Abstract:
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Purpose: Due to the wide availability of various genetically altered mice in genomics research, drug discovery and development, the murine model has become unprecedentedly useful for studying osteoporosis. This study was designed to characterize 3D trabecular microstructure and volumetric bone mineral density (vBMD) of a murine model of osteoporosis and the effects of hormone replacement therapy. Capturing true 3D trabecular microstructural information and vBMD may help to understand the pathophysiology of osteoporosis and to estimate bone mechanical competence in terms of fracture resistance which is a function of density and 3D distribution. These changes can not be evaluated by 2D histological sections in bone histomorphometry based on a parallel plate model assumption.
Methods and Materials: Seventy 3-month old Swiss Webster mice were equally divided into 7 groups: 1 baseline, 2 sham surgery with placebo, 2 ovariectomy with placebo (OVX), and 2 OVX with 17β-estradiol at 250 µg/kg/week s.c. (ERT). One each of the 2 sham, OVX, and ERT groups were sacrificed at 5 weeks and the remaining groups were sacrificed at 13 weeks post-surgery. The distal femur was scanned using a micro CT scanner with isotropic resolution of 9 µ. 3D trabecular structure in the secondary spongiosa was directly measured without stereological model assumption. The values of 0 and 3 for structure model index (SMI) represent a perfect plate and a perfect rod structure, respectively. The vBMD in the distal femur, including both cortical and trabecular bone, was measured using a pQCT scanner. Serum osteocalcin and NTx were measured as indicators of bone turnover.
Results: At 5 weeks post-ovariectomy, there was a significant change in 3D trabecular bone volume fraction (-50%), trabecular number (-29%), trabecular thickness (-8%), trabecular separation (+54.38%), SMI (+14%), and degree of anisotropy (-10%) in the OVX group compared with those in the sham group. These changes were similar at 13 weeks post-ovariectomy, and no further bone loss was observed. Estradiol prevented ovariectomy-induced changes up to the sham level. Percentage changes in vBMD were similar to the changes in structure but less pronounced. The OVX group showed increased bone turnover at 5 weeks post-ovariectomy.
Conclusion: Ovariectomy induces high-turnover accelerated deterioration of 3D trabecular structure and density in mouse. The trabeculae become more rod-like and more isotropic after ovariectomy. Hormone replacement therapy prevents ovariectomy-induced changes.
Jiang MD, PhD, Y,
Three-dimensional Trabecular Microarchitecture and Density of a Postmenopausal Osteoporotic Model and Hormone Replacement Therapy: Micro CT Evaluation. Radiological Society of North America 2003 Scientific Assembly and Annual Meeting, November 30 - December 5, 2003 ,Chicago IL.
http://archive.rsna.org/2003/3102540.html
