| Project/Area Number |
02454342
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | University of Occupational and Environmental Health, Japan (UOEH). |
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Principal Investigator |
NAKAMURA Toshitaka University of Occupational and Environmental Health, Japan. Department of Orthopedics. Associate Professor., 医学部, 助教授 (50082235)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMITSU Shin-ichi UOEH, Dept. of Orthopedics, Lecturer, 医学部, 助手 (00227878)
MISHIMA Shin-ichi UOEH, Dept. of Orthopedics, Lecturer, 医学部, 講師 (90229683)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1990: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | 24R,25-dihydroxyvitamin D3 / Bone mass increase / Osteoclast / Osteoblast / Bone histomorphometry / Postmenopausal osteoporosis / 1,25-dihydroxyvitamin D3 / Bone matrix / ビーグル犬 / 卵巣摘出骨粗鬆症モデル / 骨ミネラル量 / 骨組織計測 / 力学試験 / 卵巣摘除ビ-グル犬 / 尿中ハイドロキシプロリン / 骨ミネラル / 骨形成率 / 骨吸収 / 24R,25(OH)_2D_3 / 低代謝回転骨 / ウサギ / 24R,25ビタミンD_3 / 大腿骨 / 骨強度 |
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| Research Abstract |
This research demonstrated the cellular mechanism of bone mass increasing action of 24R,25-dihydroxyvitamin D3 and indicated its application for the treatment of postmenopausal osteoporosis. We have observed that the massive administration of the agent greatly cincreases the bone mass without increasing serum calcium level in rats and rabbits. Mechanical properties of the bone were found to be normal by breaking tests. Bone histomorphometry demonstrated that both the eroded surface and the osteoclast number reduced and bone formation also reduced. Both the osteoid thickness and the mineral apposition rate increased. These data are the most important results obtained in this research project. Then, we applied this agent on the postovariectomy bone loss in beagles. The 24R,25-dihydroxyvitamin D3 administration well preserved the bone mass. Histomorphometrical analyses showed an increase of osteoclastic boner esorption and a reduction in osteoblast bunctions in ovariectomized animals, and in animals treated with the agent, both of these cellular functions maintained the same level as in the sham group. These data clearly demonstrated that the agent administration is able to maintain the bone cell functions in estrogen deficient condition. It is uncertain whether these functions are specific for 24R,25-dihydroxyvitamin D3. Vitamin D-repletion is found to be the prerequisite for the action of 24R,25-dihydroxyvitamin D3, and the actions of decreasing the osteoclast number and increasing the bone matrix production in osteoblast are both closely related to the actions of 1,25-dihydroxyvitamin D3. Therefore, it may be rather reasonable to anticipate that the bone mass increasing action of 24R,25-dihydroxy vitamin D3 are exerted through the modification of 1,25-dihydroxyvitamin D3 actions on bone cells. This study may well warrant further studies to obtain other bone mass increasing substances by modifying the chemical structure of 1,25-dihydroxyvitamin D3.
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