Trial Outcomes & Findings for Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis (NCT NCT00095498)

Results Overview

Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism \[EULAR\]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

227 participants

Primary outcome timeframe

Baseline, Month 6

Results posted on

2021-10-25

Participant Flow

First Subject Enrolled: 11-Aug-2004 Last Subject Enrolled: 07-Apr-2005

Participant milestones

Participant milestones
Measure	Denosumab 180 mg Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Overall Study STARTED	76	73	78
Overall Study Received Investigational Product	72	71	75
Overall Study COMPLETED	39	38	39
Overall Study NOT COMPLETED	37	35	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Denosumab 180 mg Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Overall Study Physician Decision	9	10	8
Overall Study Adverse Event	1	0	1
Overall Study Withdrawal by Subject	15	16	15
Overall Study Disease progression	0	1	1
Overall Study Ineligibility determined	3	0	2
Overall Study Lost to Follow-up	1	1	2
Overall Study Noncompliance	1	0	1
Overall Study Other	6	7	6
Overall Study Protocol Violation	0	0	1
Overall Study Requirement for alternative therapy	1	0	2

Baseline Characteristics

Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Denosumab 180 mg n=76 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=73 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=78 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.	Total n=227 Participants Total of all reporting groups
Age, Continuous	58 Years STANDARD_DEVIATION 11 • n=5 Participants	57.3 Years STANDARD_DEVIATION 11.4 • n=7 Participants	57 Years STANDARD_DEVIATION 11.1 • n=5 Participants	57.4 Years STANDARD_DEVIATION 11.2 • n=4 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	51 Participants n=7 Participants	62 Participants n=5 Participants	166 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	22 Participants n=7 Participants	16 Participants n=5 Participants	61 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Japanese	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized White or Caucasian	66 Participants n=5 Participants	59 Participants n=7 Participants	62 Participants n=5 Participants	187 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	21 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism \[EULAR\]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6	0.00 units on a scale Full Range 3.49 • Interval -13.0 to 12.53	0.00 units on a scale Full Range 3.43 • Interval -17.86 to 9.0	0.49 units on a scale Full Range 5.08 • Interval -5.5 to 37.0

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.

TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12	0 units on a scale Interval 0.0 to 1.5	0 units on a scale Interval -0.5 to 1.0	0.5 units on a scale Interval 0.0 to 2.0

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6	0 units on a scale Interval 0.0 to 0.5	0 units on a scale Interval 0.0 to 1.0	0 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.

The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Radiographic Erosion Score at Month 12	0 units on a scale Interval 0.0 to 0.5	0 units on a scale Interval 0.0 to 0.5	0 units on a scale Interval 0.0 to 1.5

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Radiographic Erosion Score at Month 6	0 units on a scale Interval 0.0 to 0.0	0 units on a scale Interval 0.0 to 0.5	0 units on a scale Interval 0.0 to 0.5

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.

Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12	0 units on a scale Interval 0.0 to 1.0	0 units on a scale Interval 0.0 to 0.5	0 units on a scale Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6	0 units on a scale Interval 0.0 to 0.5	0 units on a scale Interval 0.0 to 0.97	0 units on a scale Interval 0.0 to 0.5

SECONDARY outcome

Timeframe: Baseline, Month 1

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 1 month.

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1	0.25 Percent change from baseline Standard Error 0.29	0.59 Percent change from baseline Standard Error 0.29	-0.34 Percent change from baseline Standard Error 0.29

SECONDARY outcome

Timeframe: Baseline, month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=68 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6	2.61 Percent change from baseline Standard Error 0.38	2.40 Percent change from baseline Standard Error 0.37	0.73 Percent change from baseline Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=62 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=62 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12	4.09 Percent change from baseline Standard Error 0.40	3.00 Percent change from baseline Standard Error 0.39	0.80 Percent change from baseline Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline, Month 1

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 1 month.

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=65 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1	0.64 Percent change from baseline Standard Error 0.38	-0.15 Percent change from baseline Standard Error 0.38	-0.16 Percent change from baseline Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6	0.84 Percent change from baseline Standard Error 0.37	0.89 Percent change from baseline Standard Error 0.37	-0.06 Percent change from baseline Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12	1.51 Percent change from baseline Standard Error 0.47	1.34 Percent change from baseline Standard Error 0.47	-0.47 Percent change from baseline Standard Error 0.47

SECONDARY outcome

Timeframe: Baseline, Month 1

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 1 month.

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=65 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1	0.06 Percent change from baseline Standard Error 0.22	0.00 Percent change from baseline Standard Error 0.22	-0.02 Percent change from baseline Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6	1.12 Percent change from baseline Standard Error 0.24	0.95 Percent change from baseline Standard Error 0.24	-0.06 Percent change from baseline Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 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. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic).

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12	1.67 Percent change from baseline Standard Error 0.33	1.56 Percent change from baseline Standard Error 0.33	-0.38 Percent change from baseline Standard Error 0.33

SECONDARY outcome

Timeframe: Baseline, Month 3

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 3 months.

Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3	-78.67 Percent change from baseline Interval -86.29 to -62.86	-80.46 Percent change from baseline Interval -86.27 to -66.84	-11.48 Percent change from baseline Interval -26.95 to 15.59

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Serum CTX at Month 6	-62.69 Percent change from baseline Interval -78.56 to -46.23	-50.64 Percent change from baseline Interval -63.31 to -22.37	-12.94 Percent change from baseline Interval -31.2 to 23.3

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.

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

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=62 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=62 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Serum CTX at Month 12	-65.65 Percent change from baseline Interval -78.62 to -48.4	-47.24 Percent change from baseline Interval -63.6 to -27.2	-23.36 Percent change from baseline Interval -45.43 to 1.67

SECONDARY outcome

Timeframe: Baseline, Month 3

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 3 months.

Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3	-55.08 Percent change from baseline Interval -69.3 to -44.4	-57.57 Percent change from baseline Interval -70.07 to -46.07	-12.23 Percent change from baseline Interval -21.57 to -0.11

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in P1NP at Month 6	-57.06 Percent change from baseline Interval -67.17 to -37.13	-51.57 Percent change from baseline Interval -64.51 to -37.35	-22.17 Percent change from baseline Interval -39.69 to -3.07

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.

Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=33 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=39 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=30 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in P1NP at Month 12	-45.84 Percent change from baseline Interval -61.36 to -30.09	-41.8 Percent change from baseline Interval -57.3 to -18.89	-17.53 Percent change from baseline Interval -31.42 to -0.02

SECONDARY outcome

Timeframe: Baseline, Month 3

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 3 months.

Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=63 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=65 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3	-46.59 Percent change from baseline Interval -71.58 to 4.17	-35.8 Percent change from baseline Interval -56.8 to 16.99	2.71 Percent change from baseline Interval -24.18 to 31.72

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 6 months.

Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=56 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=63 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6	7.17 Percent change from baseline Interval -32.43 to 88.27	9.65 Percent change from baseline Interval -21.79 to 51.16	4.54 Percent change from baseline Interval -27.44 to 56.52

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All randomized patients who received at least 1 dose of investigational product with a non-missing baseline and at least 1 non-missing postbaseline measurement, and with available data at 12 months.

Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=29 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=35 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=22 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12	36.92 Percent change from baseline Interval 4.5 to 111.51	61.92 Percent change from baseline Interval -15.84 to 108.6	-3.93 Percent change from baseline Interval -37.7 to 126.65

SECONDARY outcome

Timeframe: Assessed at Baseline and at Months 1, 3, 6 and 12.

Population: Patients who received at least 1 dose of investigational product and with at least one postbaseline sample taken.

Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=72 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=70 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=75 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Number of Participants With Anti-Denosumab Binding Antibodies	4 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline to Month 12

Population: Patients who were positive for anti-denosumab antibodies

Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=4 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=2 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody	0 Participants	—	0 Participants

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory Chemistry Albumin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Albumin at Month 1	-0.36 g/L Standard Deviation 2.29	-0.24 g/L Standard Deviation 2.25	-0.30 g/L Standard Deviation 2.21

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry albumin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Albumin at Month 3	-0.30 g/L Standard Deviation 2.18	-0.12 g/L Standard Deviation 2.28	-0.18 g/L Standard Deviation 2.07

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry albumin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Albumin at Month 6	-0.30 g/L Standard Deviation 2.49	-0.90 g/L Standard Deviation 2.56	-0.77 g/L Standard Deviation 2.40

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry albumin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Albumin at Month 12	-0.13 g/L Standard Deviation 2.41	-0.06 g/L Standard Deviation 2.26	-0.59 g/L Standard Deviation 2.49

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry alkaline phoshatatse

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alkaline Phosphatase at Month 1	-5.87 U/L Standard Deviation 10.52	-3.66 U/L Standard Deviation 11.97	1.18 U/L Standard Deviation 15.62

SECONDARY outcome

Timeframe: baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemisrty alkaline phosphatase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alkaline Phosphatase at Month 3	-13.27 U/L Standard Deviation 15.91	-12.38 U/L Standard Deviation 13.09	-2.03 U/L Standard Deviation 8.37

SECONDARY outcome

Timeframe: baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry alkaline phosphatase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alkaline Phosphatase at Month 6	-7.84 U/L Standard Deviation 31.94	-12.49 U/L Standard Deviation 12.61	-0.54 U/L Standard Deviation 18.46

SECONDARY outcome

Timeframe: baseine, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry alkaline phosphatase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alkaline Phosphatase at Month 12	-11.92 U/L Standard Deviation 16.74	-11.34 U/L Standard Deviation 18.18	-4.63 U/L Standard Deviation 16.70

SECONDARY outcome

Timeframe: baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry bicarbonate

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Bicarbonate at Month 1	0.78 mmol/L Standard Deviation 2.31	0.06 mmol/L Standard Deviation 3.06	0.54 mmol/L Standard Deviation 2.94

SECONDARY outcome

Timeframe: baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry bicarbonate

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Bicarbonate at Month 3	0.12 mmol/L Standard Deviation 2.40	0.39 mmol/L Standard Deviation 2.84	-0.67 mmol/L Standard Deviation 3.17

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry bicarbonate

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Bicarbonate at Month 6	0.45 mmol/L Standard Deviation 2.29	-0.12 mmol/L Standard Deviation 2.61	-0.18 mmol/L Standard Deviation 2.67

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry bicarbonate

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=62 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Bicarbonate at Month 12	0.81 mmol/L Standard Deviation 2.12	0.58 mmol/L Standard Deviation 2.68	0.23 mmol/L Standard Deviation 2.50

SECONDARY outcome

Timeframe: baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry total bilirubin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Bilirubin at Month 1	0.26 umol/L Standard Deviation 2.39	-0.23 umol/L Standard Deviation 2.45	0.42 umol/L Standard Deviation 2.83

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry total bilirubin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Bilirubin at Month 3	0.92 umol/L Standard Deviation 2.17	-0.23 umol/L Standard Deviation 2.36	0.44 umol/L Standard Deviation 2.74

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry total bilirubin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Bilirubin at Month 6	1.08 umol/L Standard Deviation 2.58	-0.61 umol/L Standard Deviation 2.49	0.34 umol/L Standard Deviation 3.30

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry total bilirubin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=62 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Bilirubin at Month 12	0.41 umol/L Standard Deviation 2.58	-0.35 umol/L Standard Deviation 2.28	0.03 umol/L Standard Deviation 2.80

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry blood urea nitrogen

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Blood Urea Nitrogen at Month 1	0 mmol/L Standard Deviation 1.35	0.15 mmol/L Standard Deviation 1.40	-0.01 mmol/L Standard Deviation 1.55

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry blood urea nitrogen

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Blood Urea Nitrogen at Month 3	0.04 mmol/L Standard Deviation 1.35	0.41 mmol/L Standard Deviation 1.59	0.06 mmol/L Standard Deviation 1.43

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry blood urea nitrogen

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Blood Urea Nitrogen at Month 6	-0.21 mmol/L Standard Deviation 1.44	-0.08 mmol/L Standard Deviation 1.41	-0.04 mmol/L Standard Deviation 2.29

SECONDARY outcome

Timeframe: baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry blood urea nitrogen

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Blood Urea Nitrogen at Month 12	0.32 mmol/L Standard Deviation 1.37	0.24 mmol/L Standard Deviation 1.46	-0.09 mmol/L Standard Deviation 1.56

SECONDARY outcome

Timeframe: baseline. month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium at Month 1	-0.05 mmol/L Standard Deviation 0.11	-0.05 mmol/L Standard Deviation 0.09	0.01 mmol/L Standard Deviation 0.09

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium at Month 3	-0.01 mmol/L Standard Deviation 0.11	-0.02 mmol/L Standard Deviation 0.10	0 mmol/L Standard Deviation 0.10

SECONDARY outcome

Timeframe: baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium at Month 6	-0.01 mmol/L Standard Deviation 0.10	-0.03 mmol/L Standard Deviation 0.11	-0.01 mmol/L Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium at Month 12	-0.01 mmol/L Standard Deviation 0.11	0.01 mmol/L Standard Deviation 0.09	0.01 mmol/L Standard Deviation 0.08

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry albumin-adjusted calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium (Corrected) at Month 1	-0.05 mmol/L Standard Deviation 0.11	-0.05 mmol/L Standard Deviation 0.09	0.01 mmol/L Standard Deviation 0.09

SECONDARY outcome

Timeframe: baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry albumin-adjusted calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium (Corrected) at Month 3	-0.01 mmol/L Standard Deviation 0.11	-0.02 mmol/L Standard Deviation 0.09	0 mmol/L Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline, Month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry albumin-adjusted calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium (Corrected) at Month 6	-0.01 mmol/L Standard Deviation 0.10	-0.02 mmol/L Standard Deviation 0.10	-0.01 mmol/L Standard Deviation 0.09

SECONDARY outcome

Timeframe: Baselien, Month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry albumin-adjusted calcium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Calcium (Corrected) at Month 12	-0.01 mmol/L Standard Deviation 0.11	0.01 mmol/L Standard Deviation 0.09	0 mmol/L Standard Deviation 0.08

SECONDARY outcome

Timeframe: baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry chloride

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Chloride at Month 1	0.24 mmol/L Standard Deviation 2.36	0.58 mmol/L Standard Deviation 2.66	0.01 mmol/L Standard Deviation 2.09

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry chloride

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Chloride at Month 3	-0.01 mmol/L Standard Deviation 2.67	0.38 mmol/L Standard Deviation 2.35	0.78 mmol/L Standard Deviation 2.20

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry chloride

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Chloride at Month 6	-0.57 mmol/L Standard Deviation 2.85	0.48 mmol/L Standard Deviation 2.19	0 mmol/L Standard Deviation 2.79

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry chloride

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Chloride at Month 12	-0.62 mmol/L Standard Deviation 2.45	-0.21 mmol/L Standard Deviation 2.58	-0.08 mmol/L Standard Deviation 2.39

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry creatinine

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Creatinine at Month 1	-0.88 µmol/L Standard Deviation 9.89	0.38 µmol/L Standard Deviation 8.63	1.47 µmol/L Standard Deviation 8.78

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry creatinine

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Creatinine at Month 3	0.62 µmol/L Standard Deviation 11.11	3.20 µmol/L Standard Deviation 8.30	3.81 µmol/L Standard Deviation 9.24

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry creatinine

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Creatinine at Month 6	3.30 µmol/L Standard Deviation 10.97	3.84 µmol/L Standard Deviation 9.88	3.54 µmol/L Standard Deviation 11.60

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry creatinine

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Creatinine at Month 12	5.44 µmol/L Standard Deviation 10.09	4.42 µmol/L Standard Deviation 9.59	3.73 µmol/L Standard Deviation 7.84

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry gamma-glutamyl transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Gamma-Glutamyl Transferase at Month 1	1.04 U/L Standard Deviation 8.13	-1.25 U/L Standard Deviation 9.67	0.26 U/L Standard Deviation 10.63

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry gamma-glutamyl transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Gamma-Glutamyl Transferase at Month 3	2.32 U/L Standard Deviation 10.94	0.04 U/L Standard Deviation 9.90	1.51 U/L Standard Deviation 15.87

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry gamma-glutamyl transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Gamma-Glutamyl Transferase at Month 6	7.37 U/L Standard Deviation 36.42	0.28 U/L Standard Deviation 12.70	5.67 U/L Standard Deviation 37.98

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry gamma-glutamyl transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Gamma-Glutamyl Transferase at Month 12	2.98 U/L Standard Deviation 10.94	1.08 U/L Standard Deviation 16.09	-1.38 U/L Standard Deviation 14.70

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry glucose

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Glucose at Month 1	0.06 mmol/L Standard Deviation 0.76	0.20 mmol/L Standard Deviation 0.65	0.05 mmol/L Standard Deviation 1.28

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry glucose

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Glucose at Month 3	0.08 mmol/L Standard Deviation 0.87	0.20 mmol/L Standard Deviation 0.63	0.04 mmol/L Standard Deviation 1.26

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry glucose

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Glucose at Month 6	0.12 mmol/L Standard Deviation 0.85	0.20 mmol/L Standard Deviation 0.65	-0.05 mmol/L Standard Deviation 1.26

SECONDARY outcome

Timeframe: baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry glucose

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Glucose at Month 12	-0.04 mmol/L Standard Deviation 0.66	0.22 mmol/L Standard Deviation 0.96	0.19 mmol/L Standard Deviation 1.27

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry potassium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Potassium at Month 1	0.06 mmol/L Standard Deviation 0.38	0.06 mmol/L Standard Deviation 0.36	0.04 mmol/L Standard Deviation 0.36

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry potassium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Potassium at Month 3	-0.01 mmol/L Standard Deviation 0.39	0.06 mmol/L Standard Deviation 0.40	0.04 mmol/L Standard Deviation 0.38

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry potassium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Potassium at Month 6	0.01 mmol/L Standard Deviation 0.44	-0.01 mmol/L Standard Deviation 0.36	0 mmol/L Standard Deviation 0.42

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry potassium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Potassium at Month 12	-0.07 mmol/L Standard Deviation 0.44	-0.08 mmol/L Standard Deviation 0.35	-0.04 mmol/L Standard Deviation 0.43

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry magnesium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Magnesium at Month 1	0.01 mmol/L Standard Deviation 0.06	0.02 mmol/L Standard Deviation 0.06	0.01 mmol/L Standard Deviation 0.05

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry magnesium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Magnesium at Month 3	-0.01 mmol/L Standard Deviation 0.06	0.02 mmol/L Standard Deviation 0.06	0 mmol/L Standard Deviation 0.06

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry magnesium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Magnesium at Month 6	0 mmol/L Standard Deviation 0.06	0.01 mmol/L Standard Deviation 0.06	0.01 mmol/L Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry magnesium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Magnesium at Month 12	-0.01 mmol/L Standard Deviation 0.06	-0.01 mmol/L Standard Deviation 0.07	-0.01 mmol/L Standard Deviation 0.08

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry sodium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Sodium at Month 1	-0.03 mmol/L Standard Deviation 1.93	-0.06 mmol/L Standard Deviation 2.62	0.33 mmol/L Standard Deviation 2.03

SECONDARY outcome

Timeframe: Baseline, Month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Change From Baseline in Sodium at Month 3

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=71 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=72 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Sodium at Month 3	-0.14 mmol/L Standard Deviation 2.13	-0.16 mmol/L Standard Deviation 2.29	0.39 mmol/L Standard Deviation 2.38

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry sodium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=69 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Sodium at Month 6	-0.12 mmol/L Standard Deviation 1.98	-0.06 mmol/L Standard Deviation 1.75	0.03 mmol/L Standard Deviation 2.27

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry sodium

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=66 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=64 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Sodium at Month 12	-0.25 mmol/L Standard Deviation 2.02	-0.27 mmol/L Standard Deviation 2.75	0.33 mmol/L Standard Deviation 2.38

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry phosphorus

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Phosphorus at Month 1	-0.09 mmol/L Standard Deviation 0.16	-0.06 mmol/L Standard Deviation 0.19	0.02 mmol/L Standard Deviation 0.14

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry phosphorus

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Phosphorus at Month 3	-0.03 mmol/L Standard Deviation 0.16	-0.03 mmol/L Standard Deviation 0.18	0.01 mmol/L Standard Deviation 0.20

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry phosphorus

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=68 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Phosphorus at Month 6	-0.05 mmol/L Standard Deviation 0.17	-0.01 mmol/L Standard Deviation 0.18	0.03 mmol/L Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Change From Baseline in Phosphorus at Month 12

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Phosphorus at Month 12	-0.05 mmol/L Standard Deviation 0.17	0 mmol/L Standard Deviation 0.17	0 mmol/L Standard Deviation 0.16

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry total protein

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Protein at Month 1	-0.46 g/L Standard Deviation 3.56	-0.40 g/L Standard Deviation 3.22	0.21 g/L Standard Deviation 3.00

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry total protein

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=70 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Protein at Month 3	-0.29 g/L Standard Deviation 3.35	0.07 g/L Standard Deviation 3.42	-0.20 g/L Standard Deviation 3.54

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry total protein

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Protein at Month 6	-0.09 g/L Standard Deviation 4.13	-0.62 g/L Standard Deviation 3.40	-0.57 g/L Standard Deviation 3.19

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry total protein

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Protein at Month 12	-0.97 g/L Standard Deviation 3.76	-0.91 g/L Standard Deviation 3.55	-0.98 g/L Standard Deviation 3.10

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry aspartate amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Aspartate Amino Transferase at Month 1	-0.79 U/L Standard Deviation 5.84	-0.26 U/L Standard Deviation 8.14	0.90 U/L Standard Deviation 8.35

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory chemistry aspartate amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=71 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Aspartate Amino Transferase at Month 3	1.99 U/L Standard Deviation 5.77	0.40 U/L Standard Deviation 8.78	2.69 U/L Standard Deviation 9.37

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry aspartate amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=68 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=68 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Aspartate Amino Transferase	3.85 U/L Standard Deviation 15.66	0.87 U/L Standard Deviation 7.58	3.24 U/L Standard Deviation 15.90

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry aspartate amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=63 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Aspartate Amino Transferase at Month 12	3.86 U/L Standard Deviation 18.62	3.75 U/L Standard Deviation 18.11	2.24 U/L Standard Deviation 7.32

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory chemistry alanine amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alanine Amino Transferase at Month 1	-1.84 U/L Standard Deviation 8.61	-1.03 U/L Standard Deviation 12.37	1.20 U/L Standard Deviation 15.44

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory Chemistry alanine amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=69 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alanine Amino Transferase at Month 3	0.04 U/L Standard Deviation 8.85	-2.10 U/L Standard Deviation 14.34	1.54 U/L Standard Deviation 13.00

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory chemistry alanine amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=65 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=67 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alanine Amino Transferase at Month 6	1.20 U/L Standard Deviation 15.83	-1.76 U/L Standard Deviation 14.12	5.44 U/L Standard Deviation 51.19

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory chemistry alanine amino transferase

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=63 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=62 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Alanine Amino Transferase at Month 12	4.86 U/L Standard Deviation 24.46	1.66 U/L Standard Deviation 14.30	1.82 U/L Standard Deviation 14.41

SECONDARY outcome

Timeframe: baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology basophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Basophils at Month 1	0 *10^9/L Standard Deviation 0.07	0 *10^9/L Standard Deviation 0.07	-0.01 *10^9/L Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology basophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Basophils at Month 3	-0.01 * 10^9/L Standard Deviation 0.06	-0.01 * 10^9/L Standard Deviation 0.07	-0.01 * 10^9/L Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology basophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Basophils at Month 6	0 * 10^9/L Standard Deviation 0.06	0 * 10^9/L Standard Deviation 0.07	0 * 10^9/L Standard Deviation 0.06

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology basophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=60 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Basophils at Month 12	0.02 * 10^9/L Standard Deviation 0.09	0 * 10^9/L Standard Deviation 0.09	0.03 * 10^9/L Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology eosinophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Eosinophils at Month 1	-0.02 * 10^9/L Standard Deviation 0.09	-0.01 * 10^9/L Standard Deviation 0.09	0.01 * 10^9/L Standard Deviation 0.08

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology eosinophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Eosinophils at Month 3	0 * 10^9/L Standard Deviation 0.10	0 * 10^9/L Standard Deviation 0.10	-0.01 * 10^9/L Standard Deviation 0.09

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology eosinophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Eosinophils at Month 6	-0.03 * 10^9/L Standard Deviation 0.09	0 * 10^9/L Standard Deviation 0.13	0 * 10^9/L Standard Deviation 0.13

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology eosinophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=60 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Eosinophils at Month 12	0.03 * 10^9/L Standard Deviation 0.16	0.02 * 10^9/L Standard Deviation 0.12	0.01 * 10^9/L Standard Deviation 0.12

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology hematocrit

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hematocrit at Month 1	0 Proportion of red blood cells in blood Standard Deviation 0.02	0 Proportion of red blood cells in blood Standard Deviation 0.02	0 Proportion of red blood cells in blood Standard Deviation 0.02

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology hematocrit

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hematocrit at Month 3	0.01 Proportion of red blood cells in blood Standard Deviation 0.02	0 Proportion of red blood cells in blood Standard Deviation 0.03	0 Proportion of red blood cells in blood Standard Deviation 0.03

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology hematocrit

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hematocrit at Month 6	0.01 Proportion of red blood cells in blood Standard Deviation 0.02	0 Proportion of red blood cells in blood Standard Deviation 0.03	0 Proportion of red blood cells in blood Standard Deviation 0.03

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology hematocrit

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=61 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hematocrit at Month 12	0 Proportion of red blood cells in blood Standard Deviation 0.02	0 Proportion of red blood cells in blood Standard Deviation 0.03	-0.01 Proportion of red blood cells in blood Standard Deviation 0.03

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology hemoglobin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hemoglobin at Month 1	-0.33 g/L Standard Deviation 6.73	-1.48 g/L Standard Deviation 6.39	-0.69 g/L Standard Deviation 6.34

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology hemoglobin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hemoglobin at Month 3	0.69 g/L Standard Deviation 7.02	-1.02 g/L Standard Deviation 8.36	-1.10 g/L Standard Deviation 6.30

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology hemoglobin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hemoglobin at Month 6	-0.36 g/L Standard Deviation 7.80	-1.69 g/L Standard Deviation 8.82	-0.69 g/L Standard Deviation 8.21

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology hemoglobin

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=61 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Hemoglobin at Month 12	1.21 g/L Standard Deviation 9.26	0.02 g/L Standard Deviation 11.66	-0.46 g/L Standard Deviation 10.08

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology lymphocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Lymphocytes at Month 1	-0.02 * 10^9/L Standard Deviation 0.41	0.10 * 10^9/L Standard Deviation 0.40	0 * 10^9/L Standard Deviation 0.45

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology lymphocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Lymphocytes at Month 3	0.07 * 10^9/L Standard Deviation 0.38	0.14 * 10^9/L Standard Deviation 0.48	0.08 * 10^9/L Standard Deviation 0.46

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology lymphocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Lymphocytes at Month 6	0.12 * 10^9/L Standard Deviation 0.41	0.05 * 10^9/L Standard Deviation 0.35	0.03 * 10^9/L Standard Deviation 0.68

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology lymphocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=60 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Lymphocytes at Month 12	-0.02 * 10^9/L Standard Deviation 0.49	0.04 * 10^9/L Standard Deviation 0.50	-0.02 * 10^9/L Standard Deviation 0.49

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology monocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Monocytes at Month 1	0.01 * 10^9/L Standard Deviation 0.13	-0.01 * 10^9/L Standard Deviation 0.10	0.01 * 10^9/L Standard Deviation 0.12

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology monocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Monocytes at Month 3	0.02 * 10^9/L Standard Deviation 0.11	0.01 * 10^9/L Standard Deviation 0.11	0.02 * 10^9/L Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology monocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Monocytes at Month 6	0.05 * 10^9/L Standard Deviation 0.17	0.04 * 10^9/L Standard Deviation 0.12	0.04 * 10^9/L Standard Deviation 0.13

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology monocytes

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=60 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Monocytes at Month 12	0.03 * 10^9/L Standard Deviation 0.15	0 * 10^9/L Standard Deviation 0.11	0.02 * 10^9/L Standard Deviation 0.13

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology total neutrophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Neutrophils at Month 1	0 * 10^9/L Standard Deviation 1.97	0.18 * 10^9/L Standard Deviation 1.99	-0.13 * 10^9/L Standard Deviation 1.68

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology total neutrophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Neutrophils at Month 3	0.11 * 10^9/L Standard Deviation 1.92	0.26 * 10^9/L Standard Deviation 1.64	-0.11 * 10^9/L Standard Deviation 1.55

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology total neutrophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=66 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Neutrophils at Month 6	0.18 * 10^9/L Standard Deviation 1.67	-0.05 * 10^9/L Standard Deviation 1.66	0.27 * 10^9/L Standard Deviation 2.36

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology total neutrophils

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=60 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Total Neutrophils at Month 12	0.65 * 10^9/L Standard Deviation 2.37	0.04 * 10^9/L Standard Deviation 1.79	0.10 * 10^9/L Standard Deviation 2.31

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology platelets

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=68 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Platelets at Month 1	1.78 * 10^9/L Standard Deviation 44.53	10.36 * 10^9/L Standard Deviation 49.34	2.96 * 10^9/L Standard Deviation 44.15

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology platelets

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=67 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=63 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=69 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Platelets at Month 3	-2.82 * 10^9/L Standard Deviation 48.86	6.86 * 10^9/L Standard Deviation 50.18	-1.97 * 10^9/L Standard Deviation 45.94

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology platelets

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=62 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=65 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Platelets at Month 6	1.95 * 10^9/L Standard Deviation 54.95	1.00 * 10^9/L Standard Deviation 45.64	1.57 * 10^9/L Standard Deviation 53.39

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology platelets

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=60 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=59 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Platelets at Month 12	3.32 * 10^9/L Standard Deviation 51.66	-4.26 * 10^9/L Standard Deviation 51.12	1.07 * 10^9/L Standard Deviation 58.16

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology red blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Red Blood Cells at Month 1	-0.01 * 10^9/L Standard Deviation 0.21	-0.01 * 10^9/L Standard Deviation 0.20	-0.01 * 10^9/L Standard Deviation 0.19

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratory hematology red blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Red Blood Cells at Month 3	0.05 * 10^9/L Standard Deviation 0.23	0.02 * 10^9/L Standard Deviation 0.28	0 * 10^9/L Standard Deviation 0.23

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology red blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Red Blood Cells at Month 6	0.01 * 10^9/L Standard Deviation 0.24	-0.04 * 10^9/L Standard Deviation 0.26	0.01 * 10^9/L Standard Deviation 0.26

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology red blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=61 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in Red Blood Cells at Month 12	0.01 * 10^9/L Standard Deviation 0.27	-0.06 * 10^9/L Standard Deviation 0.30	-0.03 * 10^9/L Standard Deviation 0.29

SECONDARY outcome

Timeframe: Baseline, month 1

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 1.

Laboratory hematology white blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=66 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in White Blood Cells at Month 1	-0.03 * 10^9/L Standard Deviation 2.07	0.26 * 10^9/L Standard Deviation 2.04	-0.10 * 10^9/L Standard Deviation 1.88

SECONDARY outcome

Timeframe: Baseline, month 3

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 3.

Laboratpry hematology white blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=68 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=64 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=70 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in White Blood Cells at Month 3	0.18 * 10^9/L Standard Deviation 1.93	0.40 * 10^9/L Standard Deviation 1.71	-0.05 * 10^9/L Standard Deviation 1.64

SECONDARY outcome

Timeframe: Baseline, month 6

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 6.

Laboratory hematology white blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=64 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=65 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=67 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in White Blood Cells at Month 6	0.30 * 10^9/L Standard Deviation 1.78	0.04 * 10^9/L Standard Deviation 1.85	0.35 * 10^9/L Standard Deviation 2.34

SECONDARY outcome

Timeframe: Baseline, month 12

Population: Subjects who received at least 1 dose of investigational product who had nonmissing data at baseline and month 12.

Laboratory hematology white blood cells

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=61 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=62 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=61 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Change From Baseline in White Blood Cells at Month 12	0.70 * 10^9/L Standard Deviation 2.40	0.11 * 10^9/L Standard Deviation 1.86	0.13 * 10^9/L Standard Deviation 2.22

SECONDARY outcome

Timeframe: Month 1, month 3, month 6, month 12

Population: Patients who received at least 1 dose of investigational product.

Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE.

Outcome measures

Outcome measures
Measure	Denosumab 180 mg n=72 Participants Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg n=71 Participants Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Placebo n=75 Participants Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 White Blood Cells-below normal (grade 3)	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 Alanine Amino Transferase-above normal (grade 3)	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 Aspartate Amino Transferase-above normal (grade 3)	0 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 Glucose-above normal (grade 3)	1 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 Lymphocytes-below normal (grade 3)	1 Participants	3 Participants	2 Participants
Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 Sodium-below normal (grade 3)	1 Participants	2 Participants	0 Participants

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 47 other events

Deaths: 0 deaths

Denosumab 60 mg

Serious events: 3 serious events

Other events: 44 other events

Deaths: 0 deaths

Denosumab 180 mg

Serious events: 6 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=75 participants at risk Participants received placebo subcutaneous injections on Day 1 and at Month 6.	Denosumab 60 mg n=71 participants at risk Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 180 mg n=72 participants at risk Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
General disorders Fatigue	4.0% 3/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.5% 6/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Bronchitis	4.0% 3/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 3/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 4/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Influenza	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 2/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 6/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Nasopharyngitis	12.0% 9/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.0% 5/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.9% 5/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Sinusitis	10.7% 8/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 4/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.1% 8/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Upper respiratory tract infection	8.0% 6/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	15.5% 11/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	11.1% 8/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urinary tract infection	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 4/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 3/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	4.0% 3/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 4/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 2/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	5.3% 4/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 2/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 2/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	32.0% 24/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	31.0% 22/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	29.2% 21/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dizziness	5.3% 4/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 2/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Headache	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	5.6% 4/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Insomnia	5.3% 4/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 3/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 5/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.0% 5/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee 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 multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=75 participants at risk Participants received placebo subcutaneous injections on Day 1 and at Month 6.	Denosumab 60 mg n=71 participants at risk Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 180 mg n=72 participants at risk Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
Blood and lymphatic system disorders Anaemia	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Coronary artery disease	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Cardiac disorders Myocardial infarction	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diabetic gastroparesis	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Cellulitis	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pyelonephritis	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Urosepsis	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Diabetic foot	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Coordination abnormal	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Diabetic neuropathy	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Transient ischaemic attack	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Renal and urinary disorders Renal artery stenosis	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Reproductive system and breast disorders Uterine prolapse	1.3% 1/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Deep vein thrombosis	0.00% 0/75 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/71 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	1.4% 1/72 • 12 months The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.