J Korean Med Sci.  2021 Jul;36(27):e186. 10.3346/jkms.2021.36.e186.

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

  • 1Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea
  • 2Department of Internal Medicine, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon, Korea
  • 3Department of Orthopaedic Surgery, School of Medicine, Konkuk University, Seoul, Korea
  • 4Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
  • 5Department of Orthopaedic Surgery, College of Medicine, Chung-Ang University, Seoul, Korea
  • 6College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Korea
  • 7Division of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
  • 8Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea


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.
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.
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.
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.


Selective Estrogen Receptor Modulators; Bisphosphonate; Osteoporosis; Venous Thromboembolism
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