Salehpour S, Tavakkoli S
Department of Pediatric Endocrinology and Metabolism, Mofid Children's Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, I.R. Iran.
J Pediatr Endocrinol Metab. 2010 Jan-Feb;23(1-2):73-80. doi: 10.1515/jpem.2010.23.1-2.73.
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.
Intravenous pamidronate was administered to 64 children (from 21 months to 10 years old) with severe OI, 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.
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 turnover 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.
Cyclic pamidronate administration is effective in improving bone mineralization and reducing fracture incidence in childhood osteogenesis imperfecta.
严重成骨不全症（OI）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。直到最近，对于该疾病尚无有效的治疗方法。本研究的主要目的是确定帕米膦酸在改善成骨不全症患者骨矿化和降低骨折发生率方面的疗效和安全性。
对64名年龄在21个月至10岁之间的重度OI儿童静脉注射帕米膦酸，剂量为每日1mg/kg，连续3天，每4个月重复一次，疗程为24 - 48个月。在治疗期间定期评估临床状况、包括骨转换标志物在内的生化特征、腰椎和股骨颈的骨密度以及放射学变化。
骨折数量从每年中位数8次（范围4 - 11次）降至每年0次（范围0 - 4次）（p <0.05）。治疗16个月后，腰椎骨密度（BMD - DEXA）z值从中位数 - 5.90（范围 - 7.01至 - 4.76）显著改善至 - 2.70（范围 - 4.46至 - 1.98）（p <0.001）。血清碱性磷酸酶（ALP）（骨形成标志物）从中位数731.0 U/l（范围438 - 998 U/l）降至183 U/l（范围95 - 286 U/l）（p <0.001），这意味着骨转换和骨吸收显著减少，骨矿化增加。生长速度或身高标准差评分（SDS）没有改善。除五名儿童（这五名儿童使用该药物的时间均少于2.5年）外，所有儿童的活动能力和行走能力均有所改善。所有使用该药物的儿童慢性疼痛和疲劳均得到显著缓解，且无不良反应。
周期性给予帕米膦酸可有效改善儿童成骨不全症的骨矿化并降低骨折发生率。
