Kapadia R D, Stroup G B, Badger A M, Koller B, Levin J M, Coatney R W, Dodds R A, Liang X, Lark M W, Gowen M
Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Technol Health Care. 1998 Dec;6(5-6):361-72.
There is a tremendous unmet therapeutic need for the treatment of osteoporosis and osteoarthritis. The ovariectomized rat and the guinea pig are widely used animal models for the evaluation of new therapeutics for osteoporosis and osteoarthritis, respectively. We have utilized X-ray micro-CT techniques to quantitatively evaluate the differences in trabecular bone in the rat proximal tibia following ovariectomy and treatment with estrogen (17-B-estradiol). Results demonstrate a loss of trabecular bone and architecture following ovariectomy (p < 0.001), and a marked inhibition of trabecular bone loss in the estrogen treated group (p < 0.001). A similar change in architecture can be visualized in images obtained by high resolution MR microscopy. In addition, a good correlation was observed between the values of trabecular bone fraction (BV/TV) in the rat tibiae as obtained from 3-dimensional micro-CT data and 2-dimensional static histomorphometry (r = 0.89, 0.73, 0.79 for sham, OVX, and treated groups, respectively). Micro-CT images were also obtained from a set of lumbar vertebrae from sham operated and ovariectomized rats. Significant bone loss can be measured as early as 8 weeks following ovariectomy (p < 0.005). Micro-CT and MR images were also obtained to study age related changes in the stifle joint of the guinea pig. Significant boney changes can be seen in the tibia and femur from the animals at various ages. Changes in cartilage and joint space can also be visualized in the images. The utility of micro-CT imaging in evaluating the mouse skeletal system is illustrated by obtaining morphological and architectural details from high resolution images of the mouse hind limb and proximal tibia, respectively. The results demonstrate the advantages that multi-dimensional imaging techniques can offer in evaluating bone and joint related changes in animal models of osteoporosis and osteoarthritis.
在骨质疏松症和骨关节炎的治疗方面，存在着巨大的未满足的治疗需求。去卵巢大鼠和豚鼠分别是广泛用于评估骨质疏松症和骨关节炎新疗法的动物模型。我们利用X射线显微CT技术定量评估了去卵巢大鼠和用雌激素（17-β-雌二醇）治疗后大鼠近端胫骨小梁骨的差异。结果表明，去卵巢后小梁骨和结构丧失（p < 0.001），而雌激素治疗组小梁骨丢失受到显著抑制（p < 0.001）。通过高分辨率磁共振显微镜获得的图像中可以看到结构上的类似变化。此外，从三维显微CT数据获得的大鼠胫骨小梁骨分数（BV/TV）值与二维静态组织形态计量学之间观察到良好的相关性（假手术组、去卵巢组和治疗组的r分别为0.89、0.73、0.79）。还从假手术和去卵巢大鼠的一组腰椎椎体获得了显微CT图像。去卵巢后早在8周就可测量到显著的骨质流失（p < 0.005）。还获得了显微CT和磁共振图像以研究豚鼠膝关节与年龄相关的变化。在不同年龄的动物的胫骨和股骨中可以看到显著的骨质变化。软骨和关节间隙的变化在图像中也可以显现出来。通过分别从小鼠后肢和近端胫骨的高分辨率图像中获得形态和结构细节，说明了显微CT成像在评估小鼠骨骼系统中的实用性。结果证明了多维成像技术在评估骨质疏松症和骨关节炎动物模型中与骨和关节相关变化方面所能提供的优势。
