Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats.
Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 micrograms/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
Binz
K
K
Department of Medicine, University Hospital, Zürich, Switzerland.
Schmid
C
C
Bouillon
R
R
Froesch
E R
ER
Jürgensen
K
K
Hunziker
E B
EB
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000097:blood; D002762:Cholecalciferol / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008903:Minerals / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014809:Vitamin D-Binding Protein / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D008903:Minerals; D011994:Recombinant Proteins; D014809:Vitamin D-Binding Protein; D015675:Osteocalcin; D002762:Cholecalciferol; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D002117:Calcitriol