Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome

Feber, Janusz; Gaboury, Isabelle; Ni, Andy; Alos, Nathalie; Arora, Sourabh; Bell, Lorraine; Blydt-Hansen, Tom; Clarson, Cheril; Filler, Guido; Hay, John; Hébert, Diane; Lentle, Brian C.; Matzinger, Mary Ann; Midgley, Julian; Moher, David; Pinsk, Maury; Rauch, Frank; Rodd, Celia; Shenouda, Nazih; Siminoski, Kerry; Ward, Leanne M.

doi:10.1007/s00198-011-1621-2

Cited by 59 publications

(74 citation statements)

References 39 publications

(50 reference statements)

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“…Through prospective study, we previously described an inverse relationship between lumbar spine bone mineral density (LS BMD) Z-scores and short-term GC therapy in pediatric GCtreated NS [9]. After a median of 18 days following GC initiation, every 1 mg/m 2 increase in GC therapy (prednisone equivalents) was associated with a decrease in spine BMD Z-score of almost 0.4 standard deviation (SD).…”

Section: Introductionmentioning

confidence: 99%

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Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

et al. 2013

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confidence: 99%

“…Feber et al [9] found that 8% of children with GC-treated NS and short-term GC exposure (maximum 37 days) had asymptomatic prevalent VF. On the other hand, a recent report described painful moderate VF in a young boy with NS following 5 years of intermittent GC therapy [12].…”

Section: Introductionmentioning

confidence: 99%

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

et al. 2013

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“…The study subjects were children with underlying diseases who had several weeks of exposure to glucocorticoids and some of whom had exposure to other bone-toxic medications [24][25][26]. Individuals with impaired limb function were excluded from the study and there is no reason to expect that the underlying conditions or drugs would selectively alter the dominant to nondominant BMC ratio at younger ages.…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were participants in the Canadian Steroid-associated Osteoporosis in the Pediatric Population (STOPP) research initiative [24][25][26]. We studied those STOPP subjects from seven research sites for whom whole body dual-energy x-ray absorptiometry (DXA) was available, who completed handedness evaluations, and who had no significant limitations to limb use.…”

Section: Study Subjectsmentioning

confidence: 99%

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The development of bone mineral lateralization in the arms

Siminoski

Abish

et al. 2012

Osteoporos Int

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Purpose-Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age.Methods-Subjects (n = 158) were children recently initiating glucocorticoid for underlying disease (leukemia 43%, rheumatic conditions 39%, nephrotic syndrome 18%). Handedness was determined by questionnaire and BMC by dual-energy x-ray absorptiometry.Results-Median age was 7.2 years (range, 1.5 to 17.0 years), 49% were male, and the spine BMD Z-score was −0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95% CI, 4.5-7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptThe slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027).Conclusions-These results show that arm BMC sidedness in this patient group develops up to age six years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest.

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

Tsampalieros

Gupta

Denburg

et al. 2012

Journal of Bone and Mineral Research

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The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric BMD (vBMD) and cortical structure over one year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty-six NS participants, ages 5–21 years, were enrolled a median of 4.3 (0.5, 8.1) years after diagnosis. Tibia peripheral quantitative CT (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, vs. 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 (i.e. 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.

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Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome

Cited by 59 publications

References 39 publications

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

The development of bone mineral lateralization in the arms

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

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