This protocol enrolled children with nephrotic syndrome (NS) and healthy controls in order to evaluate glucocorticoid (GC)-induced osteopenia. A total of 130 children with NS and 200 healthy controls were enrolled. The NS subjects exhibited significantly decreased longitudinal growth and increased adiposity in the setting of chronic exposure to GC. However, standard DXA measures (anteroposterior lumbar spine z-scores) failed to detect any impairment of mineralization in these subjects. The application of newer DXA techniques that combined the anteroposterior (AP) and lateral spine scans and edited out the vertebral spinous processes demonstrated decreased trabecular density in pubertal and post-pubertal NS subjects, compared to healthy controls. Whole body DXA data suggested that the NS subjects have decreased bone area for height (narrow bones) and decreased lean muscle mass, adjusting for other growth parameters. Despite these advances, cortical thickness and density could not be addressed due to the limitations of DXA. In performing this study, we have learned that DXA techniques are limited in the assessment of steroid effects in the growing skeleton: DXA techniques lump together cortical and trabecular bone mass, prohibiting separate assessment of the cortical and trabecular architecture and density. In addition, recent studies suggest that DXA estimates of overall bone dimensions are artificially influenced by differences in the thickness and fat mass of surrounding tissues. The recent availability of peripheral quantitative computed tomography (pQCT) substantially improves the assessment of discrete bone components, with significantly less radiation exposure than conventional CT and without interference from surrounding tissues. This method addresses bone quality and architecture, integrating these data to estimate bone strength. A recent abstract describing pQCT results in children suggested that GC therapy was associated with decreased cortical thickness, muscle mass and bone strength. A recent animal study underscores the impact of GC on the growing skeleton: young growing rats treated with GC exhibited significant impairment of growth-related cortical expansion and trabecular mineralization.
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