Meulenbeld 2012.

Study characteristics
Methods	Recruitment period: January 2004 to April 2010 Outcomes: overall survival, disease progression, pain response, adverse events Pain assessment tool: PPI scale Randomization: intervention vs control
Participants	Eligibility criteria: men with castration‐resistant prostate cancer age ≥ 18 years ECOG performance status ≤ 2 adequate hepatic, renal, and hematologic function people with disease‐related pain with ≥ 1 week on stable analgesic regimen Exclusion criteria: prior use of bisphosphonates radiation therapy within 4 weeks of enrollment central nervous system (CNS) involvement or other serious illness Participants randomized: 592 randomized, 291 intervention, 301 control Mean age: intervention: 68 years control: 69 years Country of participants: the Netherlands and Norway
Interventions	Previous interventions: LHRH analogues for some participants Interventions during study period: intervention: risedronate 30 mg orally daily, docetaxel 75 mg/m2 IV every 3 weeks, prednisone 5 mg orally daily control: docetaxel 75 mg/m2 IV every 3 weeks, prednisone 5 mg orally daily
Outcomes	Reported and analyzed in this review: overall survival pain response adverse events
Funding sources	Funding sources: Sanofi‐Aventis, Gouda, the Netherlands
Declarations of interest	Conflicts of interest: senior author received honoraria and research funding from Sanofi‐Aventis, Gouda, the Netherlands
Notes
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 randomized, open label, phase II/III trial [...]."
Blinding of participants and personnel (performance bias) Blinding of personnel	High risk	"This randomized, open label, phase II/III trial [...]."
Blinding of outcome assessment (detection bias) Outcomes subjective to participants	High risk	"This randomized, open label, phase II/III trial [...]."
Blinding of outcome assessment (detection bias) Outcomes subjective to outcome assessors	Unclear risk	No information on blinding of outcome assessor
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	No known reason for bias
Incomplete outcome data (attrition bias) Time‐to‐event data	Low risk	"All participants with bone metastasis from prostate cancer were included in the analysis of efficacy and safety." Reasons given for every dropout.
Incomplete outcome data (attrition bias) Patient‐reported outcomes (other than safety data)	Low risk	"All participants with bone metastasis from prostate cancer were included in the analysis of efficacy and safety." Reasons given for every dropout.
Incomplete outcome data (attrition bias) Safety data	Low risk	"All randomized patients were analyzed for safety."
Selective reporting (reporting bias)	Low risk	Protocol available (ISRCTN22844568), prespecified outcomes reported.
Other bias	Low risk	None identified