Time course of femoral neck osteopenia in ovariectomized rats

Abstract

To characterize osteopenic changes in the femoral neck of ovariectomized (ovx) rats, female Sprague-Dawley rats were ovx or sham operated upon at 3 months of age and killed at various times from 0 to 360 days postsurgery. Quantitative bone histomorphometry was performed on undecalcified longitudinal sections of the proximal femur from each rat. This skeletal site was found to be slowly growing, as its rate of longitudinal bone growth in 3-month-old baseline control rats (5 μm/day) was nearly a factor of 10 less than that of a more commonly used sample site, the proximal tibia. In control rats, cancellous bone volume and cortical bone width of the femoral neck remained relatively constant, but cancellous mineral apposition rate declined with age during the course of the study. In contrast, cancellous bone volume in ovx rats was significantly decreased to 75%–82% of control level at 30–90 days and further decreased to 50%–56% of control level at later times postovariectomy. Indices of cancellous bone turnover such as osteoclast and osteoblast surfaces and bone formation rate were markedly increased in ovx rats at 30 days, declined toward control levels by 90 days, then increased moderately at 180–360 days. In comparison to control rats, a slight decrease in cortical width of the femoral neck was observed in ovx rats at 180 days and reached statistical significance at 360 days postovariectomy. Endocortical bone formation rate was increased significantly in ovx rats compared with control rats at most time points. The results indicate that both cancellous and cortical osteopenia associated with high bone turnover occur in the femoral neck of ovx rats. Cancellous bone loss at this skeletal site is statistically significant as early as 30 days postovariectomy, but remains relatively moderate for the first 90 days before becoming more pronounced at later times after ovariectomy. In contrast, cortical osteopenia was not observed in the femoral neck of ovx rats until 1 year postovariectomy. This histomorphometric characterization of osteopenic changes in the femoral neck of ovx rats may serve as a basis for use of this slowly growing sample site in preclinical studies of the prevention and treatment of bone loss in the estrogen-depleted skeleton.