L. Mosekilde et al., GROWTH-HORMONE INCREASES VERTEBRAL AND FEMORAL BONE STRENGTH IN OSTEOPENIC, OVARIECTOMIZED, AGED RATS IN A DOSE-DEPENDENT AND SITE-SPECIFICMANNER, Bone (New York, N.Y.), 23(4), 1998, pp. 343-352
The aim of the study was to assess the effect of growth hormone (GH) a
s restorative therapy in an aged, ovariectomized rat model with establ
ished osteopenia, The study was planned as a dose-response study, and
four different skeletal sites were investigated by mechanical testing
and measurements of hone mass and dimensions. Twelve-month-old virgin
F344 rats were divided into eight groups with ten animals per group: (
1) sham operated (sham); (2) ovariectomized (ovx); (3) sham + solvent
vehicle (sv); (4) ovx + sv; (5) ovx + GH 50 mu g/kg body weight/day; (
6) ovx + GH 1.25 mg/kg body weight/day; (7) ovx + GH 2.5 mg/kg body we
ight/day; and (8) ovx + GH 5.0 mg/kg body weight/day. Groups 1 and 2 w
ere killed after 3 months to establish that bone loss had occurred due
to ovx, One month later, the remaining groups began 3 months of treat
ment, at the end of which the animals were also killed. The effects of
ovariectomy (ovx) and GH therapy were measured at four skeletal sites
: lumbar vertebrae; femoral diaphysis; femoral neck; and distal femora
l metaphysis, Ovariectomy induced a significant loss of bone strength
at all sites apart from the femoral neck, The loss was most pronounced
at the distal femoral metaphysis, GH was able to reverse the ovx-indu
ced loss of strength at the vertebral site in a dose-dependent manner.
At the femoral diaphyseal site, GH not only reversed the ovx-induced
changes but increased load values significantly above sham level. Howe
ver, at the distal femoral metaphysis, which is dominated by cancellou
s bone, only partial reversal was seen after GH treatment. The lowest
GH dose had no significant effect at any site tested. We conclude that
GH treatment can reestablish vertebral bone loss due to ovariectomy i
n a dose-dependent manner. The restorative effect is only partial at t
he distal femoral metaphysis even at a high dose. At skeletal sites wi
th less pronounced ovx-induced bone loss (femoral neck and diaphysis),
GH treatment increased bone strength to sham level or above sham leve
l. Therefore, the effect of ovariectomy is dependent upon the skeletal
site investigated, and the effect of GH treatment is dependent on bot
h the skeletal site and the size of the ovx-induced bone loss at this
site. (C) 1998 by Elsevier Science Inc. All rights reserved.