Background <p>Despite the association between osteoporosis treatment and reduced mortality, evidence on specific-cause mortality is lacking. Therefore, this study explored the association between osteoporosis under treatment and all-cause and specific-cause mortalities using nationwide retrospective cohort data from South Korea.</p> Methods <p>This study utilized data from the National Health Insurance Service screening cohort of South Korea from 2002 to 2019. Participants with osteoporosis who had undergone treatment at least twice and were diagnosed based on bone densitometry were included. Control groups were matched 1:1 based on age, sex, income, and region. Propensity score overlap weighting was applied to balance covariates. Cox proportional hazards models and Fine–Gray sub-distribution hazard models were used to assess all-cause and specific-cause mortalities across 14 disease categories based on the Korean standard classification of diseases.</p> Results <p>Finally, 34,181 participants were included in both osteoporosis and control groups. The largest age group was 55–59 years, with a majority of female participants (81.60%). Osteoporosis under treatment was significantly associated with reduced all-cause mortality with consistent results across various demographic and clinical subgroups. Specific-cause mortality analysis revealed lower mortality due to neoplasms and metabolic diseases and higher mortality from respiratory and muscular diseases. However, increased risks of respiratory and muscular disease-related mortality were observed.</p> Conclusions <p>Osteoporosis treatment was associated with reduced all-cause and specific-cause mortalities, particularly from neoplasms and metabolic diseases. Further studies, particularly randomized controlled trials, are required to confirm these results, establish causality, and explore the medication-specific effects on mortality.</p>