A nationwide cohort study of inflammatory bowel disease, histological activity and fracture risk

• Published in: Alimentary pharmacology & therapeutics 2024-12, Vol.60 (11-12), p.1549-1560
• Main Authors: Mårild, Karl, Söderling, Jonas, Axelrad, Jordan, Halfvarson, Jonas, Forss, Anders, Michaëlsson, Karl, Olén, Ola, Ludvigsson, Jonas F.
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones; Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Biopsy; Bone; Cohort Studies; Comorbidity; complications; Corticosteroids; Crohn's disease; epidemiology; etiology; Female; Fractures; Fractures, Bone - epidemiology; Fractures, Bone - etiology; Gastroenterologi; Gastroenterology and Hepatology; Humans; IBD Histology and Fracture Risk; Inflammation; Inflammatory bowel disease; Inflammatory Bowel Diseases; Inflammatory Bowel Diseases - complications; Intestine; Male; Medicin och hälsovetenskap; Middle Aged; Original; Patients; Proportional Hazards Models; Remission; Remission (Medicine); Risk Factors; Sensitivity analysis; Steroids; therapeutic use; Ulcerative colitis; Young Adult
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.18275

Summary Background Individuals with inflammatory bowel disease (IBD) are at increased risk of fracture. It is unclear if this risk varies by recent histological activity. Aims To determine the fracture risk in IBD during periods with and without histological inflammation. Methods We studied a nationwide cohort of 54,591 individuals diagnosed with IBD in 1990–2016 with longitudinal data on ileo‐colorectal biopsies. Fractures were identified by inpatient and hospital‐based outpatient diagnoses. We derived Cox regression estimated hazard ratios (HRs) for fracture during 12 months following a histological inflammation (vs. histological remission) record after adjusting for socio‐demographics, comorbidities, IBD duration, IBD‐related surgery and hospitalization. We adjusted sensitivity analyses for medical IBD treatment including corticosteroids. Results Mean age of patients was 44.0 (SD = 18.3) and 45.5 (SD = 17.1) years at biopsy with histological inflammation and remission, respectively. For histological inflammation, there were 1.37 (95% CI 1.29–1.46) fractures per 100 years' follow‐up versus 1.31 (95% CI 1.19–1.44) for remission (adjusted [a]HR 1.12; 95% CI 1.00–1.26; p = 0.04). HRs were similar with histological inflammation of Crohn's disease (1.11; 95% CI 0.91–1.36) and ulcerative colitis (1.18; 95% CI 1.02–1.36). Estimates were consistent across age groups. An overall small excess risk of any fracture remained after accounting for corticosteroids. A more prominently raised fracture risk was observed in corticosteroid‐naïve IBD patients with histological inflammation versus histological remission (aHR 1.41; 95% CI 1.07–1.85). The aHR of hip fracture following histological inflammation was 1.29 (95% CI 0.87–1.92). Conclusions Histological inflammation in IBD predicted a small increase in short‐term fracture risk. Measures to reduce disease activity may reduce fracture risk in IBD. In this nationwide IBD cohort, there was a 12% increased fracture risk during 1‐year periods with versus without histological inflammation. The findings reinforce the notion that measures to reduce disease activity may prevent fracture risk in IBD.