed that CD and vitamin D deficiency are predictive factors for both osteoporosis and osteopenia (P = 0.024, P = 0.027, respectively). CONCLUSION Low BMD was found to be more frequent among patients with CD than UC; in addition CD and vitamin D deficiency act as predictive factors for low BMD. We recommend that calcium and vitamin D should be given to all IBD patients; in addition, bisphosphonate administration should be put into consideration.
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Affiliation(s)
- Yasser Ezzat
- Department of Rheumatology, Al-Fayoum University, Cairo, Egypt.
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Larsen S, Bendtzen K, Nielsen OH. Extraintestinal manifestations of inflammatory bowel disease: epidemiology, diagnosis, and management. Ann Med 2010; 42:97-114. [PMID: 20166813 DOI: 10.3109/07853890903559724] [Citation(s) in RCA: 201] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Abstract Extraintestinal manifestations occur rather frequently in inflammatory bowel disease (IBD), e.g. ulcerative colitis (UC) and Crohn's disease (CD). The present paper provides an overview of the epidemiology, clinical characteristics, diagnostic process, and management of rheumatic, metabolic, dermatologic (mucocutaneous), ophthalmologic, hepatobiliary, hematologic, thromboembolic, urinary tract, pulmonary, and pancreatic extraintestinal manifestations related to IBD. Articles were identified through search of the PubMed and Embase databases, the Cochrane Library, and the web sites of the European Agency for the Evaluation of Medicinal Products (EMEA) and the US Food and Drug Administration (FDA) (cut-off date October 2009). The search terms 'Crohn's disease', 'inflammatory bowel disease', or 'ulcerative colitis' were combined with the terms 'adalimumab', 'anemia', 'arthritis', 'bronchiectasis', 'bronchitis', 'cutaneous manifestations', 'erythema nodosum', 'extraintestinal manifestations', 'hyperhomocysteinemia', 'infliximab', 'iridocyclitis', 'lung disease', 'ocular manifestations', 'osteomalacia', 'pancreatitis', 'primary sclerosing cholangitis', 'renal stones', 'sulfasalazine', 'thromboembolism', and 'treatment'. The search was performed on English-language reviews, practical guidelines, letters, and editorials. Articles were selected based on their relevance, and additional papers were retrieved from their reference lists. Since some of the diseases discussed are uncommon, valid evidence of treatment was difficult to obtain, and epidemiologic data on the rarer forms of extraintestinal manifestations are scarce. However, updates on the pathophysiology and treatment regimens are given for each of these disorders. This paper offers a current review of original research papers and randomized clinical trials, if any, within the field and makes an attempt to point out practical guidelines for the diagnosis and treatment of various extraintestinal manifestations related to IBD.
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Affiliation(s)
- Signe Larsen
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Denmark
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McLaughlin SD, Perry-Woodford ZL, Clark SK, Johnson MW, Tekkis PP, Ciclitira PJ, Nicholls RJ. Osteoporosis in patients over 50 years of age following restorative proctocolectomy for ulcerative colitis: is DXA screening warranted? Inflamm Bowel Dis 2010; 16:250-5. [PMID: 19591132 DOI: 10.1002/ibd.21041] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Ulcerative colitis (UC) and increasing age are associated with an increased risk of osteoporosis. Screening of postmenopausal women and men older than 50 years with ulcerative colitis for osteoporosis is recommended. The prevalence of osteoporosis in restorative proctocolectomy (RPC) patients more than 50 years old is not known. METHODS Fifty-three consecutive patients older than age 50 who had undergone RPC for UC underwent a bone density scan (DXA). Sex, smoking status, age at diagnosis of UC, duration of UC, age at RPC, years since RPC, age at DXA, and pouch histological inflammatory score were recorded. The Kruskal-Wallis test and Spearman's correlation coefficient were used to analyze the data. RESULTS Fifty-three patients were studied; their median age was 58 years, and the median age at RPC was 45. The prevalence of osteopenia and osteoporosis was 43.4% and 13.2%, respectively. Age at RPC was negatively correlated with bone density (P = 0.041, r = 0.281), and there was a negative correlation approaching significance with age at the time of DXA (P = 0.071, r = -0.250). No other factor studied correlated with bone density. CONCLUSIONS The prevalence of osteoporosis and osteopenia found in this study is similar to that reported for UC patients who have not undergone RPC. Patients having RPC should be screened in line with current UC guidelines, targeting those older than 50 years.
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Affiliation(s)
- Simon D McLaughlin
- Department of Biosurgery and Surgical Technology, Imperial College London, United Kingdom.
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Vosse D, Landewé R, van der Heijde D, van der Linden S, van Staa TP, Geusens P. Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study. Ann Rheum Dis 2009; 68:1839-42. [PMID: 19066179 DOI: 10.1136/ard.2008.100503] [Citation(s) in RCA: 124] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND AND AIMS Ankylosing spondylitis (AS) is associated with bone loss in the vertebrae and an increased prevalence of vertebral fractures, but literature about the magnitude of the risk of fracturing is limited. One retrospective cohort study provided evidence of an increased risk of clinical vertebral fractures but not of non-vertebral fractures. This study further explores the risk of clinical vertebral and non-vertebral fractures in a large population database. METHODS In a primary care-based nested case-control study, 231,778 patients with fracture and 231,778 age- and sex-matched controls were recruited. A history of AS was assessed from the medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for medication, other illnesses, smoking and body mass index when known. RESULTS AS was diagnosed in 758 subjects. The prevalence of AS was 0.18% in patients with fracture and 0.15% in controls. Patients with AS had an increased risk of clinical vertebral fracture (OR 3.26; 95% CI 1.51 to 7.02). The risk of fractures of the forearm and hip was not significantly increased (OR 1.21; 95% CI 0.87 to 1.69 and OR 0.77; 95% CI 0.43 to 1.37, respectively). The risk of any clinical fracture was increased in patients with AS with a history of inflammatory bowel disease (OR 2.79; 95% CI 1.10 to 7.08), whereas it was decreased in patients with AS taking non-steroidal anti-inflammatory drugs (OR 0.65; 95% CI 0.50 to 0.84). The risk was not associated with recent back pain, psoriasis, joint replacement therapy and use of sulfasalazine. CONCLUSIONS Patients with AS have an increased risk of clinical vertebral fracture but not of non-vertebral fractures, while the risk of any clinical fracture is increased in patients with concomitant inflammatory bowel disease. The mechanism by which non-steroidal anti-inflammatory drugs reduce the risk of any clinical fracture warrants further research.
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Affiliation(s)
- D Vosse
- Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands.
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Abstract
Patients with inflammatory bowel disease (IBD) often rely on their gastroenterologist for healthcare maintenance. In addition, the gastroenterologist also provides guidance to the patient's primary care physician on a broad range of issues such as vaccinations, osteoporosis screening, and cancer/dysplasia surveillance. Appropriate vaccinations should be administered to patients with IBD, particularly those likely to receive immunosuppression. Live virus vaccines are not appropriate for patients on immunosuppressive therapy, and therefore should be anticipated and given prior to initiating immunosuppression. Screening for osteoporosis is based on a combination of individual risk factors, but a history of prolonged (>3 months) steroid use over 10 mg is reason enough to obtain dual-energy x-ray absorptiometry scanning. Smoking cessation also falls within the realm of the gastroenterologist, as current smoking has a negative impact on Crohn's disease and cessation can be related to exacerbation in ulcerative colitis. Cancer screening includes not only colorectal cancer, but discussion regarding cervical dysplasia, skin cancer, and prostate cancer. Other primary care issues include hypertension and cholesterol monitoring, depression, and ocular health. A comprehensive understanding of all of the issues that can affect a patient with IBD throughout their life cycle is important, as it can impact their natural history, medication decisions, and overall outcomes.
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Affiliation(s)
- Maria Moscandrew
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
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Proinflammatory cytokines and receptor activator of nuclear factor kappaB-ligand/osteoprotegerin associated with bone deterioration in patients with Crohn's disease. Eur J Gastroenterol Hepatol 2009; 21:159-66. [PMID: 19098682 DOI: 10.1097/meg.0b013e3283200032] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES The high incidence of bone disease and the increasing evidence of Crohn's disease (CD) bone decline in corticosteroid users and nonusers suggest that bone metabolism is affected by inflammatory process. The aim of the study was to compare serum levels of proinflammatory cytokines, markers of bone turnover and regulatory molecules of osteoclast biogenesis, receptor activator of nuclear factor kappaB-ligand (RANKL) and osteoprotegerin (OPG), between naïve and long-standing CD patients. METHODS The study included 95 CD patients, 15 of them with newly diagnosed and previously untreated CD. The spine and hip bone mineral density was measured by dual-energy X-ray absorptiometry. Biochemical markers were determined by immunoassay. RESULTS Osteopenia was recorded at diagnosis in 53% of naïve patients and osteoporosis was found in 26% of long-standing CD patients. The newly diagnosed patients showed correlation between TNF-alpha and soluble RANKL (sRANKL) (r=0.5; P=0.04), and this positive relationship characterized the study population as a whole (r=0.3; P=0.003). Analysis of the OPG and sRANKL relationship showed absence of correlation in patients with healthy skeleton, whereas an inverse correlation was found in those with osteopenia (r=-0.31; P=0.033) and osteoporosis (r=-0.48; P=0.028). In naïve patients with reduced T score, the correlation between sRANKL and OPG was highly inverse (r=-0.8; P=0.02) and these patients were characterized by lower BMI, significantly higher level of proinflammatory cytokines, elevated C-reactive protein, and increased activity of free sRANKL and OPG. CONCLUSION Bone disease that accompanies CD at diagnosis suggests that bone metabolism is affected by the underlying inflammatory process per se, as probably confirmed by our finding of the central proinflammatory cytokine TNF-alpha being strongly associated with the osteoclastogenic mediator RANKL, and inversely with bone density.
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Leslie WD, Miller N, Rogala L, Bernstein CN. Body mass and composition affect bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Inflamm Bowel Dis 2009; 15:39-46. [PMID: 18623166 DOI: 10.1002/ibd.20541] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND This prospective study was undertaken to clarify the role of body mass and composition as a determinant of bone mineral density (BMD) in recently diagnosed inflammatory bowel disease (IBD). METHODS A nested subgroup of 101 adult subjects of the population-based Manitoba IBD Cohort Study were enrolled. Baseline BMD and body composition were measured and repeated 2.3 +/- 0.3 years later. RESULTS Greater weight, height, and body mass measurements were positively correlated with bone density at all sites (P < 0.01). Although both fat tissue and lean tissue showed positive relationships with BMD, lean tissue showed a much stronger correlation than fat tissue, especially for the total hip (r = 0.66, P < 0.001 versus r = 0.23, P < 0.05) and total body measurements (r = 0.59, P < 0.001 versus r = 0.04, P NS). Increase (or decrease) in hip bone density was strongly associated with an increase (or decrease) in all body mass variables (r = 0.49-0.54, P < 0.001). CONCLUSIONS Measures of body mass are important determinants of baseline BMD in recently diagnosed IBD patients. Furthermore, change in body mass is correlated with change in BMD, especially at the total hip. Early optimization and maintenance of nutrition and body weight, particularly toward lean tissue mass, may play an important role in preventing IBD-related bone disease.
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Affiliation(s)
- William D Leslie
- Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
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Pluskiewicz W, Zdrzałek J, Karasek D. Spine bone mineral density and VDR polymorphism in subjects with ulcerative colitis. J Bone Miner Metab 2009; 27:567-73. [PMID: 19365702 DOI: 10.1007/s00774-009-0072-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2008] [Accepted: 01/06/2009] [Indexed: 01/05/2023]
Abstract
This study established bone mineral density in subjects with ulcerative colitis with respect to disease dissemination and severity and the association between skeletal status and vitamin D receptor (VDR) polymorphism. Forty-seven patients aged 47.6 +/- 14.8 years and 47 age- and sex-matched control subjects were evaluated. Disease duration was 8.6 +/- 7.2 years. Twenty-four subjects demonstrated mild, 17 moderate, and 5 severe forms of ulcerative colitis; local (proctitis and proctosigmoiditis) changes were present in 26 and disseminated changes in 21. Bone mineral density (BMD, g/cm(2)) was assessed at the spine, and distribution of VDR polymorphism was established. In six patients (12.8%) and in two controls (4.25%), T-score for BMD was below -2.5, but mean values of BMD did not differ between all patients and controls. Patients with moderate and severe form of disease had lower BMD measurements than patients with a mild form of colitis ulcerosa (P < 0.05), and subjects with disseminated intestinal changes had lower BMD measurements than subjects with local changes (P < 0.001). Distribution of VDR polymorphism did not differ between patients and controls. Spine Z-score was dependent on VDR polymorphism (P < 0.05) in male and female patients but not in controls. We concluded that, in patients with ulcerative colitis (UC), spine bone mineral density decreases with progression and dissemination of the disease, and that VDR polymorphism is associated with spine bone mineral density. VDR genotype bb is significantly less likely to cause low BMD in male UC patients, and VDR genotype tt is more likely to cause low BMD in female patients.
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Affiliation(s)
- Wojciech Pluskiewicz
- Department and Clinic of Internal Diseases, Diabetology and Nephrology, Metabolic Bone Diseases Unit, Medical University of Silesia, Katowice, 3 Maja 13/15 str, 41-800, Zabrze, Poland.
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Garcia Planella E. [Inflammatory bowel disease. Should bone densitometry always be performed when corticosteroids are prescribed in a flare of inflammatory bowel disease?]. GASTROENTEROLOGIA Y HEPATOLOGIA 2008; 31:618-9. [PMID: 19091254 DOI: 10.1157/13128305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Esther Garcia Planella
- Servicio de Patología Digestiva, Hospital de la Santa Creu i Sant Pau, Barcelona, España.
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46
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Lopes LHC, Sdepanian VL, Szejnfeld VL, de Morais MB, Fagundes-Neto U. Risk factors for low bone mineral density in children and adolescents with inflammatory bowel disease. Dig Dis Sci 2008; 53:2746-53. [PMID: 18351466 DOI: 10.1007/s10620-008-0223-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2006] [Accepted: 02/19/2008] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To evaluate bone mineral density of the lumbar spine in children and adolescents with inflammatory bowel disease, and to identify the clinical risk factors associated with low bone mineral density. METHODS Bone mineral density of the lumbar spine was evaluated using dual-energy X-ray absorptiometry (DXA) in 40 patients with inflammatory bowel disease. Patients were 11.8 (SD = 4.1) years old and most of them were male (52.5%). Multiple linear regression analysis was performed to identify potential associations between bone mineral density Z-score and age, height-for-age Z-score, BMI Z-score, cumulative corticosteroid dose in milligrams and in milligrams per kilogram, disease duration, number of relapses, and calcium intake according to the dietary reference intake. RESULTS Low bone mineral density (Z-score bellow -2) was observed in 25% of patients. Patients with Crohn's disease and ulcerative colitis had equivalent prevalence of low bone mineral density. Multiple linear regression models demonstrated that height-for-age Z-score, BMI Z-score, and cumulative corticosteroid dose in mg had independent effects on BMD, respectively, beta = 0.492 (P = 0.000), beta = 0.460 (P = 0.001), beta = - 0.014 (P = 0.000), and these effects remained significant after adjustments for disease duration, respectively, beta = 0.489 (P = 0.013), beta = 0.467 (P = 0.001), and beta = - 0.005 (P = 0.015). The model accounted for 54.6% of the variability of the BMD Z-score (adjusted R2 = 0.546). CONCLUSIONS The prevalence of low bone mineral density in children and adolescents with inflammatory bowel disease is considerably high and independent risk factors associated with bone mineral density are corticosteroid cumulative dose in milligrams, height-for-age Z-score, and BMI Z-score.
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Affiliation(s)
- Letícia Helena Caldas Lopes
- Division of Pediatric Gastroenterology, Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, Brazil
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Van Schaik FDM, Verhagen MAMT, Siersema PD, Oldenburg B. High prevalence of low bone mineral density in patients with Inflammatory Bowel Disease in the setting of a peripheral Dutch hospital. J Crohns Colitis 2008; 2:208-13. [PMID: 21172212 DOI: 10.1016/j.crohns.2008.03.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2008] [Accepted: 03/18/2008] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Osteopenia and osteoporosis are frequently encountered in patients with Inflammatory Bowel Disease (IBD). Our aims were to evaluate the actual practice of screening for low bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA), to determine the prevalence of low BMD and to investigate the risk factors associated with a low BMD in the IBD population of a regional Dutch hospital. METHODS A retrospective chart review was performed in 474 patients (259 with ulcerative colitis, 210 with Crohn's disease and 5 with indeterminate colitis). DEXA results and potential predictive factors of low BMD were documented. Predictive factors of low BMD were assessed by logistic regression. RESULTS DEXA was performed in 168 IBD patients (35.4%). A low BMD (T-score<-1) was present in 64.3%. Osteoporosis (T-score<-2.5) was found in 23.8%. Low BMI, older age at the moment of diagnosis and male gender were found to be predictive factors of low BMD. For patients with osteoporosis, disease duration was an additional predictive factor. After subgroup analysis predictive factors were found to be the same in patients with Crohn's disease. CONCLUSIONS The prevalence of osteopenia and osteoporosis in IBD patients in a regional centre is as high as the prevalence rates reported from tertiary referral centres. A low BMI, an older age at the moment of diagnosis and male gender were predictive factors of low BMD. Prediction of osteoporosis and osteopenia using risk factors identified in this and previous studies is presently not feasible.
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Affiliation(s)
- Fiona D M Van Schaik
- Department of Gastroenterology, University Medical Centre Utrecht, The Netherlands
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Predicting the need for azathioprine at first presentation in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2008; 47:123-9. [PMID: 18664861 DOI: 10.1097/mpg.0b013e318156a834] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVE Although azathioprine usually is reserved for inflammatory bowel disease that proves difficult to control, routine early use has recently been advocated for children with Crohn disease. However, this practice carries with it an increased risk of adverse reactions. The objective of this study was to look for characteristics at first presentation that may identify those likely to benefit from early azathioprine. PATIENTS AND METHODS Study setting was a tertiary pediatric gastroenterology department. Retrospective cohort study of 156 children (93 Crohn disease, 47 ulcerative colitis, 16 indeterminate colitis), comparing characteristics at presentation in those who did and did not eventually require azathioprine. Azathioprine was reserved for patients with frequent relapses and steroid dependence/resistance. Twenty variables were examined, including patient and disease characteristics and initial treatment response. These were analysed using Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazard regression. RESULTS Median follow-up was 3.9 years (range 0.5-10.6 years). Azathioprine was used in 36% with Crohn disease and 40% with ulcerative colitis. Median time to commencing azathioprine was 14 months (range 3-77.5 months). Multifactorial analysis revealed an association with endoscopic colitis severity in Crohn disease (P < 0.02). However, only 50% with severe Crohn colitis actually needed azathioprine. There was an association with need for intravenous corticosteroids for induction of remission in Crohn disease (P < 0.006) and ulcerative colitis (P < 0.05). Of these patients, 75% required azathioprine. CONCLUSIONS These findings support the early use of azathioprine in children who require intravenous corticosteroids to induce initial remission. No other characteristics examined were of clinical utility in predicting need for azathioprine.
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Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Am J Gastroenterol 2008; 103:1451-9. [PMID: 18422819 DOI: 10.1111/j.1572-0241.2007.01753.x] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Bone mineral density (BMD) is usually normal at the time of inflammatory bowel disease (IBD) diagnosis. The purpose of this study was to evaluate the role of vitamin D metabolism in recently diagnosed IBD. METHODS Adult subjects with recently diagnosed IBD (median 4 yr) were recruited from the University of Manitoba IBD Research Registry into the Manitoba IBD Cohort Study. Baseline BMD and serum 25-hydroxy vitamin D (25OHD) were measured in a nested subgroup of 101 subjects of whom 94 had repeat BMD measurements 2.3 +/- 0.3 yr later. RESULTS Only a minority (22 [21.8%]) of recently diagnosed IBD participants had optimal serum 25OHD levels (75 nmol/L or greater). Serum 25OHD was positively correlated with baseline BMD for the lumbar spine, total hip, and total body (all P < 0.05). MANOVA confirmed significant between-group differences in baseline T-scores when vitamin D status was categorized according to serum 25OHD quartile (P < 0.05). Gain in total body BMD between the baseline and follow-up DXA scans was positively correlated with 25OHD (r = 0.20, P < 0.05). CONCLUSIONS Poorer vitamin D status correlates with lower baseline BMD at all measurement sites and better vitamin D status is correlated with a gain in total body BMD. Early optimization of vitamin D may play an important role in preventing IBD-related bone disease.
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Affiliation(s)
- William D Leslie
- Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008; 294:G208-16. [PMID: 17962355 DOI: 10.1152/ajpgi.00398.2007] [Citation(s) in RCA: 488] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR(+/+) mice were mostly resistant to 2.5% DSS, VDR(-/-) mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR(-/-) mice. Severe ulceration in VDR(-/-) mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR(+/+) mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR(-/-) mice after 3-day DSS treatment. Therefore, VDR(-/-) mice were much more susceptible to DSS-induced mucosal injury than VDR(+/+) mice. In cell cultures, 1,25-dihydroxy-vitamin D(3) [1,25(OH)(2)D(3)] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)(2)D(3) can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.
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Affiliation(s)
- Juan Kong
- Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
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