| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Lack of estrogen after menopause and reduced activity (hypokinesis) are both important factors in the pathogenesis of osteoporosis in the elderly women. To compare the contribution of these two factors independently, we developed an animal model of ovariectomized (OVX) and sham-operated rats, which were housed in cages with limited space. The experimental cages restricted standing and walking, while allowing other activities such as eating, drinking and changing positions. After sacrificing rats at week 12, femora and tibia were examined with peripheral quantitative computed tomography (pQCT), laser Raman spectroscopy, three point bending, and histopathology. Although significantly elevated levels of metabolic markers, CTx, and osteocalcin were recorded in OVX groups compared to the Sham groups, results of bone strength as well as geometric parameters revealed significant differences only between Sham and Restricted groups. In the Restricted rat tibial cortices, both the number of empty osteocytic lacunae and lacuno-canalicular sclerostin staining were significantly increased. Not only was the bone thinner, narrowed marrow space was accompanied by the increased endocortical bone formation rate. Osteoclast activity was not necessarily associated with the osteoporotic pathology in the restrained rat bones. The uncoupling of osteoblastic and osteoclastic activities as well as the disorganized osteocyte network suggests a predominant role of osteocytic control over the cortical bone loss in the sedentary individuals. This model proved useful in evaluating the effect of drugs on bone by showing synergy between PTH and walking. The uneven outward extension of cortical bone was suggested from the local variation in the intensity of the synergistic effect.
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