Evaluation of the pathogenesis of skeletal changes in ovariectomized rats

Young adult ovariectomized rats were used to investigate the pathogenesis of ovarian hormone deficiency osteopenia, uncomplicated by other forms of age-related bone loss. It was observed that the femurs of ovariectomized rats were less dense with less hydroxyproline and less calcium (Ca) and phosphorus per unit volume of bone than those of age-matched controls. Compared to animals killed at the beginning of the study to serve as baseline controls, ovariectomized rats and their age-matched controls had increased periosteal and cortical areas, but in contrast to the age-matched controls, ovariectomized rats had markedly increased medullary area and the ratio of their cortical area to periosteal area was decreased (P less than 0.02). When the changes in cross-sectional areas were expressed as percent of the baseline levels, the medullary area was increased 32% in ovariectomized rats, and only 14% in the age-matched controls; the net increase in cortical area was 17% for the controls and 11% for the ovariectomized rats and there was only 3% difference between the increases in their periosteal areas. Furthermore, ovariectomy caused a marked decrease in serum calcitonin and Ca levels but not in PTH levels. As expected, PTH administration increased serum Ca in all rats, but the rise was greater in ovariectomized calcitonin-deficient rats than in rats that were only ovariectomized or only thyroidectomized. Whereas these findings support the concept of increased sensitivity of bone to PTH in ovarian hormone deficiency osteopenia, the decrease in serum Ca in ovariectomized rats indicates that other factors may be involved as well.