Estradiol treatment transiently increases trabecular bone volume in ovariectomized rats

The effect of short-term estradiol treatment, administered from the time of ovariectomy, on increased bone turnover and subsequent bone loss was studied in the rat. Adult female Sprague-Dawley rats were ovariectomized and administered daily subcutaneous (s.c.) injections of 17β-estradiol at 8 μg/ kg per day (Low) and 20 μg/kg per day (High) or vehicle alone (Veh). Femoral trabecular bone volume (BV/TV) and trabecular number (Tb.N) in the distal femur were transiently increased at 6 days postoperation in a dose-dependent manner following estradiol administration [mean ± SEM: BV/TV (%), day 0, 6.6 ± 0.2; day 6, Veh 7.8 ± 0.4, Low 10.2 ± 2.2, High 12.8 ± 1.7 (p< 0.05); Tb.N (/mm), day 0, 2.30 ± 0.24; day 6, Veh 2.89 ± 0.33, Low 3.4 ± 0.7, High 4.39 ± 0.34 (p< 0.05)]. Estradiol prevented the ovariectomy-induced decrease in BV/TV and Tb.N between 9 and 15 days observed in Veh rats. Both serum alkaline phosphatase and urine hydroxyproline excretion were maintained at preoperative levels or lower from day 6 postoperation with high dose estradiol. Serum osteocalcin, however, rose above preoperative levels with estradiol at days 6 and 9, but returned to these values on days 15 and 21 postoperation. These results suggest that estradiol, administered from the time of ovariectomy, immediately suppressed markers associated with osteoblast proliferation/matrix synthesis and bone resorption. Mineralization does not appear to be so rapidly suppressed by estradiol with relatively high levels immediately following administration, resulting in a transient increase in trabecular bone volume and trabecular number.