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. 2014 Mar 13;2014(3):CD002010. doi: 10.1002/14651858.CD002010.pub4

Papaioannou 2008.

Methods Randomised, placebo‐controlled trial.
Trial duration: 12 months.
Multi‐centre, 6 Canadian CF specialty clinics.
Participants Inclusion criteria: participants had CF confirmed by positive sweat test result or DNA acid analysis and a BMD T score of 1.0, as determined by dual‐energy radiograph absorptiometry.
Exclusion criteria: organ transplantation; endoscopy‐proven oesophagitis, gastritis, and ulceration; metabolic bone disorders; severe renal disease; use of systemic corticosteroids (dose 7.5 mg/day) or other drugs known to influence bone metabolism in the previous 6 months; osteomalacia and other documented contraindications.
Total adults randomised: n = 56 (22 female). 9 withdrew, 47 completed study.
Treatment group: n = 27 (10 female); mean (SD) age 28.1 (7.7) years. 4 withdrew, 23 completed study.
Control group: n = 29 (12 female); mean (SD) age 30.9 (9.7) years. 5 withdrew, 24 completed study.
Interventions Treatment group: oral alendronate (70 mg) once weekly for 12 months.
Control group: placebo.
Medication was taken while sitting upright and with water only on an empty stomach at least 30 min before first food or beverage of the day. In addition,
 all participants received 800 IU of vitamin D and 1000 mg of calcium (500 mg supplementation, 500 mg from diet) daily.
Outcomes In‐clinic assessments at baseline, 6 and 12 months; telephone follow‐up conducted by study staff at months 3 and 9.

  • Compliance (measured through pill counts at each visit and patient self‐report during telephone contact)

  • Physical examination ‐ vital signs (at baseline, 6 and 12 months)

  • Biochemical measurements: serum and urine tests (at baseline, 6 and 12 months)

  • Pulmonary function tests: including FEV1 and FVC (at baseline, 6 and 12 months)

  • Medical Outcomes Study 36‐item short form version 2 (SF‐36v2) (at baseline, 6 and 12 months)

  • Radiographs of the thoracic and lumbar spine, and DXA (at baseline, 6 and 12 months)

  • Adverse events and drug reactions (reported spontaneously and at each contact)


Safety analyses included all vertebral fractures, osteoporosis‐related fractures, adverse reactions, and abnormal findings that had been detected through laboratory tests and physical examinations.
Documentation for all adverse events were blinded and adjudicated by the external Data Safety Monitoring Committee. All adverse events were reported regardless of attribution to study medication.
Notes Participants who received at least 80% of the study drug were classified as being adherent to the protocol. 5 participants completed the study protocol but received sub‐optimal dosing (< 80% adherence; treatment group, 3 participants; control group, 2 participants). 1 of the participants in the treatment group missed > 50% of doses.
Stopping and study withdrawal rules were monitored by an external Data Safety Monitoring Committee.
During the study, 3 participants in the treatment group used oral corticosteroids compared to none in the control group.
Study funding provided by Merck Frosst Canada.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Computer‐generated randomisation code, stratified according to institution was prepared by an independent randomisation centre and block allocation was employed to ensure equitable distribution to each treatment group.
Allocation concealment (selection bias) Low risk The randomisation code was prepared by an independent randomisation centre and the medication treatment arm was concealed from all participants, central and local site coordinators, physicians, staff, and caregivers.
Blinding (performance bias and detection bias) 
 All outcomes Low risk Person(s) responsible for participants care, participants and outcome assessors were blinded to treatment group allocation.
A medical physicist, who was blinded to the study treatment arm and study status, reviewed all DXA scans. Radiographs were sent to the central methods centre, and read independently by two radiologists who were blinded to the study treatment arm. Differences between radiologists were resolved by consensus.
Incomplete outcome data (attrition bias) 
 All outcomes Low risk All analyses were performed as intention‐to‐treat and included all available data.
Withdrawals were described.
Treatment group: 27 randomised, 4 withdrew (2 non‐compliance, 1 due to adverse event, 1 withdrew consent). 23 completed study.
Control group: 29 randomised, 5 withdrew (2 non‐compliance, 2 due to adverse event, 1 lost to follow‐up). 24 completed study.
Selective reporting (reporting bias) Unclear risk Outcome measures that were described in the methods section were reported in the results section. It was reported that there were no differences in baseline CRP, 25‐hydroxyvitamin D, PTH or CTX levels between the risedronate patients who experienced bone pain and those that did not (but data not shown).
Other bias Low risk None identified.

ALP: alkaline phosphatase
 ALT: alanine aminotransferase
 BMD: bone mineral density
 BMI: body mass index
 CF: cystic fibrosis
 DXA: dual‐energy x‐ray absorptiometry
 FEV1: forced expiratory volume in one second
 IU: international units
 PTH: parathyroid hormone
 SD: standard deviation
 SF‐36v2: Medical Outcomes Study 36‐item short form, version 2
 SXA: single energy x‐ray absorptiometry