Archives of Osteoporosis

, 13:80 | Cite as

Risk of fractures at different anatomic sites in patients with irritable bowel syndrome: a nationwide population-based cohort study

  • Herng-Sheng Lee
  • Chi-Yi Chen
  • Wan-Ting Huang
  • Li-Jen Chang
  • Solomon Chih-Cheng Chen
  • Hsin-Yi YangEmail author
Original Article



This study was to investigate the fracture risk of irritable bowel syndrome (IBS) in comparison with non-IBS group. Our results found that IBS group has increased risk for fracture, in particular of the spine, forearm, hip, and hand.


Patients with IBS might also be at increased risk of osteoporosis and osteoporotic fractures. Up to now, the association between IBS and the risk of fractures at different anatomic sites occurrences is not completely clear. We conducted a population-based cohort analysis to investigate the fracture risk of IBS in comparison with non-IBS group.


We identified 29,505 adults aged ≥ 20 years with newly diagnosed IBS using the Taiwan National Health Insurance Research Database in 2000–2012. A comparison group was constructed of patients without IBS who were matched according to gender and age. The occurrence of fracture was monitored until the end of 2013. We analyzed the risk of fracture events to occur in IBS by using Cox proportional hazards regression models.


Patients with IBS had a higher incidence of osteoporotic fractures compared with the non-IBS group (12.34 versus 9.45 per 1000 person-years) and an increased risk of osteoporotic fractures (adjusted hazard ratio [aHR] = 1.27, 95% confidence interval [CI] = 1.20–1.35). Site-specific analysis showed that the IBS group had a higher risk of fractures for spine, forearm, hip, and hand than did the non-IBS group. With further stratification for gender and age, a higher aHR value for osteoporotic fractures in the IBS group was seen across all age groups in males, but seen in elderly females. In addition, female, elderly, low income, hypertension, coronary artery disease, cerebrovascular disease, and depressive disorders as independent osteoporotic fracture risk factors in IBS patients.


The IBS is considered as a risk factor for osteoporotic fractures, particularly in female individuals and fracture sites located at the spine, forearm, hip, and hand.


Irritable bowel syndrome Fracture Gender difference Longitudinal health insurance database Public health 



This study was based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance and the Department of Health and Welfare and managed by the National Health Research Institutes. The interpretation and conclusions contained within do not represent those of the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes.

Compliance with ethical standards

This study was approved by the Institutional Review Board (IRB) of Ditmanson Medical Foundation Chia-Yi Christian Hospital (CYCH-IRB No.2018032), Taiwan, and because the data were obtained from the LHID 2005, informed consent from the participants was not obtained.

Conflicts of interest


Supplementary material

11657_2018_496_MOESM1_ESM.docx (20 kb)
ESM 1 (DOCX 16 kb)


  1. 1.
    Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733CrossRefGoogle Scholar
  2. 2.
    Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S (2016) Major osteoporotic fragility fractures: risk factor updates and societal impact. World J Orthop 7:171–181CrossRefGoogle Scholar
  3. 3.
    Briot K, Roux C (2015) Glucocorticoid-induced osteoporosis. RMD Open 1:e000014CrossRefGoogle Scholar
  4. 4.
    Sealand R, Razavi C, Adler RA (2013) Diabetes mellitus and osteoporosis. Curr Diab Rep 13:411–418CrossRefGoogle Scholar
  5. 5.
    Heidari B, Hassanjani Roushan MR (2012) Rheumatoid arthritis and osteoporosis. Caspian J Int Med 3:445–446Google Scholar
  6. 6.
    Handzlik-Orlik G, Holecki M, Wilczynski K, Dulawa J (2016) Osteoporosis in liver disease: pathogenesis and management. Ther Adv Endocrinol Metab 7:128–135CrossRefGoogle Scholar
  7. 7.
    Krela-Kazmierczak I, Szymczak A, Lykowska-Szuber L, Eder P, Linke K (2016) Osteoporosis in gastrointestinal diseases. Adv Clin Exp Med 25:185–190CrossRefGoogle Scholar
  8. 8.
    Irwin R, Raehtz S, Parameswaran N, McCabe LR (2016) Intestinal inflammation without weight loss decreases bone density and growth. Am J Phys Regul Integr Comp Phys 311:R1149–r1157Google Scholar
  9. 9.
    Ali T, Lam D, Bronze MS, Humphrey MB (2009) Osteoporosis in inflammatory bowel disease. Am J Med 122:599–604CrossRefGoogle Scholar
  10. 10.
    Tilg H, Moschen AR, Kaser A, Pines A, Dotan I (2008) Gut, inflammation and osteoporosis: basic and clinical concepts. Gut 57:684–694CrossRefGoogle Scholar
  11. 11.
    Wada Y, Hisamatsu T, Naganuma M, Matsuoka K, Okamoto S, Inoue N, Yajima T, Kouyama K, Iwao Y, Ogata H, Hibi T, Abe T, Kanai T (2015) Risk factors for decreased bone mineral density in inflammatory bowel disease: a cross-sectional study. Clin Nutr (Edinb, Scotl) 34:1202–1209CrossRefGoogle Scholar
  12. 12.
    Abdul Rani R, Raja Ali RA, Lee YY (2016) Irritable bowel syndrome and inflammatory bowel disease overlap syndrome: pieces of the puzzle are falling into place. Intest Res 14:297–304CrossRefGoogle Scholar
  13. 13.
    Lu CL, Chen CY, Lang HC, Luo JC, Wang SS, Chang FY, Lee SD (2003) Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire on a Chinese population. Aliment Pharmacol Ther 18:1159–1169CrossRefGoogle Scholar
  14. 14.
    Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480–1491CrossRefGoogle Scholar
  15. 15.
    Theodorou V, Ait Belgnaoui A, Agostini S, Eutamene H (2014) Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome. Gut Microbes 5:430–436CrossRefGoogle Scholar
  16. 16.
    Stobaugh DJ, Deepak P, Ehrenpreis ED (2013) Increased risk of osteoporosis-related fractures in patients with irritable bowel syndrome. Osteoporos Int 24:1169–1175CrossRefGoogle Scholar
  17. 17.
    Yen CM, Muo CH, Lin MC, Chang SN, Chang YJ, Kao CH (2014) A nationwide population cohort study: irritable bowel syndrome is a risk factor of osteoporosis. Eur J Intern Med 25:87–91CrossRefGoogle Scholar
  18. 18.
    Carroccio A, Soresi M, D'Alcamo A et al (2014) Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC Med 12:230CrossRefGoogle Scholar
  19. 19.
    Norgaard M, Farkas DK, Pedersen L, Erichsen R, de la Cour ZD, Gregersen H, Sorensen HT (2011) Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study. Br J Cancer 104:1202–1206CrossRefGoogle Scholar
  20. 20.
    Hsiao CW, Huang WY, Ke TW, Muo CH, Chen WT, Sung FC, Kao CH (2014) Association between irritable bowel syndrome and colorectal cancer: a nationwide population-based study. Eur J Intern Med 25:82–86CrossRefGoogle Scholar
  21. 21.
    Lai SW, Liao KF, Lin CL, Sung FC (2014) Irritable bowel syndrome correlates with increased risk of Parkinson’s disease in Taiwan. Eur J Epidemiol 29:57–62CrossRefGoogle Scholar
  22. 22.
    Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739CrossRefGoogle Scholar
  23. 23.
    Kanis JA, Hans D, Cooper C et al (2011) Interpretation and use of FRAX in clinical practice. Osteoporos Int 22:2395–2411CrossRefGoogle Scholar
  24. 24.
    Lai SW, Liao KF, Lai HC, Tsai PY, Lin CL, Chen PC, Sung FC (2013) Risk of major osteoporotic fracture after cardiovascular disease: a population-based cohort study in Taiwan. J Epidemiol 23:109–114CrossRefGoogle Scholar
  25. 25.
    Dinan TG, Quigley EM, Ahmed SM, Scully P, O'Brien S, O'Mahony L, O'Mahony S, Shanahan F, Keeling PW (2006) Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology 130:304–311CrossRefGoogle Scholar
  26. 26.
    Dinan TG, Clarke G, Quigley EM, Scott LV, Shanahan F, Cryan J, Cooney J, Keeling PW (2008) Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors. Am J Gastroenterol 103:2570–2576CrossRefGoogle Scholar
  27. 27.
    Katz S, Weinerman S (2010) Osteoporosis and gastrointestinal disease. Gastroenterol Hepatol (NY) 6:506–517Google Scholar
  28. 28.
    Khayyat Y, Attar S (2015) Vitamin D deficiency in patients with irritable bowel syndrome: does it exist? Oman Med J 30:115–118CrossRefGoogle Scholar
  29. 29.
    Williams CE, Williams EA, Corfe BM (2018) Vitamin D status in irritable bowel syndrome and the impact of supplementation on symptoms: what do we know and what do we need to know? Eur J Clin Nutr.
  30. 30.
    Cozma-Petrut A, Loghin F, Miere D, Dumitrascu DL (2017) Diet in irritable bowel syndrome: what to recommend, not what to forbid to patients! World J Gastroenterol 23:3771–3783CrossRefGoogle Scholar
  31. 31.
    McKenzie YA, Bowyer RK, Leach H et al (2016) British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update). J Hum Nutr Diet 29:549–575CrossRefGoogle Scholar
  32. 32.
    Warden SJ, Robling AG, Haney EM, Turner CH, Bliziotes MM (2010) The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Bone 46:4–12CrossRefGoogle Scholar
  33. 33.
    Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G (2008) Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135:825–837CrossRefGoogle Scholar
  34. 34.
    Fernandes BS, Hodge JM, Pasco JA, Berk M, Williams LJ (2016) Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression. Drugs Aging 33:21–25CrossRefGoogle Scholar
  35. 35.
    Sikander A, Rana SV, Prasad KK (2009) Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta 403:47–55CrossRefGoogle Scholar
  36. 36.
    Wu Q, Bencaz AF, Hentz JG, Crowell MD (2012) Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int 23:365–375CrossRefGoogle Scholar
  37. 37.
    Zhou C, Fang L, Chen Y, Zhong J, Wang H, Xie P (2018) Effect of selective serotonin reuptake inhibitors on bone mineral density: a systematic review and meta-analysis. Osteoporos Int 29:1243–1251CrossRefGoogle Scholar
  38. 38.
    Nevitt MC, Cummings SR, Stone KL, Palermo L, Black DM, Bauer DC, Genant HK, Hochberg MC, Ensrud KE, Hillier TA, Cauley JA (2005) Risk factors for a first-incident radiographic vertebral fracture in women > or = 65 years of age: the study of osteoporotic fractures. J Bone Miner Res 20:131–140CrossRefGoogle Scholar
  39. 39.
    Melton LJ 3rd, Hartmann LC, Achenbach SJ, Atkinson EJ, Therneau TM, Khosla S (2012) Fracture risk in women with breast cancer: a population-based study. J Bone Miner Res 27:1196–1205CrossRefGoogle Scholar
  40. 40.
    Chen Z, Maricic M, Bassford TL, Pettinger M, Ritenbaugh C, Lopez AM, Barad DH, Gass M, Leboff MS (2005) Fracture risk among breast cancer survivors: results from the Women’s Health Initiative Observational Study. Arch Intern Med 165:552–558CrossRefGoogle Scholar
  41. 41.
    Khosla S, Amin S, Orwoll E (2008) Osteoporosis in men. Endocr Rev 29:441–464CrossRefGoogle Scholar
  42. 42.
    Houghton LA, Jackson NA, Whorwell PJ, Morris J (2000) Do male sex hormones protect from irritable bowel syndrome? Am J Gastroenterol 95:2296–2300CrossRefGoogle Scholar
  43. 43.
    Kim BJ, Rhee PL, Park JH, Chang DK, Kim YH, Son HJ, Kim JJ, Rhee JC, Lee H (2008) Male sex hormones may influence the symptoms of irritable bowel syndrome in young men. Digestion 78:88–92CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • Herng-Sheng Lee
    • 1
  • Chi-Yi Chen
    • 2
  • Wan-Ting Huang
    • 3
  • Li-Jen Chang
    • 2
  • Solomon Chih-Cheng Chen
    • 4
    • 5
  • Hsin-Yi Yang
    • 3
    Email author
  1. 1.Department of Pathology and Laboratory MedicineKaohsiung Veterans General HospitalKaohsiungTaiwan
  2. 2.Department of Internal medicine, Division of Gastroenterology and HepatologyDitmanson Medical Foundation Chia-Yi Christian HospitalChia-Yi CityTaiwan
  3. 3.Clinical Medicine Research CenterDitmanson Medical Foundation Chia-Yi Christian HospitalChia-Yi CityTaiwan
  4. 4.Heng Chun Christian HospitalPingtung CountyTaiwan
  5. 5.Department of Pediatrics, School of MedicineTaipei Medical UniversityTaipeiTaiwan

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