Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a
randomized placebo-controlled study.
Author(s): Rauch F, Munns CF, Land C, Cheung M, Glorieux FH.
Affiliation(s): Genetics Unit, Shriners Hospital for Children, Quebec, Canada.
frauch@shriners.mcgill.ca
Publication date & source: 2009, J Bone Miner Res. , 24(7):1282-9
Intravenous pamidronate is the most widely used treatment for moderate to severe
osteogenesis imperfecta (OI). Currently, there is no medical treatment for
patients with mild OI. We conducted a single-center randomized double-blind
placebo-controlled trial to examine the efficacy and safety of oral risedronate
in the treatment of pediatric patients with mild OI. A total of 26 children and
adolescents (age, 6.1-17.7 yr; 11 girls) with OI type I were randomized to either
placebo (N = 13) or risedronate (N = 13) for 2 yr. Risedronate doses were 15 mg
once per week in patients weighing <40 kg and 30 mg once per week in patients
weighing >40 kg. After 2 yr of treatment, risedronate decreased serum levels of
the bone resorption marker collagen type I N-telopeptide by 35% compared with a
6% reduction with placebo (p = 0.003). Risedronate increased lumbar spine areal
BMD Z-scores by 0.65, whereas patients receiving placebo experienced a decrease
of 0.15 (p = 0.002). In contrast, no significant treatment differences in bone
mass and density were found at the radial metaphysis and diaphysis, the hip, and
the total body. Histomorphometric analysis of transiliac bone biopsies at the end
of the study period did not show a significant treatment difference in cortical
width, trabecular bone volume, or parameters of bone turnover. Similarly, there
was no detectable treatment effect on vertebral morphometry, second metacarpal
cortical width, grip force, bone pain, or number of new fractures. Regarding
safety, risedronate was generally well tolerated, and the incidence of clinical
or laboratory adverse experiences was similar among treatment groups. These
results suggest that the skeletal effects of oral risedronate are weaker than
those that are commonly observed with intravenous pamidronate treatment but still
lead to an increase in lumbar spine areal BMD. Future studies should investigate
whether oral risedronate is effective in reducing fracture rates in children and
adolescents with mild OI type I.
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