Pamidronate in Children and Adolescents with Osteogenesis Imperfecta: Effect of Treatment Discontinuation

Context: Cyclical iv pamidronate is a widely used symptomatic therapy of osteogenesis imperfecta (OI). What happens after treatment discontinuation is unknown.

Objective: The objective of this study was to assess the effect of pamidronate discontinuation in pediatric patients with moderate to severe OI types I, III, and IV.

Design: This was an open-label controlled and observational study in patients who had received pamidronate for more than 3 yr.

Setting: This study was performed at a pediatric metabolic bone research unit.

Patients: In the controlled study, 12 pairs of patients were matched for age, OI severity, and duration of pamidronate treatment. Pamidronate was stopped in one patient of each pair; the other continued to receive treatment. In the observational study, 38 OI patients were examined (mean age, 13.8 yr).

Intervention: The intervention was discontinuation of pamidronate treatment for 2 yr.

Main Outcome Measures: The main outcome measures were lumbar spine bone mineral content and areal bone mineral density (aBMD), biochemical markers of bone metabolism, fracture incidence, and clinical evaluation.

Results: In the controlled study, bone resorption activity was higher after treatment discontinuation. Bone mineral content continued to increase in both groups. aBMD z-scores decreased in the untreated group, but increased in the continuation cohort. Fracture rates and functional status were similar between groups. In the observational study, bone resorption activity increased after treatment discontinuation, but remained significantly lower than in untreated OI patients. Bone mineral content and aBMD continued to increase, whereas aBMD z-scores decreased. Changes were faster in patients who continued growing.

Conclusions: Bone metabolism is still suppressed 2 yr after pamidronate discontinuation. Bone mass gains continue after treatment is stopped, but lumbar spine aBMD increases less than in healthy subjects. The size of these effects is growth dependent.