ZABTON‐PC.

Study characteristics
Methods	Recruitment period: July 2006 to June 2011 Outcomes: SREs, disease progression, adverse events Pain assessment tool: not reported Randomization: intervention vs control
Participants	Eligibility criteria: histologically confirmed prostate cancer and bone metastases present in bone scintigraphy non‐therapy prostate cancer (possible inclusion of men with hormone therapy for < 1 month) ECOG performance status ≤ 3 leukocyte count > 3000/mm3 platelet count > 100,000/mm3 hemoglobin level > 9 mg/dL serum ALT ≥ 3 times the institutional reference blood urea nitrogen (BUN) < 30 mg/dL, ≥ 3 times the institutional reference serum creatinine < 3.0 mg/dL serum calcium 8.5 to 11.5 mg/dL Exclusion criteria: prior use of bisphosphonates radiation therapy within 3 months of therapy initiation serum correction calcium values < 8.0 mg/dL or in active cancer ≥ 11.6 mg/dL other active malignancy within 3 years prior to therapy initiation grave complications planned invasive dental treatment or a treatment within 6 months prior to study entry anaphylactic medical history regarding bisphosphonates Participants randomized: 60 randomized, 29 intervention, 31 control Mean age: intervention: 71.1 years control: 71.8 years Country of participants: Japan
Interventions	Previous interventions: participants had no prior intervention Interventions during study period: intervention: zoledronic acid 4 mg IV infusion every 4 weeks (started 1 month after combined androgen blockade), combined androgen blockade with bicalutamide 80 mg and an LHRH agonist control: combined androgen blockade with bicalutamide 80 mg and an LHRH agonist
Outcomes	Reported and analyzed in this review: SREs adverse events
Funding sources	Funding sources: not reported
Declarations of interest	Conflicts of interest: not reported
Notes	Inclusion of "bone pain" in SREs
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information on sequence generation
Allocation concealment (selection bias)	Unclear risk	Insufficient information on allocation concealment
Blinding of participants and personnel (performance bias) Blinding of participants	High risk	"This study was under a still ongoing randomized multicenter collaborative open‐labeled project [...]."
Blinding of participants and personnel (performance bias) Blinding of personnel	High risk	"This study was under a still ongoing randomized multicenter collaborative open‐labeled project [...]."
Blinding of outcome assessment (detection bias) Outcomes subjective to participants	High risk	"This study was under a still ongoing randomized multicenter collaborative open‐labeled project [...]."
Blinding of outcome assessment (detection bias) Outcomes subjective to outcome assessors	Unclear risk	Insufficient information on blinding of outcome assessors
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	No known reason for bias
Incomplete outcome data (attrition bias) Time‐to‐event data	Unclear risk	All participants were included in statistical analysis. 3 participants out of 60 were lost to follow‐up, and 20 participants died. No information on intention‐to‐treat analysis.
Incomplete outcome data (attrition bias) Patient‐reported outcomes (other than safety data)	Unclear risk	All participants were included in statistical analysis. 3 participants out of 60 were lost to follow‐up, and 20 participants died. No information on intention‐to‐treat analysis.
Incomplete outcome data (attrition bias) Safety data	Unclear risk	All participants were included in statistical analysis. 3 participants out of 60 were lost to follow‐up, and 20 participants died. No information on intention‐to‐treat analysis.
Incomplete outcome data (attrition bias) Other outcomes	Unclear risk	All participants were included in statistical analysis. 3 participants out of 60 were lost to follow‐up, and 20 participants died. No information on intention‐to‐treat analysis.
Selective reporting (reporting bias)	High risk	Protocol available (UMIN000001137). Survival data not reported as planned.
Other bias	Low risk	None identified