Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: High predictive value of the carboxyterminal propeptide of type I procollagen
Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: High predictive value of the carboxyterminal propeptide of type I procollagen
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DOI：
10.1359/jbmr.2003.18.2.237
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发表时间：
2003-02-01
影响因子：
6.2
通讯作者：
Reing, CM
中科院分区：
文献类型：
--
作者：
Marini, JC;Hopkins, E;Reing, CM
极度矮小的身材是严重成骨不全症（III型和IV型）的主要特征。我们对成骨不全症儿童进行了生长激素治疗试验，并跟踪了线性生长速度、骨代谢标志物、组织形态计量学和椎体骨密度。26例III型和IV型成骨不全症儿童，年龄4.5-12岁，采用重组生长激素（rGH）治疗，每天0.1-0.2 IU/kg，每周6天，至少1年。每隔6个月通过DXA评估长度、胰岛素样生长因子（IGF-I）、胰岛素样生长因子结合蛋白（IGFBP-3）、骨代谢标志物和椎体骨密度。在基线和12个月时进行髂嵴活检。在接受治疗的成骨不全儿童中，大约有一半的患者在基线生长速率基础上保持了50%或更多的线性增长。大多数应答者（14人中有10人）患有中度IV型OI。所有参与者的igf - 1、IGFBP-3、骨钙素和骨特异性碱性磷酸酶反应均呈阳性。只有线性生长应答者的椎体DXA z-score显著增加，长骨骨折显著减少。治疗1年后，应答者的髂嵴活检显示松质骨体积、小梁数量和骨形成率显著增加。应答者与无应答者的区别在于基线羧基端前肽（PICP）值较高（p < 0.05），表明应答者本质上具有更高的胶原生成能力。结果表明，生长激素可以导致成骨不全儿童的线性生长速率持续增加，尽管他们的骨基质中胶原蛋白异常。在治疗的第一年，生长应答者的骨形成率和密度增加，骨折率降低。PICP的基线血浆浓度是阳性反应的一个很好的预测指标。
Extreme short stature is a cardinal feature of severe osteogenesis imperfecta (OI), types III and IV. We conducted a treatment trial of growth hormone in children with OI and followed linear growth velocity, bone metabolism markers, histomorphometrics, and vertebral bone density. Twenty-six children with types III and IV OI, ages 4.5-12 years, were treated with recombinant growth hormone (rGH), 0.1-0.2 IU/kg per day for 6 days/week, for at least 1 year. Length, insulin-like growth factor (IGF-I), insulin-like growth factor binding protein (IGFBP-3), bone metabolic markers, and vertebral bone density by DXA were evaluated at 6-month intervals. An iliac crest biopsy was obtained at baseline and 12 months. Approximately one-half of the treated OI children sustained a 50% or more increase in linear growth over their baseline growth rate. Most responders (10 of 14) had moderate type IV OI. All participants had positive IGF-I, IGFBP-3, osteocalcin, and bone-specific alkaline phosphatase responses. Only the linear growth responders had a significant increase in vertebral DXA z-score and a significant decrease in long bone fractures. After 1 year of treatment, responders' iliac crest biopsy showed significant increases in cancellous bone volume, trabecular number, and bone formation rate. Responders were distinguished from nonresponders by higher baseline carboxyterminal propeptide (PICP) values (p < 0.05), suggesting they have in intrinsically higher capacity for collagen production. The results show that growth hormone can cause a sustained increase in the linear growth rate of children with OI, despite the abnormal collagen in their bone matrix. In the first year of treatment, growth responders achieve increased bone formation rate and density, and decreased fracture rates. The baseline plasma concentration of PICP was an excellent predictor of positive response.