Bone Deficits and Mechanical Loading in Ambulatory Cerebral Palsy

动态脑瘫的骨缺损和机械负荷

基本信息

批准号：
9768507
负责人：
TISHYA A L WREN
金额：
$ 47.79万
依托单位：
CHILDREN'S HOSPITAL OF LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-22 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9768507
关键词：
Adult Affect Age Aging Area Cerebral Palsy Characteristics Child Childhood Comorbidity Development Diet Dietary Assessment Distal Dual-Energy X-Ray Absorptiometry Femur Fracture Future Goals Hip region structure Image Impairment Individual Intervention Lateral Lead Life Live Birth Longevity Longitudinal Studies Maintenance Measurement Measures Medical Modeling Monitor Motor Movement Musculoskeletal Osteoporosis Outcome Measure Patients Pattern Persons Physical Examination Physical activity Population Property Research Risk Self-Help Devices Structure Vertebral column Vulnerable Populations Walking X-Ray Computed Tomography age group bone bone mass bone strength critical period density design disability falls fracture risk fragility fracture gait examination mechanical load peer prevent primary outcome response sex skeletal therapy design tibia trauma exposure young adult

项目摘要

Cerebral palsy (CP) is the most common motor disability originating in childhood, often resulting in reduced physical activity, low bone mass, and increased fracture risk. While children with severe CP are known to have substantial bone deficits and greatly increased fracture risk, little is known about potential bone deficits in ambulatory individuals with CP who comprise the majority of the CP population. Persons with mild or moderate CP may have smaller bone deficits than those with severe CP, but also have greater loading exposure due to higher activity levels. Even modest bone deficits are concerning because low bone mass can lead to greater risk of osteoporosis and fragility fractures later in life. As individuals with CP live longer, they are susceptible to developing comorbidities associated with aging such as early osteoporosis. The goal of this study is to determine the extent of bone deficits and their relationship to skeletal loading in ambulatory children and adults with CP. The specific aims are: 1) quantify bone deficits in ambulatory children and adults with CP (Aim 1A) and relate these deficits to dynamic skeletal loading (Aim 1B), 2) determine the extent to which bone deficits increase or decrease with age in ambulatory CP both longitudinally over 2 years (Aim 2A) and cross-sectionally across the lifespan (Aim 2B), and 3) identify the loading characteristics (loading magnitude vs. number of cycles) most closely associated with higher bone properties to guide future development of physical interventions to maximize bone accrual and maintenance. We hypothesize that independently ambulatory individuals with CP (GMFCS I-II) have skeletal loading and bone properties close to normal, while individuals who walk with assistive devices (GMFCS III) have decreased loading and lower than normal bone mass, density, and cross-sectional area (CSA). We further hypothesize that bone deficits increase with age as walking activity decreases and that bone properties are more strongly related to the magnitude of skeletal loading than the number of loading cycles. To achieve our aims, 148 ambulatory children and adults with CP (GMFCS I-III) will undergo physical examination, functional and dietary assessment, activity monitoring, gait analysis, musculoskeletal modeling, dual-energy x-ray absorptiometry (DXA) imaging of the lumbar spine and lateral distal femur, and quantitative computed tomography (QCT) imaging of the lumbar spine and tibia at baseline, 1 year, and 2 years. Bone mass, density, and CSA Z-scores from the DXA and QCT will be the primary outcome measures. Magnitude and repetitions of skeletal loading derived from the gait analysis, musculoskeletal modeling, and activity monitoring will be the primary predictors of the bone outcome measures, with other patient characteristics being considered as covariates. The results will be used to determine which ambulatory individuals with CP are most at risk for developing osteoporosis, identify critical periods for intervention, and guide the future design of interventions aimed at maximizing bone accrual and maintenance in this vulnerable population.

脑瘫（CP）是童年时期最常见的运动障碍，通常导致体育锻炼降低，骨骼质量低以及骨折风险增加。而严重CP的儿童是已知有大量的骨缺损，骨折风险大大增加，对潜在的骨骼知之甚少占CP大多数CP人群的门诊个人的缺陷。温和或中度CP可能比严重CP的骨缺损较小，但负载也更大由于较高的活动水平而导致的暴露。甚至适度的骨骼缺陷也令人担忧，因为低骨头可以导致骨质疏松症和脆弱性骨折的风险更大。随着CP的个人寿命更长，他们容易受到与衰老相关的合并症，例如早期骨质疏松症。这项研究的目的是确定骨缺损的程度及其与骨骼的关系在患有CP的门诊儿童和成人中加载。具体目的是：1）量化骨骼缺陷具有CP的门诊儿童和成人（AIM 1A），并将这些缺陷与动态骨骼负荷联系起来（AIM 1B）， 2）确定骨骼缺陷在卧床CP中随着年龄的增长而增加或减少的程度在整个寿命（AIM 2B）上纵向2年（AIM 2A）和横截面（AIM 2B），3）确定加载特性（加载幅度与循环数）与较高的骨骼密切相关指导未来的物理干预措施发展的特性，以最大化骨骼应计和维护。我们假设具有CP（GMFCS I-II）的独立门诊个人具有骨骼载荷和接近正常的骨骼特性，而使用辅助设备（GMFCS III）行走的人减少了负载和低于正常骨骼，密度和横截面区域（CSA）。我们进一步假设随着步行活动的降低，骨骼缺陷随着年龄的增长而增加，骨骼特性更强与骨骼载荷的大小相比，与负载周期的数量相关。为了实现我们的目标，有148名具有CP（GMFCS I-III）的门诊儿童和成人将经历身体检查，功能和饮食评估，活动监测，步态分析，肌肉骨骼建模，双能X射线吸收法（DXA）成像的腰椎和远端股骨和定量基线1年和2年时，腰椎和胫骨的计算机断层扫描（QCT）成像。骨来自DXA和QCT的质量，密度和CSA Z得分将是主要结果指标。震级从步态分析，肌肉骨骼建模和活动中得出的骨骼负荷的重复监测将是骨结局指标的主要预测指标，并具有其他患者特征被视为协变量。结果将用于确定哪些具有CP的门诊个人大多数人有发展骨质疏松症的风险，确定干预的关键时期，并指导未来的设计干预措施旨在最大程度地提高这种脆弱人群中的骨骼和维护。