Single Dosing of Zoledronic Acid in Cancer Therapy Induced Bone Loss (CTIBL)

Inclusion Criteria:

- Postmenopausal women with Stage I, II or IIIa breast cancer being treated with a
non-steroidal AI.Negative bone scan (no bone metastases).

- Calculated creatinine clearance > 40 ml/min

- Documented T score of less than or equal to -1.5 on DXA scan at the lumbar spine or
femoral neck within 3 months prior to screening.

- Urine NTx > 50nM BCE based on second morning void.

- Signed informed consent.

- Ambulatory patients at least 18 years of age.

- ECOG 0-2.

- Ability to comply with trial requirements.

Exclusion Criteria:

- Bone Metastases.

- Any woman of child bearing potential.

- Patients with fractures occurring within three months prior to randomization. -
Greater than a 2+ protein on urine dipstick without evidence of contamination or
bacteriuria (may be repeated one time, at least a day apart).

- Calculated creatinine clearance less than 30 mL/min at screening.

- Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL).

- AST or ALT > 2.0 x ULN.

- Serum alkaline phosphatase > 1.5 x ULN. History of hypersensitivity to
bisphosphonates.

- Evidence of vitamin D deficiency (serum 25-(OH) D of less than 15 ng/ml).

- History of uveitis or iritis, except when secondary to trauma, and must have resolved
> 2 years prior to entry.

- A history of invasive malignancy of any organ system, treated or untreated, within
the past 12 months prior to screening; excluding, basal cell or squamous cell
carcinoma of the skin, colonic polyps with non-invasive malignancy which have been
removed, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and
Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed.

- Previous major solid organ transplant recipient or on a transplant waiting list.

- Treatment with any investigational drug within 30 days prior to randomization.

- History of hyperparathyroidism, hypoparathyroidism, Osteogenesis imperfecta, Paget's
disease or any metabolic bone disease other than osteoporosis.

- Any medical condition which would interfere with the action of the study drug or
limit life expectancy to less than 6 months.

- Any medical or psychiatric condition which, in the opinion of the investigator, would
preclude the participant from adhering to the protocol or completing the trial.

- Prior treatment with IV bisphosphonates within the last 2 years.

- Previous use of oral bisphosphonates within the past 2 years (unless used for less
than 8 weeks*). *NOTE: If used less than 8 weeks, the washout period is 6 months.

- Treatment with raloxifene, calcitonin, tibolone or hormone replacement therapy. The
washout period for these medications is 6 months prior to randomization.

- Any treatment with strontium renalate, samarium, sodium fluoride or parathyroid
hormone.

- Use of systemic high dose corticosteroids at an average dose of > 7.5 mg per day of
oral prednisone or equivalent for a period of three months or more prior to
screening.

- Known hypersensitivity to zoledronic acid or other bisphosphonates.

- Current active dental problems including infection of the teeth or jawbone (maxilla
or mandibular); dental or fixture trauma, or a current or prior diagnosis of
osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing
after dental procedures.

- Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction,
implants).