Denosumab China Phase III Study

Inclusion Criteria

• Subject is willing and able to provide written informed consent.
• Of Chinese origin - defined as being born in China, having four ethnic Chinese grandparents.
• Ambulatory woman between the age of 60 and 90 years, inclusive.
• The subject has a BMD absolute value consistent with a T-score -4.0 at either the lumbar spine or total hip.
• All subjects must have at least one of following additional the risk factors:

history of fracture parental history of hip fracture increased bone turnover rate at screening (s-CTX >1.0 SD above the mean in healthy premenopausal women) low body weight (BMI≤19kg/m2) elderly (age≥70y) current smoker

• Postmenopausal defined as >5 years postmenopausal, which can be >5 years of spontaneous amenorrhea or >5 years post surgical bilateral oophorectomy. Use follicle stimulating hormone (FSH) levels >40 mIU/mL to confirm surgical postmenopausal status, where bilateral oophorectomy status is uncertain.

Exclusion Criteria

• Bone/metabolic disease:

Any metabolic bone disease, e.g., osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings.

Paget's disease Cushing's disease Hyperprolactinemia

• Current hyperparathyroidism or hypoparathyroidism by medical record
• Thyroid condition: Hyperthyroidism or hypothyroidism. Only subjects with hypothyroidism who are on stable thyroid hormone replacement therapy may be allowed per the following criteria:

If TSH level is below normal range, subject is not eligible for the study. If TSH level is elevated (>5.5 μIU/mL and ≤10.0 μIU/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 > 10.0 μIU/mL, subject is not eligible.

• Rheumatoid arthritis
• Malignancy:

Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5years.

• Malabsorption syndrome: malabsorption syndrome or any gastrointestinal disorders associated with malabsorption, for example Crohn's Disease and chronic pancreatitis.
• Renal disease - severe renal impairment
• Liver disease:

Cirrhosis of the liver Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Chronic stable hepatitis B and C are acceptable if the subject otherwise meets study entry criteria (e.g., presence of hepatitis B surface antigen or positive Hepatitis C test result within 3 months of Screening).

• Drug or alcohol abuse: Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study.
• Biological abnormalities:

Any disorder that compromises the ability of the subject to give written informed consent or to comply with study procedures.

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.

Known to have tested positive for human immunodeficiency virus (HIV).

• Vitamin D deficiency: Vitamin D deficiency (25-(OH) vitamin D level 3-months but 5 mg prednisone equivalent per day for more than 10 days).

Systemic hormone replacement therapy. Selective estrogen receptor modulators (SERMs), e.g., raloxifene Tibolone. 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.

• Investigational drug exposure: Currently enrolled in an investigational device or drug trial(s) or it has not