To investigate the changes in bone metabolism markers after second‐line treatment with loading dose intravenous (i.v.) ibandronate in patients with bone metastases (BM) from breast cancer, 80 patients were enrolled in this study during January 2010 to April 2014. All the patients were treated with a second‐line loading dose ibandronate for advanced breast cancer with BM and moderate‐to‐severe bone pain. Ibandronate (6 mg) was intravenously administered on three consecutive days followed by maintenance treatment every 3‐4 weeks. Clinical data, including pain score, Karnofsky performance status (KPS) score, and changes in bone metabolism markers, were analyzed. Sixty‐two patients were included in the final analysis. Compared with their pre‐treatment scores, patients exhibited significantly increased KPS scores (P < .01) and a reduced dose of analgesic medication (oxycodone) (P < .01) after 3 and 6 weeks’ post‐treatment. The levels of serum bone alkaline phosphatase (BAP), tartrate‐resistant acid phosphatase (TRACP‐5b), and cross‐linked carboxy‐terminal telopeptide of type I collagen (ICTP) were significantly reduced after 3 and 6 weeks’ post‐treatment (P < .001). Aside from a few adverse events, no liver or renal toxicity was observed. Bone metabolism markers decreased by varying degrees after treatment with a loading dose of ibandronate in patients with BM from breast cancer. It might be convenient using bone metabolism markers to potentially evaluate the efficacy of bisphosphonates treatment for bone metastasis.