Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis

Inclusion Criteria:

- Ambulatory postmenopausal women.

- Age 55 years or older

- Subject has provided informed consent prior to any study specific procedures

- Received oral bisphosphonate therapy for osteoporosis at least 2 years prior to
screening visit

- Screening BMD (g/cm²) values at the lumbar spine, total hip or femoral neck values of
equal to or less than those listed in the protocol.

- At least 2 lumbar vertebrae and one hip must be evaluable by dual energy x-ray
absorptiometry (DXA) at the screening visit

Exclusion Criteria:

- Received other osteoporosis treatment or bone active treatment

- Evidence of history of any of the following:

- hyperthyroidism (stable on antithyroid therapy is allowed)

- hypothyroidism (stable on thyroid replacement therapy is allowed)

- hypo- or hyperparathyroidism

- hypo- or hypercalcemia based on the central laboratory reference ranges

- Recent tooth extraction (within 6 months of screening visit)

- Paget disease of bone (subject report or chart review)

- other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis
imperfecta) (chart review)

- Abnormalities of the following per central laboratory reference ranges:

- vitamin D deficiency (25[OH] vitamin D level < 20 ng/mL), repletion will be
allowed and subjects may be re-screened

- hypercalcemia

- elevated transaminases ≥ 2.0 x upper limits of normal (ULN)

- History of any solid organ or bone marrow transplant

- Malignancy (except nonmelanoma skin cancers, cervical or breast ductal carcinoma in
situ) within the last 5 years

- Known intolerance to calcium or vitamin D supplements

- Self-reported alcohol or drug abuse within 12 months prior to screening

- Currently receiving treatment in another investigational device or drug study, or less
than 30 days since ending treatment on another investigational device or drug study(s)

- History or evidence of any other clinically significant disorder, condition or disease
that in the opinion of the Investigator or Amgen physician, if consulted, would pose a
risk to subject safety or interfere with the study evaluation, procedures or
completion