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.