Abstract: Background　Bone metastases are common in breast cancer patients. With the application of new bone-modifying drugs, the prognosis of patients has been improved. However, long-term use of these drugs may lead to medication-related osteonecrosis of the jaw (MRONJ). Due to its low incidence and difficulty in treatment, it is urgent to study its patterns and mechanisms. Objective　To analyze the clinical characteristics, features of jaw necrosis, prognostic differences, and potential predictive factors in breast cancer patients with bone metastases who develop jaw necrosis after bone-modifying agent therapy, and construct a prediction model to provide reference for clinical diagnosis and treatment.Methods　Female patients diagnosed with breast cancer with bone metastases who received bone-modifying drugs treatment for more than one year at the Fifth Medical Center of PLA General Hospital from January 2011 to January 2025 were enrolled. Among patients with MRONJ, the clinical characteristics, risk factors, and prognostic differences among different drug groups were analyzed. Additionally, by comparing the differences in clinical characteristics and risk factors between patients with MRONJ and those without MRONJ, a multi-factor combined prediction model was constructed, and the predictive efficacy of the model was analyzed.Results　Among the 1 782 patients, 35 cases (1.96%) developed medication-related osteonecrosis of the jaw (MRONJ), including 23 patients who received bisphosphonates (bisphosphonate group) with a mean age of 49.7 years, and 12 patients who received denosumab with or without bisphosphonates (denosumab group) with a mean age of 46.25 years. There were no statistically significant differences in clinical characteristics between the two groups, including age, molecular subtypes, bone metastases status, duration of bone-modifying drugs, location and stage of osteonecrosis of the jaw, and skeletal-related events after drug discontinuation(P＞0.05). Before the occurrence of osteonecrosis of the jaw in breast cancer patients with bone metastasis treated with bone-modifying drugs, patients had a history of poor oral hygiene, tooth extraction, periodontal infection, comorbidities such as cardiopulmonary diseases and diabetes mellitus, as well as prior use of anti-angiogenic drugs and dexamethasone for prophylaxis of chemotherapy-induced allergy and antiemesis. The median time to osteonecrosis of the jaw occurrence in the denosumab group was 42 (IQR: 31 – 64) months, which was earlier than 47 (IQR: 39 – 76) months in the bisphosphonate group. The median overall survival (OS) from the application of bone-modifying drugs to death was 7.3 (IQR: 5.7 – 10.0) years. The OS in the denosumab group was 6.75 (IQR: 5.9 – NE Not Estimated) years, and that in the bisphosphonate group was 7.3 (IQR: 4.6 – 9.6) years, with no statistically significant difference between the two groups (P=0.593). The presence of tooth extraction, dexamethasone pretreatment dose (≥150 mg), and duration of bone-modifying drugs use (≥4 years) were closely associated with the development of medication-related osteonecrosis of the jaw, with OR (95% CI) of 1.197 (1.006 – 1.425), 1.573 (1.253 – 1.975), and 3.514 (1.802–6.858), respectively. Nomogram analysis of the predictive model for medication-related osteonecrosis of the jaws showed that the duration of bone-modifying drugs use was the most significant contributing factor in the model. ROC analysis showed that the area under the receiver operating characteristic curve (ROC-AUC) of the predictive model was 0.834 (95% CI: 0.734 – 0.936), with a Youden index of 0.686.Conclusion　In breast cancer patients with bone metastasis, osteonecrosis of the jaw tends to occur after ≥4 years of bone-modifying drugs use, accompanied by poor quality of life. Prolonged duration of bone-modifying drugs use is the most critical risk factor. The predictive model developed in this study demonstrates high application value in clinical practice.