Sakkers 2004.

Methods	Single centre, double‐blinded, placebo‐controlled RCT. Parallel trial.
Participants	34 children (16 male) were randomised. Age range: 3 ‐ 18 years. OI types I, III and IV.
Interventions	Oral olpadronate versus placebo. Dosage: 10 mg/m2 daily. Trial period: 24 months.
Outcomes	Fractures, spinal BMC, spinal BMD, calcaneal BMC, calcaneal BMD, muscle strength, self care, mobility, height (body and seated), arm span, head circumference, body weight, heights of each lumbar vertebral body, urinary analysis, blood samples (but only 9 from each group). Adverse effects reported. BMC and BMD of the lumbar spine (L1 – L4) and of the os calcis were measured before randomisation, after 1 year, and at the end of the trial. Domains of functional outcome were measured at the beginning of the trial and every 6 months, and anthropometric and radiographic variables were measured every 12 months. All laboratory assessments were done at baseline and at 3 months, 12 months, and 24 months.
Notes	Allocation of intervention by computer‐generated randomisation.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation.
Allocation concealment (selection bias)	Low risk	Researchers were not aware of treatment allocation. Generation of the randomisation sequence was done independently of the researchers by an outside group. For each participant the Julius Centre was contacted by telephone for treatment allocation.
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blinded (outcome assessors blind).
Incomplete outcome data (attrition bias) All outcomes	Low risk	An intention‐to‐treat analysis was undertaken. 2 participants (1 placebo and 1 treatment) withdrew from the trial but were accounted for in the final analysis. Consort diagram presented.
Selective reporting (reporting bias)	High risk	Reported no significant change in biochemical markers of bone and mineral metabolism and narratively reported no differences in seated height or radiographic assessments of lumbar vertebral height between olpadronate and placebo at 24 months follow up.
Other bias	Low risk	None.