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 o f osteoporosis. We have earlier shown that long-term glucocorticoid ad ministration results in a decrease in longitudinal bone growth, cortic al bone mass, and biomechanical strength, while growth hormone adminis tration increases these parameters. The result of biomechanical testin g also indicates that glucocorticoid administration reduces the qualit y of bone. The glucocorticoid-induced osteopenia could not be inhibite d by concomitant administration of large doses of growth hormone. The aim of the present study was to evaluate why glucocorticoid administra tion decreases the quality of cortical bone and why growth hormone adm inistration had no beneficial effect on glucocorticoid-induced osteope nia. Five groups of female rats (31/2 months old) were treated for 80 days as follows: (1) glucocorticoid (prednisolone: Delcortol 5 mg/kg/d ay); (2) glucocorticoid and growth hormone; (3) saline; (4) growth hor mone (recombinant human growth hormone 5 mg/kg/day); (5) Food restrict ion (consisting of restricted access to food to reduce their weight ga in to match with that of the glucocorticoid injected rats). The animal s were injected with tetracycline (15 mg/kg), 18 and 3 days before sac rifice, respectively. Furthermore, a baseline group (31/2-month-old fe male rats) was examined in order to enable us to differentiate between age-related changes and changes due to the hormone administration. Co rtical mid-diaphysial cross sections of the femora were prepared and u sed for histological examination including determination of bone poros ity, bone formation rate, and determination of the area of endosteal c avities as an indication of bone resorption. Furthermore, a cortical b one cylinder was cut from the mid-diaphysis and used for examinations of wet weight, dry weight, ash weight, volume, collagen content, and a pparent density. Glucocorticoid administration resulted in an almost c omplete arrest of bone formation as shown by a decreased bone formatio n rate and a decreased periosteal mineralizing surface. Glucocorticoid administration also increased the porosity of bone indicating increas ed osteoclast activity. The increased porosity was due to aa glucocort icoid-induced increase in the number of endosteal cavities in the mid- diaphysial cross section of the femora. The decreased bone formation a nd the increased bone resorption can explain the decrease in bone mass (volume and ash weight) found after glucocorticoid administration. Gr owth hormone administration, on the other hand, resulted in a marked i ncrease in bone formation as shown by a marked increase in hone format ion rate and periosteal mineralizing surface. Glucocorticoid administr ation also increased the porosity of bone indicating increased osteocl ast activity. The increased porosity was due to a glucocorticoid-induc ed increase in the number of endosteal cavities in the mid-diaphysial cross section of the femora. The decreased bone formation and the incr eased bone resorption can explain the decrease in bone mass (volume an d ash weight) found after glucocorticoid administration. Growth hormon e administration, on the other hand, resulted in a marked increase in bone formation as shown by a marked increase in hone formation rate an d 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 n ot increase bone formation. Our findings indicate the reason why growt h hormone has no beneficial effect on cortical osteopenia induced by a high dose of glucocorticoid with protracted effect.