P0699 Comparative Effectiveness and Safety of Denosumab Versus Bisphosphonates in Osteoporosis Management Among Patients with Inflammatory Bowel Disease: A U.S. Propensity Matched Cohort Study

Abstract Background Denosumab, a fully monoclonal antibody, is approved for the treatment of osteoporosis, including glucocorticoid-induced osteoporosis. Denosumab is an alternative to bisphosphonate therapy and has been shown to improve bone mineral density, and reduce the incidence of new fractures, however there is limited data in patients with inflammatory bowel disease (IBD). Through this study we evaluate the effectiveness of denosumab versus bisphosphonates in reducing osteoporosis-related fractures and safety related to IBD-specific outcomes. Methods We conducted a retrospective cohort study using a U.S. multi-institutional database (TriNetX), examining patients with IBD with osteoporosis who were initiated on denosumab or bisphosphonates from 2013 to 2022. The primary aim of the study was to assess the 1- and 2-year risk of de-novo fractures (spine and/or hip) in the denosumab cohort compared to bisphosphonate cohort. Cox proportional hazard model was used to identify predictors of denosumab failure. The secondary aim was to evaluate the 2-year risk of IBD-related outcomes which included corticosteroid use, advanced therapy initiation, and surgery. 1:1 propensity score matching (PSM) was performed for demographics, comorbid conditions, BMI, hemoglobin, albumin, calcium/vitamin D supplementation, IBD medications including steroid use. Results Among 2,423 patients with IBD and osteoporosis (mean age 62.8, female sex 67.3%, Crohn’s disease 48.5%), 520 received denosumab and 1,903 received bisphosphonates. After PSM, there was no difference in the 1-year (2.33% vs 3.49%, aOR 0.65, 95% CI 0.31-1.38) and 2-year risk (4.65% vs 6.78%, aOR 0.65, 95% CI 0.39-1.14) of fractures between the denosumab cohort compared to the bisphosphonates cohort. In terms of IBD-related outcomes, denosumab was associated with a lower risk of prednisone use (aOR 0.73, 95% CI 0.56–0.96) but no significant difference in the risk of de-novo advanced therapy use (aOR: 0.76, 95% CI 0.442–1.334), IV steroid use (aOR 1.13, 95% CI 0.78–1.64) and surgery (aOR 0.79, 95% CI 0.49-1.27) [Table 1]. After cox regression analysis, chronic steroid use (HR 1.99, 95% CI 1.26-3.1), prednisone use (HR 1.71, 95% CI: 1.07–2.72) and history of falls (HR 3.00, 95% CI 1.34-4.09) as significant predictors of treatment failure with denosumab [Figure 1]. Conclusion Our study highlights the comparable effectiveness of denosumab compared to bisphosphonates in reducing the risk of fractures in patients with IBD and osteoporosis. There were no IBD-related safety signals related to denosumab use compared to bisphosphonates. Further prospective studies are needed to optimize osteoporosis management in this high-risk population.