Pamidronate in children and adolescents with osteogenesis imperfecta: Effect of treatment discontinuation
Pamidronate in children and adolescents with osteogenesis imperfecta: Effect of treatment discontinuation
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DOI：
10.1210/jc.2005-2413
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发表时间：
2006-04-01
影响因子：
5.8
通讯作者：
Glorieux, FH
中科院分区：
文献类型：
--
作者：
Rauch, F;Munns, C;Glorieux, FH
背景：周期性静脉注射帕米膦酸是一种广泛使用的成骨不全症 (OI) 对症治疗方法。停止治疗后发生的情况尚不清楚。目的：本研究的目的是评估中度至重度 OI 型 I、III 和 IV 型儿科患者停用帕米膦酸钠的效果。设计：这是一项针对接受帕米膦酸钠超过 3 年的患者进行的开放标签对照和观察性研究。背景：本研究在儿科代谢骨研究单位进行。患者：在对照研究中，12 对患者的年龄、OI 相匹配帕米膦酸钠治疗的严重程度和持续时间。每对中的一名患者停用帕米膦酸钠；另一人继续接受治疗。在观察性研究中，对 38 名成骨不全患者进行了检查（平均年龄 13.8 岁）。干预：干预措施是停止帕米膦酸钠治疗 2 年。主要结果指标：主要结果指标是腰椎骨矿物质含量和面积骨矿物质密度（aBMD）、骨代谢生化标志物、骨折发生率和临床评估。结果：在对照研究中，停止治疗后骨吸收活性较高。两组的骨矿物质含量均持续增加。未经治疗组的 aBMD z 分数下降，但在继续治疗组中增加。各组之间的骨折率和功能状态相似。在观察性研究中，治疗停止后骨吸收活性有所增加，但仍显着低于未经治疗的成骨不全患者。骨矿物质含量和 aBMD 持续增加，而 aBMD z 得分下降。继续生长的患者的变化更快。结论：停药 2 年后骨代谢仍然受到抑制。治疗停止后骨量继续增加，但腰椎 aBMD 的增加少于健康受试者。这些影响的大小取决于增长。
Context: Cyclical iv pamidronate is a widely used symptomatic therapy of osteogenesis imperfecta (OI). What happens after treatment discontinuation is unknown.Objective: The objective of this study was to assess the effect of pamidronate discontinuation in pediatric patients with moderate to severe OI types I, III, and IV.Design: This was an open-label controlled and observational study in patients who had received pamidronate for more than 3 yr.Setting: This study was performed at a pediatric metabolic bone research unit.Patients: In the controlled study, 12 pairs of patients were matched for age, OI severity, and duration of pamidronate treatment. Pamidronate was stopped in one patient of each pair; the other continued to receive treatment. In the observational study, 38 OI patients were examined (mean age, 13.8 yr).Intervention: The intervention was discontinuation of pamidronate treatment for 2 yr.Main Outcome Measures: The main outcome measures were lumbar spine bone mineral content and areal bone mineral density (aBMD), biochemical markers of bone metabolism, fracture incidence, and clinical evaluation.Results: In the controlled study, bone resorption activity was higher after treatment discontinuation. Bone mineral content continued to increase in both groups. aBMD z-scores decreased in the untreated group, but increased in the continuation cohort. Fracture rates and functional status were similar between groups. In the observational study, bone resorption activity increased after treatment discontinuation, but remained significantly lower than in untreated OI patients. Bone mineral content and aBMD continued to increase, whereas aBMD z-scores decreased. Changes were faster in patients who continued growing.Conclusions: Bone metabolism is still suppressed 2 yr after pamidronate discontinuation. Bone mass gains continue after treatment is stopped, but lumbar spine aBMD increases less than in healthy subjects. The size of these effects is growth dependent.