Buckler 1999.

Methods	RCT. Randomisation ratio: 1:1:1:1:1 (placebo: zoledronate 50 µg: 100 µg; 200 µg; 400 µg) Superiority design
Participants	Diagnostic criteria: x‐ray evidence of Paget's disease of bone Inclusion criteria: Paget's disease of bone and serum alkaline phosphatase concentrations at least twice the ULN Exclusion criteria: Treatment with bisphosphonates in the previous 6 months or calcitonin or plicamycin in the previous 3 months. Creatinine clearance < 60 mL/min. Abnormal liver function Number screened: not stated Number randomised: 176 Number analysed: 172 (71 years, 61% male; percentages monostotic, symptomatic or previously treated for Paget's disease of bone were not stated)
Interventions	5 parallel treatment groups; placebo and zoledronate in 4 doses (50 µg, 100 µg, 200 µg and 400 µg in a single intravenous infusion) Co‐interventions: Not reported
Outcomes	Outcomes reported in abstract Primary endpoint: Mean percentage change from baseline in serum total alkaline phosphatase activity Secondary endpoints: Numbers of participants who experienced adverse events related to use of bisphosphonates Time points for measurement: Baseline, 5 days, 10 days, 30 days, 45 days, 60 days and 90 days. How were the outcomes measured: prospectively
Setting and date	20 sites in USA and UK. Period when the study was conducted: Not stated
Follow up period	3 months
Publication details and funding source	Language of publication: English. Publication status: peer‐reviewed journal; full article. Funding source: Funding source not reported in the manuscript, but one author, P Richardson, indicated "Ciba Pharmaceuticals" (abstract) and "Clinical Research, Novartis Pharmaceuticals, East Hanover, NJ, USA" (primary reference) affiliations Declarations of interest among primary researchers: Not stated
Notes	Zoledronate groups data were pooled for meta‐analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The patients were randomized in a double‐blind manner". The allocation method was not described
Allocation concealment (selection bias)	Unclear risk	The allocation method was not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Randomized in a double blind manner". Comment: Probably done.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient information to permit judgement. The risk of bias was likely to be low for serum data because assays for bone‐specific alkaline phosphatase, urinary calcium, creatinine, hydroxyproline, pyridinoline and deoxypiridinoline were conducted in a central laboratory (Nichols Institute, San Juan Capistrano, CA, USA)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "All efficacy analyses were based on all randomised patients who had at least one post baseline measurement (intention‐to‐treat analysis). Four of the 176 patients did not complete all post baseline evaluations". Comment: Attrition data were provided
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement. Methods and results sections were consistent. We did not have access to a trial register record or study protocol to know if there was a prespecified record of the studies outcomes
Other bias	Unclear risk	There were no data on exposure to co‐interventions other than bisphosphonates. No other risks of bias found, but reporting was insufficient to permit judgement