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Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT00043186
Collaborator
(none)
412
Enrollment
9
Arms
61
Duration (Months)

Study Details

Study Description

Brief Summary

To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar spine bone mineral density and will be well tolerated.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
412 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density
Study Start Date :
May 1, 2002
Actual Primary Completion Date :
Apr 1, 2007
Actual Study Completion Date :
Jun 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.

Drug: Placebo
Placebo subcutaneous injection
Experimental: Denosumab 6 mg every 3 months

Participants received denosumab 6 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

Drug: Denosumab
Denosumab for subcutaneous injection
Other Names:
  • AMG 162
  • Prolia

    		•
    Experimental: Denosumab 14 mg every 3 months

    Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
  • AMG 162
  • Prolia

    		•
    Experimental: Denosumab 30 mg every 3 months

    Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.

    Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
  • AMG 162
  • Prolia

    		•
    Experimental: Denosumab 14 mg every 6 months

    Participants received denosumab 14 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
  • AMG 162
  • Prolia

    		•
    Experimental: Denosumab 60 mg every 6 months

    Participants received denosumab 60 mg SC every 6 months until Month 42.

    Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
  • AMG 162
  • Prolia

    		•
    Experimental: Denosumab 100 mg every 6 months

    Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.

    Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
  • AMG 162
  • Prolia

    		•
    Experimental: Denosumab 210 mg every 6 months

    Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.

    Drug: Denosumab
    Denosumab for subcutaneous injection
    Other Names:
  • AMG 162
  • Prolia

    		•
    Active Comparator: Alendronate 70 mg

    Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.

    Drug: Alendronate
    Alendronate 70 mg tablets
    Other Names:
  • Fosamax

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms [Baseline and Month 12]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    Secondary Outcome Measures

    1. Serum CTX Percent Change From Baseline at Month 12 [Baseline and Month 12]

      Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    2. Urine NTX/Creatinine Percent Change From Baseline at Month 12 [Baseline and Month 12]

      Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    3. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm [Baseline and Month 12]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    4. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    5. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    6. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    7. Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    8. Serum CTX Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    9. Serum CTX Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    10. Serum CTX Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    11. Serum CTX Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    12. Urine NTX/Creatinine Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    13. Urine NTX/Creatinine Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    14. Urine NTX/Creatinine Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    15. Urine NTX/Creatinine Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    16. Total Hip Bone Mineral Density Percent Change From Baseline at Month 12 [Baseline and 12 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    17. Total Hip Bone Mineral Density Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    18. Total Hip Bone Mineral Density Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    19. Total Hip Bone Mineral Density Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    20. Total Hip Bone Mineral Density Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    21. Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12 [Baseline and 12 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    22. Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    23. Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    24. Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    25. Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    26. Total Body Bone Mineral Density Percent Change From Baseline at Month 12 [Baseline and 12 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    27. Total Body Bone Mineral Density Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    28. Total Body Bone Mineral Density Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    29. Total Body Bone Mineral Density Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    30. Total Body Bone Mineral Density Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    31. Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12 [Baseline and 12 months]

      Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

    32. Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24 [Baseline and 24 months]

      Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

    33. Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36 [Baseline and 36 months]

      Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

    34. Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42 [Baseline and 42 months]

      Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

    35. Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48 [Baseline and 48 months]

      Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 80 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • women not more than 80 years of age on date of randomization

    • ≥ 1 year postmenopausal on date of randomization

    • ambulatory

    • if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) > 50 mU/mL or serum estradiol < 20 pg/mL

    • low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been < -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip)

    • before any study-specific procedure, including the screening dual X-ray absorptiometry (DXA) scan, gave informed consent for participation in the study.

    Exclusion Criteria

    • fluoride treatment for osteoporosis within the 2 years before the enrollment date

    • bisphosphonate use within the 12 months before the enrollment date

    • administration of the following medications within the 6 months before the enrollment date

    • tibolone

    • Parathyroid hormone (PTH) (or any derivative)

    • systemic glucocorticosteroids (> 5 mg oral prednisone equivalent per day for > 10 days)

    • inhaled corticosteroids (> 2000 μg per day for > 10 days)

    • anabolic steroids or testosterone

    • administration of the following medications within the 3 months before the enrollment date

    • systemic hormone replacement therapy

    • selective estrogen receptor modulators

    • calcitonin

    • calcitriol

    • current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range)

    • current hyper- or hypoparathyroidism

    • albumin-adjusted serum calcium < 8.5 mg/dL (< 2.125 mol/L)

    • osteomalacia

    • rheumatoid arthritis

    • Paget's disease

    • malignancy within the 5 years before enrollment (except cervical carcinoma in situ or basal cell carcinoma, which were acceptable)

    • renal disease; ie, creatinine clearance ≤ 35 mL/min

    • any bone disease, other than osteoporosis, which could interfere with the interpretation of the findings (eg, osteogenesis imperfecta or osteopetrosis)

    • malabsorption syndrome

    • weight, height, or girth that could preclude accurate DXA measurements

    • < 2 lumbar vertebrae (L1 through L4) evaluable by DXA

    • recent long bone fracture (within 6 months)

    • osteoporotic-related fracture (ie, crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 2 years of randomization

    • 1 single, grade 1 vertebral fracture

    • currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.)

    • known sensitivity to mammalian-derived drug preparations (eg, Herceptin®)

    • any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results

    • self-reported alcohol or drug abuse within the previous 12 months

    • any disorder that compromised the ability to give truly informed consent for participation in the study

    • previous administration of denosumab

    • known sensitivity or contraindication to alendronate

    • known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT00043186
    Other Study ID Numbers:
    • 20010223
    First Posted:
    Aug 7, 2002
    Last Update Posted:
    Sep 18, 2013
    Last Verified:
    Sep 1, 2013
    Keywords provided by Amgen
    bone loss
    osteoporosis
    Additional relevant MeSH terms:
    Bone Diseases, Metabolic
    Denosumab
    Alendronate

    Study Results

    Participant Flow

    Recruitment Details First Subject Enrolled: 11-May-2002 Last Subject Enrolled: 30-Apr-2003
    Pre-assignment Detail
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Period Title: Overall Study
    STARTED 46 44 44 41 54 47 42 47 47
    COMPLETED 29 29 24 19 36 39 25 31 30
    NOT COMPLETED 17 15 20 22 18 8 17 16 17

    Baseline Characteristics

    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg Total
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment. Total of all reporting groups
    Overall Participants 46 44 44 41 54 47 42 47 47 412
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    63.7
    (9.1)
    62.8
    (8.6)
    62.3
    (6)
    61.2
    (8.5)
    61.4
    (8.1)
    63.1
    (8.1)
    64.9
    (8.2)
    60.5
    (7.8)
    62.8
    (8.2)
    62.5
    (8.1)
    Sex: Female, Male (Count of Participants)
    Female
    46
    100%
    44
    100%
    44
    100%
    41
    100%
    54
    100%
    47
    100%
    42
    100%
    47
    100%
    47
    100%
    412
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Number) [Number]
    White or Caucasian
    37
    80.4%
    33
    75%
    42
    95.5%
    36
    87.8%
    49
    90.7%
    39
    83%
    37
    88.1%
    42
    89.4%
    40
    85.1%
    355
    86.2%
    Black or African American
    0
    0%
    1
    2.3%
    1
    2.3%
    2
    4.9%
    1
    1.9%
    1
    2.1%
    3
    7.1%
    0
    0%
    3
    6.4%
    12
    2.9%
    Hispanic or Latino
    8
    17.4%
    8
    18.2%
    1
    2.3%
    3
    7.3%
    3
    5.6%
    5
    10.6%
    2
    4.8%
    5
    10.6%
    4
    8.5%
    39
    9.5%
    Asian
    1
    2.2%
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    2
    4.3%
    0
    0%
    0
    0%
    0
    0%
    4
    1%
    Japanese
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    American Indian or Alaska Native
    0
    0%
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%

    Outcome Measures

    1. Primary Outcome
    Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.
    Measure Participants 40 36 36 32 48 41 37 41
    Least Squares Mean (Standard Error) [Percent change]
    -0.81
    (0.48)
    4.41
    (0.50)
    4.71
    (0.50)
    6.69
    (0.54)
    3.03
    (0.43)
    4.55
    (0.47)
    5.52
    (0.49)
    5.07
    (0.47)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.87
    Confidence Interval () 95%
    4.59 to 7.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.33
    Confidence Interval () 95%
    5.01 to 7.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.35
    Confidence Interval () 95%
    4.07 to 6.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.84
    Confidence Interval () 95%
    2.60 to 5.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.50
    Confidence Interval () 95%
    6.13 to 8.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.52
    Confidence Interval () 95%
    4.19 to 6.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.21
    Confidence Interval () 95%
    3.88 to 6.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Serum CTX Percent Change From Baseline at Month 12
    Description Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 36 35 36 31 47 41 36 42 40
    Median (Inter-Quartile Range) [Percent change]
    -4.699
    -61.366
    -77.989
    -87.238
    -12.054
    -70.757
    -78.617
    -84.107
    -72.603
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.166
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    3. Secondary Outcome
    Title Urine NTX/Creatinine Percent Change From Baseline at Month 12
    Description Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 36 35 36 31 47 40 36 42 40
    Median (Inter-Quartile Range) [Percent change]
    24.300
    -40.018
    -54.688
    -60.652
    -2.027
    -36.523
    -51.256
    -58.502
    -45.409
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    4. Secondary Outcome
    Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and Month 12

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Alendronate 70 mg
    Arm/Group Description Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 45
    Least Squares Mean (Standard Error) [Percent change]
    4.59
    (0.45)
    5. Secondary Outcome
    Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 34 32 33 27 41 41 33 36 39
    Least Squares Mean (Standard Error) [Percent change]
    -1.25
    (0.68)
    7.42
    (0.69)
    7.21
    (0.68)
    8.83
    (0.76)
    3.94
    (0.60)
    7.19
    (0.62)
    7.31
    (0.67)
    7.86
    (0.65)
    6.09
    (0.63)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.34
    Confidence Interval () 95%
    5.56 to 9.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 9.11
    Confidence Interval () 95%
    7.31 to 10.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.56
    Confidence Interval () 95%
    6.71 to 10.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.44
    Confidence Interval () 95%
    6.69 to 10.19
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.19
    Confidence Interval () 95%
    3.43 to 6.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 10.08
    Confidence Interval () 95%
    8.14 to 12.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.46
    Confidence Interval () 95%
    6.62 to 10.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.66
    Confidence Interval () 95%
    6.80 to 10.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 30 31 25 23 38 38 29 38 33
    Least Squares Mean (Standard Error) [Percent change]
    -1.80
    (0.82)
    8.57
    (0.80)
    9.17
    (0.89)
    1.94
    (0.94)
    7.99
    (0.72)
    9.04
    (0.74)
    10.63
    (0.82)
    0.85
    (0.72)
    4.70
    (0.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.50
    Confidence Interval () 95%
    4.32 to 8.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.65
    Confidence Interval () 95%
    0.55 to 4.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 12.43
    Confidence Interval () 95%
    10.19 to 14.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 10.84
    Confidence Interval () 95%
    8.74 to 12.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 9.79
    Confidence Interval () 95%
    7.69 to 11.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.74
    Confidence Interval () 95%
    1.37 to 6.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 10.97
    Confidence Interval () 95%
    8.63 to 13.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 10.37
    Confidence Interval () 95%
    8.16 to 12.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 8 5 7 5 15 12 6 7 10
    Least Squares Mean (Standard Error) [Percent change]
    1.09
    (1.70)
    7.21
    (2.13)
    10.04
    (1.86)
    5.06
    (2.13)
    9.46
    (1.24)
    9.59
    (1.40)
    9.99
    (1.93)
    1.06
    (1.80)
    6.51
    (1.51)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.02
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.42
    Confidence Interval () 95%
    0.89 to 9.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.992
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.03
    Confidence Interval () 95%
    -5.07 to 5.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.90
    Confidence Interval () 95%
    3.72 to 14.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.50
    Confidence Interval () 95%
    4.15 to 12.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.37
    Confidence Interval () 95%
    4.11 to 12.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.292
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.98
    Confidence Interval () 95%
    -1.42 to 9.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.95
    Confidence Interval () 95%
    3.94 to 13.96
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.094
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.12
    Confidence Interval () 95%
    0.57 to 11.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 29 29 24 20 37 39 27 30 31
    Least Squares Mean (Standard Error) [Percent change]
    -2.39
    (1.11)
    9.35
    (1.09)
    9.93
    (1.20)
    9.03
    (1.33)
    10.10
    (0.96)
    10.34
    (0.96)
    11.76
    (1.13)
    2.50
    (1.07)
    4.54
    (1.06)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.93
    Confidence Interval () 95%
    3.97 to 9.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.89
    Confidence Interval () 95%
    1.92 to 7.85
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 14.15
    Confidence Interval () 95%
    11.08 to 17.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 12.73
    Confidence Interval () 95%
    9.94 to 15.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 12.49
    Confidence Interval () 95%
    9.66 to 15.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.42
    Confidence Interval () 95%
    8.12 to 14.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 12.32
    Confidence Interval () 95%
    9.15 to 15.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 11.74
    Confidence Interval () 95%
    8.72 to 14.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Serum CTX Percent Change From Baseline at Month 24
    Description Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 32 30 32 25 38 39 31 33 38
    Median (Inter-Quartile Range) [Percent change]
    -5.940
    -50.687
    -74.078
    -83.985
    -8.467
    -68.437
    -80.460
    -85.680
    -69.386
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.622
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    10. Secondary Outcome
    Title Serum CTX Percent Change From Baseline at Month 36
    Description Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 29 30 24 22 31 36 27 36 32
    Median (Inter-Quartile Range) [Percent change]
    -16.577
    -62.298
    -53.643
    56.286
    -57.500
    -54.418
    -45.057
    72.135
    -33.982
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.026
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    11. Secondary Outcome
    Title Serum CTX Percent Change From Baseline at Month 42
    Description Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participantswith non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 23 27 21 16 30 35 24 31 27
    Median (Inter-Quartile Range) [Percent change]
    -16.279
    -63.543
    -40.827
    -62.334
    -46.408
    -57.255
    -56.377
    33.999
    -46.743
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    12. Secondary Outcome
    Title Serum CTX Percent Change From Baseline at Month 48
    Description Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 27 29 24 16 34 37 24 30 29
    Median (Inter-Quartile Range) [Percent change]
    -14.561
    -40.016
    -34.999
    -52.656
    -39.899
    -51.494
    -36.480
    7.067
    -43.724
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.050
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    13. Secondary Outcome
    Title Urine NTX/Creatinine Percent Change From Baseline at Month 24
    Description Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 32 30 32 25 38 39 31 33 39
    Median (Inter-Quartile Range) [Percent change]
    14.422
    -19.699
    -37.691
    -49.907
    2.134
    -32.303
    -37.001
    -47.105
    -44.482
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.409
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    14. Secondary Outcome
    Title Urine NTX/Creatinine Percent Change From Baseline at Month 36
    Description Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 29 30 24 22 31 36 26 36 31
    Median (Inter-Quartile Range) [Percent change]
    0.508
    -33.294
    -47.752
    82.910
    -44.301
    -36.874
    -27.174
    70.997
    -15.627
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.077
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    15. Secondary Outcome
    Title Urine NTX/Creatinine Percent Change From Baseline at Month 42
    Description Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 24 27 21 16 30 35 24 31 27
    Median (Inter-Quartile Range) [Percent change]
    -18.102
    -40.741
    -40.043
    -58.893
    -47.188
    -39.269
    -46.674
    26.277
    -33.102
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.022
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.032
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    16. Secondary Outcome
    Title Urine NTX/Creatinine Percent Change From Baseline at Month 48
    Description Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 27 28 24 16 32 35 24 30 28
    Median (Inter-Quartile Range) [Percent change]
    -21.064
    -23.311
    -38.002
    -50.864
    -46.128
    -40.375
    -41.998
    7.884
    -32.198
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.172
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.029
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.168
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.168
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.172
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    17. Secondary Outcome
    Title Total Hip Bone Mineral Density Percent Change From Baseline at Month 12
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 40 36 36 32 48 42 37 41 45
    Least Squares Mean (Standard Error) [Percent change]
    -0.56
    (0.37)
    2.89
    (0.38)
    2.45
    (0.39)
    3.32
    (0.42)
    1.94
    (0.33)
    3.56
    (0.36)
    2.53
    (0.38)
    2.33
    (0.36)
    2.11
    (0.35)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.67
    Confidence Interval () 95%
    1.70 to 3.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.90
    Confidence Interval () 95%
    1.90 to 3.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.09
    Confidence Interval () 95%
    2.07 to 4.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.12
    Confidence Interval () 95%
    3.13 to 5.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.5
    Confidence Interval () 95%
    1.55 to 3.46
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.89
    Confidence Interval () 95%
    2.83 to 4.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.01
    Confidence Interval () 95%
    1.99 to 4.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.46
    Confidence Interval () 95%
    2.43 to 4.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    18. Secondary Outcome
    Title Total Hip Bone Mineral Density Percent Change From Baseline at Month 24
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 35 32 33 27 41 41 33 35 39
    Least Squares Mean (Standard Error) [Percent change]
    -1.92
    (0.44)
    4.04
    (0.45)
    3.55
    (0.44)
    5.03
    (0.50)
    2.62
    (0.39)
    4.96
    (0.40)
    3.67
    (0.44)
    4.18
    (0.43)
    3.27
    (0.41)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.19
    Confidence Interval () 95%
    4.04 to 6.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.10
    Confidence Interval () 95%
    4.93 to 7.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.59
    Confidence Interval () 95%
    4.40 to 6.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.89
    Confidence Interval () 95%
    5.76 to 8.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.54
    Confidence Interval () 95%
    3.41 to 5.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.95
    Confidence Interval () 95%
    5.69 to 8.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.48
    Confidence Interval () 95%
    4.29 to 6.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.97
    Confidence Interval () 95%
    4.76 to 7.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    19. Secondary Outcome
    Title Total Hip Bone Mineral Density Percent Change From Baseline at Month 36
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 30 31 25 23 38 37 29 38 33
    Least Squares Mean (Standard Error) [Percent change]
    -2.84
    (0.60)
    4.79
    (0.58)
    4.41
    (0.65)
    -1.23
    (0.68)
    4.31
    (0.52)
    5.83
    (0.54)
    4.33
    (0.60)
    -1.43
    (0.53)
    0.93
    (0.57)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.78
    Confidence Interval () 95%
    2.19 to 5.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.07
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.41
    Confidence Interval () 95%
    -0.12 to 2.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.17
    Confidence Interval () 95%
    5.54 to 8.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.67
    Confidence Interval () 95%
    7.13 to 10.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.15
    Confidence Interval () 95%
    5.62 to 8.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.07
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.61
    Confidence Interval () 95%
    -0.12 to 3.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.26
    Confidence Interval () 95%
    5.56 to 8.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.63
    Confidence Interval () 95%
    6.02 to 9.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    20. Secondary Outcome
    Title Total Hip Bone Mineral Density Percent Change From Baseline at Month 42
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 8 5 7 5 15 12 6 7 10
    Least Squares Mean (Standard Error) [Percent change]
    -1.96
    (1.16)
    5.01
    (1.43)
    3.98
    (1.28)
    2.37
    (1.46)
    4.54
    (0.85)
    6.34
    (0.98)
    4.70
    (1.32)
    -2.67
    (1.23)
    2.98
    (1.03)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.94
    Confidence Interval () 95%
    1.86 to 8.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.677
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.71
    Confidence Interval () 95%
    -4.10 to 2.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.66
    Confidence Interval () 95%
    3.14 to 10.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.29
    Confidence Interval () 95%
    5.26 to 11.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.50
    Confidence Interval () 95%
    3.59 to 9.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.047
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.33
    Confidence Interval () 95%
    0.61 to 8.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.94
    Confidence Interval () 95%
    2.53 to 9.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.97
    Confidence Interval () 95%
    3.28 to 10.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    21. Secondary Outcome
    Title Total Hip Bone Mineral Density Percent Change From Baseline at Month 48
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 29 29 24 20 37 39 27 30 31
    Least Squares Mean (Standard Error) [Percent change]
    -3.52
    (0.65)
    5.45
    (0.63)
    4.03
    (0.70)
    3.86
    (0.77)
    4.82
    (0.56)
    6.06
    (0.56)
    4.99
    (0.66)
    -1.37
    (0.62)
    1.17
    (0.62)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.69
    Confidence Interval () 95%
    2.97 to 6.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.015
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.16
    Confidence Interval () 95%
    0.43 to 3.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.52
    Confidence Interval () 95%
    6.74 to 10.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 9.58
    Confidence Interval () 95%
    7.95 to 11.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.34
    Confidence Interval () 95%
    6.70 to 9.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.38
    Confidence Interval () 95%
    5.45 to 9.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.55
    Confidence Interval () 95%
    5.72 to 9.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 8.97
    Confidence Interval () 95%
    7.23 to 10.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    22. Secondary Outcome
    Title Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 39 35 35 32 44 43 37 37 42
    Least Squares Mean (Standard Error) [Percent change]
    -1.97
    (0.50)
    0.89
    (0.52)
    0.40
    (0.53)
    1.10
    (0.55)
    0.94
    (0.46)
    1.29
    (0.48)
    1.07
    (0.50)
    1.09
    (0.51)
    -0.53
    (0.47)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.44
    Confidence Interval () 95%
    0.11 to 2.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.06
    Confidence Interval () 95%
    1.69 to 4.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.04
    Confidence Interval () 95%
    1.68 to 4.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.26
    Confidence Interval () 95%
    1.94 to 4.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.91
    Confidence Interval () 95%
    1.60 to 4.21
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.07
    Confidence Interval () 95%
    1.65 to 4.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.37
    Confidence Interval () 95%
    0.99 to 3.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.86
    Confidence Interval () 95%
    1.47 to 4.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    23. Secondary Outcome
    Title Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 34 32 32 27 38 41 33 33 35
    Least Squares Mean (Standard Error) [Percent change]
    -2.78
    (0.56)
    1.31
    (0.57)
    0.62
    (0.58)
    1.30
    (0.63)
    2.48
    (0.52)
    1.89
    (0.51)
    1.48
    (0.56)
    0.81
    (0.56)
    -0.78
    (0.55)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.99
    Confidence Interval () 95%
    0.49 to 3.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.58
    Confidence Interval () 95%
    2.06 to 5.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.26
    Confidence Interval () 95%
    2.73 to 5.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.09
    Confidence Interval () 95%
    2.55 to 5.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.67
    Confidence Interval () 95%
    3.23 to 6.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.26
    Confidence Interval () 95%
    3.78 to 6.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.08
    Confidence Interval () 95%
    2.48 to 5.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.39
    Confidence Interval () 95%
    1.86 to 4.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    24. Secondary Outcome
    Title Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 29 31 24 23 37 39 29 35 30
    Least Squares Mean (Standard Error) [Percent change]
    -3.64
    (0.63)
    1.99
    (0.60)
    1.06
    (0.69)
    1.05
    (0.71)
    2.08
    (0.55)
    2.69
    (0.55)
    1.92
    (0.62)
    0.12
    (0.57)
    -0.95
    (0.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.69
    Confidence Interval () 95%
    1.01 to 4.38
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.77
    Confidence Interval () 95%
    2.14 to 5.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.56
    Confidence Interval () 95%
    3.87 to 7.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.33
    Confidence Interval () 95%
    4.75 to 7.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.73
    Confidence Interval () 95%
    4.12 to 7.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.70
    Confidence Interval () 95%
    2.89 to 6.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.70
    Confidence Interval () 95%
    2.92 to 6.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.63
    Confidence Interval () 95%
    3.96 to 7.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    25. Secondary Outcome
    Title Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 2 2 2 2 7 3 1 3 1
    Least Squares Mean (Standard Error) [Percent change]
    -6.59
    (3.00)
    1.00
    (3.26)
    0.82
    (2.92)
    -3.91
    (3.39)
    1.29
    (2.14)
    -0.87
    (2.93)
    0.02
    (5.00)
    0.59
    (2.52)
    -3.32
    (3.95)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.496
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.27
    Confidence Interval () 95%
    -7.16 to 13.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.527
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.60
    Confidence Interval () 95%
    -6.38 to 19.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.503
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.72
    Confidence Interval () 95%
    -2.90 to 14.33
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.527
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.68
    Confidence Interval () 95%
    -6.54 to 11.89
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.503
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.41
    Confidence Interval () 95%
    -2.19 to 17.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.503
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.59
    Confidence Interval () 95%
    -1.85 to 17.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.503
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.18
    Confidence Interval () 95%
    -2.45 to 16.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.233
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.88
    Confidence Interval () 95%
    0.78 to 14.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    26. Secondary Outcome
    Title Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 28 29 22 19 35 38 27 28 28
    Least Squares Mean (Standard Error) [Percent change]
    -4.67
    (0.75)
    1.04
    (0.73)
    1.42
    (0.84)
    1.77
    (0.91)
    1.74
    (0.66)
    1.71
    (0.65)
    1.37
    (0.75)
    -0.94
    (0.74)
    -2.67
    (0.75)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.41
    Confidence Interval () 95%
    4.48 to 8.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.44
    Confidence Interval () 95%
    4.19 to 8.70
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.09
    Confidence Interval () 95%
    3.91 to 8.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.72
    Confidence Interval () 95%
    3.70 to 7.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.054
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.00
    Confidence Interval () 95%
    -0.04 to 4.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.74
    Confidence Interval () 95%
    1.71 to 5.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.05
    Confidence Interval () 95%
    4.00 to 8.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.39
    Confidence Interval () 95%
    4.49 to 8.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    27. Secondary Outcome
    Title Total Body Bone Mineral Density Percent Change From Baseline at Month 12
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 36 36 35 29 43 42 34 38 39
    Least Squares Mean (Standard Error) [Percent change]
    -0.21
    (0.46)
    1.82
    (0.45)
    1.80
    (0.46)
    2.74
    (0.51)
    0.55
    (0.41)
    2.51
    (0.43)
    1.78
    (0.46)
    2.08
    (0.44)
    1.51
    (0.44)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.30
    Confidence Interval () 95%
    1.09 to 3.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.73
    Confidence Interval () 95%
    0.52 to 2.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.00
    Confidence Interval () 95%
    0.74 to 3.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.72
    Confidence Interval () 95%
    1.54 to 3.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.202
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.77
    Confidence Interval () 95%
    -0.41 to 1.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.95
    Confidence Interval () 95%
    1.65 to 4.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.02
    Confidence Interval () 95%
    0.78 to 3.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.03
    Confidence Interval () 95%
    0.80 to 3.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    28. Secondary Outcome
    Title Total Body Bone Mineral Density Percent Change From Baseline at Month 24
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 33 31 33 24 37 40 32 32 34
    Least Squares Mean (Standard Error) [Percent change]
    -1.64
    (0.53)
    2.59
    (0.54)
    2.91
    (0.53)
    4.44
    (0.62)
    0.89
    (0.49)
    2.57
    (0.49)
    3.00
    (0.53)
    2.75
    (0.53)
    1.50
    (0.52)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.14
    Confidence Interval () 95%
    1.71 to 4.56
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.40
    Confidence Interval () 95%
    2.95 to 5.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.64
    Confidence Interval () 95%
    3.19 to 6.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.22
    Confidence Interval () 95%
    2.85 to 5.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.53
    Confidence Interval () 95%
    1.13 to 3.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.09
    Confidence Interval () 95%
    4.53 to 7.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.55
    Confidence Interval () 95%
    3.12 to 5.98
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.23
    Confidence Interval () 95%
    2.76 to 5.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    29. Secondary Outcome
    Title Total Body Bone Mineral Density Percent Change From Baseline at Month 36
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 28 31 25 21 35 39 27 36 28
    Least Squares Mean (Standard Error) [Percent change]
    -1.61
    (0.94)
    3.14
    (0.88)
    3.04
    (0.98)
    2.34
    (1.09)
    2.04
    (0.83)
    2.80
    (0.80)
    2.59
    (0.94)
    -0.29
    (0.83)
    4.55
    (0.94)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.16
    Confidence Interval () 95%
    3.63 to 8.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.275
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.32
    Confidence Interval () 95%
    -1.06 to 3.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.20
    Confidence Interval () 95%
    1.65 to 6.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.41
    Confidence Interval () 95%
    2.07 to 6.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.65
    Confidence Interval () 95%
    1.25 to 6.05
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.95
    Confidence Interval () 95%
    1.22 to 6.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.65
    Confidence Interval () 95%
    2.05 to 7.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 4.75
    Confidence Interval () 95%
    2.28 to 7.22
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    30. Secondary Outcome
    Title Total Body Bone Mineral Density Percent Change From Baseline at Month 42
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 2 1 2 1 6 2 1 3 1
    Least Squares Mean (Standard Error) [Percent change]
    1.61
    (1.76)
    1.90
    (3.71)
    4.05
    (1.70)
    8.85
    (3.07)
    3.72
    (1.97)
    4.92
    (1.83)
    3.79
    (3.63)
    -0.75
    (1.50)
    2.85
    (2.67)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.18
    Confidence Interval () 95%
    -8.73 to 13.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 3.30
    Confidence Interval () 95%
    -2.70 to 9.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.709
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.24
    Confidence Interval () 95%
    -6.81 to 9.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.36
    Confidence Interval () 95%
    -8.55 to 3.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.10
    Confidence Interval () 95%
    -4.51 to 8.72
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.484
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.23
    Confidence Interval () 95%
    -0.83 to 15.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.44
    Confidence Interval () 95%
    -3.77 to 8.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.949
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.29
    Confidence Interval () 95%
    -10.82 to 11.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    31. Secondary Outcome
    Title Total Body Bone Mineral Density Percent Change From Baseline at Month 48
    Description Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 28 28 23 17 35 38 25 29 27
    Least Squares Mean (Standard Error) [Percent change]
    -2.54
    (0.99)
    3.68
    (0.98)
    3.38
    (1.07)
    3.76
    (1.27)
    3.42
    (0.86)
    3.43
    (0.87)
    3.68
    (1.03)
    -0.29
    (0.96)
    4.49
    (1.00)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 7.02
    Confidence Interval () 95%
    4.35 to 9.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.092
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 2.25
    Confidence Interval () 95%
    -0.37 to 4.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.22
    Confidence Interval () 95%
    3.50 to 8.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.97
    Confidence Interval () 95%
    3.51 to 8.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.96
    Confidence Interval () 95%
    3.44 to 8.48
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.29
    Confidence Interval () 95%
    3.25 to 9.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 5.91
    Confidence Interval () 95%
    3.13 to 8.70
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 6.22
    Confidence Interval () 95%
    3.58 to 8.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    32. Secondary Outcome
    Title Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12
    Description Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 12 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 12.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 36 35 36 31 47 40 36 42 39
    Median (Inter-Quartile Range) [Percent change]
    -4.609
    -62.716
    -60.098
    -70.256
    -39.474
    -65.215
    -61.979
    -67.634
    -61.059
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    33. Secondary Outcome
    Title Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24
    Description Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 24 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 24.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 32 30 32 25 38 37 31 33 39
    Median (Inter-Quartile Range) [Percent change]
    16.464
    -41.225
    -47.597
    -57.905
    -22.350
    -43.448
    -50.176
    -48.833
    -48.778
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    34. Secondary Outcome
    Title Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36
    Description Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 36 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 36.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 29 29 24 22 31 36 26 34 31
    Median (Inter-Quartile Range) [Percent change]
    1.955
    -39.012
    -56.021
    22.343
    -47.500
    -42.541
    -47.418
    61.747
    -8.209
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.049
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.146
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    35. Secondary Outcome
    Title Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42
    Description Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 42 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 42.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 24 27 21 16 31 35 23 31 27
    Median (Inter-Quartile Range) [Percent change]
    1.288
    -40.182
    -40.819
    -52.684
    -53.763
    -44.892
    -48.303
    17.841
    -22.069
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.061
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.058
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    36. Secondary Outcome
    Title Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48
    Description Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
    Time Frame Baseline and 48 months

    Outcome Measure Data

    Analysis Population Description
    Randomized participants with non-missing Baseline and non-missing value at Month 48.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    Measure Participants 27 29 24 16 34 37 24 30 29
    Median (Inter-Quartile Range) [Percent change]
    18.122
    -34.727
    -45.779
    -47.770
    -46.286
    -34.361
    -42.653
    21.053
    -17.891
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Alendronate 70 mg
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.142
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 210 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.218
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 100 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 60 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q6M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 30 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 14 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, Denosumab 6 mg Q3M
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments

    Adverse Events

    Time Frame 48 months
    Adverse Event Reporting Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
    Arm/Group Title Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Arm/Group Description Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42. Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42. Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 60 mg SC every 6 months until Month 42. Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42. Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42. Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.
    All Cause Mortality
    Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/46 (10.9%) 7/43 (16.3%) 13/44 (29.5%) 9/40 (22.5%) 7/53 (13.2%) 5/47 (10.6%) 9/41 (22%) 6/46 (13%) 8/46 (17.4%)
    Blood and lymphatic system disorders
    Anaemia 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Cardiac disorders
    Acute coronary syndrome 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Angina pectoris 1/46 (2.2%) 2/43 (4.7%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 2/46 (4.3%) 0/46 (0%)
    Aortic valve stenosis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Arrhythmia 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Atrial fibrillation 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 1/46 (2.2%)
    Atrial flutter 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Bradycardia 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Coronary artery disease 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Coronary artery stenosis 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Myocardial infarction 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Pericardial effusion 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Sick sinus syndrome 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Ear and labyrinth disorders
    Vertigo 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Abdominal strangulated hernia 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Gastrooesophageal reflux disease 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Pancreatitis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    General disorders
    Non-cardiac chest pain 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 2/46 (4.3%)
    Pyrexia 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Soft tissue inflammation 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Gallbladder disorder 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Infections and infestations
    Appendicitis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Bacteraemia 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Bronchopneumonia 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Catheter site cellulitis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Diverticulitis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Labyrinthitis 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Pneumonia 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Pneumonia primary atypical 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Urinary tract infection 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 1/46 (2.2%) 0/46 (0%)
    Injury, poisoning and procedural complications
    Carbon monoxide poisoning 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Femur fracture 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Fibula fracture 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Lumbar vertebral fracture 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Lung injury 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Rib fracture 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Sternal fracture 0/46 (0%) 1/43 (2.3%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Tibia fracture 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Diabetes mellitus non-insulin-dependent 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Hypoglycaemia 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Hyponatraemia 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Osteoarthritis 0/46 (0%) 1/43 (2.3%) 0/44 (0%) 0/40 (0%) 2/53 (3.8%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 2/46 (4.3%)
    Pain in jaw 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Brain neoplasm 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Breast cancer 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Breast cancer in situ 0/46 (0%) 0/43 (0%) 2/44 (4.5%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Colon cancer 1/46 (2.2%) 1/43 (2.3%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 1/46 (2.2%)
    Diffuse large B-cell lymphoma 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Follicle centre lymphoma, follicular grade I, II, III stage II 0/46 (0%) 1/43 (2.3%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Gastric cancer 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Hypergammaglobulinaemia benign monoclonal 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Malignant melanoma in situ 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Non-Hodgkin's lymphoma 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Ovarian epithelial cancer 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Pancreatic carcinoma 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Nervous system disorders
    Carotid artery stenosis 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Cerebral haemorrhage 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Cerebrovascular accident 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Convulsion 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Lacunar infarction 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Neurological symptom 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Syncope 0/46 (0%) 1/43 (2.3%) 1/44 (2.3%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Psychiatric disorders
    Alcoholism 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Renal and urinary disorders
    Bladder prolapse 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Reproductive system and breast disorders
    Adenomyosis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Endometrial hyperplasia 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperactivity 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Chronic obstructive pulmonary disease 1/46 (2.2%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Dyspnoea 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Interstitial lung disease 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Surgical and medical procedures
    Colostomy closure 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Vascular disorders
    Hypotension 0/46 (0%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Thrombosis 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Denosumab 6 mg Q3M Denosumab 14 mg Q3M Denosumab 30 mg Q3M Denosumab 14 mg Q6M Denosumab 60 mg Q6M Denosumab 100 mg Q6M Denosumab 210 mg Q6M Alendronate 70 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 43/46 (93.5%) 38/43 (88.4%) 39/44 (88.6%) 35/40 (87.5%) 44/53 (83%) 42/47 (89.4%) 38/41 (92.7%) 41/46 (89.1%) 42/46 (91.3%)
    Blood and lymphatic system disorders
    Anaemia 1/46 (2.2%) 1/43 (2.3%) 1/44 (2.3%) 1/40 (2.5%) 1/53 (1.9%) 0/47 (0%) 1/41 (2.4%) 0/46 (0%) 5/46 (10.9%)
    Cardiac disorders
    Palpitations 0/46 (0%) 1/43 (2.3%) 2/44 (4.5%) 1/40 (2.5%) 3/53 (5.7%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Eye disorders
    Blepharitis 3/46 (6.5%) 1/43 (2.3%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Cataract 0/46 (0%) 3/43 (7%) 3/44 (6.8%) 3/40 (7.5%) 3/53 (5.7%) 2/47 (4.3%) 4/41 (9.8%) 2/46 (4.3%) 3/46 (6.5%)
    Gastrointestinal disorders
    Abdominal distension 3/46 (6.5%) 1/43 (2.3%) 1/44 (2.3%) 4/40 (10%) 3/53 (5.7%) 2/47 (4.3%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Abdominal pain 2/46 (4.3%) 4/43 (9.3%) 1/44 (2.3%) 2/40 (5%) 1/53 (1.9%) 3/47 (6.4%) 3/41 (7.3%) 2/46 (4.3%) 0/46 (0%)
    Abdominal pain lower 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 1/53 (1.9%) 2/47 (4.3%) 3/41 (7.3%) 1/46 (2.2%) 1/46 (2.2%)
    Abdominal pain upper 0/46 (0%) 0/43 (0%) 3/44 (6.8%) 1/40 (2.5%) 3/53 (5.7%) 2/47 (4.3%) 2/41 (4.9%) 0/46 (0%) 3/46 (6.5%)
    Constipation 1/46 (2.2%) 3/43 (7%) 1/44 (2.3%) 2/40 (5%) 5/53 (9.4%) 5/47 (10.6%) 3/41 (7.3%) 1/46 (2.2%) 6/46 (13%)
    Diarrhoea 6/46 (13%) 5/43 (11.6%) 5/44 (11.4%) 3/40 (7.5%) 3/53 (5.7%) 1/47 (2.1%) 6/41 (14.6%) 5/46 (10.9%) 4/46 (8.7%)
    Diverticulum 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 1/53 (1.9%) 2/47 (4.3%) 0/41 (0%) 0/46 (0%) 3/46 (6.5%)
    Dyspepsia 3/46 (6.5%) 5/43 (11.6%) 5/44 (11.4%) 1/40 (2.5%) 12/53 (22.6%) 6/47 (12.8%) 6/41 (14.6%) 4/46 (8.7%) 12/46 (26.1%)
    Flatulence 1/46 (2.2%) 1/43 (2.3%) 3/44 (6.8%) 1/40 (2.5%) 2/53 (3.8%) 3/47 (6.4%) 0/41 (0%) 3/46 (6.5%) 2/46 (4.3%)
    Gastritis 0/46 (0%) 0/43 (0%) 2/44 (4.5%) 1/40 (2.5%) 2/53 (3.8%) 0/47 (0%) 2/41 (4.9%) 3/46 (6.5%) 2/46 (4.3%)
    Gastrooesophageal reflux disease 2/46 (4.3%) 8/43 (18.6%) 2/44 (4.5%) 5/40 (12.5%) 8/53 (15.1%) 8/47 (17%) 4/41 (9.8%) 5/46 (10.9%) 7/46 (15.2%)
    Haemorrhoids 0/46 (0%) 2/43 (4.7%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 3/47 (6.4%) 0/41 (0%) 0/46 (0%) 2/46 (4.3%)
    Hiatus hernia 0/46 (0%) 0/43 (0%) 3/44 (6.8%) 0/40 (0%) 1/53 (1.9%) 0/47 (0%) 1/41 (2.4%) 1/46 (2.2%) 2/46 (4.3%)
    Nausea 2/46 (4.3%) 3/43 (7%) 6/44 (13.6%) 6/40 (15%) 6/53 (11.3%) 5/47 (10.6%) 3/41 (7.3%) 9/46 (19.6%) 10/46 (21.7%)
    Stomach discomfort 2/46 (4.3%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 1/46 (2.2%) 3/46 (6.5%)
    Toothache 1/46 (2.2%) 3/43 (7%) 0/44 (0%) 1/40 (2.5%) 1/53 (1.9%) 2/47 (4.3%) 0/41 (0%) 3/46 (6.5%) 2/46 (4.3%)
    Vomiting 2/46 (4.3%) 2/43 (4.7%) 2/44 (4.5%) 3/40 (7.5%) 1/53 (1.9%) 1/47 (2.1%) 1/41 (2.4%) 2/46 (4.3%) 2/46 (4.3%)
    General disorders
    Chills 0/46 (0%) 0/43 (0%) 3/44 (6.8%) 0/40 (0%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Fatigue 3/46 (6.5%) 3/43 (7%) 2/44 (4.5%) 1/40 (2.5%) 4/53 (7.5%) 2/47 (4.3%) 1/41 (2.4%) 4/46 (8.7%) 2/46 (4.3%)
    Influenza like illness 5/46 (10.9%) 4/43 (9.3%) 4/44 (9.1%) 3/40 (7.5%) 10/53 (18.9%) 11/47 (23.4%) 6/41 (14.6%) 3/46 (6.5%) 7/46 (15.2%)
    Injection site bruising 0/46 (0%) 0/43 (0%) 0/44 (0%) 1/40 (2.5%) 0/53 (0%) 0/47 (0%) 1/41 (2.4%) 3/46 (6.5%) 0/46 (0%)
    Injection site erythema 3/46 (6.5%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Oedema peripheral 5/46 (10.9%) 0/43 (0%) 1/44 (2.3%) 4/40 (10%) 2/53 (3.8%) 4/47 (8.5%) 1/41 (2.4%) 3/46 (6.5%) 3/46 (6.5%)
    Pain 0/46 (0%) 3/43 (7%) 4/44 (9.1%) 1/40 (2.5%) 2/53 (3.8%) 1/47 (2.1%) 1/41 (2.4%) 3/46 (6.5%) 3/46 (6.5%)
    Immune system disorders
    Hypersensitivity 1/46 (2.2%) 2/43 (4.7%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 3/47 (6.4%) 0/41 (0%) 0/46 (0%) 1/46 (2.2%)
    Seasonal allergy 2/46 (4.3%) 3/43 (7%) 2/44 (4.5%) 4/40 (10%) 3/53 (5.7%) 3/47 (6.4%) 0/41 (0%) 2/46 (4.3%) 1/46 (2.2%)
    Infections and infestations
    Bronchitis 5/46 (10.9%) 2/43 (4.7%) 1/44 (2.3%) 10/40 (25%) 4/53 (7.5%) 3/47 (6.4%) 1/41 (2.4%) 5/46 (10.9%) 4/46 (8.7%)
    Dental caries 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 3/40 (7.5%) 1/53 (1.9%) 1/47 (2.1%) 1/41 (2.4%) 0/46 (0%) 1/46 (2.2%)
    Diverticulitis 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 3/40 (7.5%) 1/53 (1.9%) 0/47 (0%) 2/41 (4.9%) 1/46 (2.2%) 1/46 (2.2%)
    Ear infection 1/46 (2.2%) 1/43 (2.3%) 0/44 (0%) 2/40 (5%) 3/53 (5.7%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Gastroenteritis 3/46 (6.5%) 0/43 (0%) 1/44 (2.3%) 1/40 (2.5%) 0/53 (0%) 3/47 (6.4%) 0/41 (0%) 1/46 (2.2%) 2/46 (4.3%)
    Gastroenteritis viral 2/46 (4.3%) 1/43 (2.3%) 1/44 (2.3%) 1/40 (2.5%) 1/53 (1.9%) 1/47 (2.1%) 4/41 (9.8%) 2/46 (4.3%) 3/46 (6.5%)
    Herpes zoster 1/46 (2.2%) 1/43 (2.3%) 2/44 (4.5%) 0/40 (0%) 2/53 (3.8%) 0/47 (0%) 1/41 (2.4%) 3/46 (6.5%) 0/46 (0%)
    Nasopharyngitis 7/46 (15.2%) 11/43 (25.6%) 9/44 (20.5%) 4/40 (10%) 4/53 (7.5%) 11/47 (23.4%) 11/41 (26.8%) 10/46 (21.7%) 6/46 (13%)
    Pneumonia 2/46 (4.3%) 1/43 (2.3%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 3/47 (6.4%) 2/41 (4.9%) 1/46 (2.2%) 1/46 (2.2%)
    Sinusitis 9/46 (19.6%) 4/43 (9.3%) 2/44 (4.5%) 6/40 (15%) 10/53 (18.9%) 6/47 (12.8%) 7/41 (17.1%) 2/46 (4.3%) 6/46 (13%)
    Tooth infection 0/46 (0%) 3/43 (7%) 0/44 (0%) 1/40 (2.5%) 3/53 (5.7%) 2/47 (4.3%) 0/41 (0%) 0/46 (0%) 2/46 (4.3%)
    Upper respiratory tract infection 11/46 (23.9%) 15/43 (34.9%) 10/44 (22.7%) 8/40 (20%) 13/53 (24.5%) 16/47 (34%) 8/41 (19.5%) 18/46 (39.1%) 14/46 (30.4%)
    Urinary tract infection 2/46 (4.3%) 3/43 (7%) 4/44 (9.1%) 8/40 (20%) 5/53 (9.4%) 6/47 (12.8%) 5/41 (12.2%) 8/46 (17.4%) 6/46 (13%)
    Viral infection 0/46 (0%) 3/43 (7%) 1/44 (2.3%) 1/40 (2.5%) 4/53 (7.5%) 3/47 (6.4%) 1/41 (2.4%) 2/46 (4.3%) 0/46 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/46 (0%) 4/43 (9.3%) 1/44 (2.3%) 1/40 (2.5%) 0/53 (0%) 3/47 (6.4%) 1/41 (2.4%) 2/46 (4.3%) 0/46 (0%)
    Contusion 3/46 (6.5%) 2/43 (4.7%) 1/44 (2.3%) 6/40 (15%) 5/53 (9.4%) 4/47 (8.5%) 6/41 (14.6%) 6/46 (13%) 1/46 (2.2%)
    Excoriation 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 3/41 (7.3%) 2/46 (4.3%) 1/46 (2.2%)
    Fall 2/46 (4.3%) 2/43 (4.7%) 1/44 (2.3%) 5/40 (12.5%) 1/53 (1.9%) 5/47 (10.6%) 4/41 (9.8%) 1/46 (2.2%) 3/46 (6.5%)
    Foot fracture 3/46 (6.5%) 0/43 (0%) 2/44 (4.5%) 2/40 (5%) 2/53 (3.8%) 4/47 (8.5%) 1/41 (2.4%) 4/46 (8.7%) 1/46 (2.2%)
    Joint sprain 2/46 (4.3%) 0/43 (0%) 0/44 (0%) 3/40 (7.5%) 3/53 (5.7%) 4/47 (8.5%) 2/41 (4.9%) 2/46 (4.3%) 1/46 (2.2%)
    Muscle strain 2/46 (4.3%) 2/43 (4.7%) 1/44 (2.3%) 1/40 (2.5%) 0/53 (0%) 3/47 (6.4%) 1/41 (2.4%) 2/46 (4.3%) 3/46 (6.5%)
    Procedural pain 2/46 (4.3%) 1/43 (2.3%) 2/44 (4.5%) 2/40 (5%) 4/53 (7.5%) 3/47 (6.4%) 0/41 (0%) 3/46 (6.5%) 1/46 (2.2%)
    Rib fracture 0/46 (0%) 0/43 (0%) 3/44 (6.8%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Skin laceration 0/46 (0%) 1/43 (2.3%) 0/44 (0%) 3/40 (7.5%) 0/53 (0%) 1/47 (2.1%) 1/41 (2.4%) 1/46 (2.2%) 2/46 (4.3%)
    Metabolism and nutrition disorders
    Dehydration 3/46 (6.5%) 0/43 (0%) 1/44 (2.3%) 0/40 (0%) 0/53 (0%) 1/47 (2.1%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Hypercholesterolaemia 0/46 (0%) 3/43 (7%) 5/44 (11.4%) 2/40 (5%) 2/53 (3.8%) 7/47 (14.9%) 2/41 (4.9%) 3/46 (6.5%) 3/46 (6.5%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 14/46 (30.4%) 7/43 (16.3%) 13/44 (29.5%) 9/40 (22.5%) 12/53 (22.6%) 11/47 (23.4%) 10/41 (24.4%) 12/46 (26.1%) 8/46 (17.4%)
    Arthritis 2/46 (4.3%) 0/43 (0%) 3/44 (6.8%) 2/40 (5%) 2/53 (3.8%) 1/47 (2.1%) 3/41 (7.3%) 1/46 (2.2%) 0/46 (0%)
    Back pain 6/46 (13%) 8/43 (18.6%) 13/44 (29.5%) 5/40 (12.5%) 10/53 (18.9%) 8/47 (17%) 10/41 (24.4%) 9/46 (19.6%) 7/46 (15.2%)
    Bursitis 2/46 (4.3%) 1/43 (2.3%) 0/44 (0%) 3/40 (7.5%) 0/53 (0%) 0/47 (0%) 2/41 (4.9%) 3/46 (6.5%) 0/46 (0%)
    Joint stiffness 1/46 (2.2%) 3/43 (7%) 1/44 (2.3%) 2/40 (5%) 1/53 (1.9%) 0/47 (0%) 2/41 (4.9%) 0/46 (0%) 1/46 (2.2%)
    Joint swelling 2/46 (4.3%) 0/43 (0%) 5/44 (11.4%) 0/40 (0%) 4/53 (7.5%) 1/47 (2.1%) 2/41 (4.9%) 2/46 (4.3%) 1/46 (2.2%)
    Muscle spasms 7/46 (15.2%) 4/43 (9.3%) 4/44 (9.1%) 3/40 (7.5%) 6/53 (11.3%) 5/47 (10.6%) 5/41 (12.2%) 5/46 (10.9%) 5/46 (10.9%)
    Musculoskeletal chest pain 2/46 (4.3%) 0/43 (0%) 0/44 (0%) 3/40 (7.5%) 2/53 (3.8%) 1/47 (2.1%) 1/41 (2.4%) 0/46 (0%) 2/46 (4.3%)
    Musculoskeletal stiffness 1/46 (2.2%) 1/43 (2.3%) 1/44 (2.3%) 3/40 (7.5%) 1/53 (1.9%) 1/47 (2.1%) 3/41 (7.3%) 1/46 (2.2%) 4/46 (8.7%)
    Myalgia 3/46 (6.5%) 2/43 (4.7%) 3/44 (6.8%) 1/40 (2.5%) 5/53 (9.4%) 5/47 (10.6%) 2/41 (4.9%) 5/46 (10.9%) 4/46 (8.7%)
    Neck pain 0/46 (0%) 3/43 (7%) 3/44 (6.8%) 1/40 (2.5%) 3/53 (5.7%) 2/47 (4.3%) 3/41 (7.3%) 2/46 (4.3%) 3/46 (6.5%)
    Osteoarthritis 4/46 (8.7%) 2/43 (4.7%) 0/44 (0%) 2/40 (5%) 0/53 (0%) 2/47 (4.3%) 1/41 (2.4%) 3/46 (6.5%) 5/46 (10.9%)
    Pain in extremity 8/46 (17.4%) 6/43 (14%) 6/44 (13.6%) 7/40 (17.5%) 11/53 (20.8%) 7/47 (14.9%) 5/41 (12.2%) 13/46 (28.3%) 7/46 (15.2%)
    Shoulder pain 7/46 (15.2%) 6/43 (14%) 5/44 (11.4%) 2/40 (5%) 3/53 (5.7%) 6/47 (12.8%) 6/41 (14.6%) 2/46 (4.3%) 4/46 (8.7%)
    Tendonitis 2/46 (4.3%) 0/43 (0%) 3/44 (6.8%) 2/40 (5%) 0/53 (0%) 2/47 (4.3%) 4/41 (9.8%) 2/46 (4.3%) 2/46 (4.3%)
    Nervous system disorders
    Dizziness 4/46 (8.7%) 1/43 (2.3%) 5/44 (11.4%) 3/40 (7.5%) 6/53 (11.3%) 4/47 (8.5%) 2/41 (4.9%) 1/46 (2.2%) 4/46 (8.7%)
    Headache 8/46 (17.4%) 1/43 (2.3%) 6/44 (13.6%) 3/40 (7.5%) 9/53 (17%) 6/47 (12.8%) 5/41 (12.2%) 8/46 (17.4%) 5/46 (10.9%)
    Hypoaesthesia 1/46 (2.2%) 0/43 (0%) 3/44 (6.8%) 1/40 (2.5%) 1/53 (1.9%) 0/47 (0%) 1/41 (2.4%) 2/46 (4.3%) 0/46 (0%)
    Migraine 1/46 (2.2%) 0/43 (0%) 1/44 (2.3%) 1/40 (2.5%) 4/53 (7.5%) 3/47 (6.4%) 0/41 (0%) 1/46 (2.2%) 1/46 (2.2%)
    Paraesthesia 2/46 (4.3%) 1/43 (2.3%) 4/44 (9.1%) 1/40 (2.5%) 2/53 (3.8%) 1/47 (2.1%) 2/41 (4.9%) 0/46 (0%) 0/46 (0%)
    Sciatica 2/46 (4.3%) 2/43 (4.7%) 2/44 (4.5%) 5/40 (12.5%) 2/53 (3.8%) 2/47 (4.3%) 2/41 (4.9%) 3/46 (6.5%) 1/46 (2.2%)
    Psychiatric disorders
    Anxiety 2/46 (4.3%) 0/43 (0%) 2/44 (4.5%) 1/40 (2.5%) 5/53 (9.4%) 1/47 (2.1%) 0/41 (0%) 4/46 (8.7%) 3/46 (6.5%)
    Depression 4/46 (8.7%) 0/43 (0%) 3/44 (6.8%) 6/40 (15%) 6/53 (11.3%) 2/47 (4.3%) 1/41 (2.4%) 3/46 (6.5%) 3/46 (6.5%)
    Insomnia 0/46 (0%) 2/43 (4.7%) 6/44 (13.6%) 4/40 (10%) 4/53 (7.5%) 4/47 (8.5%) 1/41 (2.4%) 2/46 (4.3%) 0/46 (0%)
    Renal and urinary disorders
    Pollakiuria 3/46 (6.5%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 2/53 (3.8%) 1/47 (2.1%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Urinary incontinence 0/46 (0%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 3/53 (5.7%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 1/46 (2.2%)
    Reproductive system and breast disorders
    Breast cyst 0/46 (0%) 0/43 (0%) 2/44 (4.5%) 0/40 (0%) 3/53 (5.7%) 1/47 (2.1%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/46 (0%) 1/43 (2.3%) 0/44 (0%) 0/40 (0%) 1/53 (1.9%) 1/47 (2.1%) 3/41 (7.3%) 0/46 (0%) 0/46 (0%)
    Cough 3/46 (6.5%) 2/43 (4.7%) 2/44 (4.5%) 4/40 (10%) 3/53 (5.7%) 3/47 (6.4%) 2/41 (4.9%) 5/46 (10.9%) 0/46 (0%)
    Epistaxis 1/46 (2.2%) 0/43 (0%) 0/44 (0%) 2/40 (5%) 1/53 (1.9%) 1/47 (2.1%) 0/41 (0%) 1/46 (2.2%) 3/46 (6.5%)
    Nasal congestion 3/46 (6.5%) 0/43 (0%) 0/44 (0%) 0/40 (0%) 2/53 (3.8%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Pharyngolaryngeal pain 4/46 (8.7%) 3/43 (7%) 2/44 (4.5%) 1/40 (2.5%) 4/53 (7.5%) 2/47 (4.3%) 3/41 (7.3%) 3/46 (6.5%) 1/46 (2.2%)
    Sinus congestion 0/46 (0%) 1/43 (2.3%) 1/44 (2.3%) 3/40 (7.5%) 5/53 (9.4%) 2/47 (4.3%) 1/41 (2.4%) 0/46 (0%) 0/46 (0%)
    Sleep apnoea syndrome 0/46 (0%) 0/43 (0%) 0/44 (0%) 3/40 (7.5%) 0/53 (0%) 0/47 (0%) 0/41 (0%) 0/46 (0%) 0/46 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis contact 0/46 (0%) 2/43 (4.7%) 2/44 (4.5%) 2/40 (5%) 3/53 (5.7%) 1/47 (2.1%) 3/41 (7.3%) 1/46 (2.2%) 1/46 (2.2%)
    Ecchymosis 0/46 (0%) 1/43 (2.3%) 0/44 (0%) 3/40 (7.5%) 2/53 (3.8%) 0/47 (0%) 0/41 (0%) 1/46 (2.2%) 0/46 (0%)
    Erythema 0/46 (0%) 1/43 (2.3%) 2/44 (4.5%) 1/40 (2.5%) 1/53 (1.9%) 1/47 (2.1%) 3/41 (7.3%) 0/46 (0%) 0/46 (0%)
    Pruritus 4/46 (8.7%) 1/43 (2.3%) 2/44 (4.5%) 1/40 (2.5%) 1/53 (1.9%) 2/47 (4.3%) 0/41 (0%) 3/46 (6.5%) 1/46 (2.2%)
    Rash 2/46 (4.3%) 2/43 (4.7%) 2/44 (4.5%) 4/40 (10%) 3/53 (5.7%) 2/47 (4.3%) 3/41 (7.3%) 5/46 (10.9%) 2/46 (4.3%)
    Skin lesion 0/46 (0%) 1/43 (2.3%) 3/44 (6.8%) 0/40 (0%) 2/53 (3.8%) 3/47 (6.4%) 0/41 (0%) 0/46 (0%) 2/46 (4.3%)
    Vascular disorders
    Hot flush 0/46 (0%) 0/43 (0%) 3/44 (6.8%) 1/40 (2.5%) 1/53 (1.9%) 0/47 (0%) 0/41 (0%) 3/46 (6.5%) 3/46 (6.5%)
    Hypertension 2/46 (4.3%) 4/43 (9.3%) 8/44 (18.2%) 5/40 (12.5%) 12/53 (22.6%) 5/47 (10.6%) 10/41 (24.4%) 4/46 (8.7%) 5/46 (10.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, the investigator agrees not to publish any results before the first multi-center publication.

    Results Point of Contact

    Name/Title Study Director
    Organization Amgen Inc.
    Phone 866-572-6436
    Email
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT00043186
    Other Study ID Numbers:
    • 20010223
    First Posted:
    Aug 7, 2002
    Last Update Posted:
    Sep 18, 2013
    Last Verified:
    Sep 1, 2013