Divergent Effects of Glucocorticoids on Cortical and Trabecular Compartment BMD in Childhood Nephrotic Syndrome

Abstract

Glucocorticoid (GC) effects on skeletal development have not been established. The objective of this pQCT study was to assess volumetric BMD (vBMD) and cortical dimensions in childhood steroid-sensitive nephrotic syndrome (SSNS), a disorder with minimal independent deleterious skeletal effects. Tibia pQCT was used to assess trabecular and cortical vBMD, cortical dimensions, and muscle area in 55 SSNS (age, 5−19 yr) and >650 control participants. Race-, sex-, and age-, or tibia length–specific Z-scores were generated for pQCT outcomes. Bone biomarkers included bone-specific alkaline phosphatase and urinary deoxypyridinoline. SSNS participants had lower height Z-scores (p < 0.0001) compared with controls. In SSNS, Z-scores for cortical area were greater (+0.37; 95% CI = 0.09, 0.66; p = 0.01), for cortical vBMD were greater (+1.17; 95% CI = 0.89, 1.45; p < 0.0001), and for trabecular vBMD were lower (−0.60; 95% CI, = −0.89, −0.31; p < 0.0001) compared with controls. Muscle area (+0.34; 95% CI = 0.08, 0.61; p = 0.01) and fat area (+0.56; 95% CI = 0.27, 0.84; p < 0.001) Z-scores were greater in SSNS, and adjustment for muscle area eliminated the greater cortical area in SSNS. Bone formation and resorption biomarkers were significantly and inversely associated with cortical vBMD in SSNS and controls and were significantly lower in the 34 SSNS participants taking GCs at the time of the study compared with controls. In conclusion, GCs in SSNS were associated with significantly greater cortical vBMD and cortical area and lower trabecular vBMD, with evidence of low bone turnover. Lower bone biomarkers were associated with greater cortical vBMD. Studies are needed to determine the fracture implications of these varied effects.

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

“…However, we did observe a decrease in BMD at the spine (a trabecular-rich site) but increased cortical thickness at the second metacarpal. Our results are therefore in line with previous reports [30,31] suggesting disparate effects of GCs on cortical and trabecular sites.…”

“…In a recent study using peripheral quantitative computed tomography (pQCT) at the tibia, GC-treated children with NS showed greater cortical volumetric BMD and cortical area, and lower trabecular volumetric BMD compared to controls [30]. Similar results were reported by Hegarty et al, who found by pQCT a significant reduction in distal radial trabecular volumetric BMD, but no reduction in total volumetric BMD in young adults who had NS during childhood [31].…”

“…On the other hand, it should be noted that an absence of association between spine BMD and vertebral fractures has also been reported in post-menopausal women with GC-treated rheumatic disorders, where those with vertebral fractures had similar LS BMD results compared to those without [43]. The absence of a relationship between spine BMD and vertebral fractures among GC-treated patients has been postulated to result from alterations in bone mass or architecture that are not readily discernable by BMD testing in the anteriorposterior direction compared to the more sensitive width-adjusted approach which removes the dense posterior spinous processes from the projected scan [30,44].…”

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

“…This is important, since DXA does not differentiate between these two structures, yet studies have shown divergent effects of GC on the two compartments [41]. Tsampalieros et al [42] recently studied a longitudinal cohort of pediatric NS treated with a similar initial GC regime as in our study, and found that tibia trabecular volumetric BMD Z-scores were lower and cortical density and area Z-scores higher compared to controls around the time of diagnosis.…”

“…The higher cortical density was associated with higher GC doses, attenuated growth in tibial length and declines in cortical area Z-scores. Higher cortical density in GCtreated disorders has been observed in other cohorts [27,41] and is attributed to low bone turnover giving rise to prolongation of the secondary mineralization phase. With improvement in bone turnover, cortical density appears to normalize [27], suggesting the abnormally high cortical density may not necessarily confer increases in bone strength.…”