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Fracture Risk in Patients With Inflammatory Bowel Disease

A Nationwide Population-Based Cohort Study From 1964 to 2014

Ludvigsson, Jonas F.1–4; Mahl, Martin5,6; Sachs, Michael C.7; Björk, Jan5,6; Michaelsson, Karl8; Ekbom, Anders9; Askling, Johan10; Backman, Ann-Sofie5,6; Olén, Ola9–11

American Journal of Gastroenterology: February 2019 - Volume 114 - Issue 2 - p 291–304
doi: 10.14309/ajg.0000000000000062

INTRODUCTION: Most studies on fractures in inflammatory bowel disease (IBD) are based on patients from tertiary centers or patients followed up before the introduction of immunomodulators or biologics. In addition, the role of corticosteroids in fracture risk has rarely been examined.

METHODS: We conducted a nationwide population-based cohort study of 83,435 patients with incident IBD (ulcerative colitis [UC]: n = 50,162, Crohn's disease [CD]: n = 26,763, and IBD unclassified: 6,510) and 825,817 reference individuals from 1964 to 2014. Using multivariable Cox regression, we estimated hazard ratios (HRs) for hip fracture and any fracture and the association with cumulative corticosteroid exposure.

RESULTS: During 1,225,415 person-years of follow-up in patients with IBD, there were 2,491 first-time hip fractures (203/100,000 person-years) compared with 20,583 hip fractures during 12,405,642 person-years in reference individuals (159/100,000 person-years). This corresponded to an HR of 1.42 (95% confidence interval [CI] = 1.36–1.48). The risk for hip fracture was higher in CD compared with UC (P < 0.001). Inflammatory bowel disease was also associated with any fracture (IBD: HR = 1.18; 95% CI = 1.15–1.20). Hazard ratios for hip fracture had not changed since the introduction of immunomodulators or biologics. Increasing exposure to corticosteroids was associated with hip fracture in both IBD and non-IBD individuals (P < 0.001), but only in elderly (>60 years) patients with IBD. The association between IBD and hip fracture was nonsignificant among individuals without corticosteroids (HR = 1.11; 95% CI = 0.86–1.44).

CONCLUSIONS: Inflammatory bowel disease (CD and UC) is associated with an increased risk of hip fracture and any fracture, but not in individuals without a history of corticosteroid treatment. The association between corticosteroids and hip fracture was restricted to elderly patients with IBD.

1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;

2Department of Paediatrics, Örebro University Hospital, Örebro, Sweden;

3Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK;

4Columbia University, New York, New York, USA;

5Patient Area Gastroenterology, Dermatovenerology and Rheumatology, Inflammation and Infection Theme Karolinska University Hospital, Stockholm, Sweden;

6Unit of Internal Medicine, Institute Medicine Solna, Karolinska Institutet, Stockholm, Sweden;

7Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden;

8Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;

9Clinical Epidemiology Unit, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden;

10Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden;

11Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.

Correspondence: Jonas F. Ludvigsson. Email:

Received June 05, 2018

Accepted October 23, 2018

© The American College of Gastroenterology 2019. All Rights Reserved.
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