Mechanisms of steroid impairment of growth.
With child growth being multifactorial and the glucocorticoids (GC) having many target physiological and biochemical mechanisms, growth and the GC collide in several meeting points. Indirectly, GC have a general anti-anabolic and catabolic influences that include bone, cartilage and muscle proteins. The GC interfere with the GH-IGF-1 axis at the hypothalamic, pituitary and target organ levels, affecting hormone release, receptor abundance, signal transduction, gene transcription, pre-mRNA splicing and mRNA translation. GC disturb normal calcium balance at the intestine and kidney. Direct effects at the growth plate include the suppression of multiple gene expression, chondrocyte proliferation and matrix proteoglycan synthesis, sulfation, release and mineralization as well as the augmentation of hypertrophic cell apoptosis. At the tissues adjacent to the growth plate, GC enhance osteoclast and suppress osteoblast recruitment and function, they reduce muscle strength and disrupt the normal control of vascular invasion at the cartilage-bone interface. Growth damage from GC is maximal during the initial months of treatment and prevention is more effective than post-factual therapy. To reduce these growth-retarding effects, the following measures, which are partly experimental, may be effective in a decreasing order: minimize GC dose and use an alternate-day treatment; utilize the oxazoline analog of prednisolone deflazacort, normalize calcium balance; employ hGH or IGF-1.
Hochberg
Ze'ev
Z
Pediatric Endocrinology, Meyer Children's Hospital, Haifa, Israel. z_hochberg@rambam.health.gov.il
D001842:Bone and Bones / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002648:Child; D005938:Glucocorticoids / Q000009:adverse effects*; D006130:Growth Disorders / Q000139:chemically induced* / Q000517:prevention & control; D006132:Growth Plate / Q000187:drug effects; D019382:Human Growth Hormone / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D009132:Muscles / Q000187:drug effects
D005938:Glucocorticoids; D009124:Muscle Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D002118:Calcium