G. Ortoft et H. Oxlund, QUALITATIVE ALTERATIONS OF CORTICAL BONE IN FEMALE RATS AFTER LONG-TERM ADMINISTRATION OF GROWTH-HORMONE AND GLUCOCORTICOID, Bone, 18(6), 1996, pp. 581-590
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.