The Effects of Glucocorticoid and Voluntary Exercise Treatment on the Development of Thoracolumbar Kyphosis in Dystrophin-Deficient Mice

The development of spinal curvature deformities is a hallmark of muscular dystrophy. While glucocorticoid treatment has been shown to prolong muscle function in dystrophic mice, its effects on the development of dystrophinopathic spinal deformation are poorly understood. In this study, we test the effects of glucocorticoid treatment on the onset of thoracolumbar kyphosis in the dystrophin-deficient mdx mouse using voluntary running exercise to exacerbate muscle fibrosis. We measure the kyphotic index, erector spinae muscle fibrosis, and vertebral bone histomorphometry in 4-month-old mdx mice in four groups: sedentary control, exercise-treated (continuous voluntary access to an activity wheel), glucocorticoid-treated, and glucocorticoid + exercise-treated. Exercise treated mice were found to have significantly lower kyphotic index (i.e., greater kyphosis) and greater muscle fibrosis relative to controls (p < 0.05). However, the deleterious effect of exercise on KI and muscle fibrosis was prevented by glucocorticoid treatment. Some differences in bone histological parameters were observed between treatment groups, suggesting there is a complex relationship between dystrophic muscular changes and vertebral bone mass. Our findings indicate glucocorticoid treatment delays the onset of thoracodorsal spinal deformation in mdx mice.