A pediatric animal model to evaluate the effects of disuse on musculoskeletal growth and development

Abstract

Prolonged immobilization in hospitalized children can lead to fragility fractures and muscle contractures and atrophy. The purpose of this study was to develop a lower-extremity disuse rabbit model with musculoskeletal changes similar to those observed in children subjected to prolonged immobilization. Six-week-old rabbits were randomly assigned to control (CTRL, n=4) or bilateral sciatic and femoral neurectomy (bSFN, n=4) groups. Trans-axial helical CT scans of each rabbit׳s hind limbs were acquired after eight weeks. The rabbits were then euthanized and the tibiae and calcanea were harvested from each rabbit. μCT imaging was performed on the tibiae and calcanea mid-diaphysis. Four-point bending, gas pycnometry, and ashing were then performed on each tibia. All comparisons reflect the differences between the bSFN and CTRL rabbits. Significant decreases in tibiae bone mineral density (≥9.41%, p≤0.006), axial rigidity (≥50.47%, p≤0.02), and soft tissue mass (55.25%, p=0.006) were observed from the trans-axial helical CT scans. The μCT results indicated significant detriments in tibia and calcaneus cortical thickness and bone volume fraction (p≤0.011). Significant changes in stiffness, yield load, ultimate load, and ultimate displacement (≥30.05%, p≤0.025) were observed from mechanical testing. These data indicate that limb disuse at a time of rapid musculoskeletal growth severely impairs muscle and bone development, reflecting the musculoskeletal complications observed in children with chronic medical conditions causing immobilization. Interventions to reduce these musculoskeletal complications in children are urgently needed. This disuse rabbit model will be useful in pre-clinical studies evaluating novel interventions for improving pediatric musculoskeletal health.