A randomized, controlled dose-ranging study of risedronate in children with
moderate and severe osteogenesis imperfecta.
Author(s): Bishop N, Harrison R, Ahmed F, Shaw N, Eastell R, Campbell M, Knowles E, Hill C,
Hall C, Chapman S, Sprigg A, Rigby A.
Affiliation(s): Academic Unit of Child Health, University of Sheffield, United Kingdon.
n.j.bishop@shef.ac.uk
Publication date & source: 2010, J Bone Miner Res. , 25(1):32-40
Moderate to severe osteogenesis imperfecta is associated with multiple fractures
in childhood. There are no published data regarding the effects of
third-generation bisphosphonates in these children. This randomized study
investigated which of three different doses of risedronate was most effective in
reducing fracture incidence. We randomly assigned 53 children with moderate to
severe osteogenesis imperfecta to receive 0.2, 1, or 2 mg/kg per week of
risedronate. We assessed safety, fracture incidence, and bone measurement
outcomes at 3, 6, 12, 18, and 24 months. At 24 months, 69% of children assigned
0.2 mg/kg per week had had new fractures compared with 44% receiving 1 mg/kg per
week and 75% receiving 2 mg/kg per week. Poisson regression with age and prior
fracture as covariates showed that there was no difference in incident
nonvertebral fracture between groups. Fracture rate diminished in each group
during the trial compared with previous the 2 years (p = .005). Lumbar spine bone
mineral density increased significantly (p = .009) only in the 2 mg/kg per week
group. Long bone bowing deformities reduced more in children receiving 1 or 2
mg/kg per week of risedronate [odds ratio (OR) 0.67, 95% confidence interval (CI)
0.48-0.93 per unit increase in risedronate dose, p = .015]. There were no serious
adverse events. Bone mass increased and bowing deformities reduced with
increasing risedronate dose. Children suffered fewer fractures irrespective of
risedronate dose. The most appropriate dose of risedronate for children with
moderate to severe osteogenesis imperfecta in this study was 2 mg/kg per week.
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