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

- 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

- 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