Sims N A, Morris H A, Moore R J, Durbridge T C
Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Adelaide, SA, Australia.
Bone. 1996 Nov;19(5):455-61. doi: 10.1016/s8756-3282(96)00242-6.
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 17 beta-estradiol at 8 micrograms/ kg per day (Low) and 20 micrograms/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.
研究了从卵巢切除时开始进行短期雌二醇治疗对大鼠骨转换增加及随后骨丢失的影响。成年雌性斯普拉格 - 道利大鼠接受卵巢切除术,并每天皮下注射17β - 雌二醇,剂量为8微克/千克/天(低剂量组)和20微克/千克/天(高剂量组),或仅注射赋形剂(对照组)。雌二醇给药后,术后6天股骨远端的骨小梁骨体积(BV/TV)和骨小梁数量(Tb.N)以剂量依赖方式短暂增加[平均值±标准误:BV/TV(%),第0天,6.6±0.2;第6天,对照组7.8±0.4,低剂量组10.2±2.2,高剂量组12.8±1.7(p<0.05);Tb.N(/mm),第0天,2.30±0.24;第6天,对照组2.89±0.33,低剂量组3.4±0.7,高剂量组4.39±0.34(p<0.05)]。雌二醇可防止对照组大鼠在9至15天观察到的卵巢切除引起的BV/TV和Tb.N降低。高剂量雌二醇从术后第6天起使血清碱性磷酸酶和尿羟脯氨酸排泄维持在术前水平或更低。然而,血清骨钙素在术后第6天和第9天随雌二醇升高至术前水平以上,但在术后第15天和第21天恢复到这些值。这些结果表明,从卵巢切除时开始给予雌二醇可立即抑制与成骨细胞增殖/基质合成及骨吸收相关的标志物。给药后相对较高水平的雌二醇似乎并未如此迅速地抑制矿化,导致骨小梁骨体积和骨小梁数量短暂增加。