A Study in Korean Postmenopausal Women With Osteoporosis to Evaluate the Efficacy and Safety of Denosumab

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01457950
• Collaborator: (none)
• Enrollment: 135
• Locations: 10
• Arms: 3
• Duration (Months): 19
• Patients Per Site: 13.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if denosumab is effective in increasing bone mineral density at the lumbar spine in Korean postmenopausal women with osteoporosis.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis, Postmenopausal	Drug: denosumab; Drug: placebo; Drug: open-label denosumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Six Month Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study With a Six Month Open-Label Extension to Evaluate the Efficacy and Safety of Denosumab in Korean Postmenopausal Women With Osteoporosis
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 denosumab 60mg subcutaneous injection, single dose at the start of the 6-month double-blind phase	Drug: denosumab; double-blind phase: 60mg subcutaneous injection, single dose
Placebo Comparator: Arm 2 placebo subcutaneous injection, single dose at the start of the 6-month double-blind phase	Drug: placebo; double-blind phase: placebo subcutaneous injection, single dose
Experimental: Arm 3 open-label phase follows the double-blind phase, denosumab 60mg subcutaneous injection, single dose at the start of the 6-month open-label phase	Drug: open-label denosumab; open-label phase: 60mg subcutaneous injection, single dose

Outcome Measures

Primary Outcome Measures

1. Mean Percent Change From Baseline in Lumbar Spine BMD at Month 6 [Baseline and Month 6]

   Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using the Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 6 - measure at Baseline) divided by the measure at Baseline * 100.

Secondary Outcome Measures

1. Mean Percent Change From Baseline in Lumbar Spine BMD at Month 1 [Baseline and Month 1]

   Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1 - measure at Baseline) divided by the measure at Baseline * 100.

2. Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 1 and Month 6 [Baseline, Month 1 and Month 6]

   Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covarience (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1/6 - measure at Baseline) divided by the measure at Baseline * 100.

3. Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Months 1, 3 and 6 [Baseline, Months 1, 3 and 6]

   Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100.

4. Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) [From Baseline up to Month 6]

   An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

5. Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6 [Baseline and Month 6]

   Change from Baseline was calculated as the Month 6 value minus the Baseline value.

6. Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 6 [Baseline and Month 6]

   Change from Baseline was calculated as the Month 6 value minus the Baseline value.

7. Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 6 [Baseline and Month 6]

   Change from Baseline was calculated as the Month 6 value minus the Baseline value.

8. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 6 [Baseline and Month 6]

   Change from Baseline was calculated as the Month 6 value minus the Baseline value.

9. Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 6 [Baseline and Month 6]

   Change from Baseline was calculated as the Month 6 value minus the Baseline value.

10. Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 6 [Baseline and Month 6]

    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

11. Change From Baseline in Hematocrit at Month 6 [Baseline and Month 6]

    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

12. Change From Baseline in Mean Corpuscle Hemoglobin at Month 6 [Baseline and Month 6]

    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

13. Change From Baseline in Mean Corpuscular Volume at Month 6 [Baseline and Month 6]

    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

14. Change From Baseline in Red Blood Cell Count at Month 6 [Baseline and Month 6]

    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

15. Change From Baseline in Red Cell Distribution Width at Month 6 [Baseline and Month 6]

    Change from Baseline was calculated as the Month 6 value minus the Baseline value.

16. Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 6 [Baseline and Month 6]

    Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 6 value minus the Baseline value.

17. Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab [Month 6]

    Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 6 was summarized.

Other Outcome Measures

1. Mean Percent Change From Baseline in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Denosumab [Baseline and Month 12]

   Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 12 - measure at Baseline) divided by the measure at Baseline * 100.

2. Mean Percent Change From Month 6 in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Placebo [Month 6 and Month 12]

   Mean percent change from Month 6 in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Month 6 BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by the measure at Month 6 * 100.

3. Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Denosumab [Baseline and Month 12]

   Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 12 - measure at Baseline) divided by the measure at Baseline * 100.

4. Mean Percent Change From Month 6 in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Placebo [Month 6 and Month 12]

   Mean percent change from Month 6 in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Month 6 BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by the measure at Month 6 * 100.

5. Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Denosumab [Baseline and Month 12]

   Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100.

6. Median Percent Change From Month 6 in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Placebo [Month 6 and Month 12]

   Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by measure at Month 6 * 100.

7. Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) During the Open-Label Extension Phase [From Month 6 to Month 12]

   An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

8. Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 12 [Baseline and Month 12]

   Change from Baseline was calculated as the Month 12 value minus the Baseline value.

9. Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 12 [Baseline and Month 12]

   Change from Baseline was calculated as the Month 12 value minus the Baseline value.

10. Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

11. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

12. Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

13. Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

14. Change From Baseline in Hematocrit at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

15. Change From Baseline in Mean Corpuscle Hemoglobin at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

16. Change From Baseline in Red Blood Cell Count at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

17. Change From Baseline in Red Cell Distribution Width at Month 12 [Baseline and Month 12]

    Change from Baseline was calculated as the Month 12 value minus the Baseline value.

18. Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 12 [Baseline and Month 12]

    Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 12 value minus the Baseline value.

19. Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 12 [Month 12]

    Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 12 was summarized.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 90 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ambulatory Korean postmenopausal women with osteoporosis

• greater than 5 years postmenopausal

• aged 60 to 90 years old

• absolute bone mineral density value consistent with a T-score less than -2.5 and greater than or equal to - 4.0 at the either the lumbar spine or total hip, as measured by dual energy x-ray absorptiometry. Subjects with a T-score less than -4.0 are at very high risk for fracture and will be excluded.

Exclusion Criteria:

• previous or current metabolic bone disease, Paget's or Cushing's disease, or hyperprolactinemia

• current hypo- or hyperparathyroidism or hypo- or hyperthyroidism unless on stable thyroid replacement therapy and TSH level meets criteria

• rheumatoid arthritis

• cirrhosis of the liver or unstable liver disease or ALT or AST greater than or equal to 2.0 times the upper limit of normal, or alkaline phosphatase and bilirubin greater than or equal to 1.5 times the upper limit of normal

• medications used to treat osteoporosis, defined for type and duration of use, and including IV and oral bisphosphonates

• medications that affect bone metabolism including parathyroid hormone or derivatives; anabolic steroids or testosterone; glucocorticosteroids; systemic hormone replacement therapy; selective estrogen receptor modulators; tibolone, calcitonin, and calcitriol or vitamin D derivatives; other bone active drugs including anticonvulsives (but not benzodiazepines) and heparin; chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, and gonadotropin-releasing hormone agonists

• malignancy within 5 years except certain resected types

• malabsorption syndrome or gastrointestinal disorders associated with malabsorption

• abnormal calcium level

• vitamin D deficiency

• any laboratory abnormality that will prevent the subject from completing the study or interfere with interpretation of study results

• severe renal impairment or on dialysis

• impaired immune system or subject is taking immunosuppressants

• oral or dental conditions including current or past history of osteomyelitis or osteonecrosis of the jaw; active dental or jaw condition with requires oral surgery; planned invasive dental procedure; un-healed dental or oral surgery

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

• any physical or psychiatric disorder that will prevent the subject from completing the study or interferes with study results

• known to have tested positive for HIV

• less than two lumbar vertebrae evaluable for DXA measurements

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

• drug or alcohol abuse within 12 months that interferes with understanding or completing the study

• known sensitivity to mammalian cell-derived drug products

• use of an investigational drug or device within 30 days of enrollment or currently receiving other investigational agent(s)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Busan		Korea, Republic of	602-739
2	GSK Investigational Site	Daegu		Korea, Republic of
3	GSK Investigational Site	Gwangju		Korea, Republic of	501-757
4	GSK Investigational Site	Seoul		Korea, Republic of	100-380
5	GSK Investigational Site	Seoul		Korea, Republic of	110-744
6	GSK Investigational Site	Seoul		Korea, Republic of	120-752
7	GSK Investigational Site	Seoul		Korea, Republic of	135-710
8	GSK Investigational Site	Seoul		Korea, Republic of	137-701
9	GSK Investigational Site	songpa-gu, Seoul		Korea, Republic of	138-736
10	GSK Investigational Site	Suwon		Korea, Republic of	443-721

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01457950
• Other Study ID Numbers: 114163
• First Posted: Oct 24, 2011
• Last Update Posted: May 7, 2014
• Last Verified: Feb 1, 2014

• Keywords provided by GlaxoSmithKline: denosumab; Republic of Korea; dual energy x-ray absorptiometry
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Denosumab

Study Results

Participant Flow

Pre-assignment Detail	This study consisted of a screening phase of up to 2.5 months, a six-month Double-Blind Treatment Phase and a six-month Open-Label Extension Phase. 371 participants (par.) were screened, 135 par. entered the Double-Blind Treatment Phase, and 123 par. continued into the Open-Label Extension Phase.

Arm/Group Title	Denosumab 60 mg	Placebo	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Period Title: Double-Blind Phase
STARTED	69	66	0	0
Completed the 6 Month Assessment	62	64	0	0
COMPLETED	60	63	0	0
NOT COMPLETED	9	3	0	0
Period Title: Double-Blind Phase
STARTED	0	0	60	63
COMPLETED	0	0	58	61
NOT COMPLETED	0	0	2	2

Baseline Characteristics

Arm/Group Title	Denosumab 60 mg	Placebo	Total
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).	Total of all reporting groups
Overall Participants	69	66	135
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.0 (4.86)	66.0 (4.77)	66.5 (4.83)
Sex: Female, Male (Count of Participants)
Female	69 100%	66 100%	135 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Asian - East Asian Heritage	69 100%	66 100%	135 100%

Outcome Measures

1. Primary Outcome

Title	Mean Percent Change From Baseline in Lumbar Spine BMD at Month 6
Description	Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using the Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 6 - measure at Baseline) divided by the measure at Baseline * 100.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Efficacy (ITTE) Population: all participants who received one dose of study medication, and had a Baseline measure and at least one post-Baseline efficacy measure during the Double-Blind Treatment Phase.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	68	66
Mean (Standard Error) [Percent change]	4.10 (0.407)	0.89 (0.413)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.21
	Confidence Interval	(2-Sided) 95%; 2.06 to 4.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Percent Change From Baseline in Lumbar Spine BMD at Month 1
Description	Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1 - measure at Baseline) divided by the measure at Baseline * 100.
Time Frame	Baseline and Month 1

Outcome Measure Data

Analysis Population Description

ITTE Population

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	68	66
Mean (Standard Error) [Percent change]	1.35 (0.375)	0.62 (0.380)

3. Secondary Outcome

Title	Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 1 and Month 6
Description	Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covarience (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 1/6 - measure at Baseline) divided by the measure at Baseline * 100.
Time Frame	Baseline, Month 1 and Month 6

Outcome Measure Data

Analysis Population Description

ITTE Population

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	69	64
Total hip, Month 1, n=67, 63	0.74 (0.238)	0.05 (0.245)
Total hip, Month 6, n=69, 64	2.23 (0.245)	0.57 (0.254)
Femoral neck, Month 1, n=67, 63	1.30 (0.344)	-0.04 (0.354)
Fermoral neck, Month 6, n=69, 64	2.23 (0.330)	0.84 (0.343)
Trochanter, Month 1, n=67, 63	0.82 (0.380)	0.39 (0.392)
Trochanter, Month n =69, 64	2.66 (0.418)	0.67 (0.434)

4. Secondary Outcome

Title	Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Months 1, 3 and 6
Description	Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100.
Time Frame	Baseline, Months 1, 3 and 6

Outcome Measure Data

Analysis Population Description

ITTE Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	69	66
s-CTx, Month 1, n=69, 66	-80.72	-14.48
s-CTx, Month 3, n=68, 65	-82.23	-27.49
s-CTx, Month 6, n=60, 63	-74.32	-21.21
s-PINP, Month 1, n=69, 66	-18.75	-4.65
s-PINP, Month 3, n=68, 65	-77.1	-21.57
s-PINP, Month 6, n=60, 63	-76.18	-21.05

5. Secondary Outcome

Title	Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE)
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From Baseline up to Month 6

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received one dose of study medication.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	69	66
Any AE	38 55.1%	32 48.5%
Any SAE	7 10.1%	2 3%

6. Secondary Outcome

Title	Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	60	63
Albumin/globulin ratio, n=60, 63	0.020 (0.1424)	0.052 (0.1390)
BUN/creatinine ratio, n=60, 63	-7.917 (25.2917)	-4.063 (27.3436)

7. Secondary Outcome

Title	Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	60	63
Albumin, n=60,63	0.217 (1.8964)	0.365 (2.2598)
Hemoglobin, n=59, 63	1.153 (5.8274)	1.778 (5.6894)
Mean corpuscle hemoglobin concentration, n=59, 63	-5.186 (9.9264)	-6.857 (9.4593)
Total protein, n=60, 63	-0.050 (2.9939)	-0.127 (3.3864)

8. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed. .

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	60	63
Alkaline phosphatase, n=60, 63	-24.283 (15.9513)	-8.222 (11.2127)
Alanine amino transferase, n=60, 63	2.117 (6.4047)	-0.397 (8.8035)
Aspartate amino transferase, n=59, 63	1.034 (4.4527)	-0.032 (7.4962)
Creatine kinase, n=60, 63	7.617 (51.6658)	3.905 (31.2052)
Gamma glutamyl transferase, n=60, 63	-0.133 (8.4381)	-2.143 (7.9532)
Lactate dehydraogenase, n=59, 63	6.119 (18.1156)	3.889 (20.4979)

9. Secondary Outcome

Title	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	58	63
Basophils, n=58, 63	-0.003 (0.0131)	-0.006 (0.0165)
Eosinophils, n=58, 63	-0.019 (0.1254)	-0.033 (0.1309)
Lymphocytes, n=58, 63	-0.047 (0.4096)	-0.206 (0.5930)
Monocytes, n=58, 63	-0.033 (0.1094)	-0.059 (0.1324)
Segmented neutrophils, n=58, 63	0.114 (1.3382)	-0.213 (1.0934)
Total neutrophils, n=58, 63	0.114 (1.3382)	-0.213 (1.0934)
Platelet count, n=58, 63	1.621 (31.7881)	-6.190 (35.7874)
White blood cell count, n=58, 63	0.014 (1.4026)	-0.517 (1.2003)

10. Secondary Outcome

Title	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	60	63
Direct bilirubin, n=60, 63	0.300 (1.0301)	0.222 (1.1974)
Indirect bilirubin, n=60, 63	1.567 (3.4757)	0.508 (3.5372)
Total bilirubin, n=60, 63	1.867 (3.8947)	0.730 (3.8404)
Creatinine, n=60, 63	2.037 (6.4916)	0.940 (5.1644)
Uric acid, n=60, 63	11.500 (38.9622)	0.159 (40.9757)

11. Secondary Outcome

Title	Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	60	63
Calcium (corrected), n=1, 1	0.110 (NA)	0.000 (NA)
Calcium, n=59, 63	-0.020 (0.0890)	0.002 (0.0768)
Chloride, n=60, 63	-0.200 (2.2981)	0.444 (2.3264)
Glucose, n=60, 63	-0.873 (2.5458)	-0.567 (1.2118)
Potassium, n=59, 63	0.000 (0.3900)	0.060 (0.3476)
Magnesium, n=60, 63	0.004 (0.0585)	0.009 (0.0462)
Sodium, n=60, 63	-0.400 (2.1249)	0.095 (1.9486)
Phosphorus inorganic, n=60, 63	-0.072 (0.1505)	-0.063 (0.1695)
Triglycerides, n=60, 63	-0.166 (0.7155)	-0.156 (0.6119)
Urea/BUN, n=60, 63	-0.258 (1.1878)	-0.119 (1.4134)
VLDL cholesterol calculation, n=59, 63	-0.098 (0.2844)	-0.072 (0.2810)

12. Secondary Outcome

Title	Change From Baseline in Hematocrit at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	59	63
Mean (Standard Deviation) [Proportion of RBCs in blood]	0.009 (0.0196)	0.013 (0.0196)

13. Secondary Outcome

Title	Change From Baseline in Mean Corpuscle Hemoglobin at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	59	63
Mean (Standard Deviation) [Picograms (PG)/cell]	0.068 (0.7111)	0.146 (0.6696)

14. Secondary Outcome

Title	Change From Baseline in Mean Corpuscular Volume at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	59	63
Mean (Standard Deviation) [Femtoliters (FL)]	1.695 (2.5000)	2.397 (2.6368)

15. Secondary Outcome

Title	Change From Baseline in Red Blood Cell Count at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	59	63
Mean (Standard Deviation) [10^12 cells per liter (TI/L)]	0.025 (0.1844)	0.037 (0.1920)

16. Secondary Outcome

Title	Change From Baseline in Red Cell Distribution Width at Month 6
Description	Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	59	63
Mean (Standard Deviation) [percentage (%) of mean RBC volume]	0.475 (1.0256)	0.556 (0.9242)

17. Secondary Outcome

Title	Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 6
Description	Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 6 value minus the Baseline value.
Time Frame	Baseline and Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	60	63
Diastolic blood pressure, Low, n=60, 63	0 0%	2 3%
Systolic blood pressure, High, n=60, 63	1 1.4%	2 3%
Systolic blood pressure, Low, n=60, 63	1 1.4%	1 1.5%
Heart rate, High, n=60, 63	0 0%	0 0%
Heart rate, Low, n=60, 63	0 0%	0 0%

18. Secondary Outcome

Title	Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab
Description	Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 6 was summarized.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

ITT Population. Only participants at the specified time points were analyzed.

Arm/Group Title	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).
Measure Participants	69	66
Neutralizing antibodies, Positive, n=0, 0	NA NaN	NA NaN
Neutralizing antibodies, Negative, n=0, 0	NA NaN	NA NaN
Binding antibodies, Positive, n=60, 63	0 0%	0 0%
Binding antibodies, Negative, n=60, 63	60 87%	63 95.5%

19. Other Pre-specified Outcome

Title	Mean Percent Change From Baseline in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Denosumab
Description	Mean percent change from Baseline in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 12 - measure at Baseline) divided by the measure at Baseline * 100.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Open-Label (ITT-OL) Population: all participants from the ITT population in the Double-Blind Phase who continued into the Open-Label Extension Phase of the study and received denosumab at Month 6. Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	59
Mean (Standard Error) [Percent change]	5.62 (3.776)

20. Other Pre-specified Outcome

Title	Mean Percent Change From Month 6 in Lumbar Spine BMD at Month 12 for Participants Previously Randomized to Placebo
Description	Mean percent change from Month 6 in lumbar spine bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Month 6 BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by the measure at Month 6 * 100.
Time Frame	Month 6 and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population. Ony those participants with a value at Month 6 and Month 12 were analyzed.

Arm/Group Title	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	59
Mean (Standard Error) [Percent change]	2.67 (3.440)

21. Other Pre-specified Outcome

Title	Mean Percent Change From Baseline in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Denosumab
Description	Mean percent change from Baseline in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Baseline BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Baseline=(measure at Month 12 - measure at Baseline) divided by the measure at Baseline * 100.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population. Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60
Total hip	3.07 (2.476)
Femoral neck	3.39 (3.158)
Trochanter	3.39 (4.653)

22. Other Pre-specified Outcome

Title	Mean Percent Change From Month 6 in Total Hip, Femoral Neck, and Trochanter BMD at Month 12 for Participants Previously Randomized to Placebo
Description	Mean percent change from Month 6 in total hip, femoral neck, and trochanter bone mineral density (BMD) was measured by the dual-energy x-ray absorptiometry (DXA) scanner. Analyses were performed using Analysis of Covariance (ANCOVA) model adjusting for treatment and Month 6 BMD for the skeletal site under consideration as a continuous covariate. Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by the measure at Month 6 * 100.
Time Frame	Month 6 and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population. Ony those participants with a value at Month 6 and Month 12 were analyzed.

Arm/Group Title	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	56
Total hip	1.46 (1.701)
Femoral neck	1.12 (2.668)
Trochanter	2.13 (2.762)

23. Other Pre-specified Outcome

Title	Median Percent Change From Baseline in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Denosumab
Description	Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Baseline=(measure at post-Baseline - measure at Baseline) divided by measure at Baseline * 100.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population. Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	57
s-CTx	-63.36
s-PINP	-78.00

24. Other Pre-specified Outcome

Title	Median Percent Change From Month 6 in s-CTX and s-P1NP Biomarkers at Month 12 for Participants Previously Randomized to Placebo
Description	Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTx) I and Serum procollagen type I N propeptide s (s-PINP) are used as serum biomarkers of bone resorption in the assessment of osteoporosis and is measured in units of micrograms (µg)/liters (L). Percentage change from Month 6=(measure at Month 12 - measure at Month 6) divided by measure at Month 6 * 100.
Time Frame	Month 6 and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population. Ony those participants with a value at Month 6 and Month 12 were analyzed.

Arm/Group Title	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60
s-CTx	-50.90
s-PINP	-66.67

25. Other Pre-specified Outcome

Title	Number of Participants With Any Adverse Events (AE) or Any Serious Adverse Events (SAE) During the Open-Label Extension Phase
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame	From Month 6 to Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Any AE	22 31.9%	29 43.9%
Any SAE	1 1.4%	3 4.5%

26. Other Pre-specified Outcome

Title	Change From Baseline in Albumin/Globulin Ratio and Blood Urea Nitrogen (BUN)/Creatinine Ratio at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Albumin/globulin ratio, n=58, 60	0.016 (0.1473)	0.032 (0.1621)
BUN/creatinine ratio, n=58, 60	-5.776 (24.4297)	2.500 (27.7962)

27. Other Pre-specified Outcome

Title	Change From Baseline in Albumin, Hemoglobin, Mean Corpuscle Hemoglobin and Total Protein at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Albumin, n=58, 60	0.293 (2.1110)	0.450 (1.9866)
Hemoglobin, n=56, 60	1.411 (5.7833)	2.033 (6.0084)
Mean corpuscle hemoglobin concentration, n=56, 60	-5.679 (6.6143)	-6.650 (7.7587)
Total protein, n=58, 60	0.224 (3.4946)	0.267 (2.8216)

28. Other Pre-specified Outcome

Title	Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Creatinine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Alkaline phosphatase, n=58, 60	-25.603 (14.4780)	-23.767 (15.7570)
Alanine amino transferase, n=58, 60	1.810 (7.9922)	-0.150 (8.9288)
Aspartate amino transferase, n=58, 60	0.879 (6.4293)	-0.467 (6.2666)
Creatine kinase, n=58, 60	-4.534 (44.0690)	4.500 (52.0731)
Gamma glutamyl transferase, n=58, 60	0.4823 (6.9541)	-0.600 (9.4961)
Lactate dehydraogenase, n=58, 60	-0.552 (19.2237)	-1.217 (24.7243)

29. Other Pre-specified Outcome

Title	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Segmented Neutrophils, Platelet Count and White Blood Cell Count at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Basophils, n=54, 59	-0.004 (0.0164)	-0.002 (0.0148)
Eosinophils, n=54, 59	0.024 (0.1489)	0.019 (0.1860)
Lymphocytes, n=54, 59	0.098 (0.4436)	-0.089 (0.5599)
Monocytes, n=54, 59	-0.009 (0.1053)	-0.039 (0.1443)
Segmented neutrophils, n=54, 59	0.014 (1.1748)	-0.259 (1.2035)
Total neutrophils, n=54, 59	0.014 (1.1748)	-0.259 (1.2035)
Platelet count, n=55, 60	-4.018 (34.8215)	-4.233 (37.7913)
White blood cell count, n=54, 59	0.122 (1.1618)	-0.369 (1.3903)

30. Other Pre-specified Outcome

Title	Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine and Uric Acid at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Direct bilirubin, n=58, 60	0.241 (1.3548)	0.100 (1.2980)
Indirect bilirubin, n=58, 60	1.034 (4.0391)	0.800 (3.3385)
Total bilirubin, n=58, 60	1.276 (4.6596)	0.900 (3.5401)
Creatinine, n=58, 60	0.948 (5.1157)	-0.015 (4.6216)
Uric acid, n=58, 60	4.483 (41.3870)	2.000 (44.0647)

31. Other Pre-specified Outcome

Title	Change From Baseline in Calcium Corrected, Calcium, Chloride, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Triglycerides, Urea/BUN, Very Low Density Lipoproteins (VLDL) Cholesterol Calculation at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Calcium (corrected), n=0, 0	NA (NA)	NA (NA)
Calcium, n=58, 60	-0.031 (0.0944)	-0.004 (0.0904)
Chloride, n=58, 60	0.328 (2.5573)	0.300 (2.4446)
Glucose, n=58, 60	-0.760 (2.9331)	-0.500 (1.2985)
Potassium, n=58, 60	0.047 (0.4398)	0.045 (0.3078)
Magnesium, n=58, 60	0.009 (0.0679)	0.004 (0.0514)
Sodium, n=58, 60	-0.172 (2.1532)	0.067 (2.2986)
Phosphorus inorganic, n=58, 60	-0.153 (0.1530)	-0.094 (0.1981)
Triglycerides, n=58, 60	-0.144 (0.7716)	-0.033 (0.8449)
Urea/BUN, n=58, 60	-0.233 (1.2183)	0.158 (1.5771)
VLDL cholesterol calculation, n=58, 59	-0.066 (0.3539)	-0.044 (0.3234)

32. Other Pre-specified Outcome

Title	Change From Baseline in Hematocrit at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	56	60
Mean (Standard Deviation) [Proportion of RBCs in blood]	0.010 (0.0182)	0.014 (0.0185)

33. Other Pre-specified Outcome

Title	Change From Baseline in Mean Corpuscle Hemoglobin at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	56	60
Mean (Standard Deviation) [Picograms (PG)/cell)]	-0.304 (0.7632)	-0.310 (0.5058)

34. Other Pre-specified Outcome

Title	Change From Baseline in Red Blood Cell Count at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	56	60
Mean (Standard Deviation) [10^12 cells per liter (TI/L)]	0.086 (0.1634)	0.103 (0.1904)

35. Other Pre-specified Outcome

Title	Change From Baseline in Red Cell Distribution Width at Month 12
Description	Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	56	60
Mean (Standard Deviation) [percentage (%) of mean RBC volume]	0.007 (0.7897)	0.203 (0.8718)

36. Other Pre-specified Outcome

Title	Number of Participants With a Change From Baseline in Vital Signs of Potential Clinical Concern at Month 12
Description	Vital Sign Changes from Baseline of potential clinical concern for Diastolic Blood Pressure (<50 or >120 Bits Per Minutes [bpm]), Systolic Blood Pressure (>170 Millimeters of Mercury [mmHg] or <100 mmHg) and Heart rate (>110 mmHg or <50 mmHg) are summarized. Change from Baseline was calculated as the Month 12 value minus the Baseline value.
Time Frame	Baseline and Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Ony those participants with a value at Baseline and Month 12 were analyzed.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	58	61
Diastolic blood pressure, High	0 0%	1 1.5%
Diastolic blood pressure, Low	2 2.9%	0 0%
Systolic blood pressure, High	0 0%	2 3%
Systolic blood pressure, Low	0 0%	2 3%
Heart rate, High	0 0%	0 0%
Heart rate, Low	0 0%	0 0%

37. Other Pre-specified Outcome

Title	Number of Participants With Positive and Negative Results for Anti-body Formation to Denosumab at Month 12
Description	Number of participants with positive and negative results for both neutralizing antibodies to denosumab, and for binding antibodies to denosumab at Month 12 was summarized.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

ITT-OL Population: Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT-OL population.

Arm/Group Title	Denosumab 60 mg to Open-Label Denosumab 60mg	Placebo to Open-Label Denosumab 60 mg
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.	Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
Measure Participants	60	63
Neutralizing antibodies, Positive, n=0, 0	NA NaN	NA NaN
Neutralizing antibodies, Negative, n=0, 0	NA NaN	NA NaN
Binding antibodies, Positive, n=58, 61	0 0%	0 0%
Binding antibodies, Negative, n=58, 61	58 84.1%	61 92.4%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of the Open-Label Phase (up to Month 12).
Adverse Event Reporting Description	SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received one dose of study medication during the Double-Blind Treatment Phase, and for members of ITT-OL Population in the Open-Label Phase.
Arm/Group Title	Randomized Phase: Denosumab 60 mg		Randomized Phase: Placebo		Open Label Denosumab 60 mg (Previously Randomized Denosumab)		Open Label Denosumab 60 mg (Previously Randomized Placebo)
Arm/Group Description	Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]).		Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU).		Participants received a denosumab 60 milligrams (mg) single subcutaneous (SC) injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 International Units [IU]). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.		Participants received a matching placebo single SC injection at the start of the Double-Blind Treatment Phase. All participants received daily oral supplementation of elemental calcium (at least 1000 mg) and vitamin D (at least 400 IU). At the end of the Double-Blind Treatment Phase, following completion of all Month 6 assessments, eligible participants entered the Open-Label Extension Phase and received a single SC injection of denosumab 60 mg and were followed up for an additional 6 months.
All Cause Mortality
	Randomized Phase: Denosumab 60 mg		Randomized Phase: Placebo		Open Label Denosumab 60 mg (Previously Randomized Denosumab)		Open Label Denosumab 60 mg (Previously Randomized Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Randomized Phase: Denosumab 60 mg		Randomized Phase: Placebo		Open Label Denosumab 60 mg (Previously Randomized Denosumab)		Open Label Denosumab 60 mg (Previously Randomized Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/69 (10.1%)		2/66 (3%)		1/60 (1.7%)		3/63 (4.8%)
Eye disorders
Macular hole	0/69 (0%)		0/66 (0%)		1/60 (1.7%)		0/63 (0%)
Gastrointestinal disorders
Haemorrhoids	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Infections and infestations
Appendicitis	0/69 (0%)		1/66 (1.5%)		0/60 (0%)		0/63 (0%)
Bronchitis	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Appendicitis perforated	0/69 (0%)		0/66 (0%)		0/60 (0%)		1/63 (1.6%)
Injury, poisoning and procedural complications
Tendon rupture	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Extradural haematoma	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Skull fractured base	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Subdural haemorrhage	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Traumatic lung injury	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Spinal compression fracture	0/69 (0%)		0/66 (0%)		0/60 (0%)		1/63 (1.6%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	2/69 (2.9%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Rotator cuff syndrome	0/69 (0%)		1/66 (1.5%)		0/60 (0%)		0/63 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma	0/69 (0%)		0/66 (0%)		0/60 (0%)		1/63 (1.6%)
Nervous system disorders
Cerebral haemorrhage	1/69 (1.4%)		0/66 (0%)		0/60 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Randomized Phase: Denosumab 60 mg		Randomized Phase: Placebo		Open Label Denosumab 60 mg (Previously Randomized Denosumab)		Open Label Denosumab 60 mg (Previously Randomized Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/69 (18.8%)		11/66 (16.7%)		12/60 (20%)		7/63 (11.1%)
Gastrointestinal disorders
Constipation	5/69 (7.2%)		2/66 (3%)		0/60 (0%)		0/63 (0%)
Dyspepsia	0/69 (0%)		0/66 (0%)		3/60 (5%)		1/63 (1.6%)
Gastritis	0/69 (0%)		0/66 (0%)		3/60 (5%)		0/63 (0%)
Infections and infestations
Nasopharyngitis	4/69 (5.8%)		8/66 (12.1%)		6/60 (10%)		6/63 (9.5%)
Injury, poisoning and procedural complications
Ligament sprain	0/69 (0%)		0/66 (0%)		3/60 (5%)		1/63 (1.6%)
Musculoskeletal and connective tissue disorders
Myalgia	4/69 (5.8%)		1/66 (1.5%)		0/60 (0%)		0/63 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.