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Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD.The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I–IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1–L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints wererate of change in the lumbar spine (L1–L4) BMD after 2, 3, 4, and 5 years;rate of change in the femoral neck BMD;rate of change in radius BMD (determined using an ultrasonic bone densitometer);changes in calcium and bone metabolism markers (TRAP 5b, bone alkaline phosphatase, and pentosidine);development of pathological fracture within 3 years;disease-free survival;overall survival (OS);adverse events; andquality of life.The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals.Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.