Influence of estrogens on bone resorption in organ culture

Estradiol benzoate, ethinyl estradiol, and human calcitonin were compared for their ability to inhibit the spontaneous or parathyroid extract-induced bone resorption in organ cultures of 19-day fetal rat fibulae. The criteria used for the assessment of bone resorption were: the release of⁴⁵Ca from paired prelabeled bone rudiments into the culture medium, the dry weight, and the number of osteoclasts per bone. Estradiol benzoate at concentrations of 1.3×10^–5 to 2.6×10^–4 M had no effect on the release of⁴⁵Ca from fetal fibulae or on the dry weight. Histologically, treated bones were well preserved and resembled the controls. Parathyroid extract (PTE) alone caused extensive bone resorption with numerous osteoclasts and enhanced⁴⁵Ca release without weight gain. The addition of estradiol benzoate to the culture medium did not prevent the resorptive action of PTE. Ethinyl estradiol alone provoked a dose-related inhibition of⁴⁵Ca release at concentrations of 3.4×10^–5 to 1.7×10^–4 M. However, this inhibition was accompanied by a decrease in bone dry weight and by various degrees of cellular damage. The same phenomenon was observed in PTE-treated fibulae. Human calcitonin, on the contrary, inhibited the release of⁴⁵Ca by decreasing the number of osteoclasts while the weight of the fibulae increased. The inhibitory action of ethinyl estradiol appears to be caused by a toxic effect on bone cells. It is concluded that estrogens have no direct physiological effect on bone resorption in vitro.