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Cyclic administration of pamidronate in children with severe osteogenesis imperfecta
F H Glorieux1, N J Bishop, H Plotkin
1Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, QC, Canada.
Insights
Pamidronate treatment significantly improved bone density and reduced fractures in children with severe osteogenesis imperfecta. This bisphosphonate therapy also alleviated chronic pain and enhanced mobility in affected children.
Area of Science:
- Pediatric Endocrinology
- Bone Metabolism
- Pharmacology
Background:
- Severe osteogenesis imperfecta (OI) causes osteopenia, fractures, deformity, immobility, and pain.
- Current therapies for severe OI are limited.
- Bisphosphonates are investigated for their effect on bone resorption.
Purpose of the Study:
- To assess the efficacy of pamidronate in treating severe osteogenesis imperfecta in children.
- To evaluate the impact of pamidronate on bone resorption, bone mineral density, and clinical outcomes.
Main Methods:
- An uncontrolled observational study involving 30 children (ages 3-16) with severe OI.
- Intravenous pamidronate administered at 4-6 month intervals for 1.3-5.0 years.
- Regular assessment of clinical status, bone turnover markers, lumbar spine bone mineral density, and radiologic changes.
Main Results:
- Sustained reduction in serum alkaline phosphatase and urinary N-telopeptide.
- Significant annualized increase in bone mineral density (41.9%) and improvement in z-scores.
- Reduced fracture incidence by 1.7 fractures/year (P<0.001), with no effect on fracture healing or growth.
- Improved mobility and ambulation in 16 children; all reported pain and fatigue relief.
Conclusions:
- Cyclic intravenous pamidronate improves clinical outcomes in children with severe OI.
- Pamidronate effectively reduces bone resorption and increases bone density.
- This treatment offers a promising therapeutic option for severe osteogenesis imperfecta.
Background:
Severe osteogenesis imperfecta is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain. There is no effective therapy for the disorder. We assessed the effects of treatment with a bisphosphonate on bone resorption.
Methods:
In an uncontrolled observational study involving 30 children who were 3 to 16 years old and had severe osteogenesis imperfecta, we administered pamidronate intravenously (mean [+/-SD] dose, 6.8+/-1.1 mg per kilogram of body weight per year) at 4-to-6-month intervals for 1.3 to 5.0 years. Clinical status, biochemical characteristics reflecting bone turnover, the bone mineral density of the lumbar spine, and radiologic changes were assessed regularly during treatment.
Results:
Administration of pamidronate resulted in sustained reductions in serum alkaline phosphatase concentrations and in the urinary excretion of calcium and type I collagen N-telopeptide. There was a mean annualized increase of 41.9+/-29.0 percent in bone mineral density, and the deviation of bone mineral density from normal, as indicated by the z score, improved from -5.3+/-1.2 to -3.4+/-1.5. The cortical width of the metacarpals increased by 27+/-20.2 percent per year. The increases in the size of the vertebral bodies suggested that new bone had formed. The mean incidence of radiologically confirmed fractures decreased by 1.7 per year (P<0.001). Treatment with pamidronate did not alter the rate of fracture healing, the growth rate, or the appearance of the growth plates. Mobility and ambulation improved in 16 children and remained unchanged in the other 14. All the children reported substantial relief of chronic pain and fatigue.
Conclusions:
In children with severe osteogenesis imperfecta, cyclic administration of intravenous pamidronate improved clinical outcomes, reduced bone resorption, and increased bone density.