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Long-term Fracture Risk in Patients with Celiac Disease: A Population-Based Study in Olmsted County, Minnesota

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Abstract

Celiac disease is associated with decreased bone density, but there are conflicting data regarding fracture risk. We determined the fracture incidence relative to matched controls in a population-based cohort with celiac disease before and after diagnosis. Olmsted County residents with celiac disease (n = 83) diagnosed between 1950 and 2002 were compared with 166 gender and age matched controls. Fracture histories were ascertained from each subject’s medical records. Celiac disease is linked to an increased fracture risk before and after diagnosis. Before the index date, cases had a fracture rate twice that of controls (CI: 1.0–3.9, P = 0.045) and 2.5-fold greater after the index date (CI: 1.1–5.6, P = 0.026). Appendicular and axial fractures were 2.5 (CI: 0.9–6.5) and 3.2 times more likely (CI: 1.0–10.5) after the index date. These observations support a rationale for earlier detection of celiac disease, and active management of bone disease before bone effects have occurred, to reduce the persistent risk of fractures.

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References

  1. Farrell RJ, Kelly CP (2002) Celiac sprue. N Engl J Med 346:180–188

    Article  PubMed  CAS  Google Scholar 

  2. Ascher H, Kristiansson B (1997) The highest incidence of celiac disease in Europe: the Swedish experience. J Pediatr Gastroenterol Nutr 24:S3–6

    Article  PubMed  CAS  Google Scholar 

  3. Talley NJ, Valsovinols M, Petterson TM, Carpenter HA, Melton LJ (1994) Epidemiology of celiac sprue: a community-based study. Am J Gastroenterol 89:843–846

    PubMed  CAS  Google Scholar 

  4. Murray JA, Van Dyke C, Plevak MF, Dierkhising RA, Zinsmeister AR, Melton LJ III (2003) Trends in the identification and clinical features of celiac disease in a North American community, 1950–2001. Clin Gastroenterol Hepatol 1:19–22

    Article  PubMed  Google Scholar 

  5. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, Elitsur Y, Green PH, Guandalini S, Hill ID, Pietzak M, Ventura A, Thorpe M, Kryszak D, Fornaroli F, Wasserman SS, Murray JA, Horvath K (2003) Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Int Med 163:286–292

    Article  Google Scholar 

  6. Selby PL, Davies M, Adams JE, Mawer EB (1999) Bone loss in celiac disease is related to secondary hyperparathyroidism. J Bone Miner Res 14:652–657

    Article  PubMed  CAS  Google Scholar 

  7. Sategna-Guidetti C, Grosso SB, Mengozzi G, Aimo G, Zaccaria T, Di Stefano M, Isaia GC (2000) The effects of 1-year withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients. Aliment Pharmacol Ther 14:35–43

    Article  PubMed  CAS  Google Scholar 

  8. Mather KJ, Meddings JB, Beck PL, Scott RB, Hanley DA (2001) Prevalence of IgA-antiendomysial antibody in asymptomatic low bone mineral density. Am J Gastroenterol 96:120–125

    Article  PubMed  CAS  Google Scholar 

  9. Meyer D, Stavropolous S, Diamond B, Shane E, Green PH (2001) Osteoporosis in a North American adult population with celiac disease. Am J Gastroenterol 96:112–119

    PubMed  CAS  Google Scholar 

  10. Stenson W, Newberry R, Lorenz R, Baldus C, Civitelli R (2005) Increased prevalence of celiac disease and need for routine screening among patients with osteoporosis. Arch Int Med 165:393–399

    Article  Google Scholar 

  11. Sugai E, Chernavsky A, Pedreira S, Vazquez H, Niveloni S, Mazure R, Mauriro E, Ravinovich GA, Bai JC (2002) Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis. J Clin Immunol 22:353–362

    Article  PubMed  CAS  Google Scholar 

  12. Fornari MC, Pedreira S, Niveloni S, Gonzalez D, Diez RA, Vazquez H (1998) Pre- and post-treatment serum levels of cytokines IL-1 beta, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia? Am J Gastroenterol 93:412–418

    Google Scholar 

  13. Bottaro G, Cataldo F, Rotolo N, Spina M, Corazza GR (1999) The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases. Am J Gastroenterol 94:691–696

    PubMed  CAS  Google Scholar 

  14. Vasquez H, Mazure R, Gonzalez D, Flores D, Pedreira S, Niveloni S, Smecuol E, Maurino E, Bai JC (2000) Risk of fractures in celiac disease patients: a cross-sectional, case-control study. Am J Gastroenterol 95:183–189

    Article  PubMed  CAS  Google Scholar 

  15. Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nation-wide follow-up of 16,416 patients in Denmark. Am J Epidemiol 156:1–10

    Article  PubMed  Google Scholar 

  16. Thomason K, West J, Logan RF, Coupland C, Holmes GK (2003) Fracture experience patients with coeliac disease: a population based survey. Gut 52:518–522

    Article  PubMed  CAS  Google Scholar 

  17. West J, Logan RF, Card TR, Smith C, Hubbard R (2003) Fracture risk in people with celiac disease: a population-based cohort study. Gastroenterology 125:429–436

    Article  PubMed  Google Scholar 

  18. Loftus EV, Crowson CS, Sandborn WJ, Tremaine WJ, O’Fallon WM, Melton LJ III (2002) Long-term fracture risk in patients with Crohn’s disease: a population-based study in Olmsted County, Minnesota. Gastroenterology 123:468–475

    Article  PubMed  Google Scholar 

  19. Bernstein CN, Leslie WD, Leboff MS (2003) AGA technical review on osteoporosis in gastrointestinal diseases. Gastroenterology 124:795–841

    Article  PubMed  Google Scholar 

  20. Valdimarsson T, Toss G, Ross I, Lofman O, Strom M (1994) Bone mineral density in coeliac disease. Scand J Gastroenterol 29:457–461

    Article  PubMed  CAS  Google Scholar 

  21. Melton LJ III (1996) History of the Rochester epidermiology program. Mayo Clin Proc 713:266–274

    Google Scholar 

  22. Kurland LT, Mogaard CA (1981) The patient record in epidermiology. Sci Am 245:54–63

    Article  PubMed  CAS  Google Scholar 

  23. Melton LJ III (1997) The threat to medical-records research. N Engl J Med 337:1466–1470

    Article  PubMed  Google Scholar 

  24. Cooper C, Atkinson EJ, O’Fallon WM, Melton LJ III (1992) Incidence of clinically diagnosed vertebral fractures: a population based study in Rochester, Minnesota (1985)–1989. J Bone Miner Res 7:221–227

    PubMed  CAS  Google Scholar 

  25. Melton LJ III (1995) Epidemiology of fractures. In: Riggs BL, Meltion LJ (eds) Osteoporosis: etiology, diagnosis, and management, 2nd edn. Lippincott-Raven, Philadelphia, pp 225–247

    Google Scholar 

  26. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 40:373–383

    Article  PubMed  CAS  Google Scholar 

  27. Gabriel SE, Crowson CS, O’Fallon WM (1999) Comorbidity in arthritis. J Rheumatol 26:2475–2479

    PubMed  CAS  Google Scholar 

  28. Hosmer DW, Lemeshow S (1999) Applied survival analysis. Wiley, New York

    Google Scholar 

  29. Hosmer DW, Lemeshow S (1989) Applied logistic regression. Wiley, New York

    Google Scholar 

  30. Meyer D, Stavropolous S, Diamond B, Shane E, Green P (2001) Osteoporosis in a North American adult population with celiac disease. Am J Gastroenterol 96:112–119

    PubMed  CAS  Google Scholar 

  31. Delco F, El Serag HB, Sonnenberg A (1999) Celiac sprue among US military veterans: association disorders and clinical manifestations. Dig Dis Sci 44:966–972

    Article  PubMed  CAS  Google Scholar 

  32. Fickling WE, McFarlane XA, Bhalla AK, Robertson DAF (2001) The clinical impact of metabolic bone disease in coeliac disease. Postgrad Med J 77:33–36

    Article  PubMed  CAS  Google Scholar 

  33. Walters J, Banks L, Butcher G, Fowler C (1995) Detection of low bone mineral density by dual energy X ray absorptionmetry in unsuspected suboptimally treated coeliac disease. Gut 37:220–224

    Article  PubMed  CAS  Google Scholar 

  34. Corazza GR, Di Sario A, Cecchetti L, Jorizzo RA, Di Stefano M, Minguzzi L, Brusco G, Bernardi M, Gasbarrini G (1996) Influence of pattern of clinical presentation and of gluten-free diet on bone mass and metabolism in adult coeliac disease. Bone 18:525–530

    Article  PubMed  CAS  Google Scholar 

  35. Keaveny AP, Freaney R, McKenna MJ, Masterson J, O-Donoghue DP (1996) Bone remodeling indices and secondary hyperparathyroidism in celiac disease. Am J Gastroenterol 91:1226–1231

    PubMed  CAS  Google Scholar 

  36. Corazza GR, Di Sario A, Cecchetti L, Tarozzi C, Corrao G, Bernardi M, Gasbarrini G (1995) Bone mass and metabolism in patients with celiac disease. Gastroenterology 109:122–128

    Article  PubMed  CAS  Google Scholar 

  37. Vestergaard P (2003) Bone loss associated with gastrointestinal disease: prevalence and pathogenesis. Eur J Gastroenterol Hepatol 15:851–856

    Article  PubMed  Google Scholar 

  38. Staun M, Jarnum S (1988) Measurement of the 10,000-molecular weight calcium-binding protein in small-intestinal biopsy specimens from patients with malabsorption syndromes. Scand J Gastroenterol 23:827–832

    Article  PubMed  CAS  Google Scholar 

  39. Caraceni MP, Molteni N, Bardella MT, Ortolani S, Nogara A, Bianchi PA (1988) Bone and mineral metabolism in adult celiac disease. Am J Gastroenterol 83:274–277

    PubMed  CAS  Google Scholar 

  40. Jameson S (2000) Coeliac disease, insulin-like growth factor, bone mineral density, and zinc. Scand J Gastroenterol 35:894–896

    Article  PubMed  CAS  Google Scholar 

  41. Devine A, Rosen C, Mohan S, Baylink D, Prince RL (1998) Effects of zinc and other nutritional factors on insulin-like growth factor I and insulin-like growth factor-binding proteins in postmenopausal women. Am J Clin Nutr 68:200–206

    PubMed  CAS  Google Scholar 

  42. Wood RJ, Zheng JJ (1997) High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr 65:1803–1809

    PubMed  CAS  Google Scholar 

  43. Valdimarsson T, Arnqvist HJ, Toss G, Jarnerot G, Nystrom F, Strom M (1999) Low circulating insulin-like growth factor I in coeliac disease and its relation to bone mineral density. Scand J Gastroenterol 34:904–908

    Article  PubMed  CAS  Google Scholar 

  44. Farthing MJ, Rees LH, Dawson AM (1983) Male gonadal function in coeliac disease III pituitary regulation. Clin Endocrinol 19:661–671

    CAS  Google Scholar 

  45. Sher KS, Jayanthi V, Probert CS, Steward CR, Mayberry JF (1994) Infertility, obstetric and gynecological problems in coeliac sprue. Dig Dis 12:186–190

    Article  PubMed  CAS  Google Scholar 

  46. Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259

    PubMed  CAS  Google Scholar 

  47. West J, Logan RF, Card TR, Smith C, Hubbard R (2003) Fracture risk in people with celiac disease: a population-based cohort study. Gastroenterology 125:429–436

    Article  PubMed  Google Scholar 

  48. Ludvigsson JF, Michaelsson K, Ekkom A, Montgomery SM (2007) Coeliac disease and the risk of fractures—a general population-based cohort study. Aliment Pharmacol Ther 25:273–285

    Article  PubMed  CAS  Google Scholar 

  49. McFarlane XA, Bhalla AK, Reeves DE, Morgan LM, Robertson DA (1995) Osteoporosis in treated adult coeliac disease. Gut 36:710–714

    Article  PubMed  CAS  Google Scholar 

  50. Bode S, Hassager C, Gudmand-Hoyer E, Christiansen C (1991) Body composition and calcium metabolism in adult treated coeliac disease. Gut 32:1342–1345

    Article  PubMed  CAS  Google Scholar 

  51. Pistorium LR, Sweldan WH, Purdle DW, Steel SA, Howey S, Bennett JR, Sutton D (1995) Coeliac disease and bone mineral density in adult female patients. Gut 37:639–642

    Article  Google Scholar 

  52. Mautalen C, Gonzalez D, Mazure R, Vazquez H, Lorenzetti MP, Maurino E, Niveloni S, Pedreira S, Smecuol E, Boerr LA, Bai JC (1997) Effect of treatment on bone mass, mineral metabolism and body composition in untreated celiac disease patients. Am J Gastroenterol 92:313–318

    PubMed  CAS  Google Scholar 

  53. Ciacci C, Maurelli L, Klain M, Savino G, Salvatore M, Mazzacca G, Cirillo M (1997) Effects of dietary treatment on bone mineral density in adults with celiac disease: factors predicting response. Am J Gastroenterol 92:992–996

    PubMed  CAS  Google Scholar 

  54. Bai JC, Gonzalez D, Mautalen C, Mazure R, Pedreira S, Vasquez H, Smecuol E, Siccardi A, Cataldi M, Niveloni S, Boerr LA, Maurino E (1997) Long-term effect of gluten restriction on bone mineral density of patients with coeliac disease. Aliment Pharmacol Ther 11:157–164

    Article  PubMed  CAS  Google Scholar 

  55. Mustalahti K, Collin P, Sievanen H, Salmi J, Maki M (1999) Osteopenia in patients with clinically silent coeliac disease warrants screening. Lancet 354:744–745

    Article  PubMed  CAS  Google Scholar 

  56. Gonzalez D, Mazure R, Mautalen C, Vasquez H, Bai J (1995) Body composition and bone mineral density in untreated and treated patients with celiac disease. Bone 16:231–234

    Article  PubMed  CAS  Google Scholar 

  57. Scott EM, Gaywood I, Scott BB (2000) Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease. Gut 46(Suppl 1):I1–I8

    Article  PubMed  Google Scholar 

  58. Mora S, Weber G, Barera G, Bellini A, Pasolini D, Prinster C, Bianchi C, Chiumello G (1993) Effect of gluten-free bone mineral content in growing patients with celiac disease. Am J Clin Nutr 57:224–228

    PubMed  CAS  Google Scholar 

  59. Rea F, Polito C, Marotta A, Di Toro A, Iovene A, Collini R, Rea L, Sessa G (1996) Restoration of body composition in celiac children after one year of gluten-free diet. J Pediatr Gastroenterol Nutr 23:408–412

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Kathryn Jensen and Sughra Naqvi for assistance with manuscript preparation. This study was supported in part by research grants DK 57982 and AR 30582 and MO1 RR00585 to the University of Rochester General Clinical Research Center from the National Institutes of Health, US Public Health Service. The funding source had no role in the design or execution of the study.

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Correspondence to Joseph A. Murray.

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Jafri, M.R., Nordstrom, C.W., Murray, J.A. et al. Long-term Fracture Risk in Patients with Celiac Disease: A Population-Based Study in Olmsted County, Minnesota. Dig Dis Sci 53, 964–971 (2008). https://doi.org/10.1007/s10620-007-9976-0

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  • DOI: https://doi.org/10.1007/s10620-007-9976-0

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