Comparative Cardiovascular Safety of Romosozumab and Denosumab in Osteoporosis Treatment: A Multinational Real-World Cohort Study
Author(s)
Balqis I. Gusbela, MBA1, Ming Hung Teng, MD2, Min Huei Hsu, PhD3, Chun Feng Huang, PhD4, Jason C. Hsu, PhD1.
1International PhD Program in Biotech and Healthcare Management, Taipei Medical University, Taipei, Taiwan, 2Department of Orthopedics, Sijhih Cathay General Hospital, New Taipei, Taiwan, 3Graduate Institute of Data Science, Taipei Medical University, Taipei, Taiwan, 4Faculty of Medicine School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
1International PhD Program in Biotech and Healthcare Management, Taipei Medical University, Taipei, Taiwan, 2Department of Orthopedics, Sijhih Cathay General Hospital, New Taipei, Taiwan, 3Graduate Institute of Data Science, Taipei Medical University, Taipei, Taiwan, 4Faculty of Medicine School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
OBJECTIVES: In this study, we evaluated the cardiovascular risk associated with romosozumab compared to denosumab in osteoporosis treatment.
METHODS: Data were sourced from TriNetX, with the romosozumab and denosumab cohorts having 3,898 and 49,067 patients, respectively. For this study, we included patients aged 60 years or older who received either drug between January 2019 and December 2024. Propensity score matching (PSM) at 1:1 was performed for baseline characteristics, with 3892 patients included in each group after PSM. Kaplan-Meier analysis was used to estimate the cumulative incidence of cardiovascular outcomes, including three-point major adverse cardiovascular events (3P-MACE) and other cardiovascular events, over a 1-year follow-up period. The primary analysis focused on patients without a prior history of cardiovascular disease. Sensitivity analyses were conducted to evaluate the robustness of the findings under varying conditions: (1) extending the follow-up to 5 years in patients without prior cardiovascular disease, and (2) assessing outcomes at both 1 and 5 years in patients with a prior cardiovascular history.
RESULTS: The analysis revealed no significant differences in 1-year cardiovascular outcomes between romosozumab and denosumab, including 3P-MACE (HR: 0.460; 95% CI: 0.421-1.044; p-value 0.074), heart failure (HR: 0.501; 95% CI: 0.473-1.102; p-value 0.129), hypertension (HR: 1.165; 95% CI: 0.612-2.218; p-value 0.562), cardiomyopathy (HR: 1.134; 95% CI: 0.436-2.95; p-value 0.796), and Peripheral Arterial Disease (PAD) (HR 0.669; 95% CI: 0.682-1.362; p-value 0.835). However, a potential long-term risk of PAD associated with romosozumab was observed in patients with a history of cardiovascular disease (HR: 1.548; 95% CI: 1.143-2.098; p-value 0.004).
CONCLUSIONS: Romosozumab may be a feasible and safe treatment option for osteoporosis, as it was not significantly associated with increased cardiovascular risk or mortality. However, in patients with a history of cardiovascular disease, the use of romosozumab should be approached with caution due to the potential long-term risk of PAD.
METHODS: Data were sourced from TriNetX, with the romosozumab and denosumab cohorts having 3,898 and 49,067 patients, respectively. For this study, we included patients aged 60 years or older who received either drug between January 2019 and December 2024. Propensity score matching (PSM) at 1:1 was performed for baseline characteristics, with 3892 patients included in each group after PSM. Kaplan-Meier analysis was used to estimate the cumulative incidence of cardiovascular outcomes, including three-point major adverse cardiovascular events (3P-MACE) and other cardiovascular events, over a 1-year follow-up period. The primary analysis focused on patients without a prior history of cardiovascular disease. Sensitivity analyses were conducted to evaluate the robustness of the findings under varying conditions: (1) extending the follow-up to 5 years in patients without prior cardiovascular disease, and (2) assessing outcomes at both 1 and 5 years in patients with a prior cardiovascular history.
RESULTS: The analysis revealed no significant differences in 1-year cardiovascular outcomes between romosozumab and denosumab, including 3P-MACE (HR: 0.460; 95% CI: 0.421-1.044; p-value 0.074), heart failure (HR: 0.501; 95% CI: 0.473-1.102; p-value 0.129), hypertension (HR: 1.165; 95% CI: 0.612-2.218; p-value 0.562), cardiomyopathy (HR: 1.134; 95% CI: 0.436-2.95; p-value 0.796), and Peripheral Arterial Disease (PAD) (HR 0.669; 95% CI: 0.682-1.362; p-value 0.835). However, a potential long-term risk of PAD associated with romosozumab was observed in patients with a history of cardiovascular disease (HR: 1.548; 95% CI: 1.143-2.098; p-value 0.004).
CONCLUSIONS: Romosozumab may be a feasible and safe treatment option for osteoporosis, as it was not significantly associated with increased cardiovascular risk or mortality. However, in patients with a history of cardiovascular disease, the use of romosozumab should be approached with caution due to the potential long-term risk of PAD.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD39
Topic
Real World Data & Information Systems
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal)