Comparisons Between Different Anti-osteoporosis Medications on Postfracture Mortality: A Population-Based Study

Context: Osteoporosis is becoming a global epidemic in aging societies. Anti-osteoporotic medications can prevent fractures, and their pleiotropic effect on mortality is interesting but not well compared among each other. Objective: To provide real-world evidence on the pleiotropic effect of different anti-osteoporotic medications on all-cause mortality, stratified by fracture site, sex, and age. Methods: This longitudinal population-based postfracture cohort study, included mega-data from subjects ≥40 years of age with osteoporotic fracture who used anti-osteoporotic medications as recorded in Taiwan's National Health Insurance Research Database from 2009 to 2017 and followed until 2018. A multivariate Cox proportional hazards model with immortal time bias was used to assess the relationship between fracture sites and mortality stratified by anti-osteoporosis medication. Results: A total of 46 729 subjects with an average age of 74.45 years (80.0% female) and a mean follow-up period of 4.73 years were enrolled. In the total fracture group, compared with raloxifene and bazedoxifene, we found that alendronate/risedronate (hazard ratio [HR] 0.83; 95% CI, 0.79-0.88), denosumab (HR 0.86; 95% CI, 0.81-0.91), and zoledronic acid (HR 0.78; 95% CI, 0.73-0.84) resulted in significantly lower mortality. Similar trends were observed in the hip, vertebral, or nonhip/nonvertebral fracture groups. Subjects receiving long-acting zoledronic acid showed the lowest mortality in the subanalysis according to sex or age over 65 years. Conclusion: This real-world mega-data study suggests that the usage of osteoporotic medication, especially a long-acting regimen, may lower postfracture mortality.