Treatment of Osteopenia in Children with Cerebral Palsy

描述（由申请人提供）： 骨质减少导致骨折，创伤小，是一个常见的问题，在许多儿科疾病，如成骨不全，青少年特发性骨质疏松症，肌营养不良症，脊髓发育不良（脊柱裂）。作为北美脑性瘫痪项目（NAGCePP）的一部分，我们广泛研究了一组这样的儿童，即脑性瘫痪（CP）儿童，以更好地确定这种情况下骨质减少的患病率，原因和后果。 双膦酸盐是一组用于治疗老年人骨质疏松症的药物。有关于这些药物用于各种儿科疾病的已发表报告，但除了极少数例外，这些都是轶事，不受控制的病例报告，涉及最多几个儿童。我们最近完成了一项小型安慰剂对照的初步试验，以评估静脉注射双膦酸盐治疗重度CP儿童低骨密度的安全性和有效性。在18个月研究期结束时，股骨远端的骨密度增加了89% ± 21%（平均值± SE），而对照组为9% ± 6%。未发现具有临床意义的不良反应。 初步试验提出了许多关于给药（频率、持续时间、数量、给药途径）、治疗适应症、长期风险和获益（包括对骨折率的影响）的问题。 初步试验的结果为更大规模的未来临床试验提供了理由，以回答这些问题。本申请的目的是支持临床试验规划项目，这是成功实施和完成未来临床试验的关键流程。 临床试验规划项目将侧重于在试点试验和现有NAGCeP合作的几个领域进行建设。主题：为更多受试者制定额外的招募策略，并根据骨折风险数据分析进一步完善入选标准。干预：选择更实用的替代药物和给药方案。成果：进一步评估DXA技术并使其适用于患有挛缩、脊柱侧凸、金属植入物、不随意肌痉挛、发育迟缓和其他具有独特挑战性特征的人群。 协作资源和基础设施：调整和扩展我们现有的NAGCePP网络（例如数据库、安全性监测），以纳入未来临床试验。

DESCRIPTION (provided by applicant): Osteopenia resulting in fractures with minimal trauma is a common problem in many pediatric conditions such as osteogenesis imperfecta, juvenile idiopathic osteoporosis, muscular dystrophy, and myelodysplasia (spina bifida). As part of the North American Growth in Cerebral Palsy Project (NAGCePP) we have extensively studied one such group of children, those with cerebral palsy (CP), to better define the prevalence, causes, and consequences of osteopenia in this condition. Bisphosphonates are a group of medications utilized to treat osteoporosis in elderly adults. There are published reports of these agents used in assorted pediatric conditions, but with rare exception these are anecdotal, uncontrolled case reports involving at most a few children. We have recently completed a small placebo-controlled Pilot Trial to assess the safety and efficacy of intravenous bisphosphonates to treat low bone density in children with severe CP. At the conclusion of the 18-month study period bone density in the distal femur had increased 89% + 21% (mean + SE) compared to 9% + 6% in controls. No clinically significant adverse effects were identified. The Pilot Trial raises many questions with regards to dosing (frequency, duration, amount, route of administration), indications for treatment, long-term risks and benefits including the effect on fracture rate. The results of the Pilot Trial provide the justification for a larger scale Future Clinical Trial to answer these many questions. The purpose of this application is to support the Clinical Trial Planning Project, a process critical to the successful implementation and completion of the Future Clinical Trial. The Clinical Trial Planning Project will focus on building from both the Pilot Trial and the existing NAGCeP collaboration in several areas. Subjects: Develop additional recruiting strategies for larger numbers of subjects and further refine criteria for inclusion based on analysis of fracture risk data. Intervention: Select alternative drugs and dosing regimens that are more practical. Outcomes: Further evaluate and adapt DXA technology to this population with contractures, scoliosis, metallic implants, involuntary muscle spasms, retardation, and other characteristics that present unique challenges. Collaborative Resources & Infrastructure: Adapt and expand our existing NAGCePP network (eg database, safety monitoring) to incorporate the Future Clinical Trial.