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

Objective: To assess the effect of pamidronate discontinuation in pediatric patients with moderate to severe OI types I, III and IV.

Design: An open-label controlled and an observational study in patients who had received pamidronate for >3 yr.

Setting: A pediatric metabolic bone research unit.

Patients: Controlled study: 12 pairs of patients, 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. Observational study: 38 OI patients (mean age 13.8 yr).

Intervention: Discontinuation of pamidronate treatment for two years.

Main Outcome Measures: Lumbar spine bone mineral content and areal bone mineral density (aBMD), biochemical markers of bone metabolism, fracture incidence, clinical evaluation.

Results: 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. 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 two years 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.