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Rudra S, Kennedy K, Neukrug S, Huang J, Cousminer DL, Patel A, Xu Y, Grant SFA, Baldassano RN, Albenberg L, Zemel BS, Stein R. Prevalence and predictors of low bone mineral density in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2025. [PMID: 40296588 DOI: 10.1002/jpn3.70047] [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: 05/09/2024] [Revised: 01/17/2025] [Accepted: 01/27/2025] [Indexed: 04/30/2025]
Abstract
OBJECTIVES Bone health is at risk in children with inflammatory bowel disease (IBD). This study examined the prevalence and predictors of low bone mineral density (BMD) in a cohort of children and young adults with IBD. METHODS This single-center retrospective study included patients with IBD, ages 3.5-22 years, with completed dual x-ray absorptiometry (DXA) scans from 2006 to 2019. Demographic, clinical, and laboratory data were collected. Logistic regression analysis identified predictors associated with low BMD (Z-scores ≤ -2 standard deviations [SDs]) for three outcomes. In an overlapping IBD cohort with available genetic data between 2002 and 2019 (n = 378), genetic risk for diminished bone health was calculated using published polygenic risk scores generated from genome-wide association studies based on DXA or heel ultrasound speed of sound (SOS). Linear regression analysis examined associations of low BMD and genetic risk. RESULTS Low BMD prevalence was 7% in our cohort (n = 600) based on spine bone mineral apparent density (BMAD), which best accounts for growth delays. Median (interquartile range [IQR]) spine BMAD Z-score was -0.37 SD (-1.11 to 0.35). Predictors of low BMAD included lower BMI Z-score (odds ratio [OR]: 0.67, p value: 0.02) and decreased height Z-score (OR: 0.6, p value: 0.005). Of those with longitudinal data (n = 118), low BMI (OR: 0.44, p value: <0.001) and steroid use (OR: 3.42, p value: 0.01) were associated with suboptimal bone health (Z-scores ≤ -1SD). In the cohort with genetic data, heel genomic SOS (β [standard error] = 0.17 [0.35], p ≤ 0.01) was associated with BMD. CONCLUSIONS Lower BMI should prompt DXA monitoring in pediatric IBD. Genetic predisposition may identify an at-risk subpopulation.
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Affiliation(s)
- Sharmistha Rudra
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Division of Gastroenterology, Hepatology, and Nutrition, Emory University, Atlanta, Georgia, USA
| | - Kanak Kennedy
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Sarah Neukrug
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Jing Huang
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Diana L Cousminer
- Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA
| | - Amit Patel
- Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA
| | - Yuwen Xu
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Struan F A Grant
- Division of Gastroenterology, Hepatology, and Nutrition, Emory University, Atlanta, Georgia, USA
- Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA
| | - Robert N Baldassano
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Lindsey Albenberg
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Babette S Zemel
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Ronen Stein
- Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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Sen P, Uday S. Bone Health in Paediatric Inflammatory Bowel Disease. Diagnostics (Basel) 2025; 15:580. [PMID: 40075827 PMCID: PMC11899547 DOI: 10.3390/diagnostics15050580] [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: 12/22/2024] [Revised: 02/17/2025] [Accepted: 02/22/2025] [Indexed: 03/14/2025] Open
Abstract
Paediatric inflammatory bowel disease (IBD) is often complicated by bone loss resulting in an increased risk of fractures and impaired quality of life. Underlying inflammation, nutritional deficiencies and glucocorticoid therapy are some of the factors contributing to secondary osteoporosis in IBD. Optimising nutrition, dietary supplementation and timely screening are essential in preventing bone loss. Bisphosphonate therapy remains the cornerstone of medical management of osteoporosis. This review explores the various mechanisms contributing towards poor bone health in IBD and the recent advances in diagnostic and preventive approaches along with updates in management strategies.
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Affiliation(s)
- Proteek Sen
- Department of Endocrinology and Diabetes, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham B4 6NH, UK;
| | - Suma Uday
- Department of Endocrinology and Diabetes, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham B4 6NH, UK;
- Department of Metabolism and Systems Science, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK
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Schaffler BC, Kingery MT, Habibi AA, Anil U, Lin C, Schwarzkopf R. Equivalent Survivorship of Total Hip Arthroplasty in Patients Who Have Inflammatory Bowel Disease. J Arthroplasty 2025; 40:449-454. [PMID: 39178975 DOI: 10.1016/j.arth.2024.08.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 08/11/2024] [Accepted: 08/14/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) can have orthopaedic manifestations related to decreased bone mineral density and increased fracture risk. The impact of IBD-spectrum diseases, including Crohn's disease (CD) and ulcerative colitis (UC), on the overall performance of total hip arthroplasty (THA), is not well understood. The present study sought to evaluate whether patients who have IBD were at an increased risk of THA failure compared to those who did not have IBD. METHODS The Statewide Planning and Research Cooperative System was used to compare postoperative outcomes between patients who have IBD (CD and UC) and patients who do not have IBD from 2010 to 2020. A total of 119,094 patients were included in the study, of whom 1,165 had a diagnosis of IBD. Overall, 501 of those had CD, while 664 had UC. RESULTS When controlling for comorbidities, patients who had CD had longer hospital length of stay (CD: 3.6 ± 2.5 versus UC: 3.4 ± 2.1 versus control: 3.2 ± 2.3 days, P < 0.001), higher rates of 90-day readmission (CD: 13.6 versus UC: 8.3 versus control: 7.7%, P < 0.001) and 1-year readmission (CD: 20.4 versus UC: 15.1 versus control: 12.8%, P < 0.001), and higher rates of 90-day emergency room visits (CD: 15.4 versus UC: 12 versus control: 11.1%, P = 0.007). There were no differences in all-cause revision or revision for periprosthetic joint infection between CD and UC compared with control patients. CONCLUSIONS Patients who have UC had more emergency room visits and hospital readmissions following THA; however, survival analysis demonstrated that IBD patients are not at an increased risk of revision or periprosthetic joint infection after THA.
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Affiliation(s)
- Benjamin C Schaffler
- Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York
| | - Matthew T Kingery
- Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York
| | - Akram A Habibi
- Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York
| | - Utkarsh Anil
- Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York
| | - Charles Lin
- Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York
| | - Ran Schwarzkopf
- Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, NYU Langone Health, New York, New York
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Alomari M, Chadalavada P, Afraz S, AlGhadir-AlKhalaileh M, Suarez ZK, Swartz A, Rashid M, Khazaaleh S, Cohen BL, Ur Rahman A, Alomari M. Post-hospitalization Short Versus Long Steroid Taper Strategies in Patients With Acute Severe Ulcerative Colitis: A Comparison of Clinical Outcomes. CROHN'S & COLITIS 360 2024; 6:otae025. [PMID: 38711857 PMCID: PMC11071514 DOI: 10.1093/crocol/otae025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Indexed: 05/08/2024] Open
Abstract
Background Ulcerative colitis (UC) is a chronic inflammatory colon disease characterized by relapsing flares and remission episodes. However, the optimal steroid tapering strategy in patients hospitalized for acute severe UC (ASUC) remains relatively unknown. We aim to examine the clinical outcomes in patients hospitalized for ASUC regarding variable prednisone taper regimens upon discharge. Methods We retrospectively reviewed all adult patients admitted to our facility with ASUC between 2000 and 2022. Patients were divided into 2 groups based on the duration of steroid taper on discharge (< 6 and > 6 weeks). Patients who had colectomy at index admission were excluded from the analysis. The primary outcome was rehospitalization for ASUC within 6 months of index admission. Secondary outcomes included the need for colectomy, worsening endoscopic disease extent and/or severity during the follow-up period (6 months), and a composite outcome as a surrogate of worsening disease (defined as a combination of all products above). Two-sample t-tests and Pearson's chi-square tests were used to compare the means of continuous and categorical variables, respectively. Multivariate logistic regression analysis was performed to identify independent predictors for rehospitalization with ASUC. Results A total of 215 patients (short steroid taper = 91 and long steroid taper = 124) were analyzed. A higher number of patients in the long steroid taper group had a longer disease duration since diagnosis and moderate-severe endoscopic disease activity (63.8 vs. 25.6 months, p < 0.0001, 46.8% vs. 23.1%, P = ≤ .05, respectively). Both groups had similar disease extent, prior biologic therapy, and the need for inpatient rescue therapy. At the 6-month follow-up, rates of rehospitalization with a flare of UC were comparable between the 2 groups (68.3% vs. 68.5%, P = .723). On univariate and multivariate logistic regression, escalation of steroid dose within four weeks of discharge (aOR 6.09, 95% CI: 1.82-20.3, P = .003) was noted to be the only independent predictor for rehospitalization with ASUC. Conclusions This is the first study comparing clinical outcomes between post-discharge steroid tapering regimens in hospitalized patients for ASUC. Both examined steroid taper regimens upon discharge showed comparable clinical results. Hence, we suggest a short steroid taper as a standard post-hospitalization strategy in patients following ASUC encounters. It is likely to enhance patient tolerability and reduce steroid-related adverse effects without adversely affecting outcomes.
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Affiliation(s)
- Mohammad Alomari
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Pravallika Chadalavada
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
| | - Sadaf Afraz
- Internal Medicine Department, Cleveland Clinic Florida, Weston, FL, USA
| | | | - Zoilo K Suarez
- Internal Medicine Department, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, FL, USA
| | - Alec Swartz
- Internal Medicine Department, Cleveland Clinic Florida, Weston, FL, USA
| | - Mamoon Rashid
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
| | - Shrouq Khazaaleh
- Internal Medicine Department, Cleveland Clinic Fairview Hospital, Cleveland, OH, USA
| | - Benjamin L Cohen
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Asad Ur Rahman
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL, USA
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Kherati R, Bansal A, Oleksiewicz J, Kadir A, Burgess N, Barr S, Naik S, Croft NM, Gasparetto M. The impact of age, disease severity, and BMI on bone health and growth in children and young people with Crohn's disease. JPGN REPORTS 2024; 5:17-28. [PMID: 38545265 PMCID: PMC10964338 DOI: 10.1002/jpr3.12037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 11/28/2023] [Accepted: 12/14/2023] [Indexed: 11/10/2024]
Abstract
Objectives The objective of this study was to explore the correlation between paediatric Crohn's disease (CD) characteristics, bone health and growth parameters at diagnosis and follow-up. Methods Retrospective data was collected for 47 children aged 4-16 who were newly diagnosed with CD between January 2018 and December 2019. Mean follow-up time was 2.5 years. Results Eleven (24%) children had growth delay at diagnosis, which persisted in 4 (44%) of 9 recorded children at follow-up. Of the 35 children tested, 20 (57%) had inadequate Vitamin D levels (<50 mmol/L) at diagnosis. Thirty-seven (79%) children had a dual-energy X-ray absorptiometry scan at diagnosis, with 20 of them having at least 1 low Z-score. Children with poorer bone mineral density and bone mineral concentration Z-scores for age had a younger age at diagnosis (p = .042 and p = .021), more severe disease (p = .04 and p = .029) and a lower BMI (p < .001) at diagnosis. Children diagnosed with CD ≥11 years had a lower-than-expected height velocity (p < .0001 and p < .001). Multivariate regression analysis demonstrated an older age of diagnosis was a significant predictor of a lower height velocity at follow-up. Conclusion Disease severity and age of diagnosis are important CD-related factors that influence bone health and growth. Vitamin D is an accessible component that if optimised can improve all three factors. Monitoring and optimising each aspect systematically has the potential to enable children to achieve their bone health and growth potentials.
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Affiliation(s)
- Rida Kherati
- Queen Mary University of LondonBarts and The London School of Medicine and DentistryLondonUK
| | - Archana Bansal
- Department of Paediatric Gastroenterology, Clinical Research Facility, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
| | - Julia Oleksiewicz
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
| | - Ahmed Kadir
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
| | - Natasha Burgess
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
| | - Sabrina Barr
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
| | - Sandhia Naik
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
- Queen Mary University of LondonCentre for Immunobiology, The Blizard InstituteLondonUK
| | - Nicholas M Croft
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
- Queen Mary University of LondonCentre for Immunobiology, The Blizard InstituteLondonUK
| | - Marco Gasparetto
- Department of Paediatric Gastroenterology, Barts Health NHS TrustThe Royal London Children's HospitalLondonUK
- Queen Mary University of LondonCentre for Immunobiology, The Blizard InstituteLondonUK
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Ahn MB, Yoo IH. Risk Factors of Low Bone Mineral Density in Newly Diagnosed Pediatric Inflammatory Bowel Disease. Nutrients 2023; 15:5048. [PMID: 38140307 PMCID: PMC10746078 DOI: 10.3390/nu15245048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/22/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing worldwide incidence. IBD is frequently diagnosed during childhood in the adolescent period of ongoing growth and development, and it can affect patients' linear growth, puberty, nutrition, and bone health. Therefore, its treatment and monitoring are critical to prevent secondary outcomes. However, few studies have highlighted the association between pediatric IBD and skeletal outcomes in Asian populations. We aimed to identify the prevalence and risk factors for low bone mineral density (BMD) in Korean children and adolescents with newly diagnosed IBD. Patients aged 10-18 years diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) who underwent lumbar spine bone mineral density (LSBMD) and femoral bone mineral density (FBMD) analyses via dual-energy X-ray absorptiometry at the time of IBD diagnosis were included. Low BMD was considered when the age- and sex-matched BMD Z-score was <-1.0. The LSBMD and FBMD Z-scores were correlated with clinical parameters, including general characteristics, anthropometry, and IBD-associated laboratory markers. Regression analyses were performed to identify the risk factors for low BMD. Although the general characteristics between CD (n = 42) and UC (n = 9) groups did not differ, the mean Z-scores of LSBMD and FBMD of the 51 subjects were -0.11 ± 1.24 and -0.58 ± 1.38, respectively. Furthermore, 7.8% and 18% of the study subjects had LSBMD and FBMD Z-scores < -2.0, whereas more than 50% had scores of 0--1.0. Among the clinical factors, body mass index (BMI) Z-score, duration of clinical manifestations, and serum alanine aminotransferase and selenium levels were associated with LSBMD Z-scores in the final multivariate regression analyses. Odds ratios of BMI < -2.0 standard deviation for low LSBMD and FBMD Z-scores were 31.97 and 41.45, respectively. A BMI Z-score < -0.93 was determined as the best cut-off for predicting low BMD. In newly diagnosed pediatric IBD, a substantial number of children are likely to have low BMD in prior to initial treatment while lower BMI, longer duration of clinical manifestation, and higher selenium concentration could affect initial BMD status. Routine bone health surveillance from initial IBD diagnosis throughout the treatment's completion is recommended for preventing the early development of secondary osteoporosis.
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Affiliation(s)
| | - In Hyuk Yoo
- Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea;
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Wei H, Zhao Y, Xiang L. Bone health in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2023; 17:921-935. [PMID: 37589220 DOI: 10.1080/17474124.2023.2248874] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 08/14/2023] [Indexed: 08/18/2023]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic disease characterized by the presence of systemic inflammation, manifesting not only as gastrointestinal symptoms but also as extraintestinal bone complications, including osteopenia and osteoporosis. However, the association between IBD and osteoporosis is complex, and the presence of multifactorial participants in the development of osteoporosis is increasingly recognized. Unlike in adults, delayed puberty and growth hormone/insulin-like growth factor-1 axis abnormalities are essential risk factors for osteoporosis in pediatric patients with IBD. AREAS COVERED This article reviews the potential pathophysiological mechanisms contributing to osteoporosis in adult and pediatric patients with IBD and provides evidence for effective prevention and treatment, focusing on pediatric patients with IBD. A search was performed from PubMed and Web of Science inception to February 2023 to identify articles on IBD, osteoporosis, pediatric, and fracture risk. EXPERT OPINION A comprehensive treatment pattern based on individualized principles can be used to manage pediatric IBD-related osteoporosis.
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Affiliation(s)
- Hao Wei
- Thoracic Oncology Ward, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yihan Zhao
- Department of Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Lisha Xiang
- Thoracic Oncology Ward, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Joshi M, Uday S. Vitamin D Deficiency in Chronic Childhood Disorders: Importance of Screening and Prevention. Nutrients 2023; 15:2805. [PMID: 37375708 DOI: 10.3390/nu15122805] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/09/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Vitamin D plays a vital role in regulating calcium and phosphate metabolism and maintaining bone health. A state of prolonged or profound vitamin D deficiency (VDD) can result in rickets in children and osteomalacia in children and adults. Recent studies have demonstrated the pleiotropic action of vitamin D and identified its effects on multiple biological processes in addition to bone health. VDD is more prevalent in chronic childhood conditions such as long-standing systemic illnesses affecting the renal, liver, gastrointestinal, skin, neurologic and musculoskeletal systems. VDD superimposed on the underlying disease process and treatments that can adversely affect bone turnover can all add to the disease burden in these groups of children. The current review outlines the causes and mechanisms underlying poor bone health in certain groups of children and young people with chronic diseases with an emphasis on the proactive screening and treatment of VDD.
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Affiliation(s)
- Madhura Joshi
- Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
| | - Suma Uday
- Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK
- Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston B15 2TT, UK
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Jois A, Perera S, Simm P, Alex G. Use of Dual-Energy X-ray Absorptiometry in Children with Inflammatory Bowel Disease: A Large Single Centre Study. Pediatr Gastroenterol Hepatol Nutr 2022; 25:473-480. [PMID: 36451689 PMCID: PMC9679306 DOI: 10.5223/pghn.2022.25.6.473] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 05/28/2022] [Accepted: 08/23/2022] [Indexed: 11/22/2022] Open
Abstract
PURPOSE Low bone mineral density (BMD) is a complication in children with inflammatory bowel disease (IBD). There are limited data evaluating dual-energy x-ray absorptiometry (DXA) as a screening tool for low BMD in children with IBD. We performed a single site retrospective analysis of DXA use. METHODS Children aged 5-18 years with IBD diagnosed between 2013 to 2017 at the Royal Children's Hospital, Australia, were included. Patient demographics, measures of disease activity, DXA scores, and factors related to BMD were collected. RESULTS Over a median follow up of 5.1 (4-6.4) years, 72/239 (30.1%) children underwent DXA, and 28/239 (11.7%) children had a second DXA. Our DXA practice differed to consensus guidelines regarding initial screening based on height and/or body mass index (BMI) z-score (8/17 [47.1%]), and repeat surveillance (13/42 [31.0%]). Children had a median lumbar spine (LS) z-score -0.80 (-1.65-0.075). Children with LS z-score≤-2.0 (n=14) had lower weight (6.57 [1.78-23.7] vs. 51.1 [26.5-68.7], p=0.0002) and height centiles (3.62 [1.17-17.1] vs. 42 [16.9-67.1], p=0.0001), and higher faecal calprotectin (FCP) (3041 [1182-4192] vs. 585 [139-2419], p=0.009) compared to children with LS z-score>-2.0. No fractures were reported. Of 28 children who underwent a second DXA 1.6 (1.1-2.2) years following initial DXA, no significant change in z-scores occurred. CONCLUSION Children with IBD had low BMD. In addition to height centile and weight centile, FCP was associated with lower BMD, and should be considered in DXA screening guidelines. Greater clinician awareness of DXA consensus guidelines is required. Future prospective studies are required.
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Affiliation(s)
- Asha Jois
- Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Victoria, Australia
| | - Sajini Perera
- General Medicine, Royal Children's Hospital, Victoria, Australia
| | - Peter Simm
- Department of Endocrinology, Royal Children's Hospital, Victoria, Australia
| | - George Alex
- Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Victoria, Australia
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Gordon RJ, Pappa HM, Vajapeyam S, Mulkern R, Ecklund K, Snapper SB, Gordon CM. Bone marrow adiposity in pediatric Crohn's disease. Bone 2022; 162:116453. [PMID: 35667602 DOI: 10.1016/j.bone.2022.116453] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 05/02/2022] [Accepted: 05/31/2022] [Indexed: 11/02/2022]
Abstract
Patients with Crohn's disease often have low bone mineral density and an increased risk of osteoporosis. Although decreased bone formation can be seen at diagnosis, the underlying pathophysiology of suboptimal bone accrual remains poorly understood. We sought to evaluate a novel mechanism affecting osteogenesis in patients with Crohn's disease. In this case series, we evaluated bone marrow composition at the distal femur and proximal tibia of the left knee measured via magnetic resonance (MR) spectroscopy and relaxometry in five adolescents with the diagnosis of Crohn's disease. The subjects were enrolled prospectively between 2011 and 2013 at Boston Children's Hospital. Additional clinical information, including DXA scans to evaluate bone mineral density and body composition, and Crohn's disease history, such as glucocorticoid use and disease duration, were assessed. Healthy adolescents have persistent hematopoietic marrow with only 40 to 50 % fat in the long bone metaphyses. The current participants with Crohn's disease had increased marrow adiposity, with a mean fat fraction of 67.8 %. There appeared to be a trend towards higher fat fraction with shorter disease duration, while participants with the longest disease duration had the lowest fat fraction. Participants also had decreased bone density, increased fat mass, and lower lean mass, as assessed by DXA and compared to pediatric reference data. Our MRI results demonstrate increased marrow adiposity in children with Crohn's disease, especially early in the course of the disease. DXA may better demonstrate longer-term effects on bone. Additional studies are needed to evaluate bone marrow composition in these patients and to elucidate further the inverse relationship between marrow adipocytes and osteogenesis, as well as the relationship between bone marrow adiposity and body composition.
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Affiliation(s)
- Rebecca J Gordon
- Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America.
| | - Helen M Pappa
- Division of Pediatric Gastroenterology, Cardinal Glennon Children's Hospital, Saint Louis University School of Medicine, Saint Louis, MO, United States of America
| | - Sridhar Vajapeyam
- Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Robert Mulkern
- Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Kirsten Ecklund
- Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Scott B Snapper
- Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Catherine M Gordon
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States of America
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Sigurdsson GV, Schmidt S, Mellström D, Ohlsson C, Saalman R, Lorentzon M. Young Adult Male Patients With Childhood-onset IBD Have Increased Risks of Compromised Cortical and Trabecular Bone Microstructures. Inflamm Bowel Dis 2022:6673056. [PMID: 35993421 DOI: 10.1093/ibd/izac181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Young adults with childhood-onset inflammatory bowel disease (IBD) have increased risks of low areal bone mineral density and low skeletal muscle mass. Volumetric BMD (vBMD), bone geometry and microstructures, in addition to possible associations with skeletal muscle index (SMI) and physical exercise have been scarcely studied in this patient group. PATIENTS AND METHODS In total, 49 young adult male patients with childhood-onset IBD and 245 age- and height-matched young adult male controls were scanned with high-resolution peripheral quantitative computed tomography. Bone geometry, vBMD, and bone microstructures were calculated as median values and compared between the patients and controls. Multivariable linear regression analyses were performed to determine the independent associations among IBD diagnosis, SMI (kg/m2), and physical exercise. RESULTS The group of young adult patients had, in comparison with the controls, significantly smaller median cortical area (126.1 mm2 vs151.1 mm2, P < .001), lower median total vBMD (296.7 mg/cm3 vs 336.7 mg/cm3, P < .001), and lower median cortical vBMD (854.4 mg/cm3 vs 878.5 mg/cm3, P < .001). Furthermore, the patients compared with the controls had lower median trabecular volume fraction (16.8% vs 18.2%, P < .001) and thinner median trabeculae (0.084 mm vs 0.089 mm, P < .001). The differences between the patients with IBD and controls persisted in multivariable analyses that included adjustments for SMI and physical exercise. CONCLUSIONS Young adult men with childhood-onset IBD are at increased risk of having reduced bone quality in both the cortical and trabecular bone structures compared with normative matched controls.
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Affiliation(s)
- Gudmundur Vignir Sigurdsson
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, and Queen Silvia's Children's Hospital, Gothenburg, Sweden.,Heilbrigdisstofnun Sudurlands, Selfoss, Iceland
| | | | - Dan Mellström
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
| | - Claes Ohlsson
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Region Västra Götaland, Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden
| | - Robert Saalman
- Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, and Queen Silvia's Children's Hospital, Gothenburg, Sweden
| | - Mattias Lorentzon
- Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.,Region Västra Götaland, Geriatric Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.,Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
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12
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Moran MM, Wessman P, Rolfson O, Bohl DD, Kärrholm J, Keshavarzian A, Sumner DR. The risk of revision following total hip arthroplasty in patients with inflammatory bowel disease, a registry based study. PLoS One 2021; 16:e0257310. [PMID: 34735461 PMCID: PMC8568118 DOI: 10.1371/journal.pone.0257310] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 08/30/2021] [Indexed: 11/25/2022] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract and is associated with decreased bone mineral density. IBD patients are at higher risk of osteopenia, osteoporosis and fracture compared to non-IBD patients. The impact of IBD on the performance of orthopedic implants has not been well studied. We hypothesized that a history of IBD at the time of primary total hip arthroplasty (THA) would increase the risk of subsequent failure as assessed by revision surgery. A retrospective implant survival analysis was completed using the Swedish Hip Arthroplasty Registry and the Sweden National Patient Register. A total of 150,073 patients undergoing THA for osteoarthritis within an 18-year period were included in the study. THA patients with (n = 2,604) and without (n = 147,469) a history of IBD at the time of THA were compared with primary revision as the main endpoint and adjusted using sex, age category and comorbidity (Elixhauser scores) as covariates. We found that patients with a history of IBD had a relatively higher risk of revision surgery for septic causes while the non-IBD patients had a relatively higher risk of revision for aseptic causes (p = 0.004). Our findings suggest there may be an association between gut health and THA performance.
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Affiliation(s)
- Meghan M. Moran
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America
| | - Peter Wessman
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ola Rolfson
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Daniel D. Bohl
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, United States of America
| | - Johan Kärrholm
- Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ali Keshavarzian
- Division of Digestive Diseases and Nutrition, Department of Internal Medicine, Rush Medical College, Chicago, IL, United States of America
| | - D. Rick Sumner
- Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America
- Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, IL, United States of America
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13
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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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Abstract
PURPOSE OF THE REVIEW Patients with inflammatory bowel disease (IBD) have increased bone fragility, demonstrated by increased fracture risk, and often have low bone density and altered bone geometry, but the underlying pathophysiology remains poorly understood. RECENT FINDINGS Children and adolescents with IBD appear to have decreased bone formation, at diagnosis, which frequently improves with treatment of their underlying IBD. There is a growing body of evidence regarding how the immune system interacts with bone metabolism. There are likely multi-factorial etiologies that contribute to suboptimal bone accrual and subsequent lack of peak bone mass attainment in growing patients with IBD. There appears to be differential effects dependent upon IBD sub-type and bone compartment. Pediatric patients with IBD require recognition of several risk factors that may adversely impact their bone accrual. Future studies are necessary to further delineate the effects of IBD on pediatric bone health.
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Affiliation(s)
- Rebecca J Gordon
- Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.
| | - Catherine M Gordon
- Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA
- Division of Adolescent/Young Adult Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA
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15
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Jasielska M, Grzybowska-Chlebowczyk U. Hypocalcemia and Vitamin D Deficiency in Children with Inflammatory Bowel Diseases and Lactose Intolerance. Nutrients 2021; 13:nu13082583. [PMID: 34444743 PMCID: PMC8400662 DOI: 10.3390/nu13082583] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 12/12/2022] Open
Abstract
Background: A diet restricted in dairy products can cause calcium and vitamin D deficiency and, secondarily, lead to malnutrition and low bone mass. The aim of the study was to determine the incidence hypocalcemia and vitamin D deficiency in children with inflammatory bowel diseases and lactose intolerance (LI). Material and Methods: A total of 107 patients were enrolled to the study (mean age 14.07 ± 3.58 years; 46.7% boys): 43 with Crohn’s disease (CD), 31 with ulcerative colitis (UC), and 33 with functional abdominal pain (AP-FGID). Hydrogen breath test with lactose and laboratory tests to assess the calcium-phosphate metabolism were performed in all patients. The results of densitometry were interpreted in 37 IBD patients. Results: LI was diagnosed in 23.2% patients with CD, 22.6% with UC, and 21.2% children with AP-FGID, (p = 0.9). Moreover, 9.5% patients with CD, in 21.4% with UC, and in 51.5% with AP-FGID had optimal concentration of 25(OH)D (p = 0.0002). Hypocalcemia was diagnosed in 21% of patients with CD, 16.1% with UC patients, AP-FGID patients had normal calcium levels (p = 0.02). There was no difference in concentrations of total calcium, phosphorus, and 25(OH)D between patients on low-lactose diet and normal diet (p > 0.05). BMD Z-score ≤ −1 SD was obtained by 12 CD patients (48%), and 6 with UC (50%). Conclusion: The use of a low-lactose diet in the course of lactose intolerance in children with inflammatory bowel diseases has no effect on the incidence of calcium-phosphate disorders and reduced bone mineral density.
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16
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Costa SA, Ribeiro CCC, de Oliveira KR, Alves CMC, Thomaz EBAF, Casarin RCV, Souza SDFC. Low bone mineral density is associated with severe periodontitis at the end of the second decade of life: A population-based study. J Clin Periodontol 2021; 48:1322-1332. [PMID: 34288024 DOI: 10.1111/jcpe.13525] [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: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 11/29/2022]
Abstract
AIM To evaluate the association between low bone mineral density (BMD) and severe periodontitis at the end of the second decade of life. MATERIALS AND METHODS This population-based study analysed 2032 youngers (18-19 years old) of the RPS cohort. BMD of lumbar spine (BMD-LS) and of the whole body (BMD-WB) were assessed by dual x-ray emission densitometry. Low BMD-LS (Z-score ≤ -2) and low BMD-WB (Z-score ≤ -1.5) were correlated with severe periodontitis. The extent of periodontal disease was also evaluated as the following outcomes: proportions of teeth affected by clinical attachment loss ≥5 mm and probing depth ≥5 mm. Multivariate models by sex, education, family income, risk of alcohol dependence, smoking, plaque, bleeding index, and body mass index were estimated through logistic regression (binary outcomes) and Poisson regression (continuous outcomes). RESULTS The prevalence of severe periodontitis was 10.97%. Low BMD-LS (odds ratio [OR] = 2.08, confidence interval [CI] = 1.12-3.85, p = .01) and low BMD-WB (OR = 1.34, CI = 1.001-1.81, p = .04) were associated with severe periodontitis in the final multivariate models. Low BMD-LS and BMD-WB were also associated with a greater extent of periodontitis (p < .05). CONCLUSIONS Low BMD was found to be associated with the severity and extent of periodontitis in adolescents. Adolescents at peak bone mass age presenting low BMD are more likely to be affected by severe periodontitis.
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17
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Masip E, Donat E, Polo Miquel B, Ribes-Koninckx C. Bone mineral density in spanish children at the diagnosis of inflammatory bowel disease. Arch Osteoporos 2021; 16:96. [PMID: 34145515 DOI: 10.1007/s11657-021-00945-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 04/28/2021] [Indexed: 02/03/2023]
Abstract
UNLABELLED The association between low bone mineral density (BMD) and inflammatory bowel disease (IBD) is already known. Our study, performed in Spanish pediatric IBD patients at diagnosis onset, shows that low BMD already existed at the beginning of the disease. Low weight and height are also associated with low BMD and have to be considered as risk factors. INTRODUCTION Inflammatory bowel disease (IBD) has been reported to be associated, even at disease onset, with low bone mass. The aim of this study was to know the bone mineral density (BMD) status in the IBD pediatric population of group of Spanish children, at the time of diagnosis. MATERIAL AND METHODS Retrospective review of patients' records from pediatric IBD patients diagnosed in our unit in the last 10 years. BMD was measured at the time of diagnosis and was expressed by Z-score. RESULTS Fifty-seven patients were included. Sixty-one percent were male and 47.4% had Crohn's disease (CD). Average age was 11.18 (SD 2.24) years old. Median BMD Z-score was - 0.30 (interquartile range: - 1.10 to + 0.10). Low BMD, defined as Z-score ≤ - 2SD, was present in 5% of patients, but there was no single patient with osteoporosis. There were no differences in BMD between Ulcerative Colitis (UC) and CD. Statistical differences appeared between healthy Spanish pediatric population and our IBD cohort, these having lower BMD for the same age and gender. A linear regression analysis showed a significant association between BMD Z-score and patient´s weight and height Z-score with a p values of 0.001 and 0.048, respectively. CONCLUSIONS Suboptimal bone density is present at diagnosis in Spanish pediatric patients with IBD. There is no difference in BMD between patients with CD and UC. Lower weight and height are associated with a lower BMD; thus these data at IBD diagnosis should be considered as a risk factor for bone disease in the pediatric population.
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Affiliation(s)
- Etna Masip
- Pediatric Gastroenterology and Hepatology Unit, University Hospital La Fe, Avda. Fernando Abril Martorell 106, 46026, Valencia, Spain.
| | - Ester Donat
- Pediatric Gastroenterology and Hepatology Unit, University Hospital La Fe, Avda. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Begoña Polo Miquel
- Pediatric Gastroenterology and Hepatology Unit, University Hospital La Fe, Avda. Fernando Abril Martorell 106, 46026, Valencia, Spain
| | - Carmen Ribes-Koninckx
- Pediatric Gastroenterology and Hepatology Unit, University Hospital La Fe, Avda. Fernando Abril Martorell 106, 46026, Valencia, Spain
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18
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Wong K, Isaac DM, Wine E. Growth Delay in Inflammatory Bowel Diseases: Significance, Causes, and Management. Dig Dis Sci 2021; 66:954-964. [PMID: 33433805 DOI: 10.1007/s10620-020-06759-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/02/2020] [Indexed: 12/16/2022]
Abstract
Growth delay with height and weight impairment is a common feature of pediatric inflammatory bowel diseases (PIBD). Up to 2/3 of Crohn Disease patients have impaired weight at diagnosis, and up to 1/3 have impaired height. Ulcerative colitis usually manifests earlier with less impaired growth, though patients can be affected. Ultimately, growth delay, if not corrected, can reduce final adult height. Weight loss, reduced bone mass, and pubertal delay are also concerns associated with growth delay in newly diagnosed PIBD patients. The mechanisms for growth delay in IBD are multifactorial and include reduced nutrient intake, poor absorption, increased fecal losses, as well as direct effects from inflammation and treatment modalities. Management of growth delay requires optimal disease control. Exclusive enteral nutrition (EEN), biologic therapy, and corticosteroids are the primary induction strategies used in PIBD, and both EEN and biologics positively impact growth and bone development. Beyond adequate disease control, growth delay and pubertal delay require a multidisciplinary approach, dependent on diligent monitoring and identification, nutritional rehabilitation, and involvement of endocrinology and psychiatry services as needed. Pitfalls that clinicians may encounter when managing growth delay include refeeding syndrome, obesity (even in the setting of malnutrition), and restrictive diets. Although treatment of PIBD has improved substantially in the last several decades with the era of biologic therapies and EEN, there is still much to be learned about growth delay in PIBD in order to improve outcomes.
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Affiliation(s)
- Kerry Wong
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Edmonton Clinic Health Academy, University of Alberta, Stollery Children's Hospital, Room 4-577, 11405 87th Avenue NW, Edmonton, AB, T6G 1C9, Canada
| | - Daniela Migliarese Isaac
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Edmonton Pediatric IBD Clinic (EPIC), Edmonton Clinic Health Academy, University of Alberta, Stollery Children's Hospital, Room 4-577, 11405 87th Avenue NW, Edmonton, AB, T6G 1C9, Canada
| | - Eytan Wine
- Division of Pediatric Gastroenterology and Nutrition, Departments of Pediatrics and Physiology, Edmonton Pediatric IBD Clinic (EPIC), Edmonton Clinic Health Academy, University of Alberta, Stollery Children's Hospital, Room 4-577, 11405 87th Avenue NW, Edmonton, AB, T6G 1C9, Canada.
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Jacobson D, Liu JZ, Lindsey JC, Shiau S, Coull B, Aldrovandi G. Immune Markers and Their Association with Bone Density in Children, Adolescents, and Young Adults with Perinatally Acquired HIV. AIDS Res Hum Retroviruses 2021; 37:122-129. [PMID: 33066711 DOI: 10.1089/aid.2020.0171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
To describe distributions of immune markers in children and young adults by sex and HIV status, and within groups, investigate associations of immune markers with bone density across Tanner stage. Using data and samples from 353 participants in a cross-sectional study in youth with perinatally acquired HIV (PHIV) and matched HIV-negative controls, distributions of inflammation and activation immune markers were described by sex and HIV status. Correlations and structural equation models (SEM) were used to explore marginal and multivariable associations of the immune markers with bone density and to assess whether patterns of association varied by sex and HIV status. Immune marker distributions did not differ by sex, but there were some differences by HIV status. Correlation patterns among bone, body composition, and immune markers were similar across the sex and HIV status groups. Conclusions from SEMs were limited by small sample sizes, but there was some indication that patterns of association between bone density and certain immune markers differed in male PHIV with more advanced Tanner stage compared to the other three groups. In conclusion, distributions of bone density, body composition, and immune markers may vary by sex and HIV status, although associations among these outcomes within sex and HIV status groups appear similar. Bone density of male PHIV appears to be more negatively affected than females, regardless of female HIV status. Larger longitudinal studies across Tanner stages are needed to further explore potential biological relationships between immune markers and bone density in youth living with HIV.
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Affiliation(s)
- Denise Jacobson
- Center for Biostatistics in AIDS Research; Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
| | - Jeremiah Zhe Liu
- Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
| | - Jane C. Lindsey
- Center for Biostatistics in AIDS Research; Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
| | - Stephanie Shiau
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, USA
| | - Brent Coull
- Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
| | - Grace Aldrovandi
- Division of Infectious Diseases, Children's Hospital of Los Angeles, Los Angeles, California, USA
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20
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Skrzypczak D, Ratajczak AE, Szymczak-Tomczak A, Dobrowolska A, Eder P, Krela-Kaźmierczak I. A Vicious Cycle of Osteosarcopeniain Inflammatory Bowel Diseases-Aetiology, Clinical Implications and Therapeutic Perspectives. Nutrients 2021; 13:nu13020293. [PMID: 33498571 PMCID: PMC7909530 DOI: 10.3390/nu13020293] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/08/2021] [Accepted: 01/18/2021] [Indexed: 12/13/2022] Open
Abstract
Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.
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21
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Jin HY, Lim JS, Lee Y, Choi Y, Oh SH, Kim KM, Yoo HW, Choi JH. Growth, puberty, and bone health in children and adolescents with inflammatory bowel disease. BMC Pediatr 2021; 21:35. [PMID: 33446154 PMCID: PMC7807425 DOI: 10.1186/s12887-021-02496-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 01/07/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Endocrine complications such as impaired growth, delayed puberty, and low bone mineral density (BMD) can be associated with inflammatory bowel disease (IBD) in children and adolescents. This study was performed to investigate the frequency, characteristics, and outcomes of endocrine complications of IBD in children and adolescents. METHODS This study included 127 patients with IBD diagnosed before 18 years of age [117 with Crohn disease (CD) and 10 with ulcerative colitis (UC)]. Growth profiles, pubertal status, 25-hydroxyvitamin D3 [25(OH)D3] levels, and BMD were reviewed retrospectively. RESULTS Short stature was observed in 14 of 127 (11.0 %) with a mean height-SDS of -2.31 ± 0.72. During a 2-year follow-up period, height-SDS did not significantly improve, while weight-SDS significantly improved. Among 109 patients who were older than 13 (girls) or 14 (boys) years of age during the study period, 11 patients (10.1 %) showed delayed puberty, which was associated with low weight-SDS. Vitamin D deficiency was documented in 81.7 % (94/115) with the average 25(OH)D3 level of 14.5 ± 7.0 ng/mL. Lumbar BMD Z-score was below - 2 SDS in 25 of 119 patients (21.0 %). Height-SDS, weight-SDS, and body mass index (BMI)-SDS were lower in patients with osteoporosis than those without osteoporosis. When pediatric CD activity index scores were high (≥ 30), weight-SDS, BMI-SDS, insulin-like growth factor 1 (IGF-1)-SDS, and testosterone levels were significantly decreased. CONCLUSIONS Vitamin D deficiency and osteoporosis are common in pediatric IBD patients. As disease severity deteriorates, weight-SDS, IGF-1-SDS, and testosterone levels were decreased. Optimal pubertal development is necessary for bone health.
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Affiliation(s)
- Hye-Young Jin
- Department of Pediatrics, Center for Pediatric Cancer, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea
| | - Jae-Sang Lim
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Yena Lee
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Yunha Choi
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Seak-Hee Oh
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Kyung-Mo Kim
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Han-Wook Yoo
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea
| | - Jin-Ho Choi
- Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, 05505, Seoul, Republic of Korea.
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22
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Sylvester FA. Effects of Digestive Diseases on Bone Metabolism. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:1023-1031.e7. [DOI: 10.1016/b978-0-323-67293-1.00091-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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23
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Ricciuto A, Aardoom M, Orlanski-Meyer E, Navon D, Carman N, Aloi M, Bronsky J, Däbritz J, Dubinsky M, Hussey S, Lewindon P, Martín De Carpi J, Navas-López VM, Orsi M, Ruemmele FM, Russell RK, Veres G, Walters TD, Wilson DC, Kaiser T, de Ridder L, Turner D, Griffiths AM. Predicting Outcomes in Pediatric Crohn's Disease for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease-Ahead Program. Gastroenterology 2021; 160:403-436.e26. [PMID: 32979356 DOI: 10.1053/j.gastro.2020.07.065] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 07/09/2020] [Accepted: 07/17/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. METHODS A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. RESULTS Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. CONCLUSIONS These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.
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Affiliation(s)
- Amanda Ricciuto
- IBD Centre, SickKids Hospital, University of Toronto, Toronto, Canada
| | - Martine Aardoom
- Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Esther Orlanski-Meyer
- Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Israel
| | - Dan Navon
- Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Israel
| | - Nicholas Carman
- Children's Hospital of Eastern Ontario, IBD Centre, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada
| | - Marina Aloi
- Pediatric Gastroenterology Unit, Sapienza University of Rome, Umberto I Hospital, Rome, Italy
| | - Jiri Bronsky
- Department of Pediatrics, University Hospital Motol, Prague, Czech Republic
| | - Jan Däbritz
- University Medical Center Rostock, Department of Pediatrics, Rostock, Germany; Queen Mary University of London, The Barts and the London School of Medicine and Dentistry, Blizard Institute, Center for Immunobiology, London, United Kingdom
| | - Marla Dubinsky
- Pediatric Gastroenterology and Nutrition, Mount Sinai Kravis Children's Hospital, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine, Mount Sinai, New York
| | - Séamus Hussey
- National Children's Research Centre, Royal College of Surgeons of Ireland and University College Dublin, Dublin, Ireland
| | | | - Javier Martín De Carpi
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain
| | | | - Marina Orsi
- Pediatric Gastroenterology, Hepatology and Transplant Unit, Hospital Italiano de Buenos Aires, Argentina
| | - Frank M Ruemmele
- Université Paris Descartes, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de Gastroentérologie Pédiatrique, Institute IMAGINE Inserm U1163, Paris, France
| | - Richard K Russell
- Department of Paediatric Gastroenterology, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom
| | - Gabor Veres
- Pediatric Institute-Clinic, University of Debrecen, Hungary
| | - Thomas D Walters
- IBD Centre, SickKids Hospital, University of Toronto, Toronto, Canada
| | - David C Wilson
- Child Life and Health, University of Edinburgh, Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, Scotland, United Kingdom
| | - Thomas Kaiser
- Department of General Pediatrics, University Hospital Münster, Germany
| | - Lissy de Ridder
- Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, the Netherlands
| | - Dan Turner
- Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, the Hebrew University of Jerusalem, Israel
| | - Anne M Griffiths
- IBD Centre, SickKids Hospital, University of Toronto, Toronto, Canada.
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Sakka SD, Cheung MS. Management of primary and secondary osteoporosis in children. Ther Adv Musculoskelet Dis 2020; 12:1759720X20969262. [PMID: 33224280 PMCID: PMC7649886 DOI: 10.1177/1759720x20969262] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 10/05/2020] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis in children differs from adults in terms of definition, diagnosis, monitoring and treatment options. Primary osteoporosis comprises primarily of osteogenesis imperfecta (OI), but there are significant other causes of bone fragility in children that require treatment. Secondary osteoporosis can be a result of muscle disuse, iatrogenic causes, such as steroids, chronic inflammation, delayed or arrested puberty and thalassaemia major. Investigations involve bone biochemistry, dual-energy X-ray absorptiometry scan for bone densitometry and vertebral fracture assessment, radiographic assessment of the spine and, in some cases, quantitative computed tomography (QCT) or peripheral QCT. It is important that bone mineral density (BMD) results are adjusted based on age, gender and height, in order to reflect size corrections in children. Genetics are being used increasingly for the diagnosis and classification of various cases of primary osteoporosis. Bone turnover markers are used less frequently in children, but can be helpful in monitoring treatment and transiliac bone biopsy can assist in the diagnosis of atypical cases of osteoporosis. The management of children with osteoporosis requires a multidisciplinary team of health professionals with expertise in paediatric bone disease. The prevention and treatment of fragility fractures and improvement of the quality of life of patients are important aims of a specialised service. The drugs used most commonly in children are bisphosphonates, that, with timely treatment, can give good results in improving BMD and reshaping vertebral fractures. The data regarding their effect on reducing long bone fractures are equivocal. Denosumab is being used increasingly for various conditions with mixed results. There are more drugs trialled in adults, but these are not yet licenced for children. Increasing awareness of risk factors for paediatric osteoporosis, screening and referral to a specialist team for appropriate management can lead to early detection and treatment of asymptomatic fractures and prevention of further bone damage.
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Affiliation(s)
- Sophia D Sakka
- Department of Endocrinology and Diabetes, Evelina London Children's Hospital, 3rd Floor, Becket House, Westminster Bridge Road, SE1 7EH, London, UK
| | - Moira S Cheung
- Department of Endocrinology and Diabetes, Evelina London Children's Hospital, London, UK
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Effects of emodin on inflammatory bowel disease-related osteoporosis. Biosci Rep 2020; 40:221874. [PMID: 31934719 PMCID: PMC6992925 DOI: 10.1042/bsr20192317] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 12/10/2019] [Accepted: 01/03/2020] [Indexed: 01/01/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are related to bone loss. Emodin can influence the activity and differentiation of osteoblasts and osteoclasts. However, few studies have shown the effects of emodin on IBD-induced bone damage. The aim of the present study was to investigate the role of emodin in IBD-induced osteoporosis in an animal model. An IBD model in Sprague Dawley male rats was established by administering 2.5% dextran sulfate sodium (DSS) in the drinking water. Emodin was administered orally (30 mg/kg body weight) every other day starting in the third week for 9 weeks. Blood, colon and bone samples were obtained for biomarker assays and histological analysis. Bone biomechanical properties, microCT, metabolic biomarkers and bone histological changes were analyzed. The bone mass was significantly decreased, and the bone biomechanical properties and bone microstructure parameters of IBD rats were significantly worse than those of control rats (P<0.05). Tartrate resistant acid phosphatase staining also showed that the number of osteoclasts in bone in IBD rats were larger than that in bone in control rats. Emodin intervention abolished the changes in bone microstructure and biomechanical properties (P<0.05) induced by IBD. Osteoclast formation and serum C-terminal cross-linked peptide (CTX) and tumor necrosis factor α (TNF-α) were also inhibited by emodin (P<0.05). Emodin significantly abolished IBD-enhanced Traf6, NFATC1 and c-fos expression. Our data demonstrated that emodin suppresses IBD-induced osteoporosis by inhibiting osteoclast formation.
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de Laffolie J, Schwerd T, Simon A, Pauli M, Broekaert I, Classen M, Posovszky C, Schmidt-Choudhury A. [Crohn's Disease Exclusion Diet - an alternative to exlusive enteral nutritional therapy in children and adolescents with Crohn's disease? Statement of the GPGE working groups CEDATA and Nutrition/Nutrition Medicine]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:890-894. [PMID: 32947634 DOI: 10.1055/a-1199-6751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Epidemiological an clinical observations as well as results from animal studies indicate that nutrition can play a role in the development of inflammatory bowel disease (IBD). Exclusive enteral nutrition therapy represents an example for modulating inflammatory responses solely through diet modification. Therefore, caretakers, patients, families, doctors and nutritionists seek for more dietary options to control IBD. These options include partial enteral nutrition therapy as for example the socalled Crohn's disease exclusion diet. The following statement summarizes existing data and provides recommendations for the current management of enteral nutrition therapy in pediatric Crohn's disease.
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Affiliation(s)
- Jan de Laffolie
- Zentrum für Kinderheilkunde, Justus Liebig Universität Gießen, Germany
| | - Tobias Schwerd
- Kindergastroenterologie, Dr. von Haunersches Kinderspital, Kinderklinik und Kinderpoliklinik der Ludwig-Maximilians-Universität München, München, Germany
| | - Annette Simon
- Zentrum für Kinderheilkunde, Justus Liebig Universität Gießen, Germany
| | | | | | | | | | - Anjona Schmidt-Choudhury
- Klinik für Kinder- und Jugendmedizin der Ruhr-Universität Bochum im St. Josef-Hospital, Katholisches Klinikum Bochum, Germany
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Leach ST, Day AS, Messenger R, Walters TD, Navas-López VM, Sladek M, Brückner A, Yerushalmi B, Saeed S, Otley A, Mack D, Gavish M, Turner D, Griffiths AM, Lemberg DA. Fecal Markers of Inflammation and Disease Activity in Pediatric Crohn Disease: Results from the ImageKids Study. J Pediatr Gastroenterol Nutr 2020; 70:580-585. [PMID: 31899733 DOI: 10.1097/mpg.0000000000002615] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Noninvasive and accurate methods to monitor inflammatory bowel disease are required. As a planned ancillary study of the prospective ImageKids cohort, we aimed to assess the performance of fecal calprotectin (FC) with comparison to 3 fecal inflammatory markers; S100A12 (FA12), tumor pyruvate kinase isoenzyme type M2 (FM2PK) and fecal osteoprotegerin (FOPG) as indicators of a number of disease characteristics. METHODS The ImageKids study was a multicenter study designed to develop 2 magnetic resonance enterography-based measures for children with Crohn disease (6-18 years old). All patients underwent magnetic resonance enterography, a complete ileocolonoscopic evaluation and provided a fecal sample. Fecal samples were assay for FC, FA12, FM2PK, and FOPG by ELISA. RESULTS One-hundred fifty-six children provided 190 fecal samples. Median (interquartile range) for fecal makers were FC, 602 (181-1185) μg/g; FA12, 21 (3-109) μg/g; FM2PK, 16 (2-20) U/mL; and FOPG, 125 (125-312) μg/g. All markers correlated with simple endoscopic severity index for Crohn disease and with other constructs of disease activity, but FC had the highest overall correlations. FA12, however, predicted mucosal healing with significantly higher specificity (87% vs 70%, P = 0.004) and equivalent sensitivity (91% vs 90%) compared to FC. CONCLUSION This study has confirmed that FC is useful, and overall best, marker to monitor mucosal inflammation in inflammatory bowel disease. FA12, however, appears to be a more suitable maker for prediction of mucosal healing in children.
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Affiliation(s)
- Steven T Leach
- School of Women's and Children's Health, University of New South Wales, Sydney, Australia
| | - Andrew S Day
- Department of Paediatrics, University of Otago (Christchurch), Christchurch, New Zealand
| | - Rachel Messenger
- Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia
| | - Thomas D Walters
- Division of Gastroenterology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Victor M Navas-López
- Pediatric Gastroenterology and Nutrition Unit. Hospital Materno. IBIMA. Málaga, Spain
| | | | - Annecarin Brückner
- Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Germany
| | - Baruch Yerushalmi
- Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Shehzad Saeed
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Anthony Otley
- Division of Gastroenterology and Nutrition, Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, Canada
| | - David Mack
- Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Centre and CHEO Research Institute, Ottawa, Ontario, Canada
- Department of Pediatrics, University of Ottawa, Ottawa, Canada
| | | | - Dan Turner
- Juliet Keidan Institute of Paediatric Gastroenterology, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Anne M Griffiths
- Division of Gastroenterology, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Daniel A Lemberg
- Department of Gastroenterology, Sydney Children's Hospital Randwick, Sydney, Australia
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Levy‐Shraga Y, Shenkar A, Modan‐Moses D, Assa A, Haberman Y, Shouval D, Guz‐Mark A, Lahad A, Weiss B. Longitudinal changes in bone mineral density in children with inflammatory bowel diseases. Acta Paediatr 2020; 109:1026-1032. [PMID: 31594031 DOI: 10.1111/apa.15046] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Revised: 08/22/2019] [Accepted: 10/04/2019] [Indexed: 12/30/2022]
Abstract
AIM Children with inflammatory bowel disease (IBD) are prone to low bone mineral density (BMD). Our aim was to assess longitudinal changes in BMD in this population. METHODS A retrospective longitudinal study of children with IBD, treated at two tertiary centres in Israel, who underwent two BMD measurements by dual-energy X-ray absorptiometry (DXA). Changes in lumbar spine BMD (∆L1-4 z-scores) were examined for correlations with clinical characteristics. RESULTS The cohort included 41 patients (age at diagnosis 12.1 ± 3.5 years, 23 females).The mean interval between the scans was 3.4 ± 2.0 years. There was a trend towards improvement in L1-4 z-scores (-1.64 ± 1.02 vs -1.45 ± 0.83, P = .12). ∆L1-4 z-scores correlated positively with ∆weight-standard deviation scores (SDS), ∆height-SDS and ∆BMI-SDS, and with age at the second scan (R = .55, P < .01; R = .42, P < .01; R = .42, P = .01; R = .35, P = .02, respectively); and negatively with L1-4 z-scores at the first scan (R = -.63, P < .01). Stepwise linear regression analysis identified the first scan L1-4 z-scores and ∆weight-SDS as independent predictors of ∆L1-4 z-scores. An L1-4 z-score ≤-2 at the first DXA scan was associated with significant improvement at the second scan. CONCLUSION Improvement in BMD was more pronounced in children who gained weight or whose BMD was low at the first scan.
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Affiliation(s)
- Yael Levy‐Shraga
- Pediatric Endocrinology and Diabetes Unit The Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel‐Hashomer Israel
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
| | - Anatoly Shenkar
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
| | - Dalit Modan‐Moses
- Pediatric Endocrinology and Diabetes Unit The Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel‐Hashomer Israel
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
| | - Amit Assa
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Institute of Gastroenterology, Nutrition and Liver Disease Schneider Children's Medical Center Petah‐Tikva Israel
| | - Yael Haberman
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Division of Pediatric Gastroenterology and Nutrition Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel Hashomer Israel
| | - Dror Shouval
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Division of Pediatric Gastroenterology and Nutrition Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel Hashomer Israel
| | - Anat Guz‐Mark
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Institute of Gastroenterology, Nutrition and Liver Disease Schneider Children's Medical Center Petah‐Tikva Israel
| | - Avishay Lahad
- Division of Pediatric Gastroenterology and Nutrition Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel Hashomer Israel
| | - Batia Weiss
- The Sackler Faculty of Medicine Tel‐Aviv University Tel‐Aviv Israel
- Division of Pediatric Gastroenterology and Nutrition Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel Hashomer Israel
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Yang HR. Updates on bone health in children with gastrointestinal diseases. Ann Pediatr Endocrinol Metab 2020; 25:10-14. [PMID: 32252211 PMCID: PMC7136502 DOI: 10.6065/apem.2020.25.1.10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 09/02/2019] [Indexed: 12/26/2022] Open
Abstract
Chronic gastrointestinal diseases such as inflammatory bowel disease, malabsorption syndromes (e.g., intestinal lymphangiectasia, celiac disease, congenital chloride diarrhea, cystic fibrosis), and postsubtotal gastrectomy state or short-bowel syndrome after extensive bowel resection are related to poor bone health in pediatric patients due to increased risks of low bone mineral density, osteoporosis, and fractures. The pathophysiology of abnormal bone health in pediatric gastrointestinal diseases may present from inflammation to malabsorption. In children with chronic gastrointestinal diseases at high risk of poor bone health, routine evaluation using dual-energy X-ray absorptiometry and appropriate prevention or treatment strategies are needed.
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Affiliation(s)
- Hye Ran Yang
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea,Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea,Address for correspondence: Hye Ran Yang, MD, PhD Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, Korea Tel: +82-31-787-7285 Fax: +82-31-787-4054 E-mail:
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RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling. BIOMED RESEARCH INTERNATIONAL 2020; 2020:6910312. [PMID: 32149122 PMCID: PMC7053481 DOI: 10.1155/2020/6910312] [Citation(s) in RCA: 155] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 01/06/2020] [Indexed: 12/21/2022]
Abstract
Bones as an alive organ consist of about 70% mineral and 30% organic component. About 200 million people are suffering from osteopenia and osteoporosis around the world. There are multiple ways of protecting bone from endogenous and exogenous risk factors. Planned physical activity is another useful way for protecting bone health. It has been investigated that arranged exercise would effectively regulate bone metabolism. Until now, a number of systems have discovered how exercise could help bone health. Previous studies reported different mechanisms of the effect of exercise on bone health by modulation of bone remodeling. However, the regulation of RANKL/RANK/OPG pathway in exercise and physical performance as one of the most important remodeling systems is not considered comprehensive in previous evidence. Therefore, the aim of this review is to clarify exercise influence on bone modeling and remodeling, with a concentration on its role in regulating RANKL/RANK/OPG pathway.
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31
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Metzger CE, Narayanan SA, Elizondo JP, Carter AM, Zawieja DC, Hogan HA, Bloomfield SA. DSS-induced colitis produces inflammation-induced bone loss while irisin treatment mitigates the inflammatory state in both gut and bone. Sci Rep 2019; 9:15144. [PMID: 31641205 PMCID: PMC6805923 DOI: 10.1038/s41598-019-51550-w] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 10/02/2019] [Indexed: 02/06/2023] Open
Abstract
Chronic pediatric inflammatory bowel disease (IBD) leads to lack of bone accrual, bone loss, and increased fractures. Presently there is no cure, and many IBD treatments incur negative side effects. We previously discovered treatment with exogenous irisin resolved inflammatory changes in the colon, gut lymphatics, and bone in a mild IBD rodent model. Here we assess irisin treatment in severe IBD induced via dextran sodium sulfate (DSS). Male Sprague Dawley rats (2-mo-old) were untreated (Con) or given 2% DSS in drinking water. In week two, half of each group (Con + Ir and DSS + Ir) received injections of recombinant irisin (i.p., 2x/wk). After 4 weeks, gut inflammation was associated with declines in bone mineral density and cancellous bone volume. Furthermore, elevated osteocyte TNF-α, interleukin-6, RANKL, OPG, and sclerostin corresponded with higher osteoclast surfaces and lower bone formation rate in DSS animals as well as lower ultimate load. While irisin treatment improved colon inflammation, there were no improvements in bone density or bone mechanical properties; however, irisin elevated bone formation rate, decreased osteoclast surfaces, and reduced osteocyte pro-inflammatory factors. These data highlight the negative impact of chronic gut inflammation on bone as well as the therapeutic potential of irisin as an anti-inflammatory treatment.
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Affiliation(s)
- Corinne E Metzger
- Department of Health and Kinesiology, Texas A&M University, College Station, TX, USA.
| | - S Anand Narayanan
- Department of Medical Physiology, Texas A&M University - Health Science Center, Temple, TX, USA.
| | - Jon P Elizondo
- Departments of Mechanical/Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Anne Michal Carter
- Department of Health and Kinesiology, Texas A&M University, College Station, TX, USA
| | - David C Zawieja
- Department of Medical Physiology, Texas A&M University - Health Science Center, Temple, TX, USA
| | - Harry A Hogan
- Departments of Mechanical/Biomedical Engineering, Texas A&M University, College Station, TX, USA
| | - Susan A Bloomfield
- Department of Health and Kinesiology, Texas A&M University, College Station, TX, USA
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Kaenkumchorn T, Kesavan A. Dietary Management of Pediatric Inflammatory Bowel Disease. J Med Food 2019; 22:1092-1099. [PMID: 31329006 DOI: 10.1089/jmf.2019.0063] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a life-long relapsing and remitting condition characterized by inflammation of the intestine. While the exact pathogenesis of IBD is unclear, the current belief is that both genetic and environmental factors play a role in development of disease. Management options include nutritional, pharmacological, and surgical therapies. In particular, nutritional therapies for IBD have garnered significant interest due to their limited side effect profile, bowel-sparing nature, and naturalistic approach. This review will examine the role of diet in the pathogenesis and malnutrition in IBD, and will discuss dietary approaches to management of IBD, including exclusive enteral nutrition, specific carbohydrate diet, anti-inflammatory diet, and food supplements (specifically curcumin and long-chain n-3 polyunsaturated fatty acids). Past and recent literature on these subjects were reviewed in Medhub and Scopus databases for this review article with a focus on pediatric and high-quality publications. At this time, these approaches seem to be safe and show promise of an efficacious sole or supplemental role in the treatment of IBD, but randomized, prospective studies are lacking. Additional studies investigating these diets and food supplements are needed to provide more information on their efficacy, mechanism, applicability, and safety.
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Affiliation(s)
- Tanyaporn Kaenkumchorn
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA
| | - Anil Kesavan
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Rush University Children's Hospital, Chicago, Illinois, USA
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Ge X, Chen Z, Xu Z, Lv F, Zhang K, Yang Y. The effects of dihydroartemisinin on inflammatory bowel disease-related bone loss in a rat model. Exp Biol Med (Maywood) 2019; 243:715-724. [PMID: 29763384 DOI: 10.1177/1535370218769420] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Compounds derived from natural products have been used to treat IBDs. However, the role of natural products on IBD-induced bone loss is not completely clarified. In the present study, we observed the effects of dihydroartemisinin (DHA), an antimalaria drug, on IBD and IBD-induced bone loss in a rat model. Chronic IBD model was established in Sprague-Dawley rats by giving them 2.5% dextran sodium sulfate in drinking water. DHA was given by intraperitoneal injection. Blood, colon, and bone samples were collected for biomarker assay and histological analysis. There was an obvious increase in tumor necrotic factor (TNF) α and receptor activator of nuclear factor (NF)-kB ligand (RANKL), and decrease in procollagen type 1 N-terminal propeptide (P1NP) level in IBD groups compared with the normal control (p < 0.05). The disease activity score of IBD rats was significantly higher than the control (p < 0.01). Obvious decrease in disease activity score, TNFα, and RANKL level and increase in P1NP were observed in DHA-treated IBD rats. Bone loss, shown as the decrease in bone mineral density, bone volume fraction, and trabecular number and increase in trabecular separation were observed in IBD rats compared with control (p < 0.01). DHA treatment obviously abolished the bone loss, in particular in the high-dose group (p < 0.05). DHA treatment also inhibited the excessive osteoclast formation; RANKL protein expression; and RANK, TRAF6, Fra-1, NFATc1 mRNA expression induced by IBD. Our data indicated that DHA may be a potential therapeutic agent for IBD and IBD-induced bone loss. Impact statement Bone loss is one of the important extra-intestinal manifestations in patients with inflammatory bowel diseases (IBDs). Studies have shown that compounds derived from natural products are useful in the treatment of IBDs. However, few studies have investigated the role of compounds derived from natural products in treatment of osteoporosis in IBDs. The current study aimed to show the effects of dihydroartemisinin (DHA), antimalaria drug, on bone loss in a rat model of IBD. The findings showed that DHA intervention dose dependently protected against bone loss in IBD rats by inhibiting tumor necrotic factor α production and osteoclast formation. These findings highlights that DHA may be beneficial for bone health in those patients with IBD.
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Affiliation(s)
- Xingtao Ge
- 1 Department of Orthopedics, Rizhao People's Hospital, Rizhao city 276800, China
| | - Zhijian Chen
- 2 Department of Nuclear Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Zhenjie Xu
- 3 Department of Clinical Laboratory, Rizhao People's Hospital, Rizhao 276800, China
| | - Fang Lv
- 4 Department of Rheumatology and Immunology, Rizhao People's Hospital, Rizhao 276800, China
| | - Kewei Zhang
- 5 Department of Nephrology, Fuyang Traditional Chinese Medicine Hospital of Hangzhou, Hangzhou 311400, China
| | - Yu Yang
- 6 Department of Geriatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
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Day AS. Exclusive Enteral Nutrition in Children With Crohn’s Disease. DIETARY INTERVENTIONS IN GASTROINTESTINAL DISEASES 2019:107-116. [DOI: 10.1016/b978-0-12-814468-8.00009-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, Veres G, Aloi M, Strisciuglio C, Braegger CP, Assa A, Romano C, Hussey S, Stanton M, Pakarinen M, de Ridder L, Katsanos K, Croft N, Navas-López V, Wilson DC, Lawrence S, Russell RK. Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67:257-291. [PMID: 30044357 DOI: 10.1097/mpg.0000000000002035] [Citation(s) in RCA: 306] [Impact Index Per Article: 43.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. CONCLUSIONS These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Frank M Ruemmele
- Université Paris Descartes, Sorbonne Paris Cité, APHP, Hôpital Necker Enfants Malades, Paris, France
| | | | - Anne M Griffiths
- The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | | | - Jiri Bronsky
- Department of Paediatrics, University Hospital Motol, Prague, Czech Republic
| | - Gabor Veres
- 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli," Napoli, Italy
| | | | - Amit Assa
- Schneider Children's Hospital, Petach Tikva, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Claudio Romano
- Pediatric Department, University of Messina, Messina, Italy
| | - Séamus Hussey
- National Children's Research Centre, Royal College of Surgeons of Ireland and University College Dublin, Dublin, Ireland
| | | | - Mikko Pakarinen
- Helsinki University Children's Hospital, Department of Pediatric Surgery, Helsinki, Finland
| | - Lissy de Ridder
- Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | | | - Nick Croft
- Barts and the London School of Medicine, Queen Mary University of London, London, UK
| | - Victor Navas-López
- Pediatric Gastroenterology and Nutrition Unit. Hospital Materno, IBIMA, Málaga, Spain
| | - David C Wilson
- Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - Sally Lawrence
- BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada
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Chouliaras G, Mantzou A, Margoni D, Tsilifis N, Pervanidou P, Panayotou I, Kanaka-Gantenbein C, Chrousos GP, Roma-Giannikou E. Body height in paediatric inflammatory bowel diseases: A structural equation model analysis. Eur J Clin Invest 2018; 48:e12969. [PMID: 29893990 DOI: 10.1111/eci.12969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 06/11/2018] [Indexed: 11/27/2022]
Abstract
BACKGROUND Linear growth restriction is a unique feature of paediatric inflammatory bowel diseases (IBD), and reduced insulin-like growth factor (IGF-1) is a major determinant of short stature. We aimed to assess factors influencing somatic height in children suffering from IBD. MATERIALS AND METHODS This was a retrospective, cross-sectional study conducted after approval by Institutional authorities. Anthropometric data, disease-related factors, biochemical and clinical indices of inflammation and endocrine parameters were recorded and considered as explanatory covariates. A structural equation model analysis was utilized. Somatic height was the outcome of interest, and possible associations of explanatory covariates directly or through the mediation effect of IGF-1 were assessed. RESULTS Systemic inflammation, as expressed by high-sensitivity intereukin-6 (IL-6), and nutritional status described by body mass index (BMI) were the pathways that significantly affected stature through the mediation effect of IGF-1. Cortisol showed a direct, positive and independent of IGF-1 association with height. CONCLUSIONS Insulin-like growth factor-1 is a key player in the process that results in impaired linear growth. Malnutrition and systemic inflammation have a restrictive action on growth by reducing circulating IGF-1. The positive relation of serum cortisol to height could correspond to suppressed pituitary-adrenal axis due to long-term use of glucocorticoids.
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Affiliation(s)
- Giorgos Chouliaras
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | - Aimilia Mantzou
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | - Daphne Margoni
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | - Nikolaos Tsilifis
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | - Panagiota Pervanidou
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | - Ioanna Panayotou
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | | | - George P Chrousos
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
| | - Eleftheria Roma-Giannikou
- First Department of Pediatrics, "Aghia Sophia" Children's Hospital, University of Athens, Athens, Greece
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Li C, Zhang J, Lv F, Ge X, Li G. Naringin protects against bone loss in steroid-treated inflammatory bowel disease in a rat model. Arch Biochem Biophys 2018; 650:22-29. [DOI: 10.1016/j.abb.2018.05.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 04/19/2018] [Accepted: 05/09/2018] [Indexed: 01/02/2023]
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Sylvester FA. Inflammatory Bowel Disease: Effects on Bone and Mechanisms. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1033:133-150. [PMID: 29101654 DOI: 10.1007/978-3-319-66653-2_7] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease (IBD) is associated with decreased bone mass and alterations in bone geometry from the time of diagnosis, before anti-inflammatory therapy is instituted. Deficits in bone mass can persist despite absence of symptoms of active IBD. The effects of IBD on the skeleton are complex. Protein-calorie malnutrition, inactivity, hypogonadism, deficits in calcium intake and vitamin D consumption and synthesis, stunted growth in children, decreased skeletal muscle mass, and inflammation all likely play a role. Preliminary studies suggest that the dysbiotic intestinal microbial flora present in IBD may also affect bone at a distance. Several mechanisms are possible. T cells activated by the gut microbiota may serve as "inflammatory shuttles" between the intestine and bone. Microbe-associated molecular patterns leaked into the circulation in IBD may activate immune responses in the bone marrow by immune cells and by osteocytes, osteoblasts, and osteoclasts that lead to decreased bone formation and increased resorption. Finally, intestinal microbial metabolites such as H2S may also affect bone cell function. Uncovering these mechanisms will enable the design of microbial cocktails to help restore bone mass in patients with IBD.
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Affiliation(s)
- Francisco A Sylvester
- Division Chief of Pediatric Gastroenterology, The University of North Carolina at Chapel Hil, 333 South Columbia Street, MacNider Hall 247, Chapel Hill, NC, 27599-7229, USA.
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Nobile S, Grand RJ, Pappa HM. Risk factors for low bone mineral density in pediatric inflammatory bowel disease: the positive role of physical activity. Eur J Gastroenterol Hepatol 2018; 30:471-476. [PMID: 29438136 DOI: 10.1097/meg.0000000000001076] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE In pediatric inflammatory bowel disease (IBD), the prevalence of low bone mineral density (BMD) and bone fractures and the relationship between these are still debated. Our aim was to report data from a cohort of pediatric patients with IBD. PATIENTS AND METHODS Cross-sectional assessment of growth and BMD [(dual-energy x-ray absorptiometry (DXA)] and retrospective chart review were performed to report the lifetime prevalence of bone fractures and clinical associations with patients' data. RESULTS We examined 216 patients with IBD, 8-25 years old (median: 14 years). Low BMD was found in 12.5% (spine) and 27% (total body). Multiple regression analysis showed that BMD was predicted by Z-scores for height and weight at DXA. History of menstrual irregularities and nasogastric tube feedings was associated with lower BMD, whereas physical activity and higher Z-score for height at DXA were associated with higher BMD.The prevalence of lifetime fractures was 11.8%. Patients with a history of fractures had lower Z-scores for spine BMD (-1.20 vs. -0.69, P=0.020) and total-body BMD (-1.30 vs. -0.75, P=0.014) compared with those without a history of fractures. Patients with spine BMD Z-score of up to -2 SD score had significantly increased prevalence of fractures compared with those with Z-score more than -2 SD score (28 vs. 10%, P=0.015). CONCLUSION This study provides further insight into risk factors for low BMD in pediatric IBD. Novel findings were the association between low BMD and fractures, and the positive relationship between BMD and physical activity.
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Affiliation(s)
- Stefano Nobile
- Department of Mother and Child Health, Salesi Children's Hospital, Ancona, Italy
| | - Richard J Grand
- Harvard Medical School, Division of Gastroenterology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| | - Helen M Pappa
- Division of Pediatric Gastroenterology and Hepatology, SSM Health Cardinal Glennon Children's Hospital, Saint Louis Unviersity, St. Louis, Missouri, USA
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Miele E, Shamir R, Aloi M, Assa A, Braegger C, Bronsky J, de Ridder L, Escher JC, Hojsak I, Kolaček S, Koletzko S, Levine A, Lionetti P, Martinelli M, Ruemmele F, Russell RK, Boneh RS, van Limbergen J, Veereman G, Staiano A. Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 66:687-708. [PMID: 29570147 DOI: 10.1097/mpg.0000000000001896] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients. METHODS A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature. RESULTS A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment; macronutrients needs; trace elements, minerals, and vitamins; nutrition as a primary therapy of pediatric IBD; probiotics and prebiotics; specific dietary restrictions; and dietary compounds and the risk of IBD. CONCLUSIONS This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.
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Affiliation(s)
- Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy
| | - Raanan Shamir
- Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Amit Assa
- Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Christian Braegger
- Division of Gastroenterology and Nutrition, University Children's Hospital Zurich, Zurich, Switzerland
| | - Jiri Bronsky
- Gastroenterology and Nutrition Unit, Department of Paediatrics, 2nd Faculty of Medicine, Charles, University and Motol University Hospital, Prague, Czech Republic
| | - Lissy de Ridder
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Johanna C Escher
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Iva Hojsak
- Department of Gastroenterology, Children Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Sanja Kolaček
- Department of Gastroenterology, Children Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Sibylle Koletzko
- Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany
| | - Arie Levine
- Wolfson Medical Center, Sackler School of Medicine, Tel-Aviv, Israel
| | - Paolo Lionetti
- Meyer Children Hospital, University of Florence, Florence, Italy
| | - Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy
| | - Frank Ruemmele
- Université Sorbonne Paris Cité, Université Paris Descartes, and Assistance publique-hôpitaux de Paris, Hôpital Necker-Enfants malades, Service de gastroentérologie pédiatrique, Paris, France
| | - Richard K Russell
- Department of Paediatric Gastroenterology, The Royal Hospital for Children, Glasgow, Scotland
| | | | - Johan van Limbergen
- Department of Pediatrics, Division of Pediatric Gastroenterology & Nutrition, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Gigi Veereman
- Department of Paediatric Gastroenterology and Nutrition, University Hospital Brussels, Free University Brussels, Brussels, Belgium
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II," Naples, Italy
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Dobie R, MacRae VE, Pass C, Milne EM, Ahmed SF, Farquharson C. Suppressor of cytokine signaling 2 ( Socs2) deletion protects bone health of mice with DSS-induced inflammatory bowel disease. Dis Model Mech 2018; 11:dmm.028456. [PMID: 29343614 PMCID: PMC5818069 DOI: 10.1242/dmm.028456] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 11/06/2017] [Indexed: 12/15/2022] Open
Abstract
Individuals with inflammatory bowel disease (IBD) often present with poor bone health. The development of targeted therapies for this bone loss requires a fuller understanding of the underlying cellular mechanisms. Although bone loss in IBD is multifactorial, the altered sensitivity and secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in IBD is understood to be a critical contributing mechanism. The expression of suppressor of cytokine signaling 2 (SOCS2), a well-established negative regulator of GH signaling, is stimulated by proinflammatory cytokines. Therefore, it is likely that SOCS2 expression represents a critical mediator through which proinflammatory cytokines inhibit GH/IGF-1 signaling and decrease bone quality in IBD. Using the dextran sodium sulfate (DSS) model of colitis, we reveal that endogenously elevated GH function in the Socs2−/− mouse protects the skeleton from osteopenia. Micro-computed tomography assessment of DSS-treated wild-type (WT) mice revealed a worsened trabecular architecture compared to control mice. Specifically, DSS-treated WT mice had significantly decreased bone volume, trabecular thickness and trabecular number, and a resulting increase in trabecular separation. In comparison, the trabecular bone of Socs2-deficient mice was partially protected from the adverse effects of DSS. The reduction in a number of parameters, including bone volume, was less, and no changes were observed in trabecular thickness or separation. This protected phenotype was unlikely to be a consequence of improved mucosal health in the DSS-treated Socs2−/− mice but rather a result of unregulated GH signaling directly on bone. These studies indicate that the absence of SOCS2 is protective against bone loss typical of IBD. This study also provides an improved understanding of the relative effects of GH/IGF-1 signaling on bone health in experimental colitis, information that is essential before these drugs are explored as bone protective agents in children and adults with IBD. Summary: Using a mouse model of inflammatory bowel disease, this article provides an improved understanding of the relative effects of GH/IGF-1 on bone health in experimental colitis.
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Affiliation(s)
- Ross Dobie
- Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK
| | - Vicky E MacRae
- Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK
| | - Chloe Pass
- Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK
| | - Elspeth M Milne
- Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK
| | - S Faisal Ahmed
- School of Medicine, University of Glasgow, Royal Hospital for Children, Govan Road, Glasgow G51 4TF, UK
| | - Colin Farquharson
- Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Roslin, Midlothian, Edinburgh EH25 9RG, UK
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Bone Mass Development from Childhood into Young Adulthood in Patients with Childhood-onset Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23:2215-2226. [PMID: 29064856 DOI: 10.1097/mib.0000000000001277] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Children who have inflammatory bowel disease (IBD) have increased risk of low bone mineral density (BMD). There is a scarcity of information on BMD development through puberty and into young adulthood in patients with childhood-onset IBD. METHODS We conducted a prospective longitudinal study of BMD in patients with childhood-onset IBD. In total, 74 children with IBD were followed into young adulthood, with a mean follow-up of 8.4 years. The BMD was assessed longitudinally using dual-energy X-ray absorptiometry of the lumbar spine, total hip and whole body, and related to anthropometric measures. RESULTS Young adult male patients with IBD had lower mean BMD Z-scores for the lumbar spine at -0.8 (±1.1 SD) and total hip at -0.5 (±0.9 SD), as compared to standard references. In young female patients, the BMD Z-scores were within the normal range at all 3 measured sites as compared to the standard references. There were no significant differences in the BMD Z-scores between patients with Crohn's disease and patients with ulcerative colitis. The female and male patients showed significantly improved mean lumbar spine BMD Z-scores during follow-up into young adulthood, indicating that bone accumulation in the lumbar spine continues beyond the expected age for achieving peak bone mass. CONCLUSIONS Male patients with childhood-onset IBD seem to have an increased risk of compromised BMD in young adulthood. Both female and male patients with IBD seem to increase their BMD beyond the age for expected peak bone mass (see Video abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B648).
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Wasserman H, O'Donnell JM, Gordon CM. Use of dual energy X-ray absorptiometry in pediatric patients. Bone 2017; 104:84-90. [PMID: 27989544 PMCID: PMC7055510 DOI: 10.1016/j.bone.2016.12.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 12/12/2016] [Accepted: 12/13/2016] [Indexed: 12/27/2022]
Abstract
Dual Energy X-ray Absorptiometry (DXA) is a vital tool for assessing bone health in patients at risk for fragility fractures. In pediatric patients, this technology is used in conjunction with clinical fracture history to diagnosis osteoporosis and monitor treatment response. Childhood and adolescence is characterized by linear growth and bone mass accrual; thus there are important differences in the interpretation of bone measurements obtained by DXA in these young patients. This review aims to explore the current indications for DXA use and interpretation of DXA in the pediatric age group using currently available reference databases. Limitations of DXA in pediatric patients, specifically in children with short stature, will be explored. We will review several pathophysiologic mechanisms that may lead to low bone density in children, discussing representative diseases and the recommendations for monitoring bone health with DXA in these conditions. Finally, we will highlight new methods by which DXA imaging can gather additional information on bone health in children and may improve our ability to predict fractures and osteoporosis.
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Affiliation(s)
- Halley Wasserman
- Department of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7012, Cincinnati, OH 45229, USA.
| | - Jennifer M O'Donnell
- Department of Adolescent and Transitional Medicine, 3244 Burnet Avenue MLC 4000, Cincinnati, OH 45229, USA.
| | - Catherine M Gordon
- Department of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7012, Cincinnati, OH 45229, USA; Department of Adolescent and Transitional Medicine, 3244 Burnet Avenue MLC 4000, Cincinnati, OH 45229, USA.
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Ward LM, Ma J, Rauch F, Benchimol EI, Hay J, Leonard MB, Matzinger MA, Shenouda N, Lentle B, Cosgrove H, Scharke M, Konji VN, Mack DR. Musculoskeletal health in newly diagnosed children with Crohn's disease. Osteoporos Int 2017; 28:3169-3177. [PMID: 28791436 DOI: 10.1007/s00198-017-4159-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 07/11/2017] [Indexed: 12/15/2022]
Abstract
UNLABELLED We evaluated the impact of Crohn's disease on muscle and bone strength, mass, density, and geometry in children with newly diagnosed CD and found profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low. INTRODUCTION Crohn's disease (CD) is an inflammatory condition of the gastrointestinal tract that can affect the musculoskeletal system. The objective of this study was to determine the prevalence of vertebral fractures and the impact of CD on muscle and bone mass, strength, density, and geometry in children with newly diagnosed CD. METHODS Seventy-three children (26 girls) aged 7.0 to 17.7 years were examined within 35 days following CD diagnosis by lateral spine radiograph for vertebral fractures and by jumping mechanography for muscle strength. Bone and muscle mass, density, and geometry were assessed by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography (pQCT). RESULTS Disease activity was moderate to severe in 66 (90%) patients. Mean height (Z-score -0.3, standard deviation (SD) 1.1, p = 0.02), weight (Z-score -0.8, SD 1.3, p < 0.01), body mass index (Z-score -1.0, SD 1.3, p < 0.01), lumbar spine areal bone mineral density (BMD; Z-score -1.1, SD 1.0, p < 0.01), total body bone mineral content (Z-score -1.5, SD 1.0, p < 0.01), and total body lean mass (Z-score -2.5, SD 1.1, p < 0.01) were all low for age and gender. pQCT showed reduced trabecular volumetric BMD at the tibial metaphysis, expansion of the bone marrow cavity and thin cortices at the diaphysis, and low calf muscle cross-sectional area. Jumping mechanography demonstrated low muscle power. Only one patient had a vertebral fracture. CONCLUSIONS Children with newly diagnosed CD have profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low.
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Affiliation(s)
- L M Ward
- Pediatric Bone Health Clinical Research Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
- Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
| | - J Ma
- Pediatric Bone Health Clinical Research Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada
| | - F Rauch
- Shriners Hospital for Children, Department of Pediatrics, McGill University, Montreal, QC, Canada
| | - E I Benchimol
- Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
| | - J Hay
- Department of Health Sciences, Brock University, St. Catharines, ON, Canada
| | - M B Leonard
- Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA
| | - M A Matzinger
- Department of Medical Imaging, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, ON, Canada
| | - N Shenouda
- Department of Medical Imaging, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, ON, Canada
| | - B Lentle
- Department of Radiology, University of British Columbia, Vancouver, BC, Canada
| | - H Cosgrove
- Pediatric Bone Health Clinical Research Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - M Scharke
- Pediatric Bone Health Clinical Research Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - V N Konji
- Pediatric Bone Health Clinical Research Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
| | - D R Mack
- Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada
- Children's Hospital of Eastern Ontario Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
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Okamoto K, Nakashima T, Shinohara M, Negishi-Koga T, Komatsu N, Terashima A, Sawa S, Nitta T, Takayanagi H. Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems. Physiol Rev 2017; 97:1295-1349. [DOI: 10.1152/physrev.00036.2016] [Citation(s) in RCA: 241] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 03/29/2017] [Accepted: 04/04/2017] [Indexed: 12/13/2022] Open
Abstract
The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system.
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Affiliation(s)
- Kazuo Okamoto
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Tomoki Nakashima
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Masahiro Shinohara
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Takako Negishi-Koga
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Noriko Komatsu
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Asuka Terashima
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Shinichiro Sawa
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Takeshi Nitta
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
| | - Hiroshi Takayanagi
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan
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Affiliation(s)
- Wednesday Marie A Sevilla
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA
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Sohn J, Chang EJ, Yang HR. Vitamin D Status and Bone Mineral Density in Children with Inflammatory Bowel Disease Compared to Those with Functional Abdominal Pain. J Korean Med Sci 2017; 32:961-967. [PMID: 28480654 PMCID: PMC5426235 DOI: 10.3346/jkms.2017.32.6.961] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 02/11/2017] [Indexed: 12/11/2022] Open
Abstract
Low vitamin D has been implicated in reduced bone mineral density (BMD) in children with inflammatory bowel disease (IBD). Our study aimed to evaluate differences in serum 25-hydroxyvitamin D (25[OH]D) and total body less head (TBLH) BMD z-scores in children with Crohn's disease (CD), ulcerative colitis (UC), and those with abdominal pain-related functional gastrointestinal disorder (AP-FGID) as the control group. We also examined the correlation between serum 25(OH)D and TBLH BMD z-score, and factors that affect each of these parameters. A total of 105 children were included and divided into 3 groups: AP-FGID (n = 45), CD (n = 43), and UC (n = 17). Among the 3 study groups, TBLH BMD z-scores were found to be significantly different (0.5 ± 0.8 in CD vs. 0.1 ± 0.8 in UC vs. -0.1 ± 1.1 in FGID; P = 0.037), despite similar levels of serum 25(OH)D. Within each study group, correlation between serum 25(OH)D and TBLH BMD z-score was not observed. Factors found to affect the TBLH BMD z-score were sex (P = 0.018), age (P = 0.005) and serum hemoglobin (P = 0.041), while factors influencing serum 25(OH)D were sex (P = 0.018), CD with reference to AP-FGID (P = 0.020), and serum phosphorus (P = 0.018). Based on our results, vitamin D is a relatively small contributor to bone loss in pediatric IBD and clinicians should consider female sex, older age, and low hemoglobin as risk factors for low BMD in children with IBD.
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Affiliation(s)
- Jenny Sohn
- Melbourne Medical School, Univeristy of Melbourne, Melbourne, Australia
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eun Jae Chang
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Ran Yang
- Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
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Supplementation with 2000 IU of Cholecalciferol Is Associated with Improvement of Trabecular Bone Mineral Density and Muscle Power in Pediatric Patients with IBD. Inflamm Bowel Dis 2017; 23:514-523. [PMID: 28267045 DOI: 10.1097/mib.0000000000001047] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) are associated with altered bone health and increased risk for fractures. Vitamin D deficiency is frequently found in IBD; however, the effect of vitamin D supplementation on bone health of children with IBD is poorly understood. We aimed to observe the changes in volumetric bone density and dynamic muscle functions after vitamin D substitution in a cohort of pediatric patients with IBD. METHODS This was a prospective observational study of 55 patients (aged 5-19 years) with IBD. Bone quality was assessed using peripheral quantitative computed tomography and muscle functions by jumping mechanography at baseline and after a median of 13.8 (interquartile range, 12.0-16.0) months of daily substitution of 2000 IU of cholecalciferol. RESULTS Median serum levels of 25-hydroxyvitamin D increased from 58 nmol/L at the baseline visit to 85 nmol/L at the last follow-up visit (P < 0.001); no signs of overdose were reported. The Z-scores of trabecular bone mineral density, cortical bone cross-sectional area, and maximal muscle power improved significantly during the follow-up period (+0.5, P = 0.001, +0.3, P = 0.002 and +0.5, P = 0.002, respectively). Cholecalciferol substitution was positively associated with trabecular bone mineral density and maximal muscle power (estimates 0.26, 95% confidence interval 0.14-0.37, P < 0.0001 and 0.60, 95% confidence interval 0.32-0.85, P < 0.0001, respectively) but not with the Strength-Strain Index or maximal muscle force (Fmax). CONCLUSIONS We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.
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Metzger CE, Narayanan A, Zawieja DC, Bloomfield SA. Inflammatory Bowel Disease in a Rodent Model Alters Osteocyte Protein Levels Controlling Bone Turnover. J Bone Miner Res 2017; 32:802-813. [PMID: 27796050 DOI: 10.1002/jbmr.3027] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 10/26/2016] [Accepted: 10/28/2016] [Indexed: 12/30/2022]
Abstract
Bone loss is a common comorbidity of inflammatory bowel disease (IBD), leading to elevated fracture risk in these patients. Inflammatory factors associated with IBD cause increased bone resorption and decreased bone formation with multiple factors implicated as instigators of these alterations. In this project, we examined the influence of IBD on osteocyte proteins in male rats (2 months old) divided into two groups: induced gut inflammation via 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema, and vehicle control. We examined the prevalence of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), an anti-inflammatory cytokine, interleukin-10 (IL-10), the anabolic factor insulin-like growth factor-I (IGF-I), osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin in osteocytes in three bone compartments 4 weeks after initiation of gut inflammation. Histomorphometry of the proximal tibia and fourth lumbar vertebra revealed lower bone volume, lower bone formation rate (BFR), lower osteoid surface (OS), and higher osteoclast surface (Oc.S) with TNBS. Tibial mid-shaft periosteal BFR was also lower with TNBS. Immunohistochemical staining of the distal femur demonstrated that %TNF-α+ , %IL-6+ , %RANKL+ , and %OPG+ osteocytes were elevated in cancellous bone in TNBS animals compared to vehicle. These changes were coincident with increased bone resorption. With regression analysis, %RANKL+ osteocytes statistically predicted the increase in cancellous Oc.S (R2 = 0.565). Increased %sclerostin+ osteocytes observed in the TNBS treatment predicted declines in cancellous OS (R2 = 0.581) as well as BFR in cancellous and cortical bone (R2 = 0.674, R2 = 0.908, respectively). Contrary to our hypothesis, %IGF-I+ osteocytes increased in TNBS animals. In conclusion, the IBD model produced a systemic inflammation that altered the regulatory protein profile in osteocytes that control bone resorption and bone formation, likely contributing to IBD-induced bone loss. These data highlight a potential mechanistic role of osteocytes in inflammatory bone loss associated with IBD and systemic inflammation. © 2017 American Society for Bone and Mineral Research.
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Affiliation(s)
- Corinne E Metzger
- Department of Health and Kinesiology, Texas A&M University Health Science Center, College Station, TX, USA
| | - Anand Narayanan
- Department of Medical Physiology, College of Medicine, Texas A&M University, College Station, TX, USA
| | - David C Zawieja
- Department of Medical Physiology, College of Medicine, Texas A&M University, College Station, TX, USA
| | - Susan A Bloomfield
- Department of Health and Kinesiology, Texas A&M University Health Science Center, College Station, TX, USA.,Graduate Faculty of Nutrition, Texas A&M University, College Station, TX, USA
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Neumeyer AM, Cano Sokoloff N, McDonnell E, Macklin EA, McDougle CJ, Misra M. Bone microarchitecture in adolescent boys with autism spectrum disorder. Bone 2017; 97:139-146. [PMID: 28088646 PMCID: PMC6309443 DOI: 10.1016/j.bone.2017.01.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/07/2017] [Accepted: 01/10/2017] [Indexed: 12/29/2022]
Abstract
BACKGROUND Boys with autism spectrum disorder (ASD) have lower areal bone mineral density (aBMD) than typically developing controls (TDC). Studies of volumetric BMD (vBMD) and bone microarchitecture provide information about fracture risk beyond that provided by aBMD but are currently lacking in ASD. OBJECTIVES To assess ultradistal radius and distal tibia vBMD, bone microarchitecture and strength estimates in adolescent boys with ASD compared to TDC. DESIGN/METHODS Cross-sectional study of 34 boys (16 ASD, 18 TDC) that assessed (i) aBMD at the whole body (WB), WB less head (WBLH), hip and spine using dual X-ray absorptiometry (DXA), (ii) vBMD and bone microarchitecture at the ultradistal radius and distal tibia using high-resolution peripheral quantitative CT (HRpQCT), and (iii) bone strength estimates (stiffness and failure load) using micro-finite element analysis (FEA). We controlled for age in all groupwise comparisons of HRpQCT and FEA measures. Activity questionnaires, food records, physical exam, and fasting levels of 25(OH) vitamin D and bone markers (C-terminal collagen crosslinks and N-terminal telopeptide (CTX and NTX) for bone resorption, N-terminal propeptide of Type 1 procollagen (P1NP) for bone formation) were obtained. RESULTS ASD participants were slightly younger than TDC participants (13.6 vs. 14.2years, p=0.44). Tanner stage, height Z-scores and fasting serum bone marker levels did not differ between groups. ASD participants had higher BMI Z-scores, percent body fat, IGF-1 Z-scores, and lower lean mass and aBMD Z-scores than TDC at the WB, WBLH, and femoral neck (P<0.1). At the radius, ASD participants had lower trabecular thickness (0.063 vs. 0.070mm, p=0.004), compressive stiffness (56.7 vs. 69.7kN/mm, p=0.030) and failure load (3.0 vs. 3.7kN, p=0.031) than TDC. ASD participants also had 61% smaller cortical area (6.6 vs. 16.4mm2, p=0.051) and thickness (0.08 vs. 0.22mm, p=0.054) compared to TDC. At the tibia, ASD participants had lower compressive stiffness (183 vs. 210kN/mm, p=0.048) and failure load (9.4 vs. 10.8kN, p=0.043) and 23% smaller cortical area (60.3 vs. 81.5mm2, p=0.078) compared to TDC. A lower proportion of ASD participants were categorized as "very physically active" (20% vs. 72%, p=0.005). Differences in physical activity, calcium intake and IGF-1 responsiveness may contribute to group differences in stiffness and failure load. CONCLUSION Bone microarchitectural parameters are impaired in ASD, with reductions in bone strength estimates (stiffness and failure load) at the ultradistal radius and distal tibia. This may result from lower physical activity and calcium intake, and decreased IGF-1 responsiveness.
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Affiliation(s)
- Ann M Neumeyer
- Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States; Harvard Medical School, Boston, MA 02115, United States.
| | - Natalia Cano Sokoloff
- Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States
| | - Erin McDonnell
- Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Eric A Macklin
- Harvard Medical School, Boston, MA 02115, United States; Biostatistics Center, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Christopher J McDougle
- Lurie Center for Autism, Massachusetts General Hospital, Lexington, MA 02421, United States; Harvard Medical School, Boston, MA 02115, United States
| | - Madhusmita Misra
- Harvard Medical School, Boston, MA 02115, United States; Pediatric Endocrine and Neuroendocrine Units, Massachusetts General Hospital, Boston, MA 02114, United States
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