GLUCOCORTICOID-INDUCED OSTEOPENIA IN CHILDREN

糖皮质激素引起的儿童骨质减少

• 批准号: 6364842
• 负责人: Mary Beth Leonard
• 金额: $ 33.7万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6364842
• 关键词: Crohn's disease; adolescence (12-20); blood chemistry; body composition; bone density; bone development; child physical development; clinical research; computed axial tomography; drug adverse effect; glucocorticoids; hormone therapy; human subject; human therapy evaluation; iatrogenic disease; longitudinal human study; middle childhood (6-11); muscle strength; nephrotic syndrome; normal ossification; osteopenia; pathologic bone resorption; pediatric pharmacology; photon absorptiometry; questionnaires; trabecular meshwork; Crohn's disease; adolescence (12-20); blood chemistry; body composition; bone density; bone development; child physical development; clinical research; computed axial tomography; drug adverse effect; glucocorticoids; hormone therapy; human subject; human therapy evaluation; iatrogenic disease; longitudinal human study; middle childhood (6-11); muscle strength; nephrotic syndrome; normal ossification; osteopenia; pathologic bone resorption; pediatric pharmacology; photon absorptiometry; questionnaires; trabecular meshwork

DESCRIPTION (provided by applicant): Skeletal development is normally characterized by marked expansion of cortical dimensions and increases in trabecular density during childhood and adolescence. Glucocorticoids (GC) are widely used for many pediatric disorders; however, GC suppresses osteoblast function and bone formation. GC-induced osteopenia may be exacerbated by the effects of the underlying disease, such as delayed growth and maturation, malnutrition, vitamin D deficiency and increased bone resorption by inflammatory cytokines. The combined effects of decreased bone formation and increased bone resorption may be particularly detrimental to the growing skeleton. The hypotheses of this study are: (a) GC therapy during growth results in impaired bone mineral accretion with decreased trabecular and cortical density, decreased cortical dimensions, and decreased bone strength; and (b) the inflammatory, nutritional and growth-related effects of the underlying disease contribute to abnormal bone mineral accretion during growth. Childhood nephrotic syndrome (NS) usually responds to GC and remains in remission as long as high-dose GC therapy is continued. In contrast, Crohn's disease (CD) is treated with GC, but is independently associated with poor growth and maturation, nutritional deficiencies and inflammation. Concurrent examination of the skeletal effects and disease characteristics of these two disorders will allow us to distinguish between GC- and disease-related effects. Unlike traditional densitometric measures of bone mass, peripheral quantitative computed tomography (pQCT) permits the discrete assessment of trabecular and cortical bone density and dimensions, and bone strength can be reliably estimated. The objective of this prospective cohort study is to use pQCT: (a) to identify determinants of trabecular and cortical bone development (density, dimensions and strength) among incident NS and CD patients prior to initiation of GC therapy; and (b) to determine the relationship between bone mineral accretion velocity (increases in density, dimensions and strength) and the pattern of GC exposure over a 12-month interval among 150 NS and 200 CD patients, adjusting for other growth- and disease-related determinants of bone mineralization. In healthy children, bone mass is highly correlated with growth and maturation; therefore, to understand the extent of bone deficits in children with NS and CD, these analyses will require a contemporary control group of similar age, gender, and ethnicity. The CHOP Normative Data Project (NDP) is an on-going initiative to collect cross-sectional measures of bone mineralization in healthy children. Our protocol will recruit 300 NDP participants to return for 6- and 12-month follow-up visits. The protocol will also examine levels of inflammatory cytokines and biomarkers of bone formation and resorption as predictors of bone mineral accretion during growth in NS and CD. Finally, the study will compare pQCT and DXA measures of bone mineral accretion in order to assess the utility of routine DXA in the assessment of GC effects in children. The accurate characterization of GC and disease effects on skeletal development is necessary to identify and evaluate targeted therapies to optimize skeletal architecture and peak bone mass in childhood.

描述（申请人提供）：骨骼发育通常是 以明显的皮质尺寸扩展和增加的特征 童年和青春期的小梁密度。糖皮质激素（GC）为 广泛用于许多儿科疾病；但是，GC抑制成骨细胞 功能和骨形成。 GC引起的骨质减少症可能会因 潜在疾病的影响，例如延迟生长和成熟， 营养不良，维生素D缺乏症和骨吸收增加 炎症细胞因子。减少骨形成和 骨吸收增加可能对增长尤其有害 骨骼。这项研究的假设是：（a）生长期间的GC治疗 导致骨矿物矿物积聚受损，小梁和 皮质密度，皮质尺寸降低和骨强度降低； （b）炎症，营养和生长有关的影响 潜在的疾病在生长过程中有助于异常的骨矿物质积聚。 儿童期肾病综合征（NS）通常对GC做出反应，并且仍在 只要继续进行大剂量GC治疗，可以缓解。相比之下，克罗恩（Crohn's） 疾病（CD）用GC处理，但与较差有关 生长和成熟，营养缺乏和炎症。并发 检查这两个的骨骼作用和疾病特征 疾病将使我们能够区分与GC和疾病相关的作用。 与传统的骨量密度测量值不同，外围定量 计算机断层扫描（PQCT）允许对小梁和 皮质骨密度和尺寸以及骨强度可以可靠 估计的。这项前瞻性队列研究的目的是使用PQCT：（a） 确定小梁和皮质骨发育的决定因素（密度， 启动之前，事件NS和CD患者之间的尺寸和强度） GC治疗； （b）确定骨矿物之间的关系 积聚速度（增加密度，尺寸和强度），并且 在150 ns和200 CD之间的12个月间隔内的GC暴露模式 患者调整骨骼的其他生长和疾病的决定因素 矿化。在健康的儿童中，骨骼与生长高度相关 和成熟；因此，了解骨骼缺陷的程度 NS和CD的儿童，这些分析将需要当代控制 年龄，性别和种族的一组。切碎规范数据项目 （NDP）是一项持续的倡议，用于收集骨骼的横断面测量 健康儿童的矿化。我们的协议将招募300 NDP 参与者返回6个月和12个月的随访。该协议将 还检查炎症细胞因子和骨形成的生物标志物的水平 并吸收作为NS生长期间骨矿物积聚的预测因子 光盘。最后，该研究将比较骨矿物质的PQCT和DXA测量 积聚以评估常规DXA在评估GC中的效用 对儿童的影响。 GC的准确表征和疾病对 骨骼发育对于识别和评估靶向疗法是必要的 优化童年时期的骨骼结构和峰值骨量。