Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome.

TitleGlucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome.
Publication TypeJournal Article
Year of Publication2013
AuthorsTsampalieros A, Gupta P, Denburg MR, Shults J, Zemel BS, Mostoufi-Moab S, Wetzsteon RJ, Herskovitz RM, Whitehead KM, Leonard MB
JournalJ Bone Miner Res
Volume28
Issue3
Pagination480-8
Date Published2013 Mar
ISSN1523-4681
KeywordsAdolescent, Bone Density, Child, Child, Preschool, Female, Glucocorticoids, Humans, Male, Nephrotic Syndrome, Tomography, X-Ray Computed
Abstract

The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric bone mineral density (vBMD) and cortical structure over 1 year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty-six NS participants, aged 5 to 21 years, were enrolled a median of 4.3 (0.5 to 8.1) years after diagnosis. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained at enrollment and 6 and 12 months later. Sex, race, and age-specific Z-scores were generated for trabecular vBMD (TrabBMD-Z), cortical vBMD (CortBMD-Z), and cortical area (CortArea-Z) based on >650 reference participants. CortArea-Z was further adjusted for tibia length-for-age Z-score. Quasi-least squares regression was used to identify determinants of changes in pQCT Z-scores. At enrollment, mean TrabBMD-Z (-0.54 ± 1.32) was significantly lower (p = 0.0001) and CortBMD-Z (0.73 ± 1.16, p < 0.0001) and CortArea-Z (0.27 ± 0.91, p = 0.03) significantly greater in NS versus reference participants, as previously described. Forty-eight (86%) participants were treated with GC over the study interval (median dose 0.29 mg/kg/day). On average, TrabBMD-Z and CortBMD-Z did not change significantly over the study interval; however, CortArea-Z decreased (p = 0.003). Greater GC dose (p < 0.001), lesser increases in tibia length (p < 0.001), and lesser increases in CortArea-Z (p = 0.003) were independently associated with greater increases in CortBMD-Z. Greater increases in tibia length were associated with greater declines in CortArea-Z (p < 0.01); this association was absent in reference participants (interaction p < 0.02). In conclusion, GC therapy was associated with increases in CortBMD-Z, potentially related to suppressed bone formation and greater secondary mineralization. Conversely, greater growth and expansion of CortArea-Z (ie, new bone formation) were associated with declines in CortBMD-Z. Greater linear growth was associated with impaired expansion of cortical area in NS. Studies are needed to determine the fracture implications of these findings.

DOI10.1002/jbmr.1785
Alternate JournalJ. Bone Miner. Res.
PubMed ID23044926
PubMed Central IDPMC3578070
Grant ListR01-DK060030 / DK / NIDDK NIH HHS / United States
R01 DK060030 / DK / NIDDK NIH HHS / United States
K23 DK093556 / DK / NIDDK NIH HHS / United States
K24-DK07680 / DK / NIDDK NIH HHS / United States
UL1-RR-024134 / RR / NCRR NIH HHS / United States
K24 DK076808 / DK / NIDDK NIH HHS / United States
UL1 RR024134 / RR / NCRR NIH HHS / United States