Objective To investigate the effect of graded prevention program for bone safety led by case manager in patients with breast cancer. Methods A total of 272 breast cancer patients were selected and divided into 2 groups of 136 cases each according to the admission time. The control group was given routine preventive measures for osteoporosis, while the intervention group joined in a graded prevention program for bone safety led by case manager. Patients in the two groups were continuously followed up for two years, and the risk levels of osteoporosis, the incidence rate of osteoporosis, and the incidence rate of osteoporotic fractures were analyzed and compared between the two groups. Results Totally,119 patients in the control group and 127 patients in the intervention group completed the entire study and follow-ups. The risk levels of osteoporosis, the incidence of osteoporosis, and the incidence rate of osteoporotic fracture in the intervention group were significantly lower than those in the control group (all P<0.05). Conclusion The graded prevention program for bone safety led by case managers can effectively improve the effectiveness of bone safety management in breast cancer patients, and improve the prognosis of patients.