Bone Metabolism in Inflammatory Bowel Disease and Celiac Disease

  • Carmen ValeroEmail author
  • Mª José García
Review Paper


Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitecture deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Several gastrointestinal disorders have been associated with osteoporosis including inflammatory bowel disease and celiac disease. Different factors can explain low bone density and fractures in these patients.


Inflammatory bowel disease Celiac disease Bone mineral density Fractures Osteoporosis 


Compliance with Ethical Standards

Conflict of Interest

Carmen Valero and Mª José García declare that they have no conflicts of interest.

Informed Consent

It is a review article in human’s studies Informed consent, It is not necessary, It is a review article.


  1. 1.
    Briot K, Geusens P, Em Bultink I, Lems WF, Roux C. Inflammatory diseases and bone fragility. Osteoporos Int. 2017;28(12):3301–14.PubMedGoogle Scholar
  2. 2.
    Oh HJ, Ryu KH, Park BJ, Yoon BH. Osteoporosis and osteoporotic fractures in gastrointestinal disease. J Bone Metab. 2018;25(4):213–7.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Bernstein CN, Benchimol EI, Bitton A, Murthy SK, Nguyen GC, Lee K, et al. The impact of inflammatory bowel disease in Canada 2018: extra-intestinal diseases in IBD. J Can Assoc Gastroenterol. 2019;2(Suppl 1):S73–80.PubMedGoogle Scholar
  4. 4.
    Chedid VG, Kane SV. Bone health in patients with inflammatory bowel diseases. J Clin Densitom. 2019.Google Scholar
  5. 5.
    Gastroenterology BSo, Lewis N, Scott BB. Guidelines for osteoporosis in inflammatory bowel disease and coeliac disease: British society of Gastroenterology; 2008.Google Scholar
  6. 6.
    Farraye FA, Melmed GY, Lichtenstein GR, Kane SV. ACG clinical guideline: preventive Care in Inflammatory Bowel Disease. Am J Gastroenterol. 2017;112(2):241–58.PubMedGoogle Scholar
  7. 7.
    Harbord M, Annese V, Vavricka SR, Allez M, Barreiro-de Acosta M, Boberg KM, et al. The first European evidence-based consensus on extra-intestinal manifestations in inflammatory bowel disease. J Crohns Colitis. 2016;10(3):239–54.PubMedGoogle Scholar
  8. 8.
    Adriani A, Pantaleoni S, Luchino M, Ribaldone DG, Reggiani S, Sapone N, et al. Osteopenia and osteoporosis in patients with new diagnosis of inflammatory bowel disease. Panminerva Med. 2014;56(2):145–9.PubMedGoogle Scholar
  9. 9.
    Szafors P, Che H, Barnetche T, Morel J, Gaujoux-Viala C, Combe B, et al. Risk of fracture and low bone mineral density in adults with inflammatory bowel diseases. A systematic literature review with meta-analysis. Osteoporos Int. 2018;29(11):2389–97.PubMedGoogle Scholar
  10. 10.
    Ali T, Lam D, Bronze MS, Humphrey MB. Osteoporosis in inflammatory bowel disease. Am J Med. 2009;122(7):599–604.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Schule S, Rossel JB, Frey D, Biedermann L, Scharl M, Zeitz J, et al. Prediction of low bone mineral density in patients with inflammatory bowel diseases. United European Gastroenterol J. 2016;4(5):669–76.PubMedPubMedCentralGoogle Scholar
  12. 12.
    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(4):1031–9.PubMedGoogle Scholar
  13. 13.
    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(10):795–9.Google Scholar
  14. 14.
    Card T, West J, Hubbard R, Logan RF. Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study. Gut. 2004;53(2):251–5.PubMedPubMedCentralGoogle Scholar
  15. 15.
    van Staa TP, Cooper C, Brusse LS, Leufkens H, Javaid MK, Arden NK. Inflammatory bowel disease and the risk of fracture. Gastroenterology. 2003;125:15917.Google Scholar
  16. 16.
    Loftus EV Jr, Crowson CS, Sandborn WJ, Tremaine WJ, O'Fallon WM, Melton LJ 3rd. Long-term fracture risk in patients with Crohn's disease: a population-based study in Olmsted County, Minnesota. Gastroenterology. 2002;123(2):468–75.PubMedGoogle Scholar
  17. 17.
    Vestergaard P. Prevalence and pathogenesis of osteoporosis in patients with inflammatory bowel disease. Minerva Med. 2004;95(6):469–80.PubMedGoogle Scholar
  18. 18.
    Ludvigsson JF, Mahl M, Sachs MC, Bjork J, Michaelsson K, Ekbom A, et al. Fracture risk in patients with inflammatory bowel disease: a Nationwide population-based cohort study from 1964 to 2014. Am J Gastroenterol. 2019;114(2):291–304.PubMedGoogle Scholar
  19. 19.
    Even Dar R, Mazor Y, Karban A, Ish-Shalom S, Segal E. Risk factors for low bone density in inflammatory bowel disease: use of glucocorticoids, low body mass index, and smoking. Dig Dis. 2019;37(4):284–90.PubMedGoogle Scholar
  20. 20.
    van Hogezand RA, Hamdy NA. Skeletal morbidity in inflammatory bowel disease. Scand J Gastroenterol Suppl. 2006:59–64.Google Scholar
  21. 21.
    Gupta S, Wu X, Moore T, Shen B. Frequency, risk factors, and adverse sequelae of bone loss in patients with ostomy for inflammatory bowel diseases. Inflamm Bowel Dis. 2014;20(2):259–64.PubMedGoogle Scholar
  22. 22.
    Ezzat Y, Hamdy K. The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseases. Int J Rheum Dis. 2010;13(3):259–65.PubMedGoogle Scholar
  23. 23.
    Naito T, Yokoyama N, Kakuta Y, Ueno K, Kawai Y, Onodera M, et al. Clinical and genetic risk factors for decreased bone mineral density in Japanese patients with inflammatory bowel disease. J Gastroenterol Hepatol. 2018;33(11):1873–81.PubMedGoogle Scholar
  24. 24.
    Adamopoulos IE. Inflammation in bone physiology and pathology. Curr Opin Rheumatol. 2018;30(1):59–64.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Tilg H, Moschen AR, Kaser A, Pines A, Dotan I. Gut, inflammation and osteoporosis: basic and clinical concepts. Gut. 2008;57(5):684–94.PubMedGoogle Scholar
  26. 26.
    Schulte CM, Dignass AU, Goebell H, Roher HD, Schulte KM. Genetic factors determine extent of bone loss in inflammatory bowel disease. Gastroenterology. 2000;119(4):909–20.PubMedGoogle Scholar
  27. 27.
    Cleynen I, Gonzalez JR, Figueroa C, Franke A, McGovern D, Bortlik M, et al. Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European project. Gut. 2013;62(11):1556–65.PubMedGoogle Scholar
  28. 28.
    Brinar M, Vermeire S, Cleynen I, Lemmens B, Sagaert X, Henckaerts L, et al. Genetic variants in autophagy-related genes and granuloma formation in a cohort of surgically treated Crohn's disease patients. J Crohns Colitis. 2012;6(1):43–50.PubMedGoogle Scholar
  29. 29.
    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(11):2521–8.PubMedGoogle Scholar
  30. 30.
    Krela-Kazmierczak I, Kaczmarek-Rys M, Szymczak A, Michalak M, Skrzypczak-Zielinska M, Drweska-Matelska N, et al. Bone metabolism and the c.-223C > T polymorphism in the 5'UTR region of the Osteoprotegerin gene in patients with inflammatory bowel disease. Calcif Tissue Int. 2016;99(6):616–24.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411(6837):599–603.PubMedGoogle Scholar
  32. 32.
    Szymczak-Tomczak A, Krela-Kazmierczak I, Kaczmarek-Rys M, Hryhorowicz S, Stawczyk-Eder K, Szalata M, et al. Vitamin D receptor (VDR) TaqI polymorphism, vitamin D and bone mineral density in patients with inflammatory bowel diseases. Adv Clin Exp Med. 2019;28:975–80.Google Scholar
  33. 33.
    Robinson RJ, Iqbal SJ, Al-Azzawi F, Abrams K, Mayberry JF. Sex hormone status and bone metabolism in men with Crohn's disease. Aliment Pharmacol Ther. 1998;12(1):21–5.Google Scholar
  34. 34.
    Miznerova E, Hlavaty T, Koller T, Toth J, Holociova K, Huorka M, et al. The prevalence and risk factors for osteoporosis in patients with inflammatory bowel disease. Bratisl Lek Listy. 2013;114(8):439–45.PubMedGoogle Scholar
  35. 35.
    Lee S, Metcalfe A, Raman M, Leung Y, Aghajafari F, Letourneau N, et al. Pregnant women with inflammatory bowel disease are at increased risk of vitamin D insufficiency: a cross-sectional study. J Crohns Colitis. 2018;12(6):702–9.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Gilman J, Shanahan F, Cashman KD. Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use. Eur J Clin Nutr. 2006;60(7):889–96.PubMedGoogle Scholar
  37. 37.
    Nielsen OH, Rejnmark L, Moss AC. Role of vitamin D in the natural history of inflammatory bowel disease. J Crohns Colitis. 2018;12(6):742–52.PubMedGoogle Scholar
  38. 38.
    Limketkai BN, Mullin GE, Limsui D, Parian AM. Role of vitamin D in inflammatory bowel disease. Nutr Clin Pract. 2017;32(3):337–45.PubMedGoogle Scholar
  39. 39.
    Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG, et al. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr. 2011;35(3):308–16.PubMedGoogle Scholar
  40. 40.
    Rodriguez-Bores L, Barahona-Garrido J, Yamamoto-Furusho JK. Basic and clinical aspects of osteoporosis in inflammatory bowel disease. World J Gastroenterol. 2007;13(46):6156–65.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Buckley L, Humphrey MB. Glucocorticoid-induced osteoporosis. N Engl J Med. 2018;379(26):2547–56.PubMedGoogle Scholar
  42. 42.
    Sylvester FA. Inflammatory bowel disease: effects on bone and mechanisms. Adv Exp Med Biol. 2017;1033:133–50.PubMedGoogle Scholar
  43. 43.
    Maldonado-Perez MB, Castro-Laria L, Caunedo-Alvarez A, Montoya-Garcia MJ, Giner-Garcia M, Arguelles-Arias F, et al. Does the antitumor necrosis factor-alpha therapy decrease the vertebral fractures occurrence in inflammatory bowel disease? J Clin Densitom. 2019;22(2):195–202.PubMedGoogle Scholar
  44. 44.
    Castro B, Rivero M, Crespo J, Riancho JA, Valero C. Influence of anti-TNF therapy on bone metabolism in patients with inflammatory bowel disease. Eur J Intern Med. 2017;39:e33–e4.PubMedGoogle Scholar
  45. 45.
    Hakimian S, Kheder J, Arum S, Cave DR, Hyatt B. Re-evaluating osteoporosis and fracture risk in Crohn's disease patients in the era of TNF-alpha inhibitors. Scand J Gastroenterol. 2018;53(2):168–72.PubMedGoogle Scholar
  46. 46.
    Veerappan SG, O'Morain CA, Daly JS, Ryan BM. Review article: the effects of antitumour necrosis factor-alpha on bone metabolism in inflammatory bowel disease. Aliment Pharmacol Ther. 2011;33(12):1261–72.PubMedGoogle Scholar
  47. 47.
    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(6):607–14.PubMedGoogle Scholar
  48. 48.
    Veerappan SG, Healy M, Walsh B, O'Morain CA, Daly JS, Ryan BM. A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients. Eur J Gastroenterol Hepatol. 2016;28(11):1335–44.PubMedGoogle Scholar
  49. 49.
    Veerappan SG, Healy M, Walsh BJ, O'Morain CA, Daly JS, Ryan BM. Adalimumab therapy has a beneficial effect on bone metabolism in patients with Crohn's disease. Dig Dis Sci. 2015;60(7):2119–29.PubMedGoogle Scholar
  50. 50.
    Augustine MV, Leonard MB, Thayu M, Baldassano RN, de Boer IH, Shults J, et al. Changes in vitamin D-related mineral metabolism after induction with anti-tumor necrosis factor-alpha therapy in Crohn's disease. J Clin Endocrinol Metab. 2014;99(6):E991–8.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Melek J, Sakuraba A. Efficacy and safety of medical therapy for low bone mineral density in patients with inflammatory bowel disease: a meta-analysis and systematic review. Clin Gastroenterol Hepatol. 2014;12:32–44 e5.PubMedGoogle Scholar
  52. 52.
    Yao L, Wang H, Dong W, Liu Z, Mao H. Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease: A meta-analysis. Medicine (Baltimore). 2017;96:e5861.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Hu Y, Chen X, Chen X, Zhang S, Jiang T, Chang J, et al. Bone loss prevention of bisphosphonates in patients with inflammatory bowel disease: a systematic review and meta-analysis. Can J Gastroenterol Hepatol. 2017;2017:2736547.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Schule S, Rossel JB, Frey D, Biedermann L, Scharl M, Zeitz J, et al. Widely differing screening and treatment practice for osteoporosis in patients with inflammatory bowel diseases in the Swiss IBD cohort study. Medicine (Baltimore). 2017;96:e6788.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Bakker SF, Dik VK, Witte BI, Lips P, Roos JC, Van Bodegraven AA. Increase in bone mineral density in strictly treated Crohn's disease patients with concomitant calcium and vitamin D supplementation. J Crohns Colitis. 2013;7(5):377–84.PubMedGoogle Scholar
  56. 56.
    Casals-Seoane F, Chaparro M, Mate J, Gisbert JP. Clinical course of bone metabolism disorders in patients with inflammatory bowel disease: a 5-year prospective study. Inflamm Bowel Dis. 2016;22(8):1929–36.PubMedGoogle Scholar
  57. 57.
    Piodi LP, Poloni A, Ulivieri FM. Managing osteoporosis in ulcerative colitis: something new? World J Gastroenterol. 2014;20(39):14087–98.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Meyer D, Stavropolous S, Diamond B, Shane E, Green PH. Osteoporosis in a north american adult population with celiac disease. Am J Gastroenterol. 2001;96:1129.Google Scholar
  59. 59.
    Ganji R, Moghbeli M, Sadeghi R, Bayat G, Ganji A. Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: a systematic review. Nutr J. 2019;18:9.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Walker MD, Williams J. Lewis SK. Lebwohl B, Green PHR. Measurement of Forearm Bone Density by Dual Energy X-Ray Absorptiometry Increases the Prevalence of Osteoporosis in Men With Celiac Disease. Clin Gastroenterol Hepatol: Bai JC; 2019.Google Scholar
  61. 61.
    Vasquez H, Mazure R, Gonzalez D, Flores D, Pedreira S, Niveloni S, et al. Risk of fractures in celiac disease patients: a cross-sectional, case-control study. Am J Gastroenterol. 2000;95(1):183–9.PubMedGoogle Scholar
  62. 62.
    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.PubMedGoogle Scholar
  63. 63.
    Legroux-Gerot I, Leloire O, Blanckaert F, Tonnel F, Grardel B, Ducrocq JL, et al. Screening for celiac disease in patients with osteoporosis. Joint Bone Spine. 2009;76(2):162–5.PubMedGoogle Scholar
  64. 64.
    Al-Toma A, Volta U, Auricchio R, Castillejo G, Sanders DS, Cellier C, et al. European Society for the Study of coeliac disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J. 2019;7(5):583–613.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Laszkowska M, Mahadev S, Sundstrom J, Lebwohl B, Green PHR, Michaelsson K, et al. Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis. Aliment Pharmacol Ther. 2018;48(6):590–7.PubMedGoogle Scholar
  66. 66.
    Galli G, Lahner E, Conti L, Esposito G, Sacchi MC, Annibale B. Risk factors associated with osteoporosis in a cohort of prospectively diagnosed adult coeliac patients. United European Gastroenterol J. 2018;6(8):1161–8.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Pritchard L, Wilson S, Griffin J, Pearce G, Murray IA, Lewis S. Prevalence of reduced bone mineral density in adults with coeliac disease - are we missing opportunities for detection in patients below 50 years of age? Scand J Gastroenterol. 2018;53(12):1433–6.PubMedGoogle Scholar
  68. 68.
    Kemppainen T, Kroger H, Janatuinen E, Arnala I, Kosma VM, Pikkarainen P, et al. Osteoporosis in adult patients with celiac disease. Bone. 1999;24(3):249–55.PubMedGoogle Scholar
  69. 69.
    Garcia-Manzanares A, Tenias JM, Lucendo AJ. Bone mineral density directly correlates with duodenal marsh stage in newly diagnosed adult celiac patients. Scand J Gastroenterol. 2012;47(8-9):927–36.PubMedGoogle Scholar
  70. 70.
    Kotze LM, Skare T, Vinholi A, Jurkonis L, Nisihara R. Impact of a gluten-free diet on bone mineral density in celiac patients. Rev Esp Enferm Dig. 2016;108(2):84–8.PubMedGoogle Scholar
  71. 71.
    Pantaleoni S, Luchino M, Adriani A, Pellicano R, Stradella D, Ribaldone DG, et al. Bone mineral density at diagnosis of celiac disease and after 1 year of gluten-free diet. ScientificWorldJournal. 2014;2014:173082.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Sategna-Guidetti C, Grosso SB, Grosso S, Mengozzi G, Aimo G, Zaccaria T, et al. The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients. Aliment Pharmacol Ther. 2000;14(1):35–43.PubMedGoogle Scholar
  73. 73.
    Kemppainen T, Kroger H, Janatuinen E, Arnala I, Lamberg-Allardt C, Karkkainen M, et al. Bone recovery after a gluten-free diet: a 5-year follow-up study. Bone. 1999;25(3):355–60.PubMedGoogle Scholar
  74. 74.
    Haere P. Hoie O. Haugeberg G. No major reduction in bone mineral density after long-term treatment of patients with Celiac Disease. Eur J Intern Med: Lundin KEA; 2019.Google Scholar
  75. 75.
    Scott EM, Gaywood I, Scott BB. Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease. British Society of Gastroenterology. Gut. 2000;46 Suppl 1:i1–8.Google Scholar
  76. 76.
    Singh P, Garber JJ. Implementation and adherence to osteoporosis screening guidelines among coeliac disease patients. Dig Liver Dis. 2016;48(12):1451–6.PubMedGoogle Scholar
  77. 77.
    Ludvigsson JF, Michaelsson K, Ekbom A, Montgomery SM. Coeliac disease and the risk of fractures - a general population-based cohort study. Aliment Pharmacol Ther. 2007;25(3):273–85.PubMedGoogle Scholar
  78. 78.
    Heikkila K, Pearce J, Maki M, Kaukinen K. Celiac disease and bone fractures: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(1):25–34.PubMedGoogle Scholar
  79. 79.
    Heikkila K, Heliovaara M, Impivaara O, Kroger H, Knekt P, Rissanen H, et al. Celiac disease autoimmunity and hip fracture risk: findings from a prospective cohort study. J Bone Miner Res. 2015;30(4):630–6.PubMedGoogle Scholar
  80. 80.
    Vestergaard P, Mosekilde L. Fracture risk in patients with celiac disease, Crohn's disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark. Am J Epidemiol. 2002;156(1):1–10.Google Scholar
  81. 81.
    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.PubMedGoogle Scholar
  82. 82.
    Zanchetta MB, Longobardi V, Bai JC. Bone and celiac disease. Curr Osteoporos Rep. 2016;14(2):43–8.PubMedGoogle Scholar
  83. 83.
    Fasano A, Catassi C. Clinical practice. Celiac disease N Engl J Med. 2012;367(25):2419–26.PubMedGoogle Scholar
  84. 84.
    Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. Gastroenterology. 1993;105(3):910–22.PubMedGoogle Scholar
  85. 85.
    Singh P, Arora A, Strand TA, Leffler DA, Catassi C, Green PH, et al. Global prevalence of celiac disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16:823–36 e2.PubMedGoogle Scholar
  86. 86.
    Singh P, Arora S, Singh A, Strand TA, Makharia GK. Prevalence of celiac disease in Asia: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2016;31(6):1095–101.PubMedGoogle Scholar
  87. 87.
    Gatti S, Lionetti E. Balanzoni L. Galeazzi T, Gesuita R, et al. Increased Prevalence of Celiac Disease in School-age Children in Italy. Clin Gastroenterol Hepatol: Verma AK; 2019.Google Scholar
  88. 88.
    Volta U, Caio G, Stanghellini V, De Giorgio R. The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center. BMC Gastroenterol. 2014;14:194.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Volta U, Caio G, Boschetti E, Giancola F, Rhoden KJ, Ruggeri E, et al. Seronegative celiac disease: shedding light on an obscure clinical entity. Dig Liver Dis. 2016;48(9):1018–22.PubMedGoogle Scholar
  90. 90.
    Caio G, Volta U. Coeliac disease: changing diagnostic criteria? Gastroenterol Hepatol Bed Bench. 2012;5(3):119–22.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Riestra S, Fernandez E, Rodrigo L, Garcia S, Ocio G. Prevalence of coeliac disease in the general population of northern Spain. Strategies of serologic screening. Scand J Gastroenterol. 2000;35(4):398–402.PubMedGoogle Scholar
  92. 92.
    Punales M, Bastos MD, Ramos ARL, Pinto RB, Ott EA, Provenzi V, et al. Prevalence of celiac disease in a large cohort of young patients with type 1 diabetes. Pediatr Diabetes. 2019;20(4):414–20.PubMedGoogle Scholar
  93. 93.
    Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017;12:43.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Bronner F, Pansu D. Nutritional aspects of calcium absorption. J Nutr. 1999;129(1):9–12.PubMedGoogle Scholar
  95. 95.
    Bronner F. Recent developments in intestinal calcium absorption. Nutr Rev. 2009;67(2):109–13.PubMedGoogle Scholar
  96. 96.
    Khundmiri SJ, Murray RD, Lederer E. PTH and vitamin D. Compr Physiol. 2016;6(2):561–601.PubMedGoogle Scholar
  97. 97.
    Blaine J, Chonchol M, Levi M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 2015;10(7):1257–72.PubMedGoogle Scholar
  98. 98.
    Riancho JA, Delgado-Calle J. [Osteoblast-osteoclast interaction mechanisms]. Reumatol Clin. 2011;7 Suppl 2:S1–4.Google Scholar
  99. 99.
    Dickson BC, Streutker CJ, Chetty R. Coeliac disease: an update for pathologists. J Clin Pathol. 2006;59(10):1008–16.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Lewis SK, Semrad CE. Capsule endoscopy and Enteroscopy in celiac disease. Gastroenterol Clin N Am. 2019;48(1):73–84.Google Scholar
  101. 101.
    Bul V, Sleesman B, Boulay B. Celiac disease presenting as profound diarrhea and weight loss - a celiac crisis. Am J Case Rep. 2016;17:559–61.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Bledsoe AC, King KS, Larson JJ, Snyder M, Absah I, Choung RS, et al. Micronutrient deficiencies are common in contemporary celiac disease despite lack of overt Malabsorption symptoms. Mayo Clin Proc. 2019;94(7):1253–60.PubMedGoogle Scholar
  103. 103.
    Ojetti V, Gabrielli M, Migneco A, Lauritano C, Zocco MA, Scarpellini E, et al. Regression of lactose malabsorption in coeliac patients after receiving a gluten-free diet. Scand J Gastroenterol. 2008;43(2):174–7.PubMedGoogle Scholar
  104. 104.
    Kruger MC, Horrobin DF. Calcium metabolism, osteoporosis and essential fatty acids: a review. Prog Lipid Res. 1997;36(2-3):131–51.PubMedGoogle Scholar
  105. 105.
    Nair R, Maseeh A. Vitamin D: The "sunshine" vitamin. J Pharmacol Pharmacother 2012;3:118–126, 2.Google Scholar
  106. 106.
    Nakamichi Y, Takahashi N. Current topics on vitamin D. the role of active forms of vitamin D in regulation of bone remodeling. Clin Calcium. 2015;25(3):395–402.PubMedGoogle Scholar
  107. 107.
    Ludvigsson JF, Kampe O, Lebwohl B, Green PH, Silverberg SJ, Ekbom A. Primary hyperparathyroidism and celiac disease: a population-based cohort study. J Clin Endocrinol Metab. 2012;97(3):897–904.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Valdimarsson T, Toss G, Lofman O, Strom M. Three years' follow-up of bone density in adult coeliac disease: significance of secondary hyperparathyroidism. Scand J Gastroenterol. 2000;35(3):274–80.PubMedGoogle Scholar
  109. 109.
    Keaveny AP, Freaney R, McKenna MJ, Masterson J, O'Donoghue DP. Bone remodeling indices and secondary hyperparathyroidism in celiac disease. Am J Gastroenterol. 1996;91(6):1226–31.PubMedGoogle Scholar
  110. 110.
    Kavak US, Yuce A, Kocak N, Demir H, Saltik IN, Gurakan F, et al. Bone mineral density in children with untreated and treated celiac disease. J Pediatr Gastroenterol Nutr. 2003;37(4):434–6.PubMedGoogle Scholar
  111. 111.
    Heydari F, Rostami-Nejad M, Moheb-Alian A, Mollahoseini MH, Rostami K, Pourhoseingholi MA, et al. Serum cytokines profile in treated celiac disease compared with non-celiac gluten sensitivity and control: a marker for differentiation. J Gastrointestin Liver Dis. 2018;27(3):241–7.PubMedGoogle Scholar
  112. 112.
    Manavalan JS, Hernandez L, Shah JG, Konikkara J, Naiyer AJ, Lee AR, et al. Serum cytokine elevations in celiac disease: association with disease presentation. Hum Immunol. 2010;71(1):50–7.PubMedGoogle Scholar
  113. 113.
    Okabe I, Kikuchi T, Mogi M, Takeda H, Aino M, Kamiya Y, et al. IL-15 and RANKL play a synergistically important role in Osteoclastogenesis. J Cell Biochem. 2017;118(4):739–47.PubMedGoogle Scholar
  114. 114.
    Vorobjova T, Tagoma A, Oras A, Alnek K, Kisand K, Talja I, et al. Celiac disease in children, particularly with accompanying type 1 diabetes, is characterized by substantial changes in the blood cytokine balance. Which May Reflect Inflammatory Processes in the Small Intestinal Mucosa J Immunol Res. 2019;2019:6179243.PubMedGoogle Scholar
  115. 115.
    Kim N, Kadono Y, Takami M, Lee J, Lee SH, Okada F, et al. Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. J Exp Med. 2005;202(5):589–95.PubMedPubMedCentralGoogle Scholar
  116. 116.
    Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–42.PubMedGoogle Scholar
  117. 117.
    Soysa NS, Alles N. NF-kappaB functions in osteoclasts. Biochem Biophys Res Commun. 2009;378(1):1–5.PubMedGoogle Scholar
  118. 118.
    Kim JH, Jin HM, Kim K, Song I, Youn BU, Matsuo K, et al. The mechanism of osteoclast differentiation induced by IL-1. J Immunol. 2009;183:1862–70.PubMedGoogle Scholar
  119. 119.
    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(7):1112–21.PubMedGoogle Scholar
  120. 120.
    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(6):417–22.PubMedGoogle Scholar
  121. 121.
    Di Stefano M, Bergonzi M, Benedetti I, De Amici M, Torre C, Brondino N, et al. Alterations of inflammatory and matrix production indices in celiac disease with low bone mass on long-term gluten-free diet. J Clin Gastroenterol. 2019;53:e221–e6.PubMedGoogle Scholar
  122. 122.
    Larussa T, Suraci E, Imeneo M, Marasco R, Luzza F. Normal bone mineral density associates with duodenal mucosa healing in adult patients with celiac disease on a gluten-free diet. Nutrients. 2017;9.PubMedCentralGoogle Scholar
  123. 123.
    Zanchetta MB, Longobardi V, Costa F, Longarini G, Mazure RM, Moreno ML, et al. Impaired bone microarchitecture improves after one year on gluten-free diet: a prospective longitudinal HRpQCT study in women with celiac disease. J Bone Miner Res. 2017;32(1):135–42.PubMedGoogle Scholar
  124. 124.
    Mautalen C, Gonzalez D, Mazure R, Vazquez H, Lorenzetti MP, Maurino E, et al. Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac disease patients. Am J Gastroenterol. 1997;92(2):313–8.PubMedGoogle Scholar
  125. 125.
    Muzzo SB, R. Burgueño, M. Ríos, G. Bergenfreid, C. Chavez, E. Leiva,L. Effect of calcium and vitamin D supplementation on bone mineral density of celiac children,. Nutr Res 2000;20:1241–1247.Google Scholar
  126. 126.
    Pazianas M, Butcher GP, Subhani JM, Finch PJ, Ang L, Collins C, et al. Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake. Osteoporos Int. 2005;16(1):56–63.PubMedGoogle Scholar
  127. 127.
    Passananti V, Santonicola A, Bucci C, Andreozzi P, Ranaudo A, Di Giacomo DV, et al. Bone mass in women with celiac disease: role of exercise and gluten-free diet. Dig Liver Dis. 2012;44(5):379–83.PubMedGoogle Scholar
  128. 128.
    Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011:CD000333.Google Scholar
  129. 129.
    Kumar M, Rastogi A, Bhadada SK, Bhansali A, Vaiphei K, Kochhar R. Effect of zoledronic acid on bone mineral density in patients of celiac disease: a prospective, randomized, pilot study. Indian J Med Res. 2013;138(6):882–7.PubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineHospital Universitario Marqués de Valdecilla, IDIVAL, University of CantabriaSantanderSpain
  2. 2.Servicio de Aparato Digestivo, Hospital Universitario Marqués de ValdecillaSantanderSpain

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