Haworth 2011.

Methods	Randomised, double‐blinded, placebo‐controlled trial; parallel design. Trial duration 24 months. Multicentre, 4 sites in United Kingdom, 1 site in Ireland.
Participants	Inclusion criteria: CF (diagnosis on the basis of a positive sweat test or gene analysis and a consistent CF phenotype); > 18 years, low BMD defined as lumbar spine, total hip or femoral neck BMD z score < 1. Exclusion criteria: prescription of daily oral glucocorticoids for 6 weeks or more in the 12 months preceding the study; breast feeding, pregnancy, desire to become pregnant within 3 years; listed for, or recipient of solid organ transplant; history of gastroscopy proven oesophageal abnormalities; renal impairment (elevated serum creatinine and an estimated creatinine clearance of  30 ml/min or less); hypocalcaemia; previous prescription of bone active drugs (bisphosphonates, hormone replacement therapy, raloxifene, calcitriol, calcitonin, teriparatide); biochemical evidence of vitamin D deficiency in the 12 months prior to the screening visit (25‐hydroxyvitamin D level < 10 ng/ml and PTH > 45 pg/ml); previous poor clinic attendance; previous poor adherence; pre‐terminal illness or other serious concomitant illness. Female participants of reproductive age were advised not to become pregnant for at least 12 months after study completion. Total participants: n = 36 (9 females). Treatment group: n = 17 (4 females); mean (SD) age 30.2 (12) years. Control group: n = 19 (5 females); mean (SD) age 27.8 (8.0) years.
Interventions	Treatment group: once weekly oral risedronate 35 mg. Control group: once weekly identical placebo. Both groups were both prescribed Calcichew D3 Forte 2 tablets daily which provides 1000 mg calcium + 800 IU vitamin D3/day. Patients were advised to continue their standard multivitamin supplements.
Outcomes	BMD assessed by dual energy x‐ray absorptiometry at lumbar spine, total hip and femoral neck (at baseline, 12 and 24 months) Lateral thoracic and lumbar spine x‐rays to assess for new vertebral fractures (at baseline and 24 months) Recorded x‐ray confirmed fractures (3, 6, 12, 18 and 24 months) Adverse events (at 3, 6, 12, 18 and 24 months) Biochemical measurements: serum concentration of C‐terminal cross‐linked telopeptide of collagen type 1 (CTX) (at baseline and 6‐month visits in 24 patients (12 risedronate, 12 placebo) Withdrawals Survival
Notes	Concomitant medications were recorded at study visits (3, 6, 12, 18 and 24 months). Pregnancy tests were performed in females at study visits (3, 6, 12, 18 and 24 months). Funded by unrestricted educational grants from Proctor & Gamble (Norwich, USA) and the Cystic Fibrosis Trust, with support to investigators from the UK National Institute of Health Research.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Patients were allocated to risedronate or placebo using a computer programme to minimise differences between groups in treatment centre, sex and baseline lumbar spine BMD.
Allocation concealment (selection bias)	Low risk	Only the study pharmacist had access to the treatment allocation.
Blinding (performance bias and detection bias) All outcomes	Low risk	Identical placebo used.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Withdrawals are described in full and fairly equally spread across groups. Intervention group: in the first 12 months, 3 out of 17 in the oral risedronate group withdrew from the study completely (due to bone pain) and 3 patients discontinued the study medication (one citing bone pain and the other 2 participants citing muscle aches or generalised pain) but remained in the study for follow up. Between 12 and 24 months one further participant withdrew, citing bone pain. At 24 months, 12 participants in the intervention group remained in study with 9 still taking the study drug. Placebo group: immediately after randomisation 1 participant in the placebo group withdrew consent before taking the study medication. Therefore, only 18 participants were commenced on placebo. By 12 months, 2 participants in the placebo group withdrew consent and 1 participant had died. By 24 months, 3 participants in the placebo group had withdrawn consent and 4 patients had died, hence at 24 months, 12 participants remained in the control group of the study. Primary outcome data included 12/17 of risedronate group (although only 9 still on drug); 12/19 placebo group. In the published abstract, it was not clear if the analysis included the 3 participants.
Selective reporting (reporting bias)	Low risk	Outcome measures that were described in the methods section were reported in the results section.
Other bias	Low risk	None identified.