Cyclic Pamidronate Therapy in Children with Osteogenesis Imperfecta

Background: Severe osteogenesis imperfecta (OI) is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain. There has been no effective therapy for the disorder until recently. The main objective of this study was to determine the efficacy and safety of pamidronate in improving bone mineralization and reducing fracture incidence in osteogenesis imperfecta. Methods: Intravenous pamidronate was administered to 64 children (from 21 months to 10 years old) with severe 01, in a 1 mg/kg single daily dose for 3 sequential days at 4-month intervals, over 24-48 months duration. Clinical status, biochemical characteristics including bone turnover markers, bone mineral density of the lumbar spine and femoral neck, and radiological changes were assessed regularly during treatment. Results: The number of fractures decreased from a median of 8 (range 4-11) to 0 fractures/year (range 0-4) (p <0.05). After 16 months of treatment, there was significant improvement in bone mineral density (BMD-DEXA) z-score of the lumbar spine from a median of -5.90 (range -7.01 to -4.76) to -2.70 (range -4.46 to -1.98) (p <0.001). Serum alkaline phosphatase (ALP) (bone formation marker) decreased from a median of 731.0 U/l (range 438-998 U/l) to 183 U/l (range 95-286 U/l) (p <0.001), implying a significant reduction in bone turn-over and resorption and increase in bone mineralization. There was no improvement in growth velocity or height SDS. Mobility and ambulation improved in all but five children (all five had taken the drug for less than 2.5 years). There was a significant relief of chronic pain and fatigue but no adverse effects in all children using the drug. Conclusion: Cyclic pamidronate administration is effective in improving bone mineralization and reducing fracture incidence in childhood osteogenesis imperfecta.