Pamidronate in children with osteogenesis imperfecta: histomorphometric effects of long-term therapy.

CONTEXT Intravenous pamidronate treatment is beneficial to children and adolescents with osteogenesis imperfecta (OI), but the effects of prolonged therapy are not well characterized. OBJECTIVE The objective of this study was to assess the effect of long-term pamidronate treatment on the bone tissue of children and adolescents with OI. DESIGN This is an observational study on OI patients receiving iv pamidronate for more than 4 yr. SETTING The study was carried out in a pediatric metabolic bone research unit. PATIENTS Patients were 25 moderately to severely affected OI patients (seven girls) aged 1.4-15.3 yr at baseline. INTERVENTION Intervention was cyclical iv pamidronate at a dose of 9 mg/kg.yr. MAIN OUTCOME MEASURES Iliac bone biopsy and lumbar spine bone mineral density measures were obtained at treatment start, after 2.7 +/- 0.5 yr (mean +/- sd), and after 5.5 +/- 0.7 yr of therapy. RESULTS Average areal bone mineral density increased by 72% in the first half of the observation period, but by only 24% in the second half. Mean cortical width and cancellous bone volume increased by 87 and 38%, respectively, between baseline and the first time point during treatment (P < 0.001 for all changes). Thereafter, cortical width did not change significantly, but there was a trend (P = 0.06) toward higher cancellous bone volume. Average bone formation rate on trabecular surfaces decreased by 70% after pamidronate treatment was initiated and showed a trend (P = 0.08) toward a further decline in the second part of the study interval. CONCLUSION The gains that can be achieved with pamidronate treatment appear to be largely realized in the first 2-4 yr.