Increased osteoporosis burden and comparative antiresorptive effectiveness in inflammatory bowel disease: a real-world cohort study.

Abstract

Contemporary IBD care lacks precise osteoporosis risk estimates and data on comparative therapy. In U.S., IBD patients had a 56% higher 5-year risk of a new osteoporosis diagnosis (highest in Crohn's disease); denosumab matched bisphosphonates for 1-2-year fracture prevention in this population. Our study prioritizes early screening, steroid-sparing strategies, and individualized antiresorptive therapy. Osteoporosis is a frequent extra-intestinal complication of inflammatory bowel disease (IBD), yet its current burden and the comparative efficacy of available anti-resorptive therapies remain uncertain. Using the US TriNetX network we formed two retrospective cohorts. (1) Adults with IBD (2013-2023) were 1:1 propensity-matched to non-IBD controls to estimate 5-year risk of new osteoporosis diagnosis and identify determinants. (2) IBD patients with osteoporosis initiating denosumab or bisphosphonates (2013-2022) were matched for demographics, comorbidities, and IBD phenotype; spine/hip fractures and risk for incident onset fractures were calculated for both the cohorts. Among 143,248 patients with IBD (mean age 44.2 y; 51.8% female), risk of new osteoporosis diagnosis exceeded controls by 58% at 1 year (adjusted odds ratio [aOR] 1.58, 95% CI 1.51-1.65) and was highest in Crohn's disease (CD) (aOR 1.79, 95% CI 1.68-1.90); ulcerative colitis (UC) also demonstrated increased 1-year risk (aOR 1.47, 95% CI 1.39-1.56). Subgroup analysis showed increased risk in patients age > 65, female sex and Asian race for UC. For CD, age > 65, female sex, nicotine dependence and alcohol use were associated with increased risk. The osteoporosis treatment cohort included 2,423 patients (520 denosumab and 1,903 bisphosphonates). After matching, denosumab produced similar 1-year (2.33% vs 3.49%, aOR 0.65 CI 0.31-1.38) and 2-year (4.65% vs 6.78%; aOR 0.67, CI: 0.39-1.14) fracture rates compared to bisphosphonates. IBD confers a substantially higher and multifactorial osteoporosis risk. Denosumab showed similar observed short-term fracture rates to bisphosphonates, although clinically meaningful differences could not be excluded. Early bone-health screening, steroid-sparing therapy, and individualized antiresorptive treatment remain essential.