| 研究生: |
周育賢 Chou, Yu-Hsien |
|---|---|
| 論文名稱: |
雙磷酸鹽與耐力運動對於去卵巢大鼠骨代謝與能量代謝之影響 The Effects of Zoledronic Acid and Endurance Exercise on Bone Metabolism and Energy Metabolism of Ovariectomized Rats |
| 指導教授: |
黃滄海
Huang, Tsang-Hai |
| 學位類別: |
碩士 Master |
| 系所名稱: |
管理學院 - 體育健康與休閒研究所 Institute of Physical Education, Health & Leisure Studies |
| 論文出版年: | 2014 |
| 畢業學年度: | 102 |
| 語文別: | 中文 |
| 論文頁數: | 51 |
| 中文關鍵詞: | 骨質疏鬆 、骨骼生物力學特性 、瘦體素 、骨品質 |
| 外文關鍵詞: | osteoporosis, biomechanical properties, leptin, bone quality |
| 相關次數: | 點閱:120 下載:2 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
目的:本研究探討雙磷酸鹽及耐力運動介入對切除卵巢大鼠之骨代謝、能量代謝、骨組織型態與骨組織生物力學特性之影響。方法:以週齡35週之雌性Sprague Dawley (SD) 大鼠為研究對象,依照卵巢切除手術 (ovariectomy, OVX) 或偽手術 (sham surgery, SHA)、注射兩種劑量 (4 & 20, μg/kg) 之雙磷酸鹽 (藥名:zoledronic acid, ZA) 及耐力運動 (endurance exercise, EXE) 等實驗設計分做七組,分別為Sham (n=9)、OVX (n=8)、OVX+EXE (n=8)、OVX+ZA4 (n=9)、OVX+ZA4 +EXE (n=9)、OVX+ZA20 (n=9)、OVX+ZA20+EXE (n=9)。12週實驗介入後,動物安樂死所得骨骼樣本進行骨密度學、動態與靜態組織型態學分析,及以三點彎曲方法測量股骨之各項骨骼生物力學特性;血液樣本則進行各項骨代謝指標分析。統計方法以雙因子變異數分析進行去卵巢組別之各變項組間差異性比較,以獨立樣本t檢定進行SHA組與OVX組之差異性比較及皮爾森相關對於骨代謝血液指標與血糖調節指標相關性分析,當p<.05時,視為達統計上之顯著水準。結果:經過12週實驗介入,OVX大鼠在接受耐力運動後,體重、三酸甘油脂與瘦體素濃度皆顯著下降,而且全股骨BMD、全股骨BMC與海綿骨BMD顯著大於無運動的OVX大鼠。另外,OVX大鼠注射ZA後降低瘦體素、骨鈣素濃度及次海綿骨區內之皮質骨區的礦化程度,但在海綿骨量與骨骼生物力學強度上皆顯著提升,而且全股骨BMC亦有顯著提升,其中注射ZA4的OVX大鼠在全股骨、股骨皮質骨及股骨海綿骨的BMD皆顯著大於注射ZA20的OVX大鼠。結論:骨頭透過ZA4注射後,不僅防止骨質大量流失而且骨頭負荷的表現亦有顯著提升。若再合併具有促進骨代謝效率之EXE,不僅促使各種骨骼組織之測試皆能有效改善去卵巢手術的影響,亦能降低體重與三酸甘油脂。
Purpose: The purpose of this study is to investigate the effects of bisphosphonate and endurance exercise (EXE) on bone metabolism, histomorphometry and biomechanical properties in ovariectomized rats. Methods: Thirty-five-week-old Sprague Dawley (SD) rats were used for the current study. All animals were assigned to seven groups in accordance with ovariectomy (OVX)/sham surgery (SHA)、zoledronic acid (ZA) injection at low or medium doses (4 & 20, μg/kg) and endurance exercise (EXE), which were Sham (n=9), OVX (n=8) , OVX+EXE (n=8), OVX+ZA4 (n=9) , OVX+ZA4 +EXE (n=9) , OVX+ZA20 (n=9) and OVX+ZA20+EXE (n=9). After 12-week interventions, all animals were euthanized. Samples of serum and bone were collected for analyses including serum marker assays, densitometry, static histomorphometry, dynamic histomorphometry and biomechanical three-point bending testing. Two-way ANOVA was used for data processing among ovariectomized groups. T-test was used for comparing the differences between the SHA group and the OVX group. Pearson’s correlation was used for analysising the relationship between serum of bone metabolism and glucose metabolism. Results: EXE rats were lower in weight, triglyceride, leptin and BMD of total femur, cortical bone and second spongiosa as comparing to non-EXE rats. On the other hand, ZA rats were lower in leptin, osteocalcin, and the mineralization degrees of second spongiosa and endocrinal bone comparing to non-injection rats. And, ZA rats were significantly higher in spongy bone volume, bone mechanical strength and total femoral BMD. Interestingly, ZA4 rats were higher in total, cortical and spongy BMD of femur when comparing to ZA20 rats. Conclusion: OVX rats treated by ZA4 had less bone loss and increased bone strength. Rats treated by ZA combined with EXE not only showed increased bone tissue but also decreased body weight and triglyceride.
林欣仕 (2008) 短期落地訓練對成長中母鼠的局部骨骼代謝之影響 (未出版碩士論文) 。國立成功大學,台南市。
蘇亦秀 (2013) 甲硫胺酸限制飲食與耐力運動對去卵巢大鼠骨骼之代謝, 組織型態與生物力學特性的影響 (未出版碩士論文) 。國立成功大學,台南市。
Allen, M. R., & Burr, D. B. (2007). Three years of alendronate treatment results in similar levels of vertebral microdamage as after one year of treatment. Journal of Bone and Miner Research, 22(11), 1759-1765.
Barengolts, E. I., Lathon, P. V., Curry, D. J., & Kukreja, S. C. (1994). Effects of endurance exercise on bone histomorphometric parameters in intact and ovariectomized rats. Bone and Mineral, 26(2), 133-140.
Black, D. M., Delmas, P. D., Eastell, R., Reid, I. R., Boonen, S., Cauley, J. A., . . . Trial, H. P. F. (2007). Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. The New England Journal of Medicine, 356(18), 1809-1822.
Bonnet, N., Beaupied, H., Vico, L., Dolleans, E., Laroche, N., Courteix, D., & Benhamou, C. L. (2007). Combined effects of exercise and propranolol on bone tissue in ovariectomized rats. Journal of Bone and Miner Research, 22(4), 578-588.
Borba-Pinheiro, C. J., de Alencar Carvalho, M. C., da Silva, N. S., Drigo, A. J., Bezerra, J. C., & Dantas, E. H. (2010). Bone density, balance and quality of life of postmenopausal women taking alendronate participating in different physical activity programs. Therapeutic Advances in Musculoskeletal Disease, 2(4), 175-185.
Cerri, P. S., Boabaid, F., & Katchburian, E. (2003). Combined TUNEL and TRAP methods suggest that apoptotic bone cells are inside vacuoles of alveolar bone osteoclasts in young rats. Journal of Periodontal Research, 38(2), 223-226.
Chavassieux, P. M., Arlot, M. E., Reda, C., Wei, L., Yates, A. J., & Meunier, P. J. (1997). Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. The Journal of Clinical Investigation, 100(6), 1475-1480.
Chien, M. Y., Wu, Y. T., Hsu, A. T., Yang, R. S., & Lai, J. S. (2000). Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women. Calcified Tissue Internal, 67(6), 443-448.
Davidson, L. E., Hudson, R., Kilpatrick, K., Kuk, J. L., McMillan, K., Janiszewski, P. M., . . . Ross, R. (2009). Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial. Archives of Internal Medicine, 169(2), 122-131.
De Oliveira, J. C., Ludemann Camargo, R., Barella, L. F., Chaves Souto Branco, R., Gravena, C., Grassiolli, S., . . . Cezar De Freitas Mathias, P. (2013). Anesthetic-induced transient hyperglycemia and insulin resistance do not depend on the sympathoadrenal axis. Minerva Endocrinologica, 38(4), 379-388.
Dengel, D. R., Pratley, R. E., Hagberg, J. M., Rogus, E. M., & Goldberg, A. P. (1996). Distinct effects of aerobic exercise training and weight loss on glucose homeostasis in obese sedentary men. Journal of Applied Physiology (1985), 81(1), 318-325.
Evangelista, P. T., & Levine, S. M. (2012). Atypical insufficiency type femoral stress fractures in patient on bisphosphonates. Medicine and Health, Rhode Island, 95(2), 61-62.
Ferron, M., Wei, J., Yoshizawa, T., Del Fattore, A., DePinho, R. A., Teti, A., . . . Karsenty, G. (2010). Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell, 142(2), 296-308.
Fleisch, H., Russell, R. G., Simpson, B., & Muhlbauer, R. C. (1969). Prevention by a diphosphonate of immobilization "osteoporosis" in rats. Nature, 223(5202), 211-212.
Frank, L. L., Sorensen, B. E., Yasui, Y., Tworoger, S. S., Schwartz, R. S., Ulrich, C. M., . . . McTiernan, A. (2005). Effects of exercise on metabolic risk variables in overweight postmenopausal women: A randomized clinical trial. Obesity Research, 13(3), 615-625.
Friedman, J. M., & Halaas, J. L. (1998). Leptin and the regulation of body weight in mammals. Nature, 395(6704), 763-770.
Fuchs, R. K., Shea, M., Durski, S. L., Winters-Stone, K. M., Widrick, J., & Snow, C. M. (2007). Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats. Bone, 41(2), 290-296.
Fulzele, K., Riddle, R. C., DiGirolamo, D. J., Cao, X., Wan, C., Chen, D., . . . Clemens, T. L. (2010). Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell, 142(2), 309-319.
Gasser, J. A., Ingold, P., Venturiere, A., Shen, V., & Green, J. R. (2008). Long-term protective effects of zoledronic acid on cancellous and cortical bone in the ovariectomized rat. Journal of Bone and Mineral Research, 23(4), 544-551.
Goodship, A. E., Blunn, G. W., Green, J., & Coathup, M. J. (2008). Prevention of strain-related osteopenia in aseptic loosening of hip prostheses using perioperative bisphosphonate. Journal of Orthopaedic Research, 26(5), 693-703.
Gourion-Arsiquaud, S., Allen, M. R., Burr, D. B., Vashishth, D., Tang, S. Y., & Boskey, A. L. (2010). Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone, 46(3), 666-672.
Hatori, M., Hasegawa, A., Adachi, H., Shinozaki, A., Hayashi, R., Okano, H., . . . Murata, K. (1993). The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women. Calcified Tissue International, 52(6), 411-414.
Hinoi, E., Gao, N., Jung, D. Y., Yadav, V., Yoshizawa, T., Myers, M. G., Jr., . . . Karsenty, G. (2008). The sympathetic tone mediates leptin's inhibition of insulin secretion by modulating osteocalcin bioactivity. The Journal of Cell Biology, 183(7), 1235-1242.
Hong, S. H., Koo, J. W., Hwang, J. K., Hwang, Y. C., Jeong, I. K., Ahn, K. J., . . . Kim, D. Y. (2013). Changes in serum osteocalcin are not associated with changes in glucose or insulin for Osteoporotic Patients Treated with Bisphosphonate. J Bone Metab, 20(1), 37-41.
Huang, T. H., Chang, F. L., Lin, S. C., Liu, S. H., Hsieh, S. S., & Yang, R. S. (2008). Endurance treadmill running training benefits the biomaterial quality of bone in growing male Wistar rats. J Bone Miner Metab, 26(4), 350-357.
Huang, T. H., Lin, S. C., Chang, F. L., Hsieh, S. S., Liu, S. H., & Yang, R. S. (2003). Effects of different exercise modes on mineralization, structure, and biomechanical properties of growing bone. J Appl Physiol (1985), 95(1), 300-307.
Iwamoto, J., Takeda, T., Sato, Y., & Uzawa, M. (2005). Effect of whole-body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate. Aging Clin Exp Res, 17(2), 157-163.
Jacques, R. M., Boonen, S., Cosman, F., Reid, I. R., Bauer, D. C., Black, D. M., & Eastell, R. (2012). Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res, 27(8), 1627-1634.
Jiang, X., Westermann, L. B., Galleo, G. V., Demko, J., Marakovits, K. A., & Schnatz, P. F. (2013). Age as a predictor of osteoporotic fracture compared with current risk-prediction models. Obstet Gynecol, 122(5), 1040-1046.
Karsenty, G., & Ferron, M. (2012). The contribution of bone to whole-organism physiology. Nature, 481(7381), 314-320.
Kawai, M., Devlin, M. J., & Rosen, C. J. (2009). Fat targets for skeletal health. Nat Rev Rheumatol, 5(7), 365-372.
Lee, N. K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J. D., Confavreux, C., . . . Karsenty, G. (2007). Endocrine regulation of energy metabolism by the skeleton. Cell, 130(3), 456-469.
Lespessailles, E., Jaffre, C., Beaupied, H., Nanyan, P., Dolleans, E., Benhamou, C. L., & Courteix, D. (2009). Does exercise modify the effects of zoledronic acid on bone mass, microarchitecture, biomechanics, and turnover in ovariectomized rats? Calcif Tissue Int, 85(2), 146-157.
Lespessailles, E., Jaffre, C., Rochefort, G. Y., Dolleans, E., Benhamou, C. L., & Courteix, D. (2010). Exercise and zoledronic acid on lipid profile and bone remodeling in ovariectomized rats: a paradoxical negative association? Lipids, 45(4), 337-344.
Mashiba, T., Hirano, T., Turner, C. H., Forwood, M. R., Johnston, C. C., & Burr, D. B. (2000). Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res, 15(4), 613-620.
Ogata, N., Chikazu, D., Kubota, N., Terauchi, Y., Tobe, K., Azuma, Y., . . . Kawaguchi, H. (2000). Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J Clin Invest, 105(7), 935-943.
Orita, S., Ohtori, S., Koshi, T., Yamashita, M., Yamauchi, K., Inoue, G., . . . Takahashi, K. (2010). The effects of risedronate and exercise on osteoporotic lumbar rat vertebrae and their sensory innervation. Spine (Phila Pa 1976), 35(22), 1974-1982.
Parfitt, A. M. (1988). Bone histomorphometry: proposed system for standardization of nomenclature, symbols, and units. Calcif Tissue Int, 42(5), 284-286.
Pasman, W. J., Westerterp-Plantenga, M. S., & Saris, W. H. (1998). The effect of exercise training on leptin levels in obese males. Am J Physiol, 274(2 Pt 1), E280-286.
Popp, A. W., Guler, S., Lamy, O., Senn, C., Buffat, H., Perrelet, R., . . . Lippuner, K. (2013). Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: a three-year study. J Bone Miner Res, 28(3), 449-454
Rochefort, G. Y., Rocher, E., Aveline, P. C., Garnero, P., Bab, I., Chappard, C., . . . Benhamou, C. L. (2011). Osteocalcin-insulin relationship in obese children: a role for the skeleton in energy metabolism. Clin Endocrinol (Oxf), 75(2), 265-270.
Rodan, G. A., & Fleisch, H. A. (1996). Bisphosphonates: mechanisms of action. J Clin Invest, 97(12), 2692-2696.
Ropelle, E. R., Flores, M. B., Cintra, D. E., Rocha, G. Z., Pauli, J. R., Morari, J., . . . Carvalheira, J. B. (2010). IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition. PLoS Biol, 8(8).
Schafer, A. L., Sellmeyer, D. E., Schwartz, A. V., Rosen, C. J., Vittinghoff, E., Palermo, L., . . . Black, D. M. (2011). Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab, 96(12), E1982-1989.
Schwartz, A. V., Schafer, A. L., Grey, A., Vittinghoff, E., Palermo, L., Lui, L. Y., . . . Reid, I. R. (2013). Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Miner Res, 28(6), 1348-1354.
Sipos, W., Rauner, M., Skalicky, M., Viidik, A., Hofbauer, G., Schett, G., . . . Pietschmann, P. (2008). Running has a negative effect on bone metabolism and proinflammatory status in male aged rats. Exp Gerontol, 43(6), 578-583.
Takeda, S., Elefteriou, F., Levasseur, R., Liu, X., Zhao, L., Parker, K. L., . . . Karsenty, G. (2002). Leptin regulates bone formation via the sympathetic nervous system. Cell, 111(3), 305-317.
Turner, C. H., Akhter, M. P., Raab, D. M., Kimmel, D. B., & Recker, R. R. (1991). A noninvasive, in vivo model for studying strain adaptive bone modeling. Bone, 12(2), 73-79.
Uusi-Rasi, K., Sievanen, H., Heinonen, A., Kannus, P., & Vuori, I. (2004). Effect of discontinuation of alendronate treatment and exercise on bone mass and physical fitness: 15-month follow-up of a randomized, controlled trial. Bone, 35(3), 799-805.
Wieczorek-Baranowska, A., Nowak, A., & Pilaczynska-Szczesniak, L. (2012). Osteocalcin and glucose metabolism in postmenopausal women subjected to aerobic training program for 8 weeks. Metabolism, 61(4), 542-545.
Xiao, Y. F., Wang, B., Wang, X., Du, F., Benzinou, M., & Wang, Y. X. (2013). Xylazine-induced reduction of tissue sensitivity to insulin leads to acute hyperglycemia in diabetic and normoglycemic monkeys. BMC Anesthesiol, 13(1), 33.
Yamazaki, S., Ichimura, S., Iwamoto, J., Takeda, T., & Toyama, Y. (2004). Effect of walking exercise on bone metabolism in postmenopausal women with osteopenia/osteoporosis. J Bone Miner Metab, 22(5), 500-508.