Trial Outcomes & Findings for AMG 162 (Denosumab) Phase 3 Study (DESIRABLE Study) in Participants With Rheumatoid Arthritis on Disease-modifying Antirheumatic Drugs (DMARDs) Treatment (NCT NCT01973569)

NCT ID: NCT01973569

Last Updated: 2020-02-12

Results Overview

Change from baseline in Total Sharp Score (TSS) from baseline to month 12 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 679 participants
• Primary outcome timeframe: baseline to month 12
• Results posted on: 2020-02-12

Participant Flow

A total of 679 participants who met all inclusion and none of the exclusion criteria were included in the study; efficacy outcomes were assessed in the Full Analysis Set (n=654).

Participant milestones

Measure	Denosumab 6 Months denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Overall Study STARTED	228	225	226
Overall Study Received Study Drug	222	222	223
Overall Study Did Not Receive Study Drug	6	3	3
Overall Study Discontinued Study Treatment	23	22	15
Overall Study Discontinued Study	23	22	15
Overall Study COMPLETED	199	200	208
Overall Study NOT COMPLETED	29	25	18

Reasons for withdrawal

Measure	Denosumab 6 Months denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Overall Study Adverse Event	9	2	4
Overall Study Protocol Violation	2	1	3
Overall Study Withdrawal by Subject	7	5	2
Overall Study Invasive dental treatment	3	5	6
Overall Study Prohibited concomitant d	1	5	0
Overall Study Disease progression	0	3	0
Overall Study Other	1	1	0
Overall Study Did not receive study drug	6	3	3

Baseline Characteristics

AMG 162 (Denosumab) Phase 3 Study (DESIRABLE Study) in Participants With Rheumatoid Arthritis on Disease-modifying Antirheumatic Drugs (DMARDs) Treatment

Baseline characteristics by cohort

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab	Total n=654 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	140 Participants n=5 Participants	150 Participants n=7 Participants	163 Participants n=5 Participants	453 Participants n=4 Participants
Age, Categorical >=65 years	77 Participants n=5 Participants	69 Participants n=7 Participants	55 Participants n=5 Participants	201 Participants n=4 Participants
Age, Continuous	58.1 years STANDARD_DEVIATION 12.3 • n=5 Participants	58.2 years STANDARD_DEVIATION 12.04 • n=7 Participants	55.8 years STANDARD_DEVIATION 11.7 • n=5 Participants	57.4 years STANDARD_DEVIATION 12.04 • n=4 Participants
Sex: Female, Male Female	168 Participants n=5 Participants	154 Participants n=7 Participants	167 Participants n=5 Participants	489 Participants n=4 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	65 Participants n=7 Participants	51 Participants n=5 Participants	165 Participants n=4 Participants
Region of Enrollment Japan	217 participants n=5 Participants	219 participants n=7 Participants	218 participants n=5 Participants	654 participants n=4 Participants
Body mass index (BMI)	22.38 kg/m^2 STANDARD_DEVIATION 3.68 • n=5 Participants	22.64 kg/m^2 STANDARD_DEVIATION 3.62 • n=7 Participants	22.65 kg/m^2 STANDARD_DEVIATION 3.49 • n=5 Participants	22.56 kg/m^2 STANDARD_DEVIATION 3.59 • n=4 Participants

PRIMARY outcome

Timeframe: baseline to month 12

Population: TSS was assessed in Full Analysis Set.

Change from baseline in Total Sharp Score (TSS) from baseline to month 12 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Change in Total Sharp Score (TSS) From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo	0.99 score on a scale Interval 0.49 to 1.49	0.72 score on a scale Interval 0.41 to 1.03	1.49 score on a scale Interval 0.99 to 1.99

SECONDARY outcome

Timeframe: baseline to month 6

Population: TSS was assessed in the Full Analysis Set.

Change from baseline in Total Sharp Score (TSS) from baseline to month 6 was assessed. The TSS was defined as the sum of the erosion score and the joint space narrowing scores from radiographic assessments. The maximum radiographic TSS from the both hands/wrists and both feet is 448. Higher values represented greater damage.

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Change in Total Sharp Score (TSS) From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo	0.62 score on a scale Interval 0.27 to 0.98	0.48 score on a scale Interval 0.24 to 0.72	0.92 score on a scale Interval 0.6 to 1.23

SECONDARY outcome

Timeframe: baseline to month 6

Population: The Erosion Score was assessed in the Full Analysis Set.

Change from baseline in Erosion Score from baseline to month 6 was assessed. The Erosion Score was defined for the sum of the joint level erosion scores among the 44 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Erosion Score from both hands/wrist and both feet is 280. Higher values represented greater damage.

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Change in Erosion Score From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo	0.34 score on a scale Interval 0.16 to 0.53	0.13 score on a scale Interval 0.03 to 0.24	0.58 score on a scale Interval 0.39 to 0.78

SECONDARY outcome

Timeframe: baseline to month 6

Population: Joint Space Narrowing was assessed in the Full Analysis Set.

Change from baseline in Joint Space Narrowing from baseline to month 6 was assessed. Joint Space Narrowing was defined for the sum of the joint level joint space narrowing scores among the 42 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Joint Space Narrowing from both hands/wrists and both feet is 168. Higher values represented greater damage.

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Change in Joint Space Narrowing From Baseline to Month 6 Following Subcutaneous Administration of Denosumab or Placebo	0.28 score on a scale Interval 0.07 to 0.5	0.35 score on a scale Interval 0.17 to 0.53	0.33 score on a scale Interval 0.18 to 0.48

SECONDARY outcome

Timeframe: baseline to month 12

Population: The Erosion Score was assessed in the Full Analysis Set.

Change from baseline in Erosion Score from baseline to month 12 was assessed. The Erosion Score was defined for the sum of the joint level erosion scores among the 44 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Erosion Score from both hands/wrist and both feet is 280. Higher values represented greater damage.

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Change in Erosion Score From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo	0.51 score on a scale Interval 0.22 to 0.8	0.22 score on a scale Interval 0.09 to 0.34	0.98 score on a scale Interval 0.65 to 1.31

SECONDARY outcome

Timeframe: baseline to month 12

Population: Joint Space Narrowing was assessed in the Full Analysis Set.

Change from baseline in Joint Space Narrowing from baseline to month 12 was assessed. Joint Space Narrowing was defined for the sum of the joint level joint space narrowing scores among the 42 joints in both hands/wrist and both feet from radiographic assessments using the van der Heijde modified Sharp scoring method. The maximum radiographic Joint Space Narrowing from both hands/wrists and both feet is 168. Higher values represented greater damage.

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Change in Joint Space Narrowing From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo	0.48 score on a scale Interval 0.2 to 0.76	0.50 score on a scale Interval 0.27 to 0.74	0.51 score on a scale Interval 0.28 to 0.74

SECONDARY outcome

Timeframe: baseline to month 12

Population: Bone mineral density was assessed in the Full Analysis Set.

The percent change from baseline in Bone Mineral Density (BMD) to month 12 was assessed. Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA).

Outcome measures

Measure	Denosumab 6 Months n=217 Participants denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=219 Participants denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=218 Participants placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Percent Change in Bone Mineral Density (BMD) From Baseline to Month 12 Following Subcutaneous Administration of Denosumab or Placebo	3.99 percent change Standard Error 0.24	4.88 percent change Standard Error 0.24	-1.03 percent change Standard Error 0.25

Adverse Events

Denosumab 6 Months

Serious events: 19 serious events

Other events: 127 other events

Deaths: 0 deaths

Denosumab 3 Months

Serious events: 19 serious events

Other events: 122 other events

Deaths: 1 deaths

Placebo

Serious events: 13 serious events

Other events: 125 other events

Deaths: 0 deaths

Serious adverse events

Measure	Denosumab 6 Months n=221 participants at risk denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=222 participants at risk denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=224 participants at risk placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Cardiac disorders Paroxysmal arrhythmia	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Cardiac disorders Ventricular tachycardia	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Congenital, familial and genetic disorders Spinal muscular atrophy	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Ear and labyrinth disorders Vertigo	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Gastrointestinal disorders Enterocolitis	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Gastrointestinal disorders Inguinal hernia	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Gastrointestinal disorders Large intestine polyp	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
General disorders Mass	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Hepatobiliary disorders Cholelithiasis	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Abscess jaw	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Arthritis bacterial	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Atypical mycobacterial infection	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Cellulitis	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Diverticulitis	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Pyelonephritis acute	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Sepsis	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Tuberculosis	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Laceration	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Investigations Platelet count decreased	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Musculoskeletal and connective tissue disorders Synovitis	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Nervous system disorders Brain stem infarction	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Nervous system disorders Cerebral infarction	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Nervous system disorders Dizziness	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Nervous system disorders Transient ischaemic attack	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Product Issues Device dislocation	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Renal and urinary disorders Acute kidney injury	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Renal and urinary disorders Calculus bladder	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Renal and urinary disorders Prerenal failure	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.90% 2/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Reproductive system and breast disorders Prostatitis	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.45% 1/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Vascular disorders Hypotension	0.00% 0/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.45% 1/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	0.00% 0/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.

Other adverse events

Measure	Denosumab 6 Months n=221 participants at risk denosumab administered subcutaneously every 6 months denosumab: denosumab administered subcutaneously	Denosumab 3 Months n=222 participants at risk denosumab administered subcutaneously every 3 months denosumab: denosumab administered subcutaneously	Placebo n=224 participants at risk placebo administered subcutaneously to match denosumab placebo: placebo administered subcutaneously to match denosumab
Gastrointestinal disorders Dental caries	5.4% 12/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	3.2% 7/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	4.0% 9/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Gastrointestinal disorders Stomatitis	10.0% 22/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	12.2% 27/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	5.8% 13/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Hepatobiliary disorders Hepatic function abnormal	6.3% 14/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	5.9% 13/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	8.9% 20/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Influenza	3.6% 8/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	4.5% 10/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	5.4% 12/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Nasopharyngitis	35.7% 79/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	31.1% 69/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	32.6% 73/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Infections and infestations Pharyngitis	5.9% 13/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	7.2% 16/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	7.1% 16/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Musculoskeletal and connective tissue disorders Back pain	2.3% 5/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	5.4% 12/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	3.1% 7/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	8.1% 18/221 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	3.6% 8/222 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.	4.0% 9/224 • Adverse event data were collected from the first dose to the last dose of study drug, up to 12 months. Adverse events that emerge (or worsen) from the first dose of study drug to the last dose of study drug were reported in the Safety Analysis Set. The Safety Analysis Set was defined as all enrolled participants who received at least one dose of the investigational product. One participant of the Denosumab 6 months group was administered the placebo mistakenly, and was thus included in the placebo group for the safety analysis.

Additional Information

Daiichi Sanyko

Contact for Clinical Trial Information

Phone: +81 362251111 (M-F 9-5 JST)

Email: dsclinicaltrial@daiichisankyo.co.jp

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place