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

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00095498
• Collaborator: (none)
• Enrollment: 227
• Arms: 3
• Actual Duration (Months): 31.6

Study Details

Study Description

Brief Summary

This study will determine the efficacy, safety, and tolerability of denosumab (AMG 162) in the treatment of Rheumatoid Arthritis (RA).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: placebo; Drug: denosumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 227 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis
• Actual Study Start Date: Aug 11, 2004
• Actual Primary Completion Date: Apr 1, 2007
• Actual Study Completion Date: Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Denosumab 180 mg Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Drug: denosumab; For subcutaneous injection; Other Names: AMG 162
Experimental: Denosumab 60 mg Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Drug: denosumab; For subcutaneous injection; Other Names: AMG 162
Placebo Comparator: Placebo Participants received placebo subcutaneous injections on Day 1 and at Month 6.	Drug: placebo; placebo subcutaneous injection

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 [Baseline, Month 6]

   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).

Secondary Outcome Measures

1. Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 [Baseline, Month 12]

   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).

2. Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 [Baseline, Month 6]

   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).

3. Change From Baseline in Radiographic Erosion Score at Month 12 [Baseline, Month 12]

   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.

4. Change From Baseline in Radiographic Erosion Score at Month 6 [Baseline, Month 6]

   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.

5. Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 [Baseline, Month 12]

   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.

6. Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 [Baseline, Month 6]

   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.

7. Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 [Baseline, Month 1]

   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).

8. Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 [Baseline, month 6]

   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).

9. Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 [Baseline, Month 12]

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

10. Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 [Baseline, Month 1]

    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).

11. Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 [Baseline, Month 6]

    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).

12. Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 [Baseline, Month 12]

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

13. Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 [Baseline, Month 1]

    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).

14. Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 [Baseline, Month 6]

    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).

15. Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 [Baseline, Month 12]

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

16. Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 [Baseline, Month 3]

    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.

17. Percent Change From Baseline in Serum CTX at Month 6 [Baseline, Month 6]

    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.

18. Percent Change From Baseline in Serum CTX at Month 12 [Baseline, Month 12]

    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.

19. Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 [Baseline, Month 3]

    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.

20. Percent Change From Baseline in P1NP at Month 6 [Baseline, Month 6]

    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.

21. Percent Change From Baseline in P1NP at Month 12 [Baseline, Month 12]

    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.

22. Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 [Baseline, Month 3]

    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.

23. Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 [Baseline, Month 6]

    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.

24. Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 [Baseline, Month 12]

    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.

25. Number of Participants With Anti-Denosumab Binding Antibodies [Assessed at Baseline and at Months 1, 3, 6 and 12.]

    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.

26. Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody [Baseline to Month 12]

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

27. Change From Baseline in Albumin at Month 1 [Baseline, month 1]

    Laboratory Chemistry Albumin

28. Change From Baseline in Albumin at Month 3 [Baseline, month 3]

    Laboratory chemistry albumin

29. Change From Baseline in Albumin at Month 6 [Baseline, month 6]

    Laboratory chemistry albumin

30. Change From Baseline in Albumin at Month 12 [Baseline, month 12]

    Laboratory chemistry albumin

31. Change From Baseline in Alkaline Phosphatase at Month 1 [Baseline, month 1]

    Laboratory chemistry alkaline phoshatatse

32. Change From Baseline in Alkaline Phosphatase at Month 3 [baseline, month 3]

    Laboratory chemisrty alkaline phosphatase

33. Change From Baseline in Alkaline Phosphatase at Month 6 [baseline, month 6]

    Laboratory chemistry alkaline phosphatase

34. Change From Baseline in Alkaline Phosphatase at Month 12 [baseine, month 12]

    Laboratory chemistry alkaline phosphatase

35. Change From Baseline in Bicarbonate at Month 1 [baseline, month 1]

    Laboratory chemistry bicarbonate

36. Change From Baseline in Bicarbonate at Month 3 [baseline, month 3]

    Laboratory chemistry bicarbonate

37. Change From Baseline in Bicarbonate at Month 6 [Baseline, month 6]

    Laboratory chemistry bicarbonate

38. Change From Baseline in Bicarbonate at Month 12 [Baseline, Month 12]

    Laboratory chemistry bicarbonate

39. Change From Baseline in Total Bilirubin at Month 1 [baseline, month 1]

    Laboratory chemistry total bilirubin

40. Change From Baseline in Total Bilirubin at Month 3 [Baseline, month 3]

    Laboratory chemistry total bilirubin

41. Change From Baseline in Total Bilirubin at Month 6 [Baseline, month 6]

    Laboratory chemistry total bilirubin

42. Change From Baseline in Total Bilirubin at Month 12 [Baseline, month 12]

    Laboratory chemistry total bilirubin

43. Change From Baseline in Blood Urea Nitrogen at Month 1 [Baseline, month 1]

    Laboratory chemistry blood urea nitrogen

44. Change From Baseline in Blood Urea Nitrogen at Month 3 [Baseline, month 3]

    Laboratory chemistry blood urea nitrogen

45. Change From Baseline in Blood Urea Nitrogen at Month 6 [Baseline, month 6]

    Laboratory chemistry blood urea nitrogen

46. Change From Baseline in Blood Urea Nitrogen at Month 12 [baseline, month 12]

    Laboratory chemistry blood urea nitrogen

47. Change From Baseline in Calcium at Month 1 [baseline. month 1]

    Laboratory chemistry calcium

48. Change From Baseline in Calcium at Month 3 [Baseline, month 3]

    Laboratory chemistry calcium

49. Change From Baseline in Calcium at Month 6 [baseline, month 6]

    Laboratory chemistry calcium

50. Change From Baseline in Calcium at Month 12 [Baseline, month 12]

    Laboratory chemistry calcium

51. Change From Baseline in Calcium (Corrected) at Month 1 [Baseline, month 1]

    Laboratory chemistry albumin-adjusted calcium

52. Change From Baseline in Calcium (Corrected) at Month 3 [baseline, month 3]

    Laboratory chemistry albumin-adjusted calcium

53. Change From Baseline in Calcium (Corrected) at Month 6 [Baseline, Month 6]

    Laboratory chemistry albumin-adjusted calcium

54. Change From Baseline in Calcium (Corrected) at Month 12 [Baselien, Month 12]

    Laboratory chemistry albumin-adjusted calcium

55. Change From Baseline in Chloride at Month 1 [baseline, month 1]

    Laboratory chemistry chloride

56. Change From Baseline in Chloride at Month 3 [Baseline, month 3]

    Laboratory chemistry chloride

57. Change From Baseline in Chloride at Month 6 [Baseline, month 6]

    Laboratory chemistry chloride

58. Change From Baseline in Chloride at Month 12 [Baseline, month 12]

    Laboratory chemistry chloride

59. Change From Baseline in Creatinine at Month 1 [Baseline, month 1]

    Laboratory chemistry creatinine

60. Change From Baseline in Creatinine at Month 3 [Baseline, month 3]

    Laboratory chemistry creatinine

61. Change From Baseline in Creatinine at Month 6 [Baseline, month 6]

    Laboratory chemistry creatinine

62. Change From Baseline in Creatinine at Month 12 [Baseline, month 12]

    Laboratory chemistry creatinine

63. Change From Baseline in Gamma-Glutamyl Transferase at Month 1 [Baseline, month 1]

    Laboratory chemistry gamma-glutamyl transferase

64. Change From Baseline in Gamma-Glutamyl Transferase at Month 3 [Baseline, month 3]

    Laboratory chemistry gamma-glutamyl transferase

65. Change From Baseline in Gamma-Glutamyl Transferase at Month 6 [Baseline, month 6]

    Laboratory chemistry gamma-glutamyl transferase

66. Change From Baseline in Gamma-Glutamyl Transferase at Month 12 [Baseline, month 12]

    Laboratory chemistry gamma-glutamyl transferase

67. Change From Baseline in Glucose at Month 1 [Baseline, month 1]

    Laboratory chemistry glucose

68. Change From Baseline in Glucose at Month 3 [Baseline, month 3]

    Laboratory chemistry glucose

69. Change From Baseline in Glucose at Month 6 [Baseline, month 6]

    Laboratory chemistry glucose

70. Change From Baseline in Glucose at Month 12 [baseline, month 12]

    Laboratory chemistry glucose

71. Change From Baseline in Potassium at Month 1 [Baseline, month 1]

    Laboratory chemistry potassium

72. Change From Baseline in Potassium at Month 3 [Baseline, month 3]

    Laboratory chemistry potassium

73. Change From Baseline in Potassium at Month 6 [Baseline, month 6]

    Laboratory chemistry potassium

74. Change From Baseline in Potassium at Month 12 [Baseline, month 12]

    Laboratory chemistry potassium

75. Change From Baseline in Magnesium at Month 1 [Baseline, month 1]

    Laboratory chemistry magnesium

76. Change From Baseline in Magnesium at Month 3 [Baseline, month 3]

    Laboratory chemistry magnesium

77. Change From Baseline in Magnesium at Month 6 [Baseline, month 6]

    Laboratory chemistry magnesium

78. Change From Baseline in Magnesium at Month 12 [Baseline, month 12]

    Laboratory chemistry magnesium

79. Change From Baseline in Sodium at Month 1 [Baseline, month 1]

    Laboratory chemistry sodium

80. Change From Baseline in Sodium at Month 3 [Baseline, Month 3]

    Change From Baseline in Sodium at Month 3

81. Change From Baseline in Sodium at Month 6 [Baseline, month 6]

    Laboratory chemistry sodium

82. Change From Baseline in Sodium at Month 12 [Baseline, month 12]

    Laboratory chemistry sodium

83. Change From Baseline in Phosphorus at Month 1 [Baseline, month 1]

    Laboratory chemistry phosphorus

84. Change From Baseline in Phosphorus at Month 3 [Baseline, month 3]

    Laboratory chemistry phosphorus

85. Change From Baseline in Phosphorus at Month 6 [Baseline, month 6]

    Laboratory chemistry phosphorus

86. Change From Baseline in Phosphorus at Month 12 [Baseline, month 12]

    Change From Baseline in Phosphorus at Month 12

87. Change From Baseline in Total Protein at Month 1 [Baseline, month 1]

    Laboratory chemistry total protein

88. Change From Baseline in Total Protein at Month 3 [Baseline, month 3]

    Laboratory chemistry total protein

89. Change From Baseline in Total Protein at Month 6 [Baseline, month 6]

    Laboratory chemistry total protein

90. Change From Baseline in Total Protein at Month 12 [Baseline, month 12]

    Laboratory chemistry total protein

91. Change From Baseline in Aspartate Amino Transferase at Month 1 [Baseline, month 1]

    Laboratory chemistry aspartate amino transferase

92. Change From Baseline in Aspartate Amino Transferase at Month 3 [Baseline, month 3]

    Laboratory chemistry aspartate amino transferase

93. Change From Baseline in Aspartate Amino Transferase [Baseline, month 6]

    Laboratory chemistry aspartate amino transferase

94. Change From Baseline in Aspartate Amino Transferase at Month 12 [Baseline, month 12]

    Laboratory chemistry aspartate amino transferase

95. Change From Baseline in Alanine Amino Transferase at Month 1 [Baseline, month 1]

    Laboratory chemistry alanine amino transferase

96. Change From Baseline in Alanine Amino Transferase at Month 3 [Baseline, month 3]

    Laboratory Chemistry alanine amino transferase

97. Change From Baseline in Alanine Amino Transferase at Month 6 [Baseline, month 6]

    Laboratory chemistry alanine amino transferase

98. Change From Baseline in Alanine Amino Transferase at Month 12 [Baseline, month 12]

    Laboratory chemistry alanine amino transferase

99. Change From Baseline in Basophils at Month 1 [baseline, month 1]

    Laboratory hematology basophils

100. Change From Baseline in Basophils at Month 3 [Baseline, month 3]

     Laboratory hematology basophils

101. Change From Baseline in Basophils at Month 6 [Baseline, month 6]

     Laboratory hematology basophils

102. Change From Baseline in Basophils at Month 12 [Baseline, month 12]

     Laboratory hematology basophils

103. Change From Baseline in Eosinophils at Month 1 [Baseline, month 1]

     Laboratory hematology eosinophils

104. Change From Baseline in Eosinophils at Month 3 [Baseline, month 3]

     Laboratory hematology eosinophils

105. Change From Baseline in Eosinophils at Month 6 [Baseline, month 6]

     Laboratory hematology eosinophils

106. Change From Baseline in Eosinophils at Month 12 [Baseline, month 12]

     Laboratory hematology eosinophils

107. Change From Baseline in Hematocrit at Month 1 [Baseline, month 1]

     Laboratory hematology hematocrit

108. Change From Baseline in Hematocrit at Month 3 [Baseline, month 3]

     Laboratory hematology hematocrit

109. Change From Baseline in Hematocrit at Month 6 [Baseline, month 6]

     Laboratory hematology hematocrit

110. Change From Baseline in Hematocrit at Month 12 [Baseline, month 12]

     Laboratory hematology hematocrit

111. Change From Baseline in Hemoglobin at Month 1 [Baseline, month 1]

     Laboratory hematology hemoglobin

112. Change From Baseline in Hemoglobin at Month 3 [Baseline, month 3]

     Laboratory hematology hemoglobin

113. Change From Baseline in Hemoglobin at Month 6 [Baseline, month 6]

     Laboratory hematology hemoglobin

114. Change From Baseline in Hemoglobin at Month 12 [Baseline, month 12]

     Laboratory hematology hemoglobin

115. Change From Baseline in Lymphocytes at Month 1 [Baseline, month 1]

     Laboratory hematology lymphocytes

116. Change From Baseline in Lymphocytes at Month 3 [Baseline, month 3]

     Laboratory hematology lymphocytes

117. Change From Baseline in Lymphocytes at Month 6 [Baseline, month 6]

     Laboratory hematology lymphocytes

118. Change From Baseline in Lymphocytes at Month 12 [Baseline, month 12]

     Laboratory hematology lymphocytes

119. Change From Baseline in Monocytes at Month 1 [Baseline, month 1]

     Laboratory hematology monocytes

120. Change From Baseline in Monocytes at Month 3 [Baseline, month 3]

     Laboratory hematology monocytes

121. Change From Baseline in Monocytes at Month 6 [Baseline, month 6]

     Laboratory hematology monocytes

122. Change From Baseline in Monocytes at Month 12 [Baseline, month 12]

     Laboratory hematology monocytes

123. Change From Baseline in Total Neutrophils at Month 1 [Baseline, month 1]

     Laboratory hematology total neutrophils

124. Change From Baseline in Total Neutrophils at Month 3 [Baseline, month 3]

     Laboratory hematology total neutrophils

125. Change From Baseline in Total Neutrophils at Month 6 [Baseline, month 6]

     Laboratory hematology total neutrophils

126. Change From Baseline in Total Neutrophils at Month 12 [Baseline, month 12]

     Laboratory hematology total neutrophils

127. Change From Baseline in Platelets at Month 1 [Baseline, month 1]

     Laboratory hematology platelets

128. Change From Baseline in Platelets at Month 3 [Baseline, month 3]

     Laboratory hematology platelets

129. Change From Baseline in Platelets at Month 6 [Baseline, month 6]

     Laboratory hematology platelets

130. Change From Baseline in Platelets at Month 12 [Baseline, month 12]

     Laboratory hematology platelets

131. Change From Baseline in Red Blood Cells at Month 1 [Baseline, month 1]

     Laboratory hematology red blood cells

132. Change From Baseline in Red Blood Cells at Month 3 [Baseline, month 3]

     Laboratory hematology red blood cells

133. Change From Baseline in Red Blood Cells at Month 6 [Baseline, month 6]

     Laboratory hematology red blood cells

134. Change From Baseline in Red Blood Cells at Month 12 [Baseline, month 12]

     Laboratory hematology red blood cells

135. Change From Baseline in White Blood Cells at Month 1 [Baseline, month 1]

     Laboratory hematology white blood cells

136. Change From Baseline in White Blood Cells at Month 3 [Baseline, month 3]

     Laboratpry hematology white blood cells

137. Change From Baseline in White Blood Cells at Month 6 [Baseline, month 6]

     Laboratory hematology white blood cells

138. Change From Baseline in White Blood Cells at Month 12 [Baseline, month 12]

     Laboratory hematology white blood cells

139. Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 [Month 1, month 3, month 6, month 12]

     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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of RA.

• All subjects will be required to have been taking a stable dose of methotrexate.

• Active RA at screening defined as greater than or equal to 6 swollen joints.

• The presence of erosive disease

Exclusion Criteria:

• Received any biologic agent (e.g., Enbrel®, Remicade®, Humira®, Kineret®) or Arava® within 8 weeks before randomization; past use of these agents is allowed.

• Steroid use greater than 15 mg/day.

• Scheduled for surgery or joint replacement in the hands, wrists or feet.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results
• To access clinical trial results information click on this link

Publications

• Cohen SB, Dore RK, Lane NE, Ory PA, Peterfy CG, Sharp JT, van der Heijde D, Zhou L, Tsuji W, Newmark R; Denosumab Rheumatoid Arthritis Study Group. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008 May;58(5):1299-309. doi: 10.1002/art.23417.
• Deodhar A, Dore RK, Mandel D, Schechtman J, Shergy W, Trapp R, Ory PA, Peterfy CG, Fuerst T, Wang H, Zhou L, Tsuji W, Newmark R. Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2010 Apr;62(4):569-74. doi: 10.1002/acr.20004.
• Dore RK, Cohen SB, Lane NE, Palmer W, Shergy W, Zhou L, Wang H, Tsuji W, Newmark R; Denosumab RA Study Group. Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis. 2010 May;69(5):872-5. doi: 10.1136/ard.2009.112920. Epub 2009 Sep 3.
• Sharp JT, Tsuji W, Ory P, Harper-Barek C, Wang H, Newmark R. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res (Hoboken). 2010 Apr;62(4):537-44. doi: 10.1002/acr.20172.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00095498
• Other Study ID Numbers: 20040144
• First Posted: Nov 8, 2004
• Last Update Posted: Oct 25, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Amgen: arthritis; joint pain; Methotrexate
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Denosumab

Study Results

Participant Flow

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Period Title: Overall Study
STARTED	76	73	78
Received Investigational Product	72	71	75
COMPLETED	39	38	39
NOT COMPLETED	37	35	39

Baseline Characteristics

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo	Total
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.	Total of all reporting groups
Overall Participants	76	73	78	227
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58 (11)	57.3 (11.4)	57 (11.1)	57.4 (11.2)
Sex: Female, Male (Count of Participants)
Female	53 69.7%	51 69.9%	62 79.5%	166 73.1%
Male	23 30.3%	22 30.1%	16 20.5%	61 26.9%
Race/Ethnicity, Customized (Number) [Number]
Asian	1 1.3%	1 1.4%	2 2.6%	4 1.8%
Japanese	1 1.3%	0 0%	1 1.3%	2 0.9%
American Indian or Alaska Native	1 1.3%	2 2.7%	1 1.3%	4 1.8%
White or Caucasian	66 86.8%	59 80.8%	62 79.5%	187 82.4%
Black or African American	1 1.3%	3 4.1%	2 2.6%	6 2.6%
Hispanic or Latino	6 7.9%	6 8.2%	9 11.5%	21 9.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 1.3%	1 0.4%
Other	0 0%	2 2.7%	0 0%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6
Description	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).
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	67	66
Median (Full Range) [units on a scale]	0.00 (3.49)	0.00 (3.43)	0.49 (5.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.264
	Comments
	Method	van Elteren stratified rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	van Elteren stratified rank test
	Comments

2. Secondary Outcome

Title	Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12
Description	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).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	71
Median (Inter-Quartile Range) [units on a scale]	0	0	0.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.180
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

3. Secondary Outcome

Title	Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6
Description	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).
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	69	71
Median (Inter-Quartile Range) [units on a scale]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.602
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.181
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

4. Secondary Outcome

Title	Change From Baseline in Radiographic Erosion Score at Month 12
Description	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.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	71
Median (Inter-Quartile Range) [units on a scale]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

5. Secondary Outcome

Title	Change From Baseline in Radiographic Erosion Score at Month 6
Description	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.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	69	71
Median (Inter-Quartile Range) [units on a scale]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.277
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

6. Secondary Outcome

Title	Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12
Description	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.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	71
Median (Inter-Quartile Range) [units on a scale]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.382
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.488
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

7. Secondary Outcome

Title	Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6
Description	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.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	69	71
Median (Inter-Quartile Range) [units on a scale]	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.236
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.712
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

8. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1
Description	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).
Time Frame	Baseline, Month 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	66	66
Least Squares Mean (Standard Error) [Percent change from baseline]	0.25 (0.29)	0.59 (0.29)	-0.34 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.93
	Confidence Interval	() 95%; 0.11 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments
	Method	Repeated measures model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.59
	Confidence Interval	() 95%; -0.23 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6
Description	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).
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	69	68
Least Squares Mean (Standard Error) [Percent change from baseline]	2.61 (0.38)	2.40 (0.37)	0.73 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.67
	Confidence Interval	() 95%; 0.62 to 2.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.89
	Confidence Interval	() 95%; 0.84 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. 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).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	62	66	62
Least Squares Mean (Standard Error) [Percent change from baseline]	4.09 (0.40)	3.00 (0.39)	0.80 (0.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.2
	Confidence Interval	() 95%; 1.1 to 3.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.29
	Confidence Interval	() 95%; 2.18 to 4.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1
Description	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).
Time Frame	Baseline, Month 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	65
Least Squares Mean (Standard Error) [Percent change from baseline]	0.64 (0.38)	-0.15 (0.38)	-0.16 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.986
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	() 95%; -1.06 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	() 95%; -0.27 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6
Description	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).
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	68	69
Least Squares Mean (Standard Error) [Percent change from baseline]	0.84 (0.37)	0.89 (0.37)	-0.06 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.95
	Confidence Interval	() 95%; -0.09 to 1.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.89
	Confidence Interval	() 95%; -0.14 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. 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).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	64	63
Least Squares Mean (Standard Error) [Percent change from baseline]	1.51 (0.47)	1.34 (0.47)	-0.47 (0.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.81
	Confidence Interval	() 95%; 0.51 to 3.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.98
	Confidence Interval	() 95%; 0.67 to 3.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1
Description	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).
Time Frame	Baseline, Month 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	65
Least Squares Mean (Standard Error) [Percent change from baseline]	0.06 (0.22)	0.00 (0.22)	-0.02 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.938
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.02
	Confidence Interval	() 95%; -0.58 to 0.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.787
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	() 95%; -0.53 to 0.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6
Description	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).
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	68	69
Least Squares Mean (Standard Error) [Percent change from baseline]	1.12 (0.24)	0.95 (0.24)	-0.06 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1
	Confidence Interval	() 95%; 0.33 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.18
	Confidence Interval	() 95%; 0.51 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12
Description	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. 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).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	64	63
Least Squares Mean (Standard Error) [Percent change from baseline]	1.67 (0.33)	1.56 (0.33)	-0.38 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.94
	Confidence Interval	() 95%; 1.02 to 2.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Repeated Measures Model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.04
	Confidence Interval	() 95%; 1.13 to 2.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3
Description	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.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	69	69
Median (Inter-Quartile Range) [Percent change from baseline]	-78.67	-80.46	-11.48

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

18. Secondary Outcome

Title	Percent Change From Baseline in Serum CTX at Month 6
Description	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.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	68	67
Median (Inter-Quartile Range) [Percent change from baseline]	-62.69	-50.64	-12.94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

19. Secondary Outcome

Title	Percent Change From Baseline in Serum CTX at Month 12
Description	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.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	62	66	62
Median (Inter-Quartile Range) [Percent change from baseline]	-65.65	-47.24	-23.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

20. Secondary Outcome

Title	Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3
Description	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.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	69	69
Median (Inter-Quartile Range) [Percent change from baseline]	-55.08	-57.57	-12.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

21. Secondary Outcome

Title	Percent Change From Baseline in P1NP at Month 6
Description	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.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	68	67
Median (Inter-Quartile Range) [Percent change from baseline]	-57.06	-51.57	-22.17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

22. Secondary Outcome

Title	Percent Change From Baseline in P1NP at Month 12
Description	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.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	33	39	30
Median (Inter-Quartile Range) [Percent change from baseline]	-45.84	-41.8	-17.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

23. Secondary Outcome

Title	Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3
Description	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.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	63	65
Median (Inter-Quartile Range) [Percent change from baseline]	-46.59	-35.8	2.71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

24. Secondary Outcome

Title	Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6
Description	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.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	56	63	63
Median (Inter-Quartile Range) [Percent change from baseline]	7.17	9.65	4.54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.673
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.589
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

25. Secondary Outcome

Title	Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12
Description	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.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	29	35	22
Median (Inter-Quartile Range) [Percent change from baseline]	36.92	61.92	-3.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Denosumab 60 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.175
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Denosumab 180 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments
	Method	van Elteren Stratified Rank Test
	Comments

26. Secondary Outcome

Title	Number of Participants With Anti-Denosumab Binding Antibodies
Description	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.
Time Frame	Assessed at Baseline and at Months 1, 3, 6 and 12.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	72	70	75
Number [Participants]	4 5.3%	0 0%	2 2.6%

27. Secondary Outcome

Title	Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody
Description	Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab.
Time Frame	Baseline to Month 12

Outcome Measure Data

Analysis Population Description

Patients who were positive for anti-denosumab antibodies

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	4	0	2
Number [Participants]	0 0%	0 0%

28. Secondary Outcome

Title	Change From Baseline in Albumin at Month 1
Description	Laboratory Chemistry Albumin
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	68	71
Mean (Standard Deviation) [g/L]	-0.36 (2.29)	-0.24 (2.25)	-0.30 (2.21)

29. Secondary Outcome

Title	Change From Baseline in Albumin at Month 3
Description	Laboratory chemistry albumin
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	71
Mean (Standard Deviation) [g/L]	-0.30 (2.18)	-0.12 (2.28)	-0.18 (2.07)

30. Secondary Outcome

Title	Change From Baseline in Albumin at Month 6
Description	Laboratory chemistry albumin
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	68	69
Mean (Standard Deviation) [g/L]	-0.30 (2.49)	-0.90 (2.56)	-0.77 (2.40)

31. Secondary Outcome

Title	Change From Baseline in Albumin at Month 12
Description	Laboratory chemistry albumin
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	63
Mean (Standard Deviation) [g/L]	-0.13 (2.41)	-0.06 (2.26)	-0.59 (2.49)

32. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase at Month 1
Description	Laboratory chemistry alkaline phoshatatse
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	72
Mean (Standard Deviation) [U/L]	-5.87 (10.52)	-3.66 (11.97)	1.18 (15.62)

33. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase at Month 3
Description	Laboratory chemisrty alkaline phosphatase
Time Frame	baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	68	72
Mean (Standard Deviation) [U/L]	-13.27 (15.91)	-12.38 (13.09)	-2.03 (8.37)

34. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase at Month 6
Description	Laboratory chemistry alkaline phosphatase
Time Frame	baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	68	70
Mean (Standard Deviation) [U/L]	-7.84 (31.94)	-12.49 (12.61)	-0.54 (18.46)

35. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase at Month 12
Description	Laboratory chemistry alkaline phosphatase
Time Frame	baseine, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	65	64
Mean (Standard Deviation) [U/L]	-11.92 (16.74)	-11.34 (18.18)	-4.63 (16.70)

36. Secondary Outcome

Title	Change From Baseline in Bicarbonate at Month 1
Description	Laboratory chemistry bicarbonate
Time Frame	baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	67	70
Mean (Standard Deviation) [mmol/L]	0.78 (2.31)	0.06 (3.06)	0.54 (2.94)

37. Secondary Outcome

Title	Change From Baseline in Bicarbonate at Month 3
Description	Laboratory chemistry bicarbonate
Time Frame	baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	67	70
Mean (Standard Deviation) [mmol/L]	0.12 (2.40)	0.39 (2.84)	-0.67 (3.17)

38. Secondary Outcome

Title	Change From Baseline in Bicarbonate at Month 6
Description	Laboratory chemistry bicarbonate
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	67	66
Mean (Standard Deviation) [mmol/L]	0.45 (2.29)	-0.12 (2.61)	-0.18 (2.67)

39. Secondary Outcome

Title	Change From Baseline in Bicarbonate at Month 12
Description	Laboratory chemistry bicarbonate
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	64	62
Mean (Standard Deviation) [mmol/L]	0.81 (2.12)	0.58 (2.68)	0.23 (2.50)

40. Secondary Outcome

Title	Change From Baseline in Total Bilirubin at Month 1
Description	Laboratory chemistry total bilirubin
Time Frame	baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	67	70
Mean (Standard Deviation) [umol/L]	0.26 (2.39)	-0.23 (2.45)	0.42 (2.83)

41. Secondary Outcome

Title	Change From Baseline in Total Bilirubin at Month 3
Description	Laboratory chemistry total bilirubin
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	67	70
Mean (Standard Deviation) [umol/L]	0.92 (2.17)	-0.23 (2.36)	0.44 (2.74)

42. Secondary Outcome

Title	Change From Baseline in Total Bilirubin at Month 6
Description	Laboratory chemistry total bilirubin
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	67	66
Mean (Standard Deviation) [umol/L]	1.08 (2.58)	-0.61 (2.49)	0.34 (3.30)

43. Secondary Outcome

Title	Change From Baseline in Total Bilirubin at Month 12
Description	Laboratory chemistry total bilirubin
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	64	62
Mean (Standard Deviation) [umol/L]	0.41 (2.58)	-0.35 (2.28)	0.03 (2.80)

44. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen at Month 1
Description	Laboratory chemistry blood urea nitrogen
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	72
Mean (Standard Deviation) [mmol/L]	0 (1.35)	0.15 (1.40)	-0.01 (1.55)

45. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen at Month 3
Description	Laboratory chemistry blood urea nitrogen
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	68	72
Mean (Standard Deviation) [mmol/L]	0.04 (1.35)	0.41 (1.59)	0.06 (1.43)

46. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen at Month 6
Description	Laboratory chemistry blood urea nitrogen
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	68	70
Mean (Standard Deviation) [mmol/L]	-0.21 (1.44)	-0.08 (1.41)	-0.04 (2.29)

47. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen at Month 12
Description	Laboratory chemistry blood urea nitrogen
Time Frame	baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	65	64
Mean (Standard Deviation) [mmol/L]	0.32 (1.37)	0.24 (1.46)	-0.09 (1.56)

48. Secondary Outcome

Title	Change From Baseline in Calcium at Month 1
Description	Laboratory chemistry calcium
Time Frame	baseline. month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	72
Mean (Standard Deviation) [mmol/L]	-0.05 (0.11)	-0.05 (0.09)	0.01 (0.09)

49. Secondary Outcome

Title	Change From Baseline in Calcium at Month 3
Description	Laboratory chemistry calcium
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	68	72
Mean (Standard Deviation) [mmol/L]	-0.01 (0.11)	-0.02 (0.10)	0 (0.10)

50. Secondary Outcome

Title	Change From Baseline in Calcium at Month 6
Description	Laboratory chemistry calcium
Time Frame	baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	68	70
Mean (Standard Deviation) [mmol/L]	-0.01 (0.10)	-0.03 (0.11)	-0.01 (0.10)

51. Secondary Outcome

Title	Change From Baseline in Calcium at Month 12
Description	Laboratory chemistry calcium
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	65	64
Mean (Standard Deviation) [mmol/L]	-0.01 (0.11)	0.01 (0.09)	0.01 (0.08)

52. Secondary Outcome

Title	Change From Baseline in Calcium (Corrected) at Month 1
Description	Laboratory chemistry albumin-adjusted calcium
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	72
Mean (Standard Deviation) [mmol/L]	-0.05 (0.11)	-0.05 (0.09)	0.01 (0.09)

53. Secondary Outcome

Title	Change From Baseline in Calcium (Corrected) at Month 3
Description	Laboratory chemistry albumin-adjusted calcium
Time Frame	baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	68	72
Mean (Standard Deviation) [mmol/L]	-0.01 (0.11)	-0.02 (0.09)	0 (0.10)

54. Secondary Outcome

Title	Change From Baseline in Calcium (Corrected) at Month 6
Description	Laboratory chemistry albumin-adjusted calcium
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	68	70
Mean (Standard Deviation) [mmol/L]	-0.01 (0.10)	-0.02 (0.10)	-0.01 (0.09)

55. Secondary Outcome

Title	Change From Baseline in Calcium (Corrected) at Month 12
Description	Laboratory chemistry albumin-adjusted calcium
Time Frame	Baselien, Month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	65	64
Mean (Standard Deviation) [mmol/L]	-0.01 (0.11)	0.01 (0.09)	0 (0.08)

56. Secondary Outcome

Title	Change From Baseline in Chloride at Month 1
Description	Laboratory chemistry chloride
Time Frame	baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	69	72
Mean (Standard Deviation) [mmol/L]	0.24 (2.36)	0.58 (2.66)	0.01 (2.09)

57. Secondary Outcome

Title	Change From Baseline in Chloride at Month 3
Description	Laboratory chemistry chloride
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	69	72
Mean (Standard Deviation) [mmol/L]	-0.01 (2.67)	0.38 (2.35)	0.78 (2.20)

58. Secondary Outcome

Title	Change From Baseline in Chloride at Month 6
Description	Laboratory chemistry chloride
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	70
Mean (Standard Deviation) [mmol/L]	-0.57 (2.85)	0.48 (2.19)	0 (2.79)

59. Secondary Outcome

Title	Change From Baseline in Chloride at Month 12
Description	Laboratory chemistry chloride
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	66	64
Mean (Standard Deviation) [mmol/L]	-0.62 (2.45)	-0.21 (2.58)	-0.08 (2.39)

60. Secondary Outcome

Title	Change From Baseline in Creatinine at Month 1
Description	Laboratory chemistry creatinine
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	69	72
Mean (Standard Deviation) [µmol/L]	-0.88 (9.89)	0.38 (8.63)	1.47 (8.78)

61. Secondary Outcome

Title	Change From Baseline in Creatinine at Month 3
Description	Laboratory chemistry creatinine
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	69	72
Mean (Standard Deviation) [µmol/L]	0.62 (11.11)	3.20 (8.30)	3.81 (9.24)

62. Secondary Outcome

Title	Change From Baseline in Creatinine at Month 6
Description	Laboratory chemistry creatinine
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	70
Mean (Standard Deviation) [µmol/L]	3.30 (10.97)	3.84 (9.88)	3.54 (11.60)

63. Secondary Outcome

Title	Change From Baseline in Creatinine at Month 12
Description	Laboratory chemistry creatinine
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	66	64
Mean (Standard Deviation) [µmol/L]	5.44 (10.09)	4.42 (9.59)	3.73 (7.84)

64. Secondary Outcome

Title	Change From Baseline in Gamma-Glutamyl Transferase at Month 1
Description	Laboratory chemistry gamma-glutamyl transferase
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	72
Mean (Standard Deviation) [U/L]	1.04 (8.13)	-1.25 (9.67)	0.26 (10.63)

65. Secondary Outcome

Title	Change From Baseline in Gamma-Glutamyl Transferase at Month 3
Description	Laboratory chemistry gamma-glutamyl transferase
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	68	72
Mean (Standard Deviation) [U/L]	2.32 (10.94)	0.04 (9.90)	1.51 (15.87)

66. Secondary Outcome

Title	Change From Baseline in Gamma-Glutamyl Transferase at Month 6
Description	Laboratory chemistry gamma-glutamyl transferase
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	68	70
Mean (Standard Deviation) [U/L]	7.37 (36.42)	0.28 (12.70)	5.67 (37.98)

67. Secondary Outcome

Title	Change From Baseline in Gamma-Glutamyl Transferase at Month 12
Description	Laboratory chemistry gamma-glutamyl transferase
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	65	64
Mean (Standard Deviation) [U/L]	2.98 (10.94)	1.08 (16.09)	-1.38 (14.70)

68. Secondary Outcome

Title	Change From Baseline in Glucose at Month 1
Description	Laboratory chemistry glucose
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	68	71
Mean (Standard Deviation) [mmol/L]	0.06 (0.76)	0.20 (0.65)	0.05 (1.28)

69. Secondary Outcome

Title	Change From Baseline in Glucose at Month 3
Description	Laboratory chemistry glucose
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	71
Mean (Standard Deviation) [mmol/L]	0.08 (0.87)	0.20 (0.63)	0.04 (1.26)

70. Secondary Outcome

Title	Change From Baseline in Glucose at Month 6
Description	Laboratory chemistry glucose
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	68	69
Mean (Standard Deviation) [mmol/L]	0.12 (0.85)	0.20 (0.65)	-0.05 (1.26)

71. Secondary Outcome

Title	Change From Baseline in Glucose at Month 12
Description	Laboratory chemistry glucose
Time Frame	baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	63
Mean (Standard Deviation) [mmol/L]	-0.04 (0.66)	0.22 (0.96)	0.19 (1.27)

72. Secondary Outcome

Title	Change From Baseline in Potassium at Month 1
Description	Laboratory chemistry potassium
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	69	72
Mean (Standard Deviation) [mmol/L]	0.06 (0.38)	0.06 (0.36)	0.04 (0.36)

73. Secondary Outcome

Title	Change From Baseline in Potassium at Month 3
Description	Laboratory chemistry potassium
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	69	72
Mean (Standard Deviation) [mmol/L]	-0.01 (0.39)	0.06 (0.40)	0.04 (0.38)

74. Secondary Outcome

Title	Change From Baseline in Potassium at Month 6
Description	Laboratory chemistry potassium
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	70
Mean (Standard Deviation) [mmol/L]	0.01 (0.44)	-0.01 (0.36)	0 (0.42)

75. Secondary Outcome

Title	Change From Baseline in Potassium at Month 12
Description	Laboratory chemistry potassium
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	66	64
Mean (Standard Deviation) [mmol/L]	-0.07 (0.44)	-0.08 (0.35)	-0.04 (0.43)

76. Secondary Outcome

Title	Change From Baseline in Magnesium at Month 1
Description	Laboratory chemistry magnesium
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	72
Mean (Standard Deviation) [mmol/L]	0.01 (0.06)	0.02 (0.06)	0.01 (0.05)

77. Secondary Outcome

Title	Change From Baseline in Magnesium at Month 3
Description	Laboratory chemistry magnesium
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	68	72
Mean (Standard Deviation) [mmol/L]	-0.01 (0.06)	0.02 (0.06)	0 (0.06)

78. Secondary Outcome

Title	Change From Baseline in Magnesium at Month 6
Description	Laboratory chemistry magnesium
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	68	70
Mean (Standard Deviation) [mmol/L]	0 (0.06)	0.01 (0.06)	0.01 (0.07)

79. Secondary Outcome

Title	Change From Baseline in Magnesium at Month 12
Description	Laboratory chemistry magnesium
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	65	64
Mean (Standard Deviation) [mmol/L]	-0.01 (0.06)	-0.01 (0.07)	-0.01 (0.08)

80. Secondary Outcome

Title	Change From Baseline in Sodium at Month 1
Description	Laboratory chemistry sodium
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	69	72
Mean (Standard Deviation) [mmol/L]	-0.03 (1.93)	-0.06 (2.62)	0.33 (2.03)

81. Secondary Outcome

Title	Change From Baseline in Sodium at Month 3
Description	Change From Baseline in Sodium at Month 3
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	71	69	72
Mean (Standard Deviation) [mmol/L]	-0.14 (2.13)	-0.16 (2.29)	0.39 (2.38)

82. Secondary Outcome

Title	Change From Baseline in Sodium at Month 6
Description	Laboratory chemistry sodium
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	69	70
Mean (Standard Deviation) [mmol/L]	-0.12 (1.98)	-0.06 (1.75)	0.03 (2.27)

83. Secondary Outcome

Title	Change From Baseline in Sodium at Month 12
Description	Laboratory chemistry sodium
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	66	64
Mean (Standard Deviation) [mmol/L]	-0.25 (2.02)	-0.27 (2.75)	0.33 (2.38)

84. Secondary Outcome

Title	Change From Baseline in Phosphorus at Month 1
Description	Laboratory chemistry phosphorus
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	68	71
Mean (Standard Deviation) [mmol/L]	-0.09 (0.16)	-0.06 (0.19)	0.02 (0.14)

85. Secondary Outcome

Title	Change From Baseline in Phosphorus at Month 3
Description	Laboratory chemistry phosphorus
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	68	71
Mean (Standard Deviation) [mmol/L]	-0.03 (0.16)	-0.03 (0.18)	0.01 (0.20)

86. Secondary Outcome

Title	Change From Baseline in Phosphorus at Month 6
Description	Laboratory chemistry phosphorus
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	68	68
Mean (Standard Deviation) [mmol/L]	-0.05 (0.17)	-0.01 (0.18)	0.03 (0.19)

87. Secondary Outcome

Title	Change From Baseline in Phosphorus at Month 12
Description	Change From Baseline in Phosphorus at Month 12
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	65	63
Mean (Standard Deviation) [mmol/L]	-0.05 (0.17)	0 (0.17)	0 (0.16)

88. Secondary Outcome

Title	Change From Baseline in Total Protein at Month 1
Description	Laboratory chemistry total protein
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	68	71
Mean (Standard Deviation) [g/L]	-0.46 (3.56)	-0.40 (3.22)	0.21 (3.00)

89. Secondary Outcome

Title	Change From Baseline in Total Protein at Month 3
Description	Laboratory chemistry total protein
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	70	68	71
Mean (Standard Deviation) [g/L]	-0.29 (3.35)	0.07 (3.42)	-0.20 (3.54)

90. Secondary Outcome

Title	Change From Baseline in Total Protein at Month 6
Description	Laboratory chemistry total protein
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	68	69
Mean (Standard Deviation) [g/L]	-0.09 (4.13)	-0.62 (3.40)	-0.57 (3.19)

91. Secondary Outcome

Title	Change From Baseline in Total Protein at Month 12
Description	Laboratory chemistry total protein
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	63
Mean (Standard Deviation) [g/L]	-0.97 (3.76)	-0.91 (3.55)	-0.98 (3.10)

92. Secondary Outcome

Title	Change From Baseline in Aspartate Amino Transferase at Month 1
Description	Laboratory chemistry aspartate amino transferase
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	68	71
Mean (Standard Deviation) [U/L]	-0.79 (5.84)	-0.26 (8.14)	0.90 (8.35)

93. Secondary Outcome

Title	Change From Baseline in Aspartate Amino Transferase at Month 3
Description	Laboratory chemistry aspartate amino transferase
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	68	71
Mean (Standard Deviation) [U/L]	1.99 (5.77)	0.40 (8.78)	2.69 (9.37)

94. Secondary Outcome

Title	Change From Baseline in Aspartate Amino Transferase
Description	Laboratory chemistry aspartate amino transferase
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	68	68
Mean (Standard Deviation) [U/L]	3.85 (15.66)	0.87 (7.58)	3.24 (15.90)

95. Secondary Outcome

Title	Change From Baseline in Aspartate Amino Transferase at Month 12
Description	Laboratory chemistry aspartate amino transferase
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	65	63
Mean (Standard Deviation) [U/L]	3.86 (18.62)	3.75 (18.11)	2.24 (7.32)

96. Secondary Outcome

Title	Change From Baseline in Alanine Amino Transferase at Month 1
Description	Laboratory chemistry alanine amino transferase
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	67	70
Mean (Standard Deviation) [U/L]	-1.84 (8.61)	-1.03 (12.37)	1.20 (15.44)

97. Secondary Outcome

Title	Change From Baseline in Alanine Amino Transferase at Month 3
Description	Laboratory Chemistry alanine amino transferase
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	69	67	70
Mean (Standard Deviation) [U/L]	0.04 (8.85)	-2.10 (14.34)	1.54 (13.00)

98. Secondary Outcome

Title	Change From Baseline in Alanine Amino Transferase at Month 6
Description	Laboratory chemistry alanine amino transferase
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	65	67	66
Mean (Standard Deviation) [U/L]	1.20 (15.83)	-1.76 (14.12)	5.44 (51.19)

99. Secondary Outcome

Title	Change From Baseline in Alanine Amino Transferase at Month 12
Description	Laboratory chemistry alanine amino transferase
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	63	64	62
Mean (Standard Deviation) [U/L]	4.86 (24.46)	1.66 (14.30)	1.82 (14.41)

100. Secondary Outcome

Title	Change From Baseline in Basophils at Month 1
Description	Laboratory hematology basophils
Time Frame	baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	69
Mean (Standard Deviation) [*10^9/L]	0 (0.07)	0 (0.07)	-0.01 (0.07)

101. Secondary Outcome

Title	Change From Baseline in Basophils at Month 3
Description	Laboratory hematology basophils
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	64	67
Mean (Standard Deviation) [* 10^9/L]	-0.01 (0.06)	-0.01 (0.07)	-0.01 (0.07)

102. Secondary Outcome

Title	Change From Baseline in Basophils at Month 6
Description	Laboratory hematology basophils
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	66
Mean (Standard Deviation) [* 10^9/L]	0 (0.06)	0 (0.07)	0 (0.06)

103. Secondary Outcome

Title	Change From Baseline in Basophils at Month 12
Description	Laboratory hematology basophils
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	60
Mean (Standard Deviation) [* 10^9/L]	0.02 (0.09)	0 (0.09)	0.03 (0.07)

104. Secondary Outcome

Title	Change From Baseline in Eosinophils at Month 1
Description	Laboratory hematology eosinophils
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	69
Mean (Standard Deviation) [* 10^9/L]	-0.02 (0.09)	-0.01 (0.09)	0.01 (0.08)

105. Secondary Outcome

Title	Change From Baseline in Eosinophils at Month 3
Description	Laboratory hematology eosinophils
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	64	67
Mean (Standard Deviation) [* 10^9/L]	0 (0.10)	0 (0.10)	-0.01 (0.09)

106. Secondary Outcome

Title	Change From Baseline in Eosinophils at Month 6
Description	Laboratory hematology eosinophils
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	66
Mean (Standard Deviation) [* 10^9/L]	-0.03 (0.09)	0 (0.13)	0 (0.13)

107. Secondary Outcome

Title	Change From Baseline in Eosinophils at Month 12
Description	Laboratory hematology eosinophils
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	60
Mean (Standard Deviation) [* 10^9/L]	0.03 (0.16)	0.02 (0.12)	0.01 (0.12)

108. Secondary Outcome

Title	Change From Baseline in Hematocrit at Month 1
Description	Laboratory hematology hematocrit
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	70
Mean (Standard Deviation) [Proportion of red blood cells in blood]	0 (0.02)	0 (0.02)	0 (0.02)

109. Secondary Outcome

Title	Change From Baseline in Hematocrit at Month 3
Description	Laboratory hematology hematocrit
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	64	70
Mean (Standard Deviation) [Proportion of red blood cells in blood]	0.01 (0.02)	0 (0.03)	0 (0.03)

110. Secondary Outcome

Title	Change From Baseline in Hematocrit at Month 6
Description	Laboratory hematology hematocrit
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	67
Mean (Standard Deviation) [Proportion of red blood cells in blood]	0.01 (0.02)	0 (0.03)	0 (0.03)

111. Secondary Outcome

Title	Change From Baseline in Hematocrit at Month 12
Description	Laboratory hematology hematocrit
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	61
Mean (Standard Deviation) [Proportion of red blood cells in blood]	0 (0.02)	0 (0.03)	-0.01 (0.03)

112. Secondary Outcome

Title	Change From Baseline in Hemoglobin at Month 1
Description	Laboratory hematology hemoglobin
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	70
Mean (Standard Deviation) [g/L]	-0.33 (6.73)	-1.48 (6.39)	-0.69 (6.34)

113. Secondary Outcome

Title	Change From Baseline in Hemoglobin at Month 3
Description	Laboratory hematology hemoglobin
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	64	70
Mean (Standard Deviation) [g/L]	0.69 (7.02)	-1.02 (8.36)	-1.10 (6.30)

114. Secondary Outcome

Title	Change From Baseline in Hemoglobin at Month 6
Description	Laboratory hematology hemoglobin
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	67
Mean (Standard Deviation) [g/L]	-0.36 (7.80)	-1.69 (8.82)	-0.69 (8.21)

115. Secondary Outcome

Title	Change From Baseline in Hemoglobin at Month 12
Description	Laboratory hematology hemoglobin
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	61
Mean (Standard Deviation) [g/L]	1.21 (9.26)	0.02 (11.66)	-0.46 (10.08)

116. Secondary Outcome

Title	Change From Baseline in Lymphocytes at Month 1
Description	Laboratory hematology lymphocytes
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	69
Mean (Standard Deviation) [* 10^9/L]	-0.02 (0.41)	0.10 (0.40)	0 (0.45)

117. Secondary Outcome

Title	Change From Baseline in Lymphocytes at Month 3
Description	Laboratory hematology lymphocytes
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	64	67
Mean (Standard Deviation) [* 10^9/L]	0.07 (0.38)	0.14 (0.48)	0.08 (0.46)

118. Secondary Outcome

Title	Change From Baseline in Lymphocytes at Month 6
Description	Laboratory hematology lymphocytes
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	66
Mean (Standard Deviation) [* 10^9/L]	0.12 (0.41)	0.05 (0.35)	0.03 (0.68)

119. Secondary Outcome

Title	Change From Baseline in Lymphocytes at Month 12
Description	Laboratory hematology lymphocytes
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	60
Mean (Standard Deviation) [* 10^9/L]	-0.02 (0.49)	0.04 (0.50)	-0.02 (0.49)

120. Secondary Outcome

Title	Change From Baseline in Monocytes at Month 1
Description	Laboratory hematology monocytes
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	69
Mean (Standard Deviation) [* 10^9/L]	0.01 (0.13)	-0.01 (0.10)	0.01 (0.12)

121. Secondary Outcome

Title	Change From Baseline in Monocytes at Month 3
Description	Laboratory hematology monocytes
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	64	67
Mean (Standard Deviation) [* 10^9/L]	0.02 (0.11)	0.01 (0.11)	0.02 (0.11)

122. Secondary Outcome

Title	Change From Baseline in Monocytes at Month 6
Description	Laboratory hematology monocytes
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	66
Mean (Standard Deviation) [* 10^9/L]	0.05 (0.17)	0.04 (0.12)	0.04 (0.13)

123. Secondary Outcome

Title	Change From Baseline in Monocytes at Month 12
Description	Laboratory hematology monocytes
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	60
Mean (Standard Deviation) [* 10^9/L]	0.03 (0.15)	0 (0.11)	0.02 (0.13)

124. Secondary Outcome

Title	Change From Baseline in Total Neutrophils at Month 1
Description	Laboratory hematology total neutrophils
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	69
Mean (Standard Deviation) [* 10^9/L]	0 (1.97)	0.18 (1.99)	-0.13 (1.68)

125. Secondary Outcome

Title	Change From Baseline in Total Neutrophils at Month 3
Description	Laboratory hematology total neutrophils
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	64	67
Mean (Standard Deviation) [* 10^9/L]	0.11 (1.92)	0.26 (1.64)	-0.11 (1.55)

126. Secondary Outcome

Title	Change From Baseline in Total Neutrophils at Month 6
Description	Laboratory hematology total neutrophils
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	66
Mean (Standard Deviation) [* 10^9/L]	0.18 (1.67)	-0.05 (1.66)	0.27 (2.36)

127. Secondary Outcome

Title	Change From Baseline in Total Neutrophils at Month 12
Description	Laboratory hematology total neutrophils
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	60
Mean (Standard Deviation) [* 10^9/L]	0.65 (2.37)	0.04 (1.79)	0.10 (2.31)

128. Secondary Outcome

Title	Change From Baseline in Platelets at Month 1
Description	Laboratory hematology platelets
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	64	68
Mean (Standard Deviation) [* 10^9/L]	1.78 (44.53)	10.36 (49.34)	2.96 (44.15)

129. Secondary Outcome

Title	Change From Baseline in Platelets at Month 3
Description	Laboratory hematology platelets
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	67	63	69
Mean (Standard Deviation) [* 10^9/L]	-2.82 (48.86)	6.86 (50.18)	-1.97 (45.94)

130. Secondary Outcome

Title	Change From Baseline in Platelets at Month 6
Description	Laboratory hematology platelets
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	62	65	65
Mean (Standard Deviation) [* 10^9/L]	1.95 (54.95)	1.00 (45.64)	1.57 (53.39)

131. Secondary Outcome

Title	Change From Baseline in Platelets at Month 12
Description	Laboratory hematology platelets
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	60	62	59
Mean (Standard Deviation) [* 10^9/L]	3.32 (51.66)	-4.26 (51.12)	1.07 (58.16)

132. Secondary Outcome

Title	Change From Baseline in Red Blood Cells at Month 1
Description	Laboratory hematology red blood cells
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	70
Mean (Standard Deviation) [* 10^9/L]	-0.01 (0.21)	-0.01 (0.20)	-0.01 (0.19)

133. Secondary Outcome

Title	Change From Baseline in Red Blood Cells at Month 3
Description	Laboratory hematology red blood cells
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	64	70
Mean (Standard Deviation) [* 10^9/L]	0.05 (0.23)	0.02 (0.28)	0 (0.23)

134. Secondary Outcome

Title	Change From Baseline in Red Blood Cells at Month 6
Description	Laboratory hematology red blood cells
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	67
Mean (Standard Deviation) [* 10^9/L]	0.01 (0.24)	-0.04 (0.26)	0.01 (0.26)

135. Secondary Outcome

Title	Change From Baseline in Red Blood Cells at Month 12
Description	Laboratory hematology red blood cells
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	61
Mean (Standard Deviation) [* 10^9/L]	0.01 (0.27)	-0.06 (0.30)	-0.03 (0.29)

136. Secondary Outcome

Title	Change From Baseline in White Blood Cells at Month 1
Description	Laboratory hematology white blood cells
Time Frame	Baseline, month 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	66	64	70
Mean (Standard Deviation) [* 10^9/L]	-0.03 (2.07)	0.26 (2.04)	-0.10 (1.88)

137. Secondary Outcome

Title	Change From Baseline in White Blood Cells at Month 3
Description	Laboratpry hematology white blood cells
Time Frame	Baseline, month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	68	64	70
Mean (Standard Deviation) [* 10^9/L]	0.18 (1.93)	0.40 (1.71)	-0.05 (1.64)

138. Secondary Outcome

Title	Change From Baseline in White Blood Cells at Month 6
Description	Laboratory hematology white blood cells
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	64	65	67
Mean (Standard Deviation) [* 10^9/L]	0.30 (1.78)	0.04 (1.85)	0.35 (2.34)

139. Secondary Outcome

Title	Change From Baseline in White Blood Cells at Month 12
Description	Laboratory hematology white blood cells
Time Frame	Baseline, month 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	61	62	61
Mean (Standard Deviation) [* 10^9/L]	0.70 (2.40)	0.11 (1.86)	0.13 (2.22)

140. Secondary Outcome

Title	Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3
Description	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.
Time Frame	Month 1, month 3, month 6, month 12

Outcome Measure Data

Analysis Population Description

Patients who received at least 1 dose of investigational product.

Arm/Group Title	Denosumab 180 mg	Denosumab 60 mg	Placebo
Arm/Group Description	Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.	Participants received placebo subcutaneous injections on Day 1 and at Month 6.
Measure Participants	72	71	75
Alanine Amino Transferase-above normal (grade 3)	0 0%	0 0%	1 1.3%
Aspartate Amino Transferase-above normal (grade 3)	0 0%	1 1.4%	0 0%
Glucose-above normal (grade 3)	1 1.3%	0 0%	0 0%
Lymphocytes-below normal (grade 3)	1 1.3%	3 4.1%	2 2.6%
Sodium-below normal (grade 3)	1 1.3%	2 2.7%	0 0%
White Blood Cells-below normal (grade 3)	0 0%	1 1.4%	1 1.3%

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Arm/Group Title	Placebo		Denosumab 60 mg		Denosumab 180 mg
Arm/Group Description	Participants received placebo subcutaneous injections on Day 1 and at Month 6.		Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6.		Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6.
All Cause Mortality
	Placebo		Denosumab 60 mg		Denosumab 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Denosumab 60 mg		Denosumab 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/75 (6.7%)		3/71 (4.2%)		6/72 (8.3%)
Blood and lymphatic system disorders
Anaemia	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Cardiac disorders
Coronary artery disease	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Myocardial infarction	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Gastrointestinal disorders
Diabetic gastroparesis	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Nausea	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Vomiting	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Infections and infestations
Cellulitis	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Pyelonephritis	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Urosepsis	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Injury, poisoning and procedural complications
Humerus fracture	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Thermal burn	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Metabolism and nutrition disorders
Diabetic foot	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Intervertebral disc degeneration	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Rheumatoid arthritis	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Breast cancer	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Breast cancer metastatic	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Lung neoplasm malignant	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Nervous system disorders
Coordination abnormal	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Diabetic neuropathy	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Transient ischaemic attack	0/75 (0%)		1/71 (1.4%)		0/72 (0%)
Renal and urinary disorders
Renal artery stenosis	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Reproductive system and breast disorders
Uterine prolapse	1/75 (1.3%)		0/71 (0%)		0/72 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Vascular disorders
Deep vein thrombosis	0/75 (0%)		0/71 (0%)		1/72 (1.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Denosumab 60 mg		Denosumab 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/75 (62.7%)		44/71 (62%)		44/72 (61.1%)
General disorders
Fatigue	3/75 (4%)		6/71 (8.5%)		0/72 (0%)
Infections and infestations
Bronchitis	3/75 (4%)		3/71 (4.2%)		4/72 (5.6%)
Influenza	0/75 (0%)		2/71 (2.8%)		6/72 (8.3%)
Nasopharyngitis	9/75 (12%)		5/71 (7%)		5/72 (6.9%)
Sinusitis	8/75 (10.7%)		4/71 (5.6%)		8/72 (11.1%)
Upper respiratory tract infection	6/75 (8%)		11/71 (15.5%)		8/72 (11.1%)
Urinary tract infection	1/75 (1.3%)		4/71 (5.6%)		3/72 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/75 (4%)		4/71 (5.6%)		2/72 (2.8%)
Back pain	4/75 (5.3%)		2/71 (2.8%)		2/72 (2.8%)
Rheumatoid arthritis	24/75 (32%)		22/71 (31%)		21/72 (29.2%)
Nervous system disorders
Dizziness	4/75 (5.3%)		2/71 (2.8%)		0/72 (0%)
Headache	1/75 (1.3%)		1/71 (1.4%)		4/72 (5.6%)
Psychiatric disorders
Insomnia	4/75 (5.3%)		1/71 (1.4%)		3/72 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	5/75 (6.7%)		5/71 (7%)		1/72 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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