Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome

N Engl J Med. 2004 Aug 26;351(9):868-75. doi: 10.1056/NEJMoa040367.


Background: Glucocorticoids suppress bone formation, impair growth, and induce obesity. We determined the effects of long-term treatment with glucocorticoids on bone mineral content in children with glucocorticoid-sensitive nephrotic syndrome, a disorder with minimal known independent effects on bone.

Methods: We performed dual-energy x-ray absorptiometry of the whole body and spine in 60 children and adolescents with the nephrotic syndrome and 195 control subjects. We used linear regression analysis of log-transformed values to compare the bone mineral content in patients with that in controls.

Results: Patients had received an average of 23,000 mg of glucocorticoids and were shorter (P=0.008) and had a greater body-mass index (P<0.001) than controls. The bone mineral content of the spine, adjusted for bone area, age, sex, degree of maturation (Tanner stage), and race, did not differ significantly between patients and controls (ratio, 0.99; 95 percent confidence interval, 0.96 to 1.02; P=0.51). After adjustment for the z score for body-mass index, the bone mineral content of the spine was significantly lower in patients than in controls (0.96; 95 percent confidence interval, 0.92 to 0.99; P=0.01). Whole-body bone mineral content, adjusted for height, age, sex, degree of maturation, and race, was significantly higher in patients than in controls (ratio, 1.11; 95 percent confidence interval, 1.05 to 1.18; P<0.001); however, the addition of the z score for body-mass index to the model eliminated the association with the nephrotic syndrome (ratio, 0.99; 95 percent confidence interval, 0.94 to 1.03; P=0.55).

Conclusions: Intermittent treatment with high-dose glucocorticoids during growth does not appear to be associated with deficits in the bone mineral content of the spine or whole body relative to age, bone size, sex, and degree of maturation. Glucocorticoid-induced increases in body-mass index were associated with increased whole-body bone mineral content and maintenance of the bone mineral content of the spine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Body Height / drug effects
  • Body Mass Index
  • Bone Density / drug effects*
  • Case-Control Studies
  • Child
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Growth / drug effects
  • Humans
  • Linear Models
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / drug effects
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / physiopathology
  • Prednisone / pharmacology*
  • Prednisone / therapeutic use


  • Glucocorticoids
  • Prednisone