Mechanisms of impaired growth: effect of steroids on bone and cartilage.
BACKGROUND
Long-term treatment with high-dose glucocorticoids (GCs) has profound effects on bone metabolism and linear growth. Bone metabolism is a balance between bone resorption by osteoclasts and new bone formation by osteoblasts. Systemically, GC treatment reduces circulating levels of estrogen and modestly increases parathyroid hormone levels. At the local level, GCs decrease insulin-like growth factor I (IGF-I) production, induce IGF-I resistance and increase nuclear factor kappaB ligand production by osteoblasts. These alterations inhibit new bone formation and stimulate bone resorption, with a net loss of bone over time. Clinically, this results in decreased bone mineral density, osteoporosis and increased risk for fracture. Local effects of GCs at the growth plate include reduction of IGF-I production, inducing IGF-I resistance and reducing production of C-type natriuretic peptide, which results in a reduction of chondrocyte proliferation, matrix synthesis and hypertrophy. These reductions in chondrocyte function result in decreased linear growth.


CONCLUSIONS
The effects of GCs on bone metabolism and linear growth are sensitive and specific and represent an evolutionary adaptation to redirect resources during times of physiologic stress. Since many of these effects result from alterations in IGF-I production, growth hormone therapy is a potential approach to ameliorate these problems.
Olney
Robert C
RC
Division of Pediatric Endocrinology, Nemours Children's Clinic, Jacksonville, FL 32207, USA. rolney@nemours.org
D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D002356:Cartilage / Q000187:drug effects* / Q000503:physiopathology; D002648:Child; D005938:Glucocorticoids / Q000009:adverse effects*; D006128:Growth / Q000187:drug effects*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D010024:Osteoporosis
D005938:Glucocorticoids; D007334:Insulin-Like Growth Factor I