OBJECTIVES: Patients with breast cancer (BC) and bone metastases are at risk for skeletal-related events (SREs) that are associated with significant morbidity, mortality, and reduced quality of life. The intravenous bisphosphonates (IVBPs) zoledronic acid (ZOL) and pamidronate (PAM) are approved for treating patients with bone metastases from BC. We compared incidence of SREs and mortality in women with BC who received ZOL or PAM, and assessed the long-term benefit of ZOL in a real-world setting. METHODS: A claims-based analysis of commercial and Medicare Advantage data from >45 US managed care plans was used to evaluate SRE rates and mortality in patients treated with ZOL or PAM. Inclusion criteria were age >18 years, BC with bone metastasis diagnosis between 01/01/01 and 12/31/06, continuous enrollment in the health plan, no evidence of bone metastasis or IVBP for 6 months before an index date of first receipt of ZOL or PAM. Patients were followed until disenrollment (including mortality) or study completion (12/31/07). Persistency was defined as the absence of a >45-day gap between treatments. SREs were defined as evidence of pathologic fracture, spinal cord compression, and radiotherapy or surgery to bone. RESULTS: Among 8,757 patients (mean age, 58.1±12.4 years) approximately 30% received ZOL, 15% received PAM, and 55% received no IVBP. Longer persistency with ZOL was associated with lower risk of fracture and of all SREs versus shorter persistency (trend test, P=.0026 and P=.0216, respectively). ZOL-treated patients had a moderately lower SRE incidence (36.2 versus 40.0 per 100 person-years; P=.0707) and significantly fewer deaths (6.2 versus 8.9 per 100 person-years; P=.0130) versus PAM-treated patients. CONCLUSIONS: In a real-world assessment of women with bone metastases from BC, ZOL reduced SRE incidence and significantly improved survival versus PAM. Longer ZOL persistency was associated with lower SRE risk, reinforcing the importance of regular monthly ZOL dosing.