Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age

Severe osteogenesis imperfecta (OI) is a hereditary disorder characterized by increased bone fragility and progressive bone deformity. Cyclical pamidr onate infusions improve clinical outcome in children older than 3 yr of age with severe OI. Because earlier treatment may have potential to prevent de formities and improve functional prognosis in young children, we studied ni ne severely affected OI patients under 2 yr of age (2.3-20.7 months at entr y) for a period of 12 months. Pamidronate was administered iv in cycles of 3 consecutive days. Patients received four to eight cycles during the treat ment period, with cumulative doses averaging 12.4 mg/kg. Clinical changes w ere evaluated regularly during treatment, and radiological changes were ass essed after 6-12 months of treatment. The control group consisted of six ag e-matched, severely affected OI patients, who had not received pamidronate treatment. During treatment bone mineral density (BMD) increased between 86 -227%. The deviation from normal, as indicated by the z-score, diminished f rom -6.5 +/- 2.1 to -3.0 +/- 2.1 (P < 0.001). In the control group the BMD z-score worsened significantly. Vertebral coronal area increased in all tre ated patients (11.4 +/- 3.4 to 14.9 +/- 1.8 cm(2); P < 0.001), but decrease d in the untreated group (P < 0.05). In the treated patients, fracture rate was lower than in control patients (2.6 +/- 2.5 vs. 6.3 +/- 1.6 fractures/ year; P < 0.01). No adverse side-effects were noted, apart from the well kn own acute phase reaction during the first infusion cycle. Pamidronate treat ment in severely affected OI patients under 3 yr of age is safe, increases BMD, and decreases fracture rate.