Glorieux F H, Bishop N J, Plotkin H, Chabot G, Lanoue G, Travers R
Shriners Hospital for Children, Department of Surgery, McGill University, Montreal, QC, Canada.
N Engl J Med. 1998 Oct 1;339(14):947-52. doi: 10.1056/NEJM199810013391402.
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.
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.
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.
In children with severe osteogenesis imperfecta, cyclic administration of intravenous pamidronate improved clinical outcomes, reduced bone resorption, and increased bone density.
严重成骨不全症是一种以骨质减少、频繁骨折、进行性畸形、活动能力丧失和慢性骨痛为特征的疾病。目前尚无针对该疾病的有效治疗方法。我们评估了双膦酸盐治疗对骨吸收的影响。
在一项非对照观察性研究中，纳入了30名3至16岁患有严重成骨不全症的儿童，我们以4至6个月的间隔静脉注射帕米膦酸盐（平均[±标准差]剂量为每年每公斤体重6.8±1.1毫克），持续1.3至5.0年。在治疗期间定期评估临床状况、反映骨转换的生化特征、腰椎骨密度和放射学变化。
帕米膦酸盐的给药导致血清碱性磷酸酶浓度以及钙和I型胶原N-端肽的尿排泄持续降低。骨密度平均每年增加41.9±29.0%，并且根据z评分所示，骨密度与正常的偏差从-5.3±1.2改善至-3.4±1.5。掌骨皮质宽度每年增加27±20.2%。椎体大小的增加表明有新骨形成。经放射学证实的骨折平均发生率每年降低1.7次（P<0.001）。帕米膦酸盐治疗未改变骨折愈合率、生长速度或生长板外观。16名儿童的活动能力和行走能力得到改善，另外14名儿童保持不变。所有儿童均报告慢性疼痛和疲劳得到显著缓解。
在患有严重成骨不全症的儿童中，静脉注射帕米膦酸盐的周期性给药改善了临床结局，减少了骨吸收，并增加了骨密度。
