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.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital of Philadelphia
United States
Zip Code
Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L et al. (2017) Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nat Commun 8:121
Agopian, A J; Goldmuntz, Elizabeth; Hakonarson, Hakon et al. (2017) Genome-Wide Association Studies and Meta-Analyses for Congenital Heart Defects. Circ Cardiovasc Genet 10:e001449
Ruan, Alexandra; Tobin, Nicole H; Mulligan, Kathleen et al. (2016) Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021. J Acquir Immune Defic Syndr 72:372-5
Medoff-Cooper, Barbara; Irving, Sharon Y; Hanlon, Alexandra L et al. (2016) The Association among Feeding Mode, Growth, and Developmental Outcomes in Infants with Complex Congenital Heart Disease at 6 and 12 Months of Age. J Pediatr 169:154-9.e1
Ollberding, Nicholas J; Gilsanz, Vicente; Lappe, Joan M et al. (2015) Reproducibility and intermethod reliability of a calcium food frequency questionnaire for use in Hispanic, non-Hispanic Black, and non-Hispanic White youth. J Acad Nutr Diet 115:519-27.e2
Medina-Gómez, Carolina; Chesi, Alessandra; Heppe, Denise H M et al. (2015) BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures. Mol Biol Evol 32:2961-72
Avitabile, Catherine M; Goldberg, David J; Zemel, Babette S et al. (2015) Deficits in bone density and structure in children and young adults following Fontan palliation. Bone 77:12-6
Rutstein, Richard M; Samson, Pearl; Fenton, Terry et al. (2015) Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: the Pediatric AIDS Clinical Trials Group Protocol 1020A. Pediatr Infect Dis J 34:162-7
Trabulsi, Jillian C; Irving, S Y; Papas, M A et al. (2015) Total Energy Expenditure of Infants with Congenital Heart Disease Who Have Undergone Surgical Intervention. Pediatr Cardiol 36:1670-9
Lappe, Joan M; Watson, Patrice; Gilsanz, Vicente et al. (2015) The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. J Bone Miner Res 30:156-64

Showing the most recent 10 out of 455 publications