FREEDOM 2009.

Study characteristics
Methods	Study design: parallel RCT Time frame: not reported Duration of study follow‐up: 36 months
Participants	Country: multinational (USA, Canada, Argentina, Brazil, Mexico, Australia, New Zealand, Denmark, Finland, France, Germany, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland, UK Czech Republic, Greece, Hungary, Latvia, Malta, Slovak Republic, Romania, Serbia) Setting: multicentre Inclusion criteria: postmenopausal women; CKD stages 3‐4; osteoporosis Number: CKD stage 3 (2,817); CKD stage 4 (73); treatment group (not reported); control group (not reported) Mean age ± SD (years): CKD stage 3 (75.1 ± 4.9); CKD stage 4 (80.0 ± 5.5) Sex: women only CKD stage: CKD stages 3‐4 BMI: not reported Diabetes: not reported Current smoker: CKD stage 3: (263); CKD stage 4 (9) Exclusion criteria: bone disorder other than postmenopausal status; use of corticosteroids; prior treatment with other anti‐osteoporotic drugs
Interventions	Treatment group Denosumab (SC): 60 mg every 6 months Control group Placebo Co‐intervention Calcium (1,000 mg/day) Actual use of calcium supplementation: CKD stage 3 (2798), CKD stage 4 (73) Vitamin D (400 to 800 IU/day) Actual use of vitamin D supplementation: not reported
Outcomes	Primary outcome New vertebral fracture Secondary outcomes Nonvertebral fracture Hip fracture New clinical vertebral fracture Multiple (≥ 2) new vertebral fractures Percentage change in the BMD of the lumbar spine and total hip from baseline Bone turnover marker: serum C‐telopeptide of type I collagen (CTX); intact serum procollagen type I N‐terminal Propeptide (PINP) Adverse events
Notes	Funding source: Amgen Further information was requested, but no response was received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study was described as randomised; method of randomisation was not reported; however "Randomization was stratified according to 5‐year age group"
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Triple‐blind study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Efficacy and safety outcomes were assessed by blinded and independent assessors
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Missing outcome data balanced between intervention groups; reasons for missing data were not reported
Selective reporting (reporting bias)	High risk	BMD was reported incompletely so that these data could not be entered in a meta‐analysis (no control group data)
Other bias	High risk	The study was funded by Amgen