Incidence and Risk of Venous Thromboembolism in Bisphosphonates and Selective Estrogen Receptor Modulators Treatment in Korea

Background Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database. Methods This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model. Results The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40-1.28) in the SERMs group compared to BP group. Older age (60-69 vs. 50-59 years: HR, 3.77; 95% CI, 2.07-6.86 and 70-79 vs. 50-59 years: HR, 5.88; 95% CI, 3.14-11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35-8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01-5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02-4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29-14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05-7.0) increased VTE risk. Conclusion SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.