Accessible Unlicensed Requires Authentication Published by De Gruyter December 16, 2020

Significant improvement in bone mineral density in pediatric celiac disease: even at six months with gluten-free diet

Nelgin Gerenli ORCID logo, Fatma Dursun ORCID logo, Coşkun Çeltik ORCID logo and Heves Kırmızıbekmez ORCID logo

Abstract

Objectives

Patients with celiac disease had significantly decreased bone mineral density even in patients with no gastrointestinal symptoms. Only few bone studies are available on pediatric patients with celiac disease.

Methods

Forty-six patients underwent measurement of areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) before the initiation of gluten-free diet. Anthropometric, laboratory and DXA measurements at baseline and at sixth month of the treatment were compared.

Results

The frequency of low aBMD Z-score (≤−1 SDS) in both or any site was found to be 78.2% in this study. Of 16 patients with an aBMD Z-score of <−2 SDS five gained more than 1 SDS, and one gained more than 2 SDS. Nine of 20 patients with an aBMD Z-score of <−1 SDS completely normalized.

Conclusions

The results of the study showed that low BMD is common in children with celiac disease at the time of diagnosis and could improve in a short period of six months with a strict gluten-free diet and adequate supplementation of calcium and vitamin D.


Corresponding author: Heves Kırmızıbekmez, Department of Pediatric Endocrinology, Ümraniye Training and Research Hospital, University of Health Sciences, Adem Yavuz Cad. No: 1, İstanbul, Turkey, Phone: 0216 6507676, Fax: 0216 6327121, E-mail:

Acknowledgments

We would like to thank our dietitians Çağla Hande Ay and Elif Yıldırım for their special attention and time for our working group patients to evaluate compliance with the diet. We wish to thank native English speaker Hasan May for his help.

  1. Research funding: None declared.

  2. Author contributions: Nelgin Gerenli: Diagnosis, treatment, follow-up of patients, study design, data collection, saving the data, writing and revising the manuscript. Fatma Dursun: Follow-up of patients, data collection and revising the final manuscript. Coşkun Çeltik: Follow-up of patients, data collection and revising the final manuscript. Heves Kırmızıbekmez: Study design, evaluation of data, statistical analyses, figures, tables, writing and revising the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  4. Informed consent: Informed consent was obtained from the parents.

  5. Ethical approval: Research involving human subjects complied with ethical committee of Umraniye Training and Research Hospital.

  6. Grant of fellowship supports: None.

  7. Conflict of interest: None declared.

References

1. Saraff, V, Högler, W. Endocrınology and adolescence: osteoporosis in children: diagnosis and management. Eur J Endocrinol 2015;173:185–97. https://doi.org/10.1530/eje-14-0865.Search in Google Scholar

2. Selby, PL, Davies, M, Adams, JE, Mawer, EB. Bone loss in celiac disease is related to secondary hyperparathyroidism. J Bone Miner Res 1999;14:652–7. https://doi.org/10.1359/jbmr.1999.14.4.652.Search in Google Scholar

3. Mager, DR, Qiao, J, Turner, J. Vitamin D and K status influences bone mineral density and bone accrual in children and adolescents with celiac disease. Eur J Clin Nutr 2012;66:488–95. https://doi.org/10.1038/ejcn.2011.176.Search in Google Scholar

4. Capriles, VD, Martini, LA, Arêas, JAG. Metabolic osteopathy in celiac disease: importance of a gluten-free diet. Nutr Rev 2009;67:599–606. https://doi.org/10.1111/j.1753-4887.2009.00232.x.Search in Google Scholar

5. Krupa-Kozak, U. Pathologic bone alterations in celiac disease: etiology, epidemiology, and treatment. Nutrition 2014;30:16–24. https://doi.org/10.1016/j.nut.2013.05.027.Search in Google Scholar

6. Fiore, CE, Pennisi, P, Ferro, G, Ximenes, B, Privitelli, L, Mangiafico, RA, et al.. Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet. Horm Metab Res 2006;38:417–22. https://doi.org/10.1055/s-2006-944548.Search in Google Scholar

7. Williams, KM. Update on bone health in pediatric chronic disease. Endocrinol Metab Clin N Am 2016;45:433–41. https://doi.org/10.1016/j.ecl.2016.01.009.Search in Google Scholar

8. Gordon, CM, Leonard, MB, Zemel, BS, International Society for Clinical Densitometry. 2013 pediatric position development conference: executive summary and reflections. J Clin Densitom 2014;17:219–24. Erratum in: J Clin Densitom. 2014;17:517. https://doi.org/10.1016/j.jocd.2014.01.007.Search in Google Scholar

9. Bianchi, ML, Bardella, MT. Bone in celiac disease. Osteoporos Int 2008;19:1705–16. https://doi.org/10.1007/s00198-008-0624-0.Search in Google Scholar

10. Duerksen, D, Pinto-Sanchez, MI, Anca, A, Schnetzler, J, Case, S, Zelin, J, et al.. Management of bone health in patients with celiac disease: practical guide for clinicians. Can Fam Physician 2018;64:433–8.Search in Google Scholar

11. Bianchi, ML, Leonard, MB, Bechtold, S, Högler, W, Mughal, MZ, Schönau, E, et al.. International Society for Clinical Densitometry. Bone health in children and adolescents with chronic diseases that may affect the skeleton: the 2013 ISCD pediatric official positions. J Clin Densitom 2014;17:281–94. https://doi.org/10.1016/j.jocd.2014.01.005.Search in Google Scholar

12. Canova, C, Pitter, G, Zanier, L, Simonato, L, Michaelsson, K, Ludvigsson, JF. Risk of fractures in youths with celiac disease-a population-based study. J Pediatr 2018;198:117–20. https://doi.org/10.1016/j.jpeds.2018.02.070.Search in Google Scholar

13. Mora, S, Barera, G, Beccio, S, Proverbio, MC, Weber, G, Bianchi, C, et al.. Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients. Am J Gastroenterol 1999;94:398. https://doi.org/10.1111/j.1572-0241.1999.867_r.x.Search in Google Scholar

14. Grace-Farfaglia, P. Bones of contention: bone mineral density recovery in celiac disease--a systematic review. Nutrients 2015;7:3347–69. https://doi.org/10.3390/nu7053347.Search in Google Scholar

15. Husby, S, Koletzko, S, Korponay-Szabó, I, Kurppa, K, Mearin, ML, Ribes-Koninckx, C, et al.. European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr 2020;70:141–56. https://doi.org/10.1097/mpg.0000000000002497.Search in Google Scholar

16. Ensari, A, Marsh, MN. Diagnosing celiac disease: a critical overview. Turk J Gastroenterol 2019;30:389–97. https://doi.org/10.5152/tjg.2018.18635.Search in Google Scholar

17. Munns, CF, Shaw, N, Kiely, M, Specker, BL, Thacher, TD, Ozono, K, et al.. Global consensus recommendations on prevention and management of nutritional rickets. Horm Res Paediatr 2016;85:83–106. https://doi.org/10.1159/000443136.Search in Google Scholar

18. Goksen, D, Darcan, S, Coker, M, Kose, T. Bone mineral density of healthy Turkish children and adolescents. J Clin Densitom 2006;9:84–90. https://doi.org/10.1016/j.jocd.2005.08.001.Search in Google Scholar

19. Yang, HR. Updates on bone health in children with gastrointestinal disease. Ann Pediatr Endocrinol Metabol 2020;25:10–4. https://doi.org/10.6065/apem.2020.25.1.10.Search in Google Scholar

20. Pantaleoni, S, Luchino, M, Adriani, A, Pellicano, R, Stradella, D, Ribaldone, DG, et al.. Bone mineral density at diagnosis of celiac disease and after one year of gluten-free diet. Sci World J 2014;2014:173082. https://doi.org/10.1155/2014/173082.Search in Google Scholar

21. Usta, M, Urganci, N. Does gluten-free diet protect children with celiac disease from low bone density? Iran J Pediatr 2014;24:429–34.Search in Google Scholar

22. Tau, C, Mautalen, C, De Rosa, S, Roca, A, Valenzuela, X. Bone mineral density in children with celiac disease. Effect of a gluten-free diet. Eur J Clin Nutr 2006;60:358–63. https://doi.org/10.1038/sj.ejcn.1602323.Search in Google Scholar

23. Kavak, US, Yüce, A, Koçak, N, Demir, H, Saltik, IN, Gürakan, F, et al.. Bone mineral density in children with untreated and treated celiac disease. J Pediatr Gastroenterol Nutr 2003;37:434–6. https://doi.org/10.1097/00005176-200310000-00007.Search in Google Scholar

24. Kalayci, AG, Kansu, A, Girgin, N, Kucuk, O, Aras, G. Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood. Pediatrics 2001;108:E89. https://doi.org/10.1542/peds.108.5.e89.Search in Google Scholar

25. Scotta, MS, Salvatore, S, Salvatoni, A, De Amici, M, Ghiringhelli, D, Broggini, M, et al.. Bone mineralization and body composition in young patients with celiac disease. Am J Gastroenterol 1997;92:1331–4.Search in Google Scholar

26. Micic, D, Rao, VL, Semrad, CE. Celiac disease and its role in the development of metabolic bone disease. J Clin Densitom 2020;23:190–9. https://doi.org/10.1016/j.jocd.2019.06.005.Search in Google Scholar

27. Kontakou, M, Przemioslo, RT, Sturgess, RP, Limb, AG, Ciclitira, PJ. Expression of tumour necrosis factor-alpha, interleukin-6, and interleukin-2 mRNA in the jejunum of patients with coeliac disease. Scand J Gastroenterol 1995;30:456–63. https://doi.org/10.3109/00365529509093307.Search in Google Scholar

28. Fornari, MC, Pedreira, S, Niveloni, S, González, D, Diez, RA, Vázquez, H, et al.. Pre- and post-treatment serum levels of cytokines IL-1beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia? Am J Gastroenterol 1998;93:413–8. https://doi.org/10.1111/j.1572-0241.1998.00413.x.Search in Google Scholar

29. Taranta, A, Fortunati, D, Longo, M, Rucci, N, Iacomino, E, Aliberti, F, et al.. Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease. J Bone Miner Res 2004;19:1112–21. https://doi.org/10.1359/jbmr.040319.Search in Google Scholar

30. Trovato, CM, Albanese, CV, Leoni, S, Celletti, I, Valitutti, F, Cavallini, C, et al.. Lack of clinical predictors for low mineral density in children with celiac disease. J Pediatr Gastroenterol Nutr 2014;59:799–802. https://doi.org/10.1097/mpg.0000000000000541.Search in Google Scholar

31. Fouda, MA, Khan, AA, Sultan, MS, Rios, LP, McAssey, K, Armstrong, D. Evaluation and management of skeletal health in celiac disease: position statement. Can J Gastroenterol 2012;26:819–29. https://doi.org/10.1155/2012/823648.Search in Google Scholar

32. Drabińska, N, Jarocka-Cyrta, E, Złotkowska, D, Abramowicz, P, Krupa-Kozak, U. Daily oligofructose-enriched inulin intake impacts bone turnover markers but not the cytokine profile in pediatric patients with celiac disease on a gluten-free diet: results of a randomised, placebo-controlled pilot study. Bone 2019;122:184–92. https://doi.org/10.1016/j.bone.2019.03.001.Search in Google Scholar

33. Jansen, MA, Kiefte-de Jong, JC, Gaillard, R, Escher, JC, Hofman, A, Jaddoe, VW, et al.. Growth trajectories and bone mineral density in anti-tissue transglutaminase antibody-positive children: the generation R study. Clin Gastroenterol Hepatol 2015;13:913–20. https://doi.org/10.1016/j.cgh.2014.09.032.Search in Google Scholar

34. Williams, KM. Update on bone health in pediatric chronic disease. Endocrinol Metab Clin North Am 2016;45:433–41. https://doi.org/10.1016/j.ecl.2016.01.009.Search in Google Scholar

35. Mora, S, Barera, G, Beccio, S, Menni, L, Proverbio, MC, Bianchi, C, et al.. A prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease. J Pediatr 2001;139:516–21. https://doi.org/10.1067/mpd.2001.116298.Search in Google Scholar

36. Golden, NH, Abrams, SA, Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics 2014;134:e1229–43. https://doi.org/10.1542/peds.2014-2173.Search in Google Scholar

37. Villanueva, J, Maranda, L, Nwosu, BU. Is vitamin D deficiency a feature of pediatric celiac disease? J Pediatr Endocrinol Metab 2012;25:607–10. https://doi.org/10.1515/jpem-2012-0048.Search in Google Scholar

38. Challa, A, Moulas, A, Cholevas, V, Karastergiou, E, Lapatsanis, D, Tsianos, E. Vitamin D metabolites in patients with coeliac disease. Eur J Pediatr 1998;157:262–3.Search in Google Scholar

39. Barera, G, Beccio, S, Proverbio, MC, Mora, S. Longitudinal changes in bone metabolism and bone mineral content in children with celiac disease during consumption of a gluten-free diet. Am J Clin Nutr 2004;79:148–54. https://doi.org/10.1093/ajcn/79.1.148.Search in Google Scholar

40. Tuna Kırsaçlıoğlu, C, Kuloğlu, Z, Tanca, A, Küçük, NÖ, Aycan, Z, Öcal, G, et al.. Bone mineral density and growth in children with coeliac disease on a gluten free-diet. Turk J Med Sci 2016;46:1816–21. https://doi.org/10.3906/sag-1508-52.Search in Google Scholar

Received: 2020-05-19
Accepted: 2020-11-05
Published Online: 2020-12-16
Published in Print: 2021-03-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston