Aris 2000.

Methods	Randomised controlled trial, parallel design. Trial duration 2 years. Single centre, university hospital, USA.
Participants	Inclusion criteria: CF; 1 to 12 months post‐lung transplantation; ambulatory. Exclusion criteria: primary graft failure or other post‐operative morbidities that precluded long‐term survival; renal insufficiency (serum creatinine > 3.0 mg/dl); or pregnancy. Total participants: n = 34 (17 female). Treatment group: n = 16 (7 female); mean (SD) age 27.5 years (6.6 years); Control group: n = 18 (10 female); mean (SD) age 29.1 years (6.4 years). Groups similar in age, gender, baseline T‐scores, renal function, hospitalisation rates, immunosuppressant levels, change in lung function and BMI over study period. 13 in treatment group and 12 controls had baseline T‐scores < ‐2.5 at a minimum of one site; all others ‐1 < T < ‐2.5 at a minimum of one site.
Interventions	Treatment group: intravenous pamidronate (30 mg every 3 months) plus oral vitamin D (800 IU/day) and oral calcium (1 g/day) Control group: oral vitamin D (800 IU/day) and oral calcium (1 g/day)
Outcomes	Primary outcome BMD (spine; 0, 6, 12, 18, 24 months; DXA Hologic QDR 1000/W Waltham MA) Secondary outcomes BMD femur (at 0, 6, 12, 18, 24 months; DXA Hologic QDR 1000/W Waltham MA) New fractures: number of fractures during study; long bone using clinical data, rib using posteroanterior chest radiographs, vertebral using lateral chest radiographs Kyphosis angles (degrees): thoracic spine curvature using lateral chest radiographs using a modification of method of Cobb (at 0, 24 months) Adverse events: number during study; thrombophlebitis, cellulitis, bone pain, fever, hypocalcaemia defined as serum calcium < 7.8 mg/dl, hypervitaminosis defined as serum 25‐hydroxyvitamin D > 55 ng/ml Bone biomarkers: serum osteocalcin, urine cross‐linked N‐telopeptides of type 1 collagen, urine free deoxypyridinoline (at 0, 3, 12, 24 months; also 2, 14 days after first pamidronate infusion in intervention group) Serum calcium, vitamin D (25‐hydroxyvitamin D, 1,25‐dihydroxyvitamin D) and PTH levels (at 0, 3, 12, 24 months) Withdrawals Survival
Notes	44 people with CF were eligible during the course of this study, 7 died immediately post‐operatively and were therefore not eligible for this trial. As outlined above, 3 people died during the course of the study before the first primary end point measurement. 34 people were included in the final analyses. Funding was provided by grants from the CF Foundation and the Verne S. Caviness General Center for Clinical Research.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Blocks of four" design stated (stratified on basis of gender and severity of osteoporosis using spine z score of ‐3.0), but actual method of randomisation is not discussed.
Allocation concealment (selection bias)	Unclear risk	Not discussed.
Blinding (performance bias and detection bias) All outcomes	High risk	Person(s) responsible for participants care and participants were not blinded. Of outcome assessors, only the radiologist who interpreted the DXA scans was blinded.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	It was described that 3 participants died during the course of the study before the first primary end‐point measurement (causes of death were one each from sepsis, acute respiratory distress syndrome and obliterative bronchiolitis). These participants were excluded from the final analysis of baseline characteristics and outcome data. However, it was not reported which treatment group they were in.
Selective reporting (reporting bias)	High risk	Serum and urine biochemical measurements that were measured at 2 days (only after first pamidronate infusion in intervention group) were not reported.
Other bias	Unclear risk	None identified.