Protocol of a randomised controlled trial assessing the impact of physical activity on bone health in children with inflammatory bowel disease

Jérémy Vanhelst, Stéphanie Coopman, Julien Labreuche, Claire Dupont, Valérie Bertrand, Djamal Djeddi, Dominique Turck, Delphine Ley, Jérémy Vanhelst, Stéphanie Coopman, Julien Labreuche, Claire Dupont, Valérie Bertrand, Djamal Djeddi, Dominique Turck, Delphine Ley

Abstract

Introduction: Low bone mineral density (BMD) is a frequent issue in children and adolescents with inflammatory bowel disease (IBD). Several studies in healthy populations have reported a positive impact of physical activity (PA) on bone health. Recently, an observational study in paediatric patients with IBD showed a significant positive relationship between daily PA and BMD. However, intervention studies investigating a causal relationship between PA and BMD are warranted to confirm these results. The aim of this randomised controlled trial will be to investigate the effect of a PA programme on BMD in paediatric patients with IBD.

Methods and analysis: This trial is a multicentre (four centres), randomised, controlled, blinded end-point study. Eighty children with IBD will be randomly assigned in a 1:1 ratio to receive a programme with adapted physical exercises (intervention group) or usual PA (control group) during a 9-month period. The primary outcome is the change from baseline at 9 months (the end of the study) in whole-body BMD assessed by dual-energy X-ray absorptiometry. Secondary efficacy outcomes include the changes from baseline at 9 months in: BMD assessed in the lumbar spine and trochanter; daily PA (time spent in moderate-to-vigorous PA); body composition (fat mass and fat-free mass); fatigue resistance; quality of life and activity of IBD.

Ethics and dissemination: The study was approved by the Research Ethics Committee in France (Comité de Protection des Personnes, Sud-Ouest and Outre-Mer III, Bordeaux, France, No 2018/27). All procedures will be performed according to the ethical standards of the Helsinki Declaration of 1975, as revised in 2008, and the European Union's Guidelines for Good Clinical Practice. Written informed consent will be obtained from the parents or legal guardian and from the children. Research findings will be disseminated in peer-reviewed journals and scientific meetings.

Trial registration number: NCT03774329.

Keywords: paediatric gastroenterology; paediatrics; sports medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Design of the study.

References

    1. Ghione S, Sarter H, Fumery M, et al. . Dramatic increase in incidence of ulcerative colitis and Crohn's disease (1988-2011): a population-based study of French adolescents. Am J Gastroenterol 2018;113:265–72. 10.1038/ajg.2017.228
    1. Ng SC, Shi HY, Hamidi N, et al. . Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2018;390:2769–78. 10.1016/S0140-6736(17)32448-0
    1. Wehren LE, Magaziner J. Hip fracture: risk factors and outcomes. Curr Osteoporos Rep 2003;1:78–85. 10.1007/s11914-003-0013-8
    1. Baxter-Jones ADG, Faulkner RA, Forwood MR, et al. . Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass. J Bone Miner Res 2011;26:1729–39. 10.1002/jbmr.412
    1. Ahmed SF, Horrocks IA, Patterson T, et al. . Bone mineral assessment by dual energy X-ray absorptiometry in children with inflammatory bowel disease: evaluation by age or bone area. J Pediatr Gastroenterol Nutr 2004;38:276–80. 10.1097/00005176-200403000-00008
    1. 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;30:471–6. 10.1097/MEG.0000000000001076
    1. Schmidt S, Mellström D, Norjavaara E, et al. . Longitudinal assessment of bone mineral density in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2012;55:511–8. 10.1097/MPG.0b013e31825817a0
    1. Walther F, Fusch C, Radke M, et al. . Osteoporosis in pediatric patients suffering from chronic inflammatory bowel disease with and without steroid treatment. J Pediatr Gastroenterol Nutr 2006;43:42–51. 10.1097/01.mpg.0000228105.91240.80
    1. Schüle S, Rossel J-B, Frey D, et al. . Prediction of low bone mineral density in patients with inflammatory bowel diseases. United European Gastroenterol J 2016;4:e76:669–76. 10.1177/2050640616658224
    1. Habtezion A, Silverberg MS, Parkes R, et al. . Risk factors for low bone density in Crohn's disease. Inflamm Bowel Dis 2002;87:e92.
    1. McCarthy D, Duggan P, O'Brien M, et al. . Seasonality of vitamin D status and bone turnover in patients with Crohn's disease. Aliment Pharmacol Ther 2005;21:e83:1073–83. 10.1111/j.1365-2036.2005.02446.x
    1. Hallal PC, Victora CG, Azevedo MR, et al. . Adolescent physical activity and health: a systematic review. Sports Med 2006;36:1019–30. 10.2165/00007256-200636120-00003
    1. García Cruz A, Figueroa Suárez J, Osorio Ciro J, et al. . Association between nutritional status and physical abilities in children aged 6–18 years in medellin (Colombia). Anales de Pediatría 2014;81:343–51. 10.1016/j.anpede.2013.10.017
    1. Cale L, Harris J. Exercise recommendations for young people: an update. Health Educ 2001;101:126–38. 10.1108/09654280110387899
    1. Bourdier P, Saidi O, Rochette E, et al. . Physical activity and sedentary levels in children with juvenile idiopathic arthritis and inflammatory bowel disease. A systematic review and meta-analysis. Pediatr Res 2019;86:149–56. 10.1038/s41390-019-0409-5
    1. Ploeger H, Obeid J, Nguyen T, et al. . Exercise and inflammation in pediatric Crohn's disease. Int J Sports Med 2012;33:671–9. 10.1055/s-0032-1304323
    1. Vanhelst J, Vidal F, Turck D, et al. . Physical activity is associated with improved bone health in children with inflammatory bowel disease. Clin Nutr 2019. 10.1016/j.clnu.2019.07.018. [Epub ahead of print: 26 Jul 2019].
    1. Werkstetter KJ, Ullrich J, Schatz SB, et al. . Lean body mass, physical activity and quality of life in paediatric patients with inflammatory bowel disease and in healthy controls. J Crohns Colitis 2012;6:665–73. 10.1016/j.crohns.2011.11.017
    1. Walker RG, Obeid J, Nguyen T, et al. . Sedentary time and Screen-Based sedentary behaviors of children with a chronic disease. Pediatr Exerc Sci 2015;27:219–25. 10.1123/pes.2014-0074
    1. Mählmann L, Gerber M, Furlano RI, et al. . Psychological wellbeing and physical activity in children and adolescents with inflammatory bowel disease compared to healthy controls. BMC Gastroenterol 2017;17:160. 10.1186/s12876-017-0721-7
    1. Wheeler DL, Graves JE, Miller GJ, et al. . Effects of running on the torsional strength, morphometry, and bone mass of the rat skeleton. Med Sci Sports Exerc 1995;27:520???529. 10.1249/00005768-199504000-00009
    1. Yingling VR, Davies S, Silva MJ. The effects of repetitive physiologic loading on bone turnover and mechanical properties in adult female and male rats. Calcif Tissue Int 2001;68:235–9. 10.1007/s00223-001-0007-4
    1. van der Wiel HE, Lips P, Graafmans WC, et al. . Additional weight-bearing during exercise is more important than duration of exercise for anabolic stimulus of bone: a study of running exercise in female rats. Bone 1995;16:73–80. 10.1016/8756-3282(95)80014-H
    1. Notomi T, Okimoto N, Okazaki Y, et al. . Effects of tower climbing exercise on bone mass, strength, and turnover in growing rats. J Bone Miner Res 2001;166:e74.
    1. Robling AG, Burr DB, Turner CH. Recovery periods restore mechanosensitivity to dynamically loaded bone. J Exp Biol 2001;204:3389–99.
    1. Greene DA, Naughton GA. Adaptive skeletal responses to mechanical loading during adolescence. Sports Med 2006;36:723–32. 10.2165/00007256-200636090-00001
    1. Gomez-Bruton A, Montero-Marín J, Gonzalez-Agüero A, et al. . The effect of swimming during childhood and adolescence on bone mineral density: a systematic review and meta-analysis. Sports Med 2016;365:e79.
    1. González-Agüero A, Olmedillas H, Gómez-Cabello A, et al. . Bone structure and geometric properties at the radius and tibia in adolescent endurance-trained cyclists. Clin J Sport Med 2017;27:e77:69–77. 10.1097/JSM.0000000000000299
    1. Vicente-Rodríguez G, Ortega FB, Rey-López JP, et al. . Extracurricular physical activity participation modifies the association between high TV watching and low bone mass. Bone 2009;45:925–30. 10.1016/j.bone.2009.07.084
    1. Tønnesen R, Schwarz P, Hovind PH, et al. . Physical exercise associated with improved BMD independently of sex and vitamin D levels in young adults. Eur J Appl Physiol 2016;116:1297–304. 10.1007/s00421-016-3383-1
    1. Robinson RJ, Krzywicki T, Almond L, et al. . Effect of a low-impact exercise program on bone mineral density in Crohn's disease: a randomized controlled trial. Gastroenterology 1998;115:36–41. 10.1016/S0016-5085(98)70362-2
    1. World Health Organization Guidelines for preclinical evaluation and clinical trials in osteoporosis. World Health organization, 1998. Available:
    1. Vanhelst J, Vidal F, Drumez E, et al. . Comparison and validation of accelerometer wear time and non-wear time algorithms for assessing physical activity levels in children and adolescents. BMC Med Res Methodol 2019;19:72. 10.1186/s12874-019-0712-1
    1. Fairclough SJ, Noonan R, Rowlands AV, et al. . Wear compliance and activity in children wearing Wrist- and Hip-Mounted Accelerometers. Med Sci Sports Exerc 2016;48:245–53. 10.1249/MSS.0000000000000771
    1. van Hees VT, Gorzelniak L, Dean León EC, et al. . Separating movement and gravity components in an acceleration signal and implications for the assessment of human daily physical activity. PLoS One 2013;8:e61691. 10.1371/journal.pone.0061691
    1. Otley A, Smith C, Nicholas D, et al. . The impact questionnaire: a valid measure of health-related quality of life in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2002;35:557–63. 10.1097/00005176-200210000-00018
    1. Lai J-S, Cella D, Kupst MJ, et al. . Measuring fatigue for children with cancer: development and validation of the pediatric functional assessment of chronic illness Therapy-Fatigue (pedsFACIT-F). J Pediatr Hematol Oncol 2007;29:471–9. 10.1097/MPH.0b013e318095057a
    1. AFSAA, CIQUAL, Maisons-Alfort French Food Composition Data base. REGAL 2007. Informatic Center for Quality of foods : Pictures of differents meals. Paris: INSERM, 1993: 1–63.
    1. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. 238 2nd edition Stanford: Stanford University Press, 1959: 393 10.1097/00000441-195909000-00030
    1. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51:170–9. 10.1136/adc.51.3.170
    1. Hyams JS, Ferry GD, Mandel FS, et al. . Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr 1991;12:439–47. 10.1097/00005176-199105000-00005
    1. Turner D, Otley AR, Mack D, et al. . Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Gastroenterology 2007;133:423–32. 10.1053/j.gastro.2007.05.029
    1. Hind K, Burrows M. Weight-Bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials. Bone 2007;40:14–27. 10.1016/j.bone.2006.07.006
    1. Samson F, Cagnard B, Leray E, et al. . Suivi longitudinal de la densité minérale osseuse depuis le diagnostic dans la maladie de Crohn de l’enfant. Gastroenterol Clin Biol 2010;34:554–61.
    1. Zeger SL, Liang KY. Longitudinal data analysis of continuous and discrete responses for pre–post designs. ankhya. The Indian Journal of Statistics 2000;62:134–48.
    1. Liu GF, Lu K, Mogg R, et al. . Should baseline be a covariate or dependent variable in analyses of change from baseline in clinical trials? Stat Med 2009;28:2509–30. 10.1002/sim.3639
    1. Vickers AJ. Parametric versus non-parametric statistics in the analysis of randomized trials with non-normally distributed data. BMC Med Res Methodol 2005;5:35. 10.1186/1471-2288-5-35
    1. Conover WJ, Iman RL. Analysis of covariance using the RANK transformation. Biometrics 1982;38:715–24. 10.2307/2530051
    1. VanBuuren S, Groothuis-Oudshoorn K. Multivariate imputation by Chained equations in R. J Stat Softw 2011;45.
    1. Rubin DB. Introduction, in multiple imputation for nonresponse in surveys. Hoboken 1987.

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