Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid.
A serious side effect of glucocorticoid treatment is the development of osteoporosis. We have earlier shown that long-term glucocorticoid administration results in a decrease in longitudinal bone growth, cortical bone mass, and biomechanical strength, while growth hormone administration increases these parameters. The result of biomechanical testing also indicates that glucocorticoid administration reduces the quality of bone. The glucocorticoid-induced osteopenia could not be inhibited by concomitant administration of large doses of growth hormone. The aim of the present study was to evaluate why glucocorticoid administration decreases the quality of cortical bone and why growth hormone administration had no beneficial effect on glucocorticoid-induced osteopenia. Five groups of female rats (3 1/2 months old) were treated for 80 days as follows: (1) glucocorticoid (prednisolone: Delcortol 5 mg/kg/day); (2) glucocorticoid and growth hormone; (3) saline; (4) growth hormone (recombinant human growth hormone 5 mg/kg/day); (5) Food restriction (consisting of restricted access to food to reduce their weight gain to match with that of the glucocorticoid injected rats). The animals were injected with tetracycline (15 mg/kg), 18 and 3 days before sacrifice, respectively. Furthermore, a baseline group (3 1/2-month-old female rats) was examined in order to enable us to differentiate between age-related changes and changes due to the hormone administration. Cortical mid-diaphysial cross sections of the femora were prepared and used for histological examination including determination of bone porosity, bone formation rate, and determination of the area of endosteal cavities as an indication of bone resorption. Furthermore, a cortical bone cylinder was cut from the mid-diaphysis and used for examinations of wet weight, dry weight, ash weight, volume, collagen content, and apparent density. Glucocorticoid administration resulted in an almost complete arrest of bone formation as shown by a decreased bone formation rate and a decreased periosteal mineralizing surface. Glucocorticoid administration also increased the porosity of bone indicating increased osteoclast activity. The increased porosity was due to a glucocorticoid-induced increase in the number of endosteal cavities in the mid-diaphysial cross section of the femora. The decreased bone formation and the increased bone resorption can explain the decrease in bone mass (volume and ash weight) found after glucocorticoid administration. Growth hormone administration, on the other hand, resulted in a marked increase in bone formation as shown by a marked increase in bone formation rate and periosteal mineralizing surface. In agreement with this, we found an increase in cortical bone mass (volume and ash weight). When the two hormones were given concomitantly, growth hormone administration did not increase bone formation. Our findings indicate the reason why growth hormone has no beneficial effect on cortical osteopenia induced by a high dose of glucocorticoid with protracted effect.
Ortoft
G
G
Department of Connective Tissue Biology, University of Aarhus, Denmark.
Oxlund
H
H
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D001862:Bone Resorption / Q000139:chemically induced; D003094:Collagen / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000473:pathology; D005508:Food Deprivation; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016062:Porosity; D011239:Prednisolone / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D003094:Collagen; D011239:Prednisolone