The type IA osteogenesis imperfecta (OI) phenotype is characterized by multiple fractures, blue sclerae, and minimal skeletal deformity without dentinogenesis imperfecta. The object of this study was to determine the effect of treatment with intravenous pamidronate (30 mg) every 3 months on bone density and bone histomorphometry in adults with type IA OI. After an initial iliac crest bone biopsy eight subjects, 5 women and 3 men, entered a treatment program lasting 21-30 months. Five subjects, all women, completed the study which included a posttreatment iliac crest bone biopsy. Pamidronate treatment led to significant increases in bone mineral density (BMD), measured by DXA, in the lumbar spine at 12 months (P = 0.05) and in the femur neck (P = 0.02) at 24 months. Significant increases in BMD were also seen in femoral trochanter at 12 months (P = 0.05) and at 24 months (P = 0.02), and in Ward's triangle at 12 months (P = 0.02) and 24 months (P = 0.05). Mean osteocalcin levels decreased 32%, C-terminal procollagen peptide and bone alkaline phosphatase declined 12% and 47% at 15 and 21 months, respectively. Deoxypyridinoline crosslink excretion decreased 31%. Posttreatment bone biopsy revealed a significant 6.3% increase in mean bone trabecular volume (P = 0.01). Mean cortical thickness increased from 848 mm to 1384 mm (P = 0.01) and cortical porosity decreased 13.2% (P = 0.01). Bone formation rate increased significantly in all 5 patients from 6.6 to 15.3 mm2/yr (P = 0.01). Mineral apposition rate was unchanged. These results indicate that intravenous pamidronate, 30 mg every 3 months, may have significant effects on bone density and histomorphometry in adults with type IA OI. Responses at higher doses remain to be evaluated.