Effects of Anticancer Therapy on Osteoporosis in Breast Cancer Patients: A Nationwide Study Using Data from the National Health Insurance Service-National Health Information Database

<b>Background/Objectives</b>: This nationwide retrospective study evaluated the effects of anticancer therapy on osteoporosis in 126,132 Korean breast cancer survivors from 2002 to 2020. <b>Methods</b>: The Cox proportional hazards model assessed the effects of treatment on osteoporosis. To circumvent the guarantee-time bias for osteoporosis development, a landmark analysis was employed. A stabilized inverse probability of treatment weighting was performed to control any confounding bias. The propensity score was calculated using a multinomial logistic regression model with age, national health insurance, and the Charlson comorbidity index. <b>Results</b>: During a median follow-up of 4.22 years, 28,603 cases of osteoporosis were documented. Aromatase inhibitors (AIs) were associated with a higher risk of osteoporosis development in comparison to tamoxifen (TMX) or chemotherapy. Notably, AIs administered subsequent to a combination of chemotherapy and anti-HER2 therapy exhibited the highest risk of osteoporosis development. Subgroup analysis revealed that the mean interval from breast cancer diagnosis to osteoporosis development was 5.00 years for women diagnosed with cancer at age < 50 and 3.89 years for those diagnosed at age ≥ 60. TMX increased the risk of osteoporosis in women diagnosed with cancer at age < 50, whereas chemotherapy was not a significant risk factor for osteoporosis development in those diagnosed at age ≥ 60. The impact of anticancer therapy on osteoporosis development was more pronounced in women diagnosed with breast cancer at a younger age compared to those diagnosed at an older age. <b>Conclusions</b>: Effective prevention and active management strategies should be implemented to address bone loss in both younger and older breast cancer patients.