Bone Deficits and Mechanical Loading in Ambulatory Cerebral Palsy

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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.