8384 Reproductive Cancer Risk in Patients Treated with Denosumab Compared with Alendronate: A Population-based Cohort Study

Abstract Disclosure: S.K. Yahyavi: Research Investigator; Self; Principal investigator (PI) on an RCT with denosumab. C. Selmer: None. C. Torp-Pedersen: None. A. Juul: None. M. Blomberg Jensen: Other; Self; Holds two patents on the use of RANKL inhibitors to treat male infertility. Background and Objective: Antiresorptive treatment is used in millions of patients with osteoporosis and cancer but during the early studies of denosumab there was a slight increase in ovarian cancer incidence. The aim of this study is to determine the association between use of denosumab and risk of reproductive cancers compared with the use of alendronate in both men and women. Methods: Using a retrospective study design, we combined the Danish registries and identified a population of subjects > 50 years of age. We compared users of Denosumab that had been on alendronate treatment for at least 6 months with a matched population of patients that had been treated for at least 6 months with alendronate alone. Using the L-TMLE method we estimate the risk of reproductive cancers and the risk difference between the groups. Secondary analysis included comparisons with a healthy background population. Results: In the main analysis, a total of 18,162 subjects were included, with 6,054 denosumab users matched 1:2 with 12,108 alendronate users and followed for 3 years. 727 women and 183 men were diagnosed with a reproductive cancer during follow-up. Use of denosumab was not associated with higher risk of reproductive cancer. Compared to alendronate, women who received treatment with denosumab had a 0.06% (95% CI -0.12%; 0.26%) higher risk of a cancer diagnosis after 3 years of treatment. In a model fully adjusted for socioeconomic factors and comorbidities the risk was 0.01% (95% CI -0.35%; 0.37%) higher. The same results were found in men, and when comparing with a healthy background population and sensitivity analysis only using CKD measurements the results were confirmed. Conclusion: When comparing treatments of denosumab and alendronate, this study finds no increased risk of either cancers overall or specific reproductive cancers in men or women. Presentation: 6/3/2024