Ryan 2007.

Study characteristics
Methods	Recruitment period: January 2000 to December 2002 Outcomes: bone mass density, NTX and BAP levels, adverse events Randomization: intervention vs control
Participants	Eligibility criteria: histological diagnosis of adenocarcinoma of the prostate and a life expectancy of ≥ 1 year patients must have been receiving androgen deprivation therapy (ADT) with an LHRH agonist or orchidectomy and have received ADT for ≤ 1 year patients who were scheduled to start ADT at the time of study entry Exclusion criteria: received previous bisphosphonate therapy Participants randomized: 42 randomized (of which half had bone metastases), 22 intervention (zoledronic acid), 20 placebo Median age: intervention group: 64.9 placebo group: 65.2 Country of participants: USA
Interventions	Intervention during study period: intervention group: zoledronic acid 4 mg in 100 mL of sterile 0.9% natriumchloride (NaCl), administered over 15 min, every 3 months placebo group: equal volume of sterile 0.9% NaCl administered in the same fashion "All patients were instructed to take calcium carbonate supplementation equivalent to 260 mg elemental calcium orally, four tablets daily."
Outcomes	Reported and analyzed in this review: none
Funding sources	Supported in part by grant M01‐RR00055‐46 to the University of Chicago General Clinical Research Center and by Novartis Pharmaceuticals
Declarations of interest	Christopher Ryan, Walter Stadler, and Nicholas Vogelzang have served as paid consultants to Novartis. Christopher Ryan and Walter Stadler are study investigators funded by the sponsor.
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	"Patients were randomized with equal probability, and in a double‐blind fashion," but the concealment process was not described in detail.
Blinding of participants and personnel (performance bias) Blinding of participants	Low risk	"Patients were randomized with equal probability, and in a double‐blind fashion"
Blinding of participants and personnel (performance bias) Blinding of personnel	Low risk	"Patients were randomized with equal probability, and in a double‐blind fashion"
Blinding of outcome assessment (detection bias) Outcomes subjective to participants	Low risk	Participants blinded to treatment, but: "Adverse events were retrospectively abstracted from patient charts."
Blinding of outcome assessment (detection bias) Outcomes subjective to outcome assessors	Unclear risk	Insufficient information. Randomization process was double‐blinded, but no 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) Safety data	High risk	"Adverse events were retrospectively abstracted from patient charts."
Incomplete outcome data (attrition bias) Other outcomes	Unclear risk	No information on ITT and reasons for dropouts
Selective reporting (reporting bias)	Unclear risk	No protocol available.
Other bias	Low risk	None identified