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