Bone Deficits and Mechanical Loading in Ambulatory Cerebral Palsy

脑性瘫痪(CP)是最常见的起源于儿童的运动障碍，通常导致 体力活动减少，骨量减少，骨折风险增加。而患有严重脑瘫的儿童 已知存在严重的骨骼缺陷和极大的骨折风险，对潜在的骨骼知之甚少。 脑瘫患者中占大多数的脑瘫患者存在缺陷。患有轻度或以下症状的人 中度CP可能比重度CP有更小的骨缺损，但也有更大的负荷 由于较高的活动水平而导致的暴露。即使是轻微的骨缺陷也令人担忧，因为低骨量可能 导致更大的骨质疏松症和脆性骨折的风险在晚年。由于患有脑瘫的人寿命更长，他们 容易患上与衰老有关的并发症，如早期骨质疏松症。 这项研究的目的是确定骨缺陷的程度及其与骨骼的关系 对患有脑瘫的儿童和成人进行门诊治疗。具体目标是：1)量化骨缺陷 并将这些缺陷与动态骨骼负荷有关(目标1B)， 2)确定非卧床CP患者的骨缺陷随年龄增加或减少的程度 纵向超过2年(目标2A)和横截面(目标2B)，以及3)确定 载荷特征(载荷大小与循环次数)与较高的骨骼关系最密切 指导未来物理干预措施的发展，以最大限度地增加和维护骨骼。 我们假设独立行走的CP患者(GMFCS I-II)具有骨骼负荷和 骨骼性能接近正常，而使用辅助设备行走的人(GMFCS III)有所下降 负荷量和低于正常骨量、密度和截面积(CSA)。我们进一步假设 随着年龄的增长，骨骼缺陷会随着年龄的增长而增加，因为步行活动减少，骨骼特性会更强 与骨骼载荷的大小有关，而不是载荷循环的次数。 为了达到我们的目标，148名患有脑瘫(GMFCS I-III)的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射线骨密度仪(DXA)成像，并定量 在基线、1年和2年对腰椎和胫骨进行计算机断层扫描(QCT)成像。骨 DXA和QCT的质量、密度和CsA Z评分将是主要的结果衡量标准。震级 以及从步态分析、肌肉骨骼建模和活动中得出的骨骼负荷的重复 监测将是骨骼结果测量的主要预测因素，并与其他患者特征一起 被认为是协变量。结果将被用来确定哪些患有脑瘫的门诊患者 最有可能发生骨质疏松症的风险，确定干预的关键时期，并指导未来的设计 旨在最大限度地增加这一脆弱人群的骨骼积累和维持的干预措施。

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.