Abstract Background With the positive outcomes associated with Ovarian Function Suppression (OFS) treatment as reported in the ASTRRA study, which compare two therapeutic strategies, tamoxifen alone and ovarian function suppression (OFS) in premenopausal patients after chemotherapy, the role of OFS has getting important. However, considering the increased risk of bone density reduction associated with postmenopause in women, the understanding these effects is crucial in devising strategies that not only effectively combat the cancer but also concurrently safeguard the patients’ bone health. This study aimed to compare the impacts of two therapeutic strategies, tamoxifen alone and OFS on bone mineral density (BMD) in premenopausal patients after chemotherapy. Methods Of the 1483 premenopausal enrolled in ASTRRA study, we focused on a subset of 522 patients who had undergone BMD examinations at diagnosis, 3 years and 5 years after diagnosis. Patients were stratified into three categories: normal, osteopenia, osteoporosis, and we examined the changes in their classifications over the 3-year and 5-year periods from baseline to identify any deterioration in bone density. Also, Patients were examined ovarian function every 6 months for 2 years and have different randomization times. Further categorization was carried out according to the time of randomization, which means starting time of OFS after recovery of ovary function. Lastly, we conducted a subset analysis using data from the Asan Medical Center (AMC), specially focused on the absolute value of one density measured in g/cm3. Results The median age of 522 patients was 41.1 and at baseline, a higher incidence of osteopenia was observed in the OFS addition group (p=0.028). Both analysis of change in BMD categories of from baseline to 3-year and baseline to 5-year period showed no significant differences between TAM only and TAM+OFS group (3-year: p=0.567, 5-year: p=0.600). However, there was a significant increased risk of bone density deterioration in the OFS addition group, when randomization occurred at the first visit (HR= 2.970, p=0.008). Within the AMC subset, statistically significant decrease in BMD were observed in the OFS addition group at the spine (p=0.023) and femur (p=0.040) over a baseline to 3-year period. Although a decrease in BMD was also observed over a baseline to 5-year period at both the spine and femur, this change was not statistically significant. Conclusion This study revealed a deleterious impact on bone density associated with the addition of OFS, compared to tamoxifen-only treatment. Remarkably, our findings also indicated that early suppression of ovarian function exerts even more detrimental influence on bone health in premenopausal, estrogen receptor-positive breast cancer patients, who have recovered ovarian function. Change between baseline to 5 years according to randomization time interval The table shows the risk associated with bone health deterioration according to the duration of randomization, thus specifying the time interval between the recovery and suppression of ovarian function. Citation Format: Eunju Shin, Seung Il Kim, Min-ho Park, Hyun-Ah Kim, Yongsik Jung, Jai Min Ryu, Eun Hwa Park, Sung Yong Kim, Eun-Gyeong Lee, Min Hyuk Lee, Jung Ho Park, Seock-Ah Im, Soong June Bae, Su Hwan Kang, Woosung Lim, Hyun Jo Youn, Heung Kyu Park, Kyong Hwa Park, Tae-Hyun Kim, Shin-Young Park, Cheol wan Lim, Geum-Hee Kwak, Chanheun Park, Hyuk-Jae Shin, Young Bum Yoo, Sun Hee Kang, Bong Kyun Kim, Hee Jeong Kim. Comparative Study on Bone Mineral Density in Premenopausal Patients with Estrogen Receptor-Positive Breast cancer in ASTRRA study: a 5-year follow-up study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-06.