Affiliations: [a] Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA | [b] Department of Bone and Cartilage Biology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA | [c] Scanco Medical, Auenring 6-8, CH-8303 Bassersdorf, Switzerland | [d] Department of Laboratory Animal Sciences, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA
Correspondence:
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Address for correspondence: Rasesh D. Kapadia, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. Tel.: +1 610 270 6701; Fax: +1 610 270 6608; E-mail: Rasesh_D_Kapadia@SBPHRD.COM.
Abstract: 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.
