Impact of antiresorptive agents on mortality risk in postmenopausal women with osteoporosis: insights from a nationwide cohort study

Abstract Importance Osteoporosis-related fractures are associated with increased mortality risk among postmenopausal women, yet the impact of antiosteoporotic medications on mortality is not fully understood. Objective This study evaluates the effect of antiresorptive agents (ARs) on mortality risk in postmenopausal women with osteoporosis. Design This is a nationwide cohort study using data from the National Screening Program for Transitional Ages (2008-2017). Setting Data were derived from a national cohort of postmenopausal women in South Korea. Participants This study included 117 871 postmenopausal women diagnosed with osteoporosis. Of them, 15 895 patients who used ARs, such as bisphosphonates or selective estrogen receptor modulators, for at least 1 year were matched 1:1 with nonusers using propensity scores. Exposures Exposure to ARs for at least 1 year was compared with no AR use. Main Outcomes and Measure Mortality outcomes were assessed using multivariable Cox proportional hazard regression models, focusing on all-cause mortality and cause-specific mortality, particularly cardiovascular disease (CVD) and injury-/fracture-related deaths. Results In AR users, there were 102 deaths (mortality rate 1.41 per 1000 person-years), compared with 221 deaths in non-users (mortality rate 3.14 per 1000 person-years), yielding a hazard ratio (HR) of 0.43 (95% CI, 0.34-0.54). Antiresorptive agent users showed a 52% reduction in CVD mortality risk (HR, 0.48; 95% CI, 0.34-0.69) and a 54% reduction in injury-/fracture-related mortality risk (HR, 0.46; 95% CI, 0.27-0.76). The analysis indicated a consistent decrease in all-cause and CVD mortality risks with longer durations of AR use. Conclusions and Relevance The use of ARs in postmenopausal women with osteoporosis is associated with significantly lower risks of all-cause mortality, especially from cardiovascular events and fractures. The mortality reduction benefits appear to be enhanced with prolonged AR therapy, highlighting the potential importance of sustained treatment in this population.