AE defined as any untoward medical occurrence in a clinical trial participant. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v3.0) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. Investigator assessed AEs for relatedness to study drug. Results are presented for treatment-emergent events (TEAEs) and included all AEs occurring from first dose in initial treatment phase to end of initial treatment phase (or for participants entering retreatment, from first dose in initial treatment phase until end of retreatment phase).

The safety analysis set included all enrolled participants who received at least one dose of denosumab on the study.

Serum samples for clinical chemistry were collected on study day 1 (baseline), day 15, week 5 and each study visit Q4W thereafter until last study visit for the on-study period (ie, until end of initial treatment phase). The parameters included albumin, calcium (albumin-adjusted), creatinine, magnesium and phosphate. Results are presented for number of participants who experienced the maximum toxicity grade for each of these clinical parameters. The maximum toxicity grade experienced by each participant was based on CTCAE, v3.0, and are summarized for Grade 3 and 4. Increases and decreases in relationship to the normal parameter ranges are indicated as 'Above' and 'Below' respectively.

The safety analysis set included all enrolled participants who received at least one dose of denosumab on the study.

Time to disease progression or recurrence during the on-study period was defined as the time interval (in days) from the date of first dose of study drug to the date of earliest Progressive Disease (PD) during the initial treatment phase. PD was defined as the response of progressive disease, locally recurrent disease or relapse as captured in the Disease Status page of the Case Report Form. If a participant had not had PD by the end of the initial treatment phase date, time to disease progression or recurrence were censored at her/his end of initial treatment phase date. Since median time to disease progression or recurrence for participants in cohort 1 was not reached, Kaplan-Meier estimates for the probability (expressed as a percentage) of participants in cohort 1 to have disease progression or recurrence at months 6, 12, 24, 36 and 60 are presented.

The efficacy analysis set included all enrolled participants who were eligible for the study, and who received at least one dose of denosumab on the study. Analysis was performed on cohort 1 only.

The percentage of participants without any surgery at month 6 was equivalent to the number of participants without any surgery by month 6 divided by the number of cohort 2 participants who had an opportunity to complete 6 months of treatment, expressed as a percentage.

The efficacy analysis set included all enrolled participants who were eligible for the study, and who received at least one dose of denosumab on the study. Analysis was performed on cohort 2 only for those who had the opportunity to be on-study for at least 6 months.

Blood samples for determination of serum denosumab concentration levels were obtained from participants included in the pharmacokinetic (PK) substudy at baseline (prior to administration of study drug on day 1) and at scheduled time points during the study up to week 25.

The PK analysis set included all participants who received at least 1 dose of denosumab with baseline PK measurement and at least 1 post-baseline PK measurement. Only participants with available data at each time point were included in the analysis.