Sato M, Kim J, Short L L, Slemenda C W, Bryant H U
Department of Endocrine Research, Lilly Research Laboratories, Indianapolis, Indiana.
J Pharmacol Exp Ther. 1995 Mar;272(3):1252-9.
To extend and confirm previous data, we examined the effects of raloxifene on the proximal tibia of ovariectomized rats, aged 6 months, longitudinally and cross-sectionally by computed tomography (pQCT) and then compared the effects to those of orally dosed estrogen. Comparative analysis of phantoms and rat bones showed that the pQCT is precise and correlates with a Hologic QDR 1000W (DXA) with R = 0.999 but is capable of measuring significant differences between groups when the DXA cannot. This may reflect the ability of the pQCT to determine bone volume, mineral content (mg) and volumetric mineral density (mg/cm3), compared with two-dimensional analyses performed with DXA. Longitudinal analysis of the proximal tibia in vivo showed a significant 17% reduction in mineral density 31 days after ovariectomy. Examination of the images from ovariectomized rats showed a progressive increase in the cross-sectional area of the proximal tibiae, loss of trabecular bone, widening of marrow spaces and thinning of the cortical bone wall opposite the fibula. Regression analysis of the dose-dependent protective effects of raloxifene showed the half-maximal efficacy on tibiae mineral density to be ED50 = 0.4 mg/kg/day per os by pQCT and 0.2 mg/kg/day by DXA. By comparison, 17 alpha ethynyl estradiol showed dose-dependent effects with ED50 = 0.013 mg/kg/day per os by pQCT. Both raloxifene and ethynyl estradiol had beneficial effects on serum lipids, producing 50% reduction of cholesterol at 0.1 mg/kg/day raloxifene and 80% reduction with 0.01 mg/kg/day ethynyl estradiol. However, raloxifene up to 10 mg/kg/day had little effect on uterine weight, whereas 0.01 mg/kg/day ethynyl estradiol increased uterine wet weight by 300%.(ABSTRACT TRUNCATED AT 250 WORDS)
为了扩展并确认先前的数据，我们通过计算机断层扫描（pQCT）对6月龄去卵巢大鼠的胫骨近端进行了纵向和横断面研究，以观察雷洛昔芬的作用，然后将其与口服雌激素的作用进行比较。对模型和大鼠骨骼的对比分析表明，pQCT精确，与Hologic QDR 1000W（双能X线吸收法，DXA）的相关性为R = 0.999，并且当DXA无法检测到组间显著差异时，pQCT能够做到。这可能反映了与DXA进行的二维分析相比，pQCT在确定骨体积、矿物质含量（mg）和体积矿物质密度（mg/cm³）方面的能力。对体内胫骨近端的纵向分析显示，去卵巢31天后矿物质密度显著降低了17%。对去卵巢大鼠的图像检查显示，胫骨近端的横截面积逐渐增加，小梁骨丢失，骨髓腔增宽，腓骨相对侧的皮质骨壁变薄。雷洛昔芬剂量依赖性保护作用的回归分析显示，通过pQCT测定，对胫骨矿物质密度的半数最大效应为ED50 = 0.4 mg/kg/天口服，通过DXA测定为0.2 mg/kg/天。相比之下，17α-乙炔雌二醇显示出剂量依赖性效应，通过pQCT测定的ED50 = 0.013 mg/kg/天口服。雷洛昔芬和乙炔雌二醇对血脂均有有益作用，雷洛昔芬0.1 mg/kg/天可使胆固醇降低50%，乙炔雌二醇0.01 mg/kg/天可使胆固醇降低80%。然而，高达10 mg/kg/天的雷洛昔芬对子宫重量影响很小，而0.01 mg/kg/天的乙炔雌二醇可使子宫湿重增加300%。（摘要截短于250字）
