Invited Symposium: Regulators of Skeletal Growth and Integrity in Health and Disease
Ward, WE (Department of Nutritional Sciences, University of Toronto, Canada)
Exogenous glucocorticoids are known to have profound physiological and pharmacological effects on bone turnover. In adults, steroid-induced osteoporosis is widely reported. Evidence is mounting that when steroid drugs are used to improve pulmonary compliance in ventilated premature infants, or as immunosuppressive agents in children with acute lyphoblastic leukemia, inflammatory bowel disease or asthma, linear and weight growth and bone mass accretion are adversely affected. Steroid drugs like dexamethasone or prednisone may act by altering the concentration or activity of specific components of the growth hormone/insulin-like growth factor axis (GH/IGF-I) which are essential for regulating somatic growth and skeletal development. In all clinical pediatric populations studied in our lab, steroid drugs caused a reduction in circulating osteocalcin (a marker of bone turnover)and in urinary N-telopeptide or pyridinoline (markers of bone resorption)as well as hypercalciuria. Bone mass was reduced with prolonged steroid use in all clinical populations. Using the rapidly growing piglet as a model for infants and children, we observed similar steroid-induced changes in bone turnover and accretion as in the children. Adjunctive therapy with GH during dexamethasone administration, partially attentuated the reductions in growth, bone mass and bone cell activity; but did not alter the IGF-I bioactivity as indicated by profiles of circulating and tissue IGF binding proteins 2 and 3. There was no added benefit of adding IGF-I to GH treatment. Further research is needed to define the long-term effects of steroids administered during critical stages of development and possible interventions to attenuate any growth abnormalities.
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|Atkinson, SA; Ward, WE; (1998). Drug-induced Bone Abnormalities. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/atkinson/atkinson0720/index.html|
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