Bone is the most common site of spread of breast cancer and bone metastases will occur in roughly 70% of women with advanced disease. These patients are at risk of developing bone complications that cause significant impact on both patient morbidity and mortality. Close to two-thirds of women with bone metastases will go on to develop at least one of these complications, termed a skeletal related event (SRE), defined as 1) pathological fractures, 2) pain requiring radiation or surgical intervention, 3)spinal cord compression, and 4) hypercalcemia. In addition to SREs, most breast cancer patients with bone metastases have some degree of pain associated with their disease. Understandably these factors negatively impact their quality of life. Furthermore, the development of an SRE in this population has been shown to be associated with shorter overall survival. Prevention or delay in onset of these complications is therefore an important therapeutic goal.

Inclusion Criteria:

1. Patients must have histologically confirmed breast cancer.
2. Radiological or pathological evidence of bone metastases. (positive bone scan, MRI, or CT or pathological fracture, or pathological sample from bone biopsy showing evidence of metastatic breast cancer).
3. Patient has not yet started on BP therapy for metastatic breast cancer to bone.
4. Renal (serum creatinine, BUN), hepatic (AST, ALT, Bilirubin) function within the institutional normal range as assessed within 1 month of study entry.
5. Age >/= 18 years.
6. Karnofsky performance status ≥ 50.
7. Life expectancy > 6 months.
8. Ability to understand and the willingness to sign a written informed consent document.
9. Patients may receive any chemotherapy, biological or endocrine treatment considered appropriate by the treating physician. This can be changed during the course of the study as clinically indicated.
10. Patients may be on another clinical trial, if allowed by the Trial Steering Committee for that trial.
11. Patients are willing to take calcium and vitamin D supplements as recommended, while on study.

Exclusion Criteria:

1. Hypersensitivity or known allergy to bisphosphonates.
2. Patient currently taking Bisphosphonate therapy for metastatic breast cancer to bone (Clodronate, Pamidronate, Zoledronic Acid, Ibandronate, Calcitonin). Bisphosphonates for the treatment of other bone disease (osteoporosis, osteopenia, Paget's disease, etc) but not Zoledronic Acid, are permitted.
3. Acute or chronic renal insufficiency.
4. Hypocalcemia as defined by serum calcium less than institutional normal range.
5. Evidence of infection/abscess on dental exam or recent dental extraction (within last 4 weeks), or presence of osteonecrosis of the jaw.
6. Acute pathological fracture, spinal cord compression, or hypercalcemia requiring urgent treatment (patient may enter study after acute issues are resolved).
7. Patients with baseline hypocalcemia.
8. Patients who have received ZA for prevention of breast cancer treatment-induced osteopenia or osteoporosis within the last 1 year.
9. History and/or electrocardiographic evidence of atrial fibrillation.
10. Pregnancy or lactation.