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.
