Abstract
Background
Poor bone acquisition and increased fracture risk are significant complications associated with Crohn’s disease (CD). The aim of this study was to determine the effects of 8 weeks of exclusive enteral nutrition (EEN) therapy upon markers of bone turnover in children with newly diagnosed CD.
Methods
Twenty-three children with newly diagnosed CD and 20 controls (without CD) were enrolled. Children with CD were treated with 8 weeks of EEN. Inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelets], nutritional markers (height, weight), and bone markers [C-terminal telopeptides of Type-1 collagen (CTX) and bone specific alkaline phosphatase (BAP)] were measured prior to and following therapy.
Results
At diagnosis, children with CD had elevated serum CTX (2.967 ± 0.881 ng/ml) compared to controls (2.059 ± 0.568 ng/ml; P = 0.0003). Following the period of EEN, CTX levels fell significantly (2.260 ± 0.547 ng/ml; P = 0.002), while serum BAP levels (51.24 ± 31.31 μg/L at diagnosis; control serum BAP = 66.80 ± 23.23 μg/L; P = 0.07) increased significantly (64.82 ± 30.51 μg/L; P = 0.02), with both normalizing to control levels.
Conclusions
As well as reducing inflammation, decreasing disease activity, and improving nutrition in children with newly diagnosed CD, EEN therapy also normalized serum markers of bone turnover, suggesting an improvement in bone health. Further investigations of short- and long-term effects of EEN on bone density and overall bone health are now required.
Similar content being viewed by others
References
Bernstein CN, Seeger LL, Sayre JW, Anton PA, Artinian L, Shanahan F. Decreased bone density in inflammatory bowel disease is related to corticosteroid use and not disease diagnosis. J Bone Miner Res. 1995;10:250–6.
Bjarnason I, Macpherson A, Mackintosh C, Buxton-Thomas M, Forgacs I, Moniz C. Reduced bone density in patients with inflammatory bowel disease. Gut. 1997;40:228–33.
Pigot F, Roux C, Chaussade S, Hardelin D, Pelleter O, Du Puy Montbrun T, et al. Low bone mineral density in patients with inflammatory bowel disease. Dig Dis Sci. 1992;37:1396–403.
Boot AM, Bouquet J, Krenning EP, de Muinck Keizer-Schrama SM. Bone mineral density and nutritional status in children with chronic inflammatory bowel disease. Gut. 1998;42:188–94.
Compston JE, Judd D, Crawley EO, Evans WD, Evans C, Church HA, et al. Osteoporosis in patients with inflammatory bowel disease. Gut. 1987;28:410–5.
Ghosh S, Cowen S, Hannan WJ, Ferguson A. Low bone mineral density in Crohn’s disease, but not in ulcerative colitis, at diagnosis. Gastroenterology. 1994;107:1031–9.
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirschner BS. Bone mineral density assessment in children with inflammatory bowel disease. Gastroenterology. 1998;114:902–11.
Jahnsen J, Falch JA, Aadland E, Mowinckel P. Bone mineral density is reduced in patients with Crohn’s disease but not in patients with ulcerative colitis: a population based study. Gut. 1997;40:313–9.
Cowan FJ, Warner JT, Dunstan FD, Evans WD, Gregory JW, Jenkins HR. Inflammatory bowel disease and predisposition to osteopenia. Arch Dis Child. 1997;76:325–9.
Issenman RM, Atkinson SA, Radoja C, Fraher L. Longitudinal assessment of growth, mineral metabolism, and bone mass in pediatric Crohn’s disease. J Pediatr Gastroenterol Nutr. 1993;17:401–6.
Semeao EJ, Jawad AF, Stouffer NO, Zemel BS, Piccoli DA, Stallings VA. Risk factors for low bone mineral density in children and young adults with Crohn’s disease. J Pediatr. 1999;135:593–600.
Semeao EJ, Jawad AF, Zemel BS, Neiswender KM, Piccoli DA, Stallings VA. Bone mineral density in children and young adults with Crohn’s disease. Inflamm Bowel Dis. 1999;5:161–6.
Schulte C, Goebell H, Roher HD, Schulte KM. Genetic determinants of IL-6 expression levels do not influence bone loss in inflammatory bowel disease. Dig Dis Sci. 2001;46:2521–8.
Pollak RD, Karmeli F, Eliakim R, Ackerman Z, Tabb K, Rachmilewitz D. Femoral neck osteopenia in patients with inflammatory bowel disease. Am J Gastroenterol. 1998;93:1483–90.
Silvennoinen JA, Karttunen TJ, Niemela SE, Manelius JJ, Lehtola JK. A controlled study of bone mineral density in patients with inflammatory bowel disease. Gut. 1995;37:71–6.
Bernstein CN, Blanchard JF, Leslie W, Wajda A, Yu BN. The incidence of fracture among patients with inflammatory bowel disease. A population-based cohort study. Ann Intern Med. 2000;133:795–9.
Roux C, Abitbol V, Chaussade S, Kolta S, Guillemant S, Dougados M, et al. Bone loss in patients with inflammatory bowel disease: a prospective study. Osteoporos Int. 1995;5:156–60.
Harpavat M, Greenspan SL, O’Brien C, Chang C-C, Bowen AD, Keljo DJ. Altered bone mass in children at diagnosis of Crohn disease: a pilot study. J Pediatr Gastroenterol Nutr. 2005;40:295–300.
Day AS, Whitten KE, Lemberg DA, Clarkson C, Vitug-Sales M, Jackson R, et al. Exclusive enteral feeding as primary therapy for Crohn’s disease in Australian children and adolescents: a feasible and effective approach. J Gastroenterol Hepatol. 2006;21:1609–14.
Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn’s disease in children. J Pediatr Gastroenterol Nutr. 2000;31:8–15.
Fell JM, Paintin M, Arnaud-Battandier F, Beattie RM, Hollis A, Kitching P, et al. Mucosal healing and a fall in mucosal pro-inflammatory cytokine mRNA induced by a specific oral polymeric diet in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2000;14:281–9.
Dear KLE, Compston JE, Hunter JO. Treatments for Crohn’s disease that minimise steroid doses are associated with a reduced risk of osteoporosis. Clin Nutr. 2001;20:541–6.
Day AS, Whitten KE, Sidler M, Lemberg DA. Systematic review: nutritional therapy in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2008;27:293–307.
Bannerjee K, Camacho-Hubner C, Babinska K, Dryhurst KM, Edwards R, Savage MO, et al. Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease. J Pediatr Gastroenterol Nutr. 2004;38:270–5.
Johnell O, Oden A, De Laet C, Garnero P, Delmas PD, Kanis JA. Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int. 2002;13:523–6.
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320:1240–3.
Silverberg MS, Satsangi J, Ahmad T, Arnott ID, Bernstein CN, Brant SR, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:5–36.
Schofield WN, Schofield L, James PWT. Predicting basal metabolic rate: new standards and review of previous work. Hum Nutr Clin Nutr. 1985;39C(Suppl 1):5–41.
Hyams JS, Mandel F, Ferry GD, Gryboski JD, Kibort PM, Kirschner BS, et al. Relationship of common laboratory parameters to the activity of Crohn’s disease in children. J Pediatr Gastroenterol Nutr. 1992;14:216–22.
Bartram SA, Peaston RT, Rawlings DJ, Walshaw D, Francis RM, Thompson NP. Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease. World J Gastroenterol. 2006;12:5680–6.
Dresner-Pollak R, Karmeli F, Eliakim R, Ackerman Z, Rachmilewitz D. Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease. Am J Gastroenterol. 2000;95:699–704.
Schulte C, Dignass AU, Mann K, Goebell H. Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease. Inflamm Bowel Dis. 1998;4:268–75.
Sylvester FA, Davis PM, Wyzga N, Hyams JS, Lerer T. Are activated T cells regulators of bone metabolism in children with Crohn disease? J Pediatr. 2006;148:461–6.
Sylvester FA, Wyzga N, Hyams JS, Davis PM, Lerer T, Vance K, et al. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:42–50.
Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr. 2008;153:484–90.
Franchimont N, Putzeys V, Collette J, Vermeire S, Rutgeerts P, De Vos M, et al. Rapid improvement of bone metabolism after infliximab treatment in Crohn’s disease. Aliment Pharmacol Ther. 2004;20:607–14.
Bernstein CN, Leslie WD. The pathophysiology of bone disease in gastrointestinal disease. Eur J Gastroenterol Hepatol. 2003;15:857–64.
Meister D, Bode J, Shand A, Ghosh S. Anti-inflammatory effects of enteral diet components on Crohn’s disease-affected tissues in vitro. Dig Liver Dis. 2002;34:430–8.
de Jong NSH, Leach ST, Day AS. Polymeric formula has direct anti-inflammatory effects on enterocytes in an in vitro model of intestinal inflammation. Dig Dis Sci. 2007;52:2029–36.
Heer M, Mika C, Grzella I, Heussen N, Herpertz-Dahlmann B. Bone turnover during inpatient nutritional therapy and outpatient follow-up in patients with anorexia nervosa compared with that in healthy control subjects. Am J Clin Nutr. 2004;80:774–81.
Acknowledgments
The study was funded in part by the Sydney Children’s Hospital Foundation. Osmolite was supplied by Abbott Australasia. Laboratory research was undertaken in the Westfield Research Laboratories.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Whitten, K.E., Leach, S.T., Bohane, T.D. et al. Effect of exclusive enteral nutrition on bone turnover in children with Crohn’s disease. J Gastroenterol 45, 399–405 (2010). https://doi.org/10.1007/s00535-009-0165-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-009-0165-0