This is a multi-center, randomized, open-label, parallel group, study being conducted in the United States and in Europe in postmenopausal women. Approximately 800 subjects will be randomized across about 65 sites in a 1:1 ratio to either denosumab 60mg SC Q6M, or ibandronate 150mg PO QM.

Inclusion Criteria:

• Ambulatory, postmenopausal women (based on medical history) 55 years or older at screening
• Postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months
• If the subject is 55 - 59 years old and there is uncertainty regarding menopausal status, confirmation of serum FSH (>= 50 mIU/mL) and serum estradiol (<= 20 pg/mL) must be obtained
• If the subject is 60 years or older, evaluation of FSH and estradiol levels is not needed to confirm menopausal status
• Have received their first prescription of daily or weekly bisphosphonate therapy at least 1 month prior to screening
• May have received
• raloxifene, calcitonin, prior to initiation of daily orweekly bisphosphonate therapy.
• up to 3 doses of monthly bisphosphonate prior to initiation of daily or weekly bisphosphonate therapy
• calcium, and vitamin D
• Hormone replacement therapy (e.g. estrogen use for mitigation of menopausal symptoms)
• Subject has:
• Stopped daily or weekly bisphosphonate therapy (is denoted as non-persistent) at least one month before the screening visit, or
• Demonstrated low adherence to therapy assessed by a score of less than 6 on the OS-MMAS
• Screening BMD (g/cm2) values, at the lumbar spine OR total hip, that occur within the following ranges, based on the particular scanner that is used:

GE Lunar Lumbar spine 0.700 < or = BMD < and = 0.940 Total hip 0.504 < or = BMD < or = 0.756

Hologic Lumbar spine 0.607 < or = BMD < or = 0.827 Total hip 0.454 < or = BMD < or = 0.698 Both the initial and the repeat DXA scan of the lumbar spine OR the total hip must meet the above eligibility criteria.

• At least 2 lumbar vertebrae must be evaluable by DXA.
• At least one hip must be evaluable by DXA (eg, no history of either bilateral hip replacement or pins in both hips)
• Provide signed informed consent before any study-specific procedures are conducted

Exclusion Criteria:

• Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
• Current or prior use of medications prescribed for osteoporosis treatment other than oral daily or weekly bisphosphonate
• Contraindicated to receive oral ibandronate 150mg PO QM, including
• Hypersensitivity to ibandronate 150mg PO QM or other constituents of ibandronate 150mg PO QM tablets
• Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 60 minutes
• Administration of any of the following treatments within 3 months of screening
• Tibolone
• Anabolic steroids or testosterone
• Glucocorticosteroids (>= 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of >= 50 mg)
• Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)] - Repletion will be allowed and subjects may be re-screened
• Evidence of any of the following per subject report, chart review or central laboratory result:
• Significantly impaired renal function as determined by estimated Glomerular Filtration Rate less that 30mL/min/1.73 m2 determined by the central laboratory
• Current hypo- or hypercalcemia based on the central laboratory reference ranges
• Active gastric or duodenal ulcer; or any history of significant gastrointestinal bleed requiring hospitalization or transfusion
• Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen
• Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years
• Any metabolic bone disease or secondary cause of bone loss that is not controlled and may interfere with the interpretation of the findings
• Previous participation in clinical trials with denosumab 60mg SC Q6M (regardless of treatment)
• Received any solid organ or bone marrow transplant
• Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results
• Known sensitivity to mammalian cell derived drug products
• Known intolerance to calcium supplements
• Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s)
• Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results
• Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study