PEDIATRIC BONE GROWTH, DENSITY, AND METABOLISM

生长减少、畸形、平片上发现的骨量减少，以及频繁的骨质疏松相关骨折，都是许多患有各种医疗和身体状况的儿童骨骼生长和新陈代谢问题的证据。虽然这些很晚的后果在临床上是显而易见的，但在骨骼生长和发育的重要年份，这些问题通常最初是沉默的。职业生涯中期奖是为了支持理查德·亨德森博士的研究计划。他是北卡罗来纳大学整形外科和儿科教授，是一名临床活跃的儿科整形外科医生。亨德森博士还长期致力于临床研究，具有公认的生产力。他的主要研究重点是各种儿科疾病中的骨质疏松症、骨折以及骨生长和代谢问题，如脑瘫、囊性纤维化、牛奶过敏、化疗治疗的恶性肿瘤和肌营养不良症。在他的研究计划的第一阶段，评估骨骼生长、密度和新陈代谢的技术被调整以适应残疾儿童的独特特征。第一阶段还包括几项单点、观察性、横断性和纵向研究，具体目的是评估这些不同条件对未成熟骨骼矿化的潜在影响。这一阶段的研究计划刚刚完成。第二阶段包括旨在更好地描述脑瘫儿童骨骼生长和代谢的项目，并更详细地评估这一人群中骨质疏松症的患病率、原因和结果。这一信息的使用在很大程度上取决于是否有预防和/或治疗替代办法。双膦酸盐是一类用于治疗老年人骨质疏松症的药物，有限的轶事数据表明，这些药物对儿童也有效。研究计划的第二阶段包括评估这些药物在儿科人群中的安全性和有效性的第一次对照临床试验。与其他研究中心的广泛合作为第二阶段的研究带来了更大的统计能力和营养方面的专业知识。第二阶段包括5个相互关联的项目，时间跨度为2-3年，最近于1998年4月开始收集数据。计划在2001-2004年进行的第三阶段将涉及评估双膦酸盐在多种儿科条件下治疗骨质疏松症的更大规模的临床试验。药物治疗在临床实践中的实用性和剂量-反应关系是这一阶段将解决的重要问题。申请职业中期奖是为了支持研究计划的第二和第三阶段。

Diminished growth, deformity, osteopenia noted on plain radiographs, and frequent osteoporosis-related fractures are evidence of problems with bone growth and metabolism in many children with an assortment of medical and physical conditions. Although these very late consequences are clinically apparent, the problems are usually initially silent during the important years of skeletal growth and development. The Midcareer Award is requested to support the Research Plan of Dr. Richard Henderson, MD, PhD. He is Professor of Orthopaedics and Pediatrics at the University of North Carolina, and in this capacity is a clinically active pediatric orthopaedic surgeon. Dr. Henderson also has a long-standing commitment to clinical research, with proven productivity. His primary research focus is on the issues of osteoporosis, fractures, and bone growth and metabolism in various pediatric conditions such as cerebral palsy, cystic fibrosis, milk allergy, chemotherapuetically treated malignancies, and muscular dystrophy. In the first phase of his Research Plan techniques for assessing bone growth, density, and metabolism are adapted to the unique features of handicapped children. The first phase also includes several single-site, observational, cross-sectional and longitudinal studies with the specific aim of assessing the potential impact of these assorted conditions on mineralization of the immature skeleton. This phase of the Research Plan has just been completed. The second phase includes projects designed to better characterize bone growth and metabolism in children with cerebral palsy, and to assess in greater detail the prevalence, causes, and outcomes of osteoporosis in this population. The utility of this information depends in great part on the availability of prevention and/or treatment alternatives. The bisphosphonates are a class of medications used for the treatment of osteoporosis in elderly adults, and limited anecdotal data suggest that these drugs are also effective in children. The second phase of the Research Plan includes the first controlled clinical trial assessing the safety and efficacy of these drugs in a pediatric population. Extensive collaboration with other research centers brings greater statistical power and expertise in nutrition to studies in the second phase. The second phase consists of 5 closely inter-related projects over a 2-3 year time span, and data collection recently began in April 1998. The third phase planned for the years 2001-2004 will involve larger-scale clinical trials assessing bisphosphonates for the treatment of osteoporosis in multiple pediatric conditions. The practicalities of drug treatment in clinical practice and the dose-response relationship are important issues that will be addressed in this phase. The Midcareer Award is requested to support the second and third phases of the Research Plan.