Published online March 1, 2007
PEDIATRICS Vol. 119 Supplement March 2007, pp. S166-S174 (doi:10.1542/peds.2006-2023J)
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SUPPLEMENT ARTICLE


Glucocorticoid-Induced Osteoporosis in Children: Impact of the Underlying Disease

Mary B. Leonard, MD, MSCE

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Glucocorticoids inhibit osteoblasts through multiple mechanisms, which results in significant reductions in bone formation. The growing skeleton may be especially vulnerable to adverse glucocorticoid effects on bone formation, which could possibly compromise trabecular and cortical bone accretion. Although decreased bone mineral density has been described in various pediatric disorders that require glucocorticoids, and a population-based study reported increased fracture risk in children who require >4 courses of glucocorticoids, some of the detrimental bone effects attributed to glucocorticoids may be caused by the underlying inflammatory disease. For example, inflammatory cytokines that are elevated in chronic disease, such as tumor necrosis factor {alpha}, suppress bone formation and promote bone resorption through mechanisms similar to glucocorticoid-induced osteoporosis. Summarized in this review are changes in bone density and dimensions during growth, the effects of glucocorticoids and cytokines on bone cells, the potential confounding effects of the underlying inflammatory-disease process, and the challenges in interpreting dual-energy x-ray absorptiometry results in children with altered growth and development in the setting of glucocorticoid therapy. Two recent studies of children treated with chronic glucocorticoids highlight the differences in the effect of underlying disease, as well as the importance of associated alterations in growth and development.

Key Words: glucocorticoids • bone mineral density • bone mineral content • glucocorticoid-induced osteoporosis • growth

Abbreviations: GIO—glucocorticoid-induced osteoporosis • BMD—bone mineral density • TNF-{alpha}—tumor necrosis factor {alpha} • DXA—dual-energy x-ray absorptiometry • QCT—quantitative computed tomography • BMC—bone mineral content • RANKL—receptor activator of nuclear factor {kappa}B ligand • IL—interleukin • SSNS—steroid-sensitive nephrotic syndrome • CI—confidence interval

Accepted Oct 5, 2006.


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