Bone Deficits and Mechanical Loading in Ambulatory Cerebral Palsy

脑性瘫痪（CP）是最常见的运动障碍起源于儿童，往往导致 减少体力活动、低骨量和增加骨折风险。虽然患有严重CP的儿童 已知有大量的骨缺损和大大增加的骨折风险，对潜在的骨 构成大多数CP人群的非卧床CP患者的缺陷。轻度或 中度CP可能比重度CP有更小的骨缺损，但也有更大的负荷 由于活动水平较高。即使是适度的骨质缺陷也是令人担忧的，因为低骨量可以 导致日后患骨质疏松症和脆性骨折风险增加。随着CP患者寿命的延长， 易患与衰老相关的合并症，如早期骨质疏松症。 本研究的目的是确定骨缺损的程度及其与骨骼发育的关系。 非卧床儿童和CP成人的负荷。具体目标是：1）量化骨缺损， 非卧床儿童和成人CP（目的1A），并将这些缺陷与动态骨骼负荷（目的1B）， 2)确定在动态CP中骨缺损随年龄增加或减少的程度， 纵向超过2年（目标2A）和横截面跨越寿命（目标2B），和3）确定 与较高骨最密切相关的载荷特征（载荷大小与循环次数） 属性，以指导物理干预的未来发展，以最大限度地增加和维持骨。 我们假设CP（GMFCS I-II）独立行走个体具有骨骼负荷， 骨特性接近正常，而使用辅助设备行走的人（GMFCS III） 负荷和低于正常的骨量，密度和横截面积（CSA）。我们进一步假设 随着年龄的增长，随着行走活动的减少，骨骼缺陷增加， 与骨骼载荷的大小有关的载荷循环次数。 为了实现我们的目标，148名患有CP（GMFCS I-III）的非卧床儿童和成人将接受体格检查。 检查，功能和饮食评估，活动监测，步态分析，肌肉骨骼建模， 腰椎和股骨远端外侧的双能X线吸收测定法（DXA）成像，以及定量 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 DXA和QCT的质量、密度和CSA Z评分将是主要结局指标。幅度 以及从步态分析、肌肉骨骼建模和活动导出的骨骼负荷的重复 监测将是骨结局指标的主要预测因素，其他患者特征 被视为协变量。结果将用于确定哪些非卧床CP患者 最有可能发生骨质疏松症的人群，确定干预的关键时期，并指导未来的 干预措施旨在最大限度地增加这一脆弱人群的骨蓄积和维持。

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.