Growth hormone increases vertebral and femoral bone strength in osteopenic, ovariectomized, aged rats in a dose-dependent and site-specific manner

Abstract

The aim of the study was to assess the effect of growth hormone (GH) as restorative therapy in an aged, ovariectomized rat model with established osteopenia. The study was planned as a dose-response study, and four different skeletal sites were investigated by mechanical testing and measurements of bone 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 μg/kg body weight/day; (6) ovx + GH 1.25 mg/kg body weight/day; (7) ovx + GH 2.5 mg/kg body weight/day; and (8) ovx + GH 5.0 mg/kg body weight/day. Groups 1 and 2 were killed after 3 months to establish that bone loss had occurred due to ovx. One month later, the remaining groups began 3 months of treatment, 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 femoral 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-induced 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. However, at the distal femoral metaphysis, which is dominated by cancellous 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 in a dose-dependent manner. The restorative effect is only partial at the distal femoral metaphysis even at a high dose. At skeletal sites with less pronounced ovx-induced bone loss (femoral neck and diaphysis), GH treatment increased bone strength to sham level or above sham level. Therefore, the effect of ovariectomy is dependent upon the skeletal site investigated, and the effect of GH treatment is dependent on both the skeletal site and the size of the ovx-induced bone loss at this site.