A Randomized, Double-Blind Study to Compare the Efficacy of Treatment With Denosumab Versus Alendronate Sodium in Postmenopausal Women With Low Bone Mineral Density.

Inclusion criteria

- Patient is an ambulatory postmenopausal woman - Patient has BMD value that corresponds to a T-score of less than or equal to -2.0 (g/cm2) at the lumbar spine OR total hip within range specific to the study protocol. Exclusion Criteria: o Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures

• Evidence of any of the following per subject report, chart review or central laboratory result:

• Hyper- or hypothyroidism; however, subjects on stable thyroid hormone replacement therapy may be allowed per the following criteria:

• If TSH level is normal, subject is eligible for the study.
• If TSH level is below normal range, subject is not eligible for the study.
• If TSH level is elevated (> 5.5 mIU/mL to 10.0 mIU/mL), serum T4 should be measured. If serum T4 is within normal range, subject is eligible. If serum T4 is outside of normal range, subject is not eligible for the study.
• If TSH level is above 10.0 mIU/mL, subject is not eligible.
• Current hyper- or hypoparathyroidism
• Elevated transaminases

• Serum aspartate aminotransferase (AST; serum glutamate-oxaloacetic transaminase [SGOT]) ³ 2.0 x upper limits of normal (ULN)
• Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transaminase [SGPT]) ³ 2.0 x ULN
• Significantly impaired renal function as determined by serum creatinine ³ 2.0 mg/dL
• Current hypo- or hypercalcemia based on the central laboratory reference ranges
• Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastroesophageal reflux disease that is uncontrolled by medication
• Rheumatoid Arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver
• 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, eg, osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings
• Malabsorption syndrome or any gastrointestinal disorders that are associated with malabsorption
• Received any solid organ or bone marrow transplant
• Vitamin D deficiency (25(OH) vitamin D level < 12 ng/mL). Vitamin D repletion will be permitted and subjects may be re-screened; see Section 7.
• 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
• Contraindicated or poorly tolerant of ALN therapy; contraindications for ALN therapy include:

• Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia.
• Inability to stand or sit upright for at least 30 minutes.
• Hypersensitivity to ALN or other constituents of ALN tablets o Known sensitivity to mammalian cell derived drug products
• Known intolerance to calcium supplements
• Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate
• Oral bisphosphonate treatment:

• ³ 3 months cumulatively in the past 2 years, OR
• ³ 1 month in the past year, OR
• Any use during the 3-month period prior to randomization
• PTH or PTH derivatives (eg, teriparatide) within the last year
• Administration of any of the following treatments within 3 months of randomization:

• Any SERM (eg, raloxifene)
• Tibolone
• Anabolic steroids or testosterone
• Glucocorticosteroids (³ 5 mg prednisone equivalent per day for more than 10 days)
• Systemic (oral, transdermal, topical) hormone replacement therapy (local vaginal estrogen preparation will be allowed)
• Calcitonin
• Calcitriol or vitamin D derivatives
• Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin
• Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists
• Height, weight or girth which may preclude accurate DXA measurements
• Less than 2 lumbar vertebrae (L1-L4) evaluable for DXA measurements
• Both hips not evaluable by DXA (eg, history of bilateral hip replacement or pins in both hips)
• Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(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