Primary Objective: 

To determine whether denosumab compared to placebo will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy (AIT).

Secondary Objective(s): 

To assess the effect of denosumab compared to placebo on the following:

• Incidence of new vertebral fractures (both clinical and morphometric)
• Incidence of new or worsening of pre-existing vertebral fractures (both clinical and morphometric)
• Bone mineral density (BMD) at lumbar spine, total hip and

To assess the safety and tolerability of denosumab in this population

Exploratory Objective(s): 

To assess the effect of denosumab compared to placebo on:

• The incidence of worsening of pre-existing vertebral fractures (both clinical and morphometric)
• Bone metastasis-free survival
• Disease free survival
• Percent change in BMD at lumbar spine, total hip and femoral neck assessed at all participating clinical sites
• Overall survival

This is a multi-center phase 3, randomized, double-blind, placebo-controlled study to determine the treatment effect of denosumab in subjects with breast cancer treated with an approved non-steroidal aromatase inhibitor (AI), (e.g. anastrazole).  Approximately 2800 subjects will be randomized in a 1:1 ratio to receive either denosumab administered at a dose of 60 mg or placebo SC Q6M in a blinded manner.  Subjects will be recruited over approximately 42 months. The randomization schedule will be stratified by: type of hospital (pre-selected centers or other centers), prior AI usage (Y/N) and total lumbar spine BMD score at baseline (T-score < –1.0 vs ³ -1.0).