目的：探討卵巢切除之前或之後介入耐力運動與飲食限制對於成年大鼠之骨代謝與骨組織型態之影響。方法：以週齡48週之雌性Sprague Dawley (SD)大鼠為實驗對象，依介入方法及犧牲時間點的不同分成實驗期為5週之控制組、去除卵巢前預先運動5週組、去除卵巢前預先40%飲食限制5週組，於介入5週後犧牲。實驗期為15週之組別則分別為：去除卵巢組、偽手術組、去除卵巢前預先運動組、去除卵巢後運動組、去除卵巢前預先40%飲食限制組、去除卵巢後40%飲食限制組，此六組動物在第5週進行去除卵巢手術或偽手術，於第15週犧牲。耐力運動訓練內容為16公尺/分鐘、60分鐘/天、5天/週之跑步訓練，限制飲食組僅提供去除卵巢組平均飲食量的60%。預先運動組在去卵巢前5週進行運動訓練，去卵巢後運動組在手術後開始進行10週運動訓練，預先飲食限制組在去卵巢前5週進行飲食限制，去卵巢後飲食限制組在手術後開始進行10週飲食限制。統計方法採用獨立樣本t檢定，進行各組和控制組的差異性比較(α = .05)。結果：(1) 體重變化：實驗介入第三週後，去除卵巢前預先運動組、去除卵巢前預先40%飲食限制組顯著低於去卵巢組；(2) 血液指標：去除卵巢前預先運動組和去除卵巢前預先40%飲食限制組的血中三酸甘油酯含量，在第五週、第七週、第十五週顯著低於去卵巢組；(3) 相對骨密度：除以體重的相對骨密度卵巢前預先運動組、去除卵巢前預先40%飲食限制組、去卵巢後40%飲食限制組在全股骨、皮質骨、幹骺區的骨密度及骨質含量顯著高於去卵巢組；(4) 骨組織型態：近端脛骨海綿股區的各組和去卵巢組皆未達顯著差異。結論：藉由耐力運動和飲食限制可以改善成年大鼠去卵巢後骨質大量流失的現象，預先於去卵巢前開始的耐力運動和飲食限制相較去卵巢後的介入有較好的效果，不僅可以調控體重和代謝狀態，也促使骨骼密度方面各項測量參數有較好的結果。

Objective: To investigate the effects of pre- and post- ovariectomy interventions of endurance exercise and dietary restriction on bone metabolism, bone mineral density and bone histomorphometry in adult rats.
Method: Female Sprague Dawley rats at age of 48 weeks old were randomly assigned to control group (CON5), Pre-ovariectomy exercise 5-week group (Pre-ovx EXE5), Pre-ovariectomy dietary restriction 5-week group (Pre-ovx DR5), ovariectomy 15-week group (OVX15), sham 15-week group (Sham15), pre-ovariectomy exercise 15-week group (Pre-ovx EXE15), post-ovariectomy exercise 15-week group (Post-ovx EXE15), pre-ovariectomy dietary restriction 15-week group (Pre-ovx DR15), post-ovariectomy dietary restriction 15-week group (Post-ovx DR15).The exercise intervention consisted of a treadmill running training at speed of 16 m/min, 60 min/day and 5 days/week. The dietary restriction groups subjected to 40% dietary restriction according to the average daily intake in the OVX15 group. Pre-and post- ovariectomy exercise groups were subjected to exercise intervention before and after ovariectomy, respectively. Similarly, pre- and post-ovariectomy dietary restriction groups received 40% dietary restriction before and after ovariectomy, respectively. After euthanasia, femoral bones were collected and prepared for micro CT scanning as well as densitometric and histomorphometric
analyses. Independent Sample t test (= .05) was used for comparing value between (1) the CON5 and time-matched groups ; (2) the OVX15 and time-matched groups.
Result: The Pre-ovx EXE15 , Post-ovx EXE15, Pre-ovx DR15 and Post-ovx DR15 groups were all significant lower in body weight gain as compared to the OVX15 group (p <0.05). Pre-ovx EXE15 and Pre-ovx DR15 groups had lower values in serum triglycerides when compared with the OVX15 group (p <0.05). In bone densitometry, Pre-ovx EXE15, Pre-ovx DR15 groups and Post-ovx DR15 group were significantly higher in total, cortical or metaphysis bone BMD and BMC when compared to the OVX15 group. There were no significantly difference among groups in any parameter of static histomorphometry.
Conclusion: Endurance exercise and dietary restriction both showed benefits on body weight control, bone densitometry and energy metabolism in mid-age ovariectomized rats. Pre-ovariectomy intervention of endurance exercise and dietary restriction showed more benefits than post-ovariectomy intervention.

Ahn, H., Seo, D. H., Kim, H. S., & Choue, R. (2014). Calorie restriction aggravated cortical and trabecular bone architecture in ovariectomy-induced estrogen-deficient rats. Nutrition Research, 34(8), 707-713.
Albala, C., Yanez, M., Devoto, E., Sostin, C., Zeballos, L., & Santos, J. (1996). Obesity as a protective factor for postmenopausal osteoporosis. International Journal of Obesity and Related Metabolic Disorders, 20(11), 1027-1032.
Alekel, L., Clasey, J. L., Fehling, P. C., Weigel, R. M., Boileau, R. A., Erdman, J. W., & Stillman, R. (1995). Contributions of exercise, body composition, and age to bone mineral density in premenopausal women. Medicine and Science in Sports and Exercise, 27(11), 1477-1485.
Avenell, A., Richmond, P., Lean, M., & Reid, D. (1994). Bone loss associated with a high fibre weight reduction diet in postmenopausal women. European Journal of Clinical Nutrition, 48(8), 561-566.
Barengolts, E. I., Curry, D. J., Bapna, M. S., & Kukreja, S. C. (1993). Effects of endurance exercise on bone mass and mechanical properties in intact and ovariectomized rats. Journal of Bone and Mineral Research, 8(8), 937-942.
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.
Beck, T. J., Petit, M. A., Wu, G., LeBoff, M. S., Cauley, J. A., & Chen, Z. (2009). Does Obesity Really Make the Femur Stronger? BMD, Geometry, and Fracture Incidence in the Women's Health Initiative‐Observational Study. Journal of Bone and Mineral Research, 24(8), 1369-1379.
Bell, K., Loveridge, N., Power, J., Garrahan, N., Stanton, M., Lunt, M., . . . Reeve, J. (1999). Structure of the femoral neck in hip fracture: cortical bone loss in the inferoanterior to superoposterior axis. Journal of Bone and Mineral Research, 14(1), 111-119.
Bouxsein, M. L., Boyd, S. K., Christiansen, B. A., Guldberg, R. E., Jepsen, K. J., & Müller, R. (2010). Guidelines for assessment of bone microstructure in rodents using micro–computed tomography. Journal of Bone and Mineral Research, 25(7), 1468-1486.
Chien, M., Wu, Y., Hsu, A.-T., Yang, R., & Lai, J. (2000). Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women. Calcified Tissue International, 67(6), 443-448.
Chow , J., Tobias, J., Colston, K., & Chambers, T. (1992). Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation. Journal of Clinical Investigation, 89(1), 74.
Chow, R., Harrison, J. E., & Notarius, C. (1987). Effect of two randomised exercise programmes on bone mass of healthy postmenopausal women. British Medical Journal, 295(6611), 1441-1444.
Compston, J. E., Watts, N. B., Chapurlat, R., Cooper, C., Boonen, S., Greenspan, S., . . . Lindsay, R. (2011). Obesity is not protective against fracture in postmenopausal women: GLOW. The American journal of medicine, 124(11), 1043-1050.
Devlin, M. J., Cloutier, A. M., Thomas, N. A., Panus, D. A., Lotinun, S., Pinz, I., . . . Bouxsein, M. L. (2010). Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. Journal of Bone and Mineral Research, 25(9), 2078-2088.
Donahue, H. J., Mazzeo, R. S., & Horvath, S. M. (1988). Endurance training and bone loss in calcium-deficient and ovariectomized rats. Metabolism, 37(8), 741-744.
Ernst, M., Schmid, C., & Froesch, E. (1988). Enhanced osteoblast proliferation and collagen gene expression by estradiol. Proceedings of the National Academy of Sciences, 85(7), 2307-2310.
Farrell, P. A., & Barboriak, J. (1980). The time course of alterations in plasma lipid and lipoprotein concentrations during eight weeks of endurance training. Atherosclerosis, 37(2), 231-238.
Garnero, P., Sornay‐Rendu, E., Chapuy, M. C., & Delmas, P. D. (1996). Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. Journal of Bone and Mineral Research, 11(3), 337-349.
Goodyear, P., Laurie J, & Kahn, M., Barbara B. (1998). Exercise, glucose transport, and insulin sensitivity. Annual Review of Medicine, 49(1), 235-261.
Halverstadt, A., Phares, D. A., Wilund, K. R., Goldberg, A. P., & Hagberg, J. M. (2007). Endurance exercise training raises high-density lipoprotein cholesterol and lowers small low-density lipoprotein and very low-density lipoprotein independent of body fat phenotypes in older men and women. Metabolism-Clinical and Experimental, 56(4), 444-450.
Hamrick, M. W., Ding, K. H., Ponnala, S., Ferrari, S. L., & Isales, C. M. (2008). Caloric restriction decreases cortical bone mass but spares trabecular bone in the mouse skeleton: implications for the regulation of bone mass by body weight. Journal of Bone and Mineral Research, 23(6), 870-878.
Harper, C., Pattinson, A. L., Fernando, H. A., Zibellini, J., Seimon, R. V., & Sainsbury, A. (2016). Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity. Hormone Molecular Biology and Clinical Investigation, 28(3), 133-149.
Hatori, M., Hasegawa, A., Adachi, H., Shínozaki, 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.
Henderson, N. K., Price, R. I., Cole, J. H., Gutteridge, D. H., & Bhagat, C. I. (1995). Bone density in young women is associated with body weight and muscle strength but not dietary intakes. Journal of Bone and Mineral Research, 10(3), 384-393.
Huang, T. H., & Ables, G. P. (2016). Dietary restrictions, bone density, and bone quality. Annals of the New York Academy of Sciences, 1363(1), 26-39.
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. Journal of Bone and Mineral Metabolism, 26(4), 350-357.
Huang, T. H., Lewis, J. L., Lin, H. S., Kuo, L. T., Mao, S. W., Tai, Y. S., . . . Yang, R. S. (2014). A methionine-restricted diet and endurance exercise decrease bone mass and extrinsic strength but increase intrinsic strength in growing male rats. The Journal of Nutrition, 144(5), 621-630.
Huang, T. H., Su, I. H., Lewis, J. L., Chang, M. S., Hsu, A. T., Perrone, C. E., & Ables, G. P. (2015). Effects of methionine restriction and endurance exercise on bones of ovariectomized rats: a study of histomorphometry, densitometry, and biomechanical properties. Journal of Applied Physiology, 119(5), 517-526.
Hughes, D. E., Dai, A., Tiffee, J. C., Li, H. H., Mundy, G. R., & Boyce, B. F. (1996). Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β. Nature Medicine, 2(10), 1132-1136.
Iwamoto, J., Takeda, T., Sato, Y., Shen, C.-L., & Yeh, J. K. (2006). Beneficial effect of pretreatment and treatment continuation with risedronate and vitamin K2 on cancellous bone loss after ovariectomy in rats: a bone histomorphometry study. Journal of Nutritional Science and Vitaminology, 52(5), 307-315.
Joo, Y.-I., Sone, T., Fukunaga, M., Lim, S.-G., & Onodera, S. (2003). Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats. Bone, 33(4), 485-493.
Kalu, D. N. (1991). The ovariectomized rat model of postmenopausal bone loss. Bone and Mineral, 15(3), 175-191.
Kalu, D. N., Hardin, R. R., Cockerham, R., Yu, B. P., Norling, B. K., & Egan, J. W. (1984). Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats. Mechanisms of Ageing and Development, 26(1), 103-112.
Kameda, T., Mano, H., Yuasa, T., Mori, Y., Miyazawa, K., Shiokawa, M., . . . Kameda, A. (1997). Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. Journal of Experimental Medicine, 186(4), 489-495.
Kelley, G. A. (1998). Aerobic exercise and bone density at the hip in postmenopausal women: a meta-analysis. Preventive Medicine, 27(6), 798-807.
Komm, B. S., Terpening, C. M., Benz, D. J., Graeme, K. A., Gallegos, A., Korc, M., . . . Haussler, M. R. (1988). Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science, 241(4861), 81-84.
LaMothe, J. M., Hepple, R. T., & Zernicke, R. F. (2003). Selected contribution: bone adaptation with aging and long-term caloric restriction in Fischer 344× Brown-Norway F1-hybrid rats. Journal of Applied Physiology, 95(4), 1739-1745.
Lane, M. A., Baer, D. J., Rumpler, W. V., Weindruch, R., Ingram, D. K., Tilmont, E. M., . . . Roth, G. S. (1996). Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents. Proceedings of the National Academy of Sciences, 93(9), 4159-4164.
Leonard, M. B., Shults, J., Wilson, B. A., Tershakovec, A. M., & Zemel, B. S. (2004). Obesity during childhood and adolescence augments bone mass and bone dimensions. The American Journal of Clinical Nutrition, 80(2), 514-523.
Lespessailles, E., Jaffre, C., Beaupied, H., Nanyan, P., Dolleans, E., Benhamou, C., & Courteix, D. (2009). Does exercise modify the effects of zoledronic acid on bone mass, microarchitecture, biomechanics, and turnover in ovariectomized rats? Calcified Tissue International, 85(2), 146-157.
Leung, F. P., Yung, L. M., Laher, I., Yao, X., Chen, Z. Y., & Huang, Y. (2008). Exercise, vascular wall and cardiovascular diseases. Sports Medicine, 38(12), 1009-1024.
Mazzeo, R. S., Cavanagh, P., Evans, W. J., Fiatarone, M., Hagberg, J., McAuley, E., & Startzell, J. (1998). Exercise and physical activity for older adults. Medicine and Science in Sports and Exercise, 30(6), 992-1008.
Nicodemus, K. K., & Folsom, A. R. (2001). Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care, 24(7), 1192-1197.
Okman-Kilic, T. (2015). Estrogen deficiency and osteoporosis Advances in Osteoporosis: InTech.
Oursler, M. J., Cortese, C., Keeting, P., Anderson, M. A., Bonde, S. K., Riggs, B. L., & Spelsberg, T. C. (1991). Modulation of transforming growth factor-β production in normal human osteoblast-like cells by 17 β-estradiol and parathyroid hormone. Endocrinology, 129(6), 3313-3320.
Oursler, M. J., Osdoby, P., Pyfferoen, J., Riggs, B. L., & Spelsberg, T. C. (1991). Avian osteoclasts as estrogen target cells. Proceedings of the National Academy of Sciences, 88(15), 6613-6617.
Pacifici, R. (1996). Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. Journal of Bone and Mineral Research, 11(8), 1043-1051.
Patsch, J. M., Burghardt, A. J., Yap, S. P., Baum, T., Schwartz, A. V., Joseph, G. B., & Link, T. M. (2013). Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. Journal of Bone and Mineral Research, 28(2), 313-324.
Ricci, T. A., Heymsfield, S. B., Pierson, R. N., Stahl, T., Chowdhury, H. A., & Shapses, S. A. (2001). Moderate energy restriction increases bone resorption in obese postmenopausal women. The American Journal of Clinical Nutrition, 73(2), 347-352.
Rizza, W., Veronese, N., & Fontana, L. (2014). What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Research Reviews, 13, 38-45.
Ryan, A. S., Nicklas, B. J., & Dennis, K. E. (1998). Aerobic exercise maintains regional bone mineral density during weight loss in postmenopausal women. Journal of Applied Physiology, 84(4), 1305-1310.
Sanderson, J. P., Binkley, N., Roecker, E. B., Champ, J. E., Pugh, T. D., Aspnes, L., & Weindruch, R. (1997). Influence of fat intake and caloric restriction on bone in aging male rats. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 52(1), 20-25.
Seals, D. R., Hagberg, J. M., Hurley, B. F., Ehsani, A. A., & Holloszy, J. O. (1984). Endurance training in older men and women. I. Cardiovascular responses to exercise. Journal of Applied Physiology, 57(4), 1024-1029.
Shapses, S. A., Von Thun, N. L., Heymsfield, S. B., Ricci, T. A., Ospina, M., Pierson, R. N., & Stahl, T. (2001). Bone turnover and density in obese premenopausal women during moderate weight loss and calcium supplementation. Journal of Bone and Mineral Research, 16(7), 1329-1336.
Stevenson, J. C., Crook, D., & Godsland, I. F. (1993). Influence of age and menopause on serum lipids and lipoproteins in healthy women. Atherosclerosis, 98(1), 83-90.
Talbott, S. M., Rothkopf, M. M., & Shapses, S. A. (1998). Dietary restriction of energy and calcium alters bone turnover and density in younger and older female rats. The Journal of Nutrition, 128(3), 640-645.
Tatsumi, S., Ito, M., Asaba, Y., Tsutsumi, K., & Ikeda, K. (2007). Life-long caloric restriction reveals biphasic and dimorphic effects on bone metabolism in rodents. Endocrinology, 149(2), 634-641.
Tremblay, A., Després, J.-P., & Bouchard, C. (1985). The effects of exercise-training on energy balance and adipose tissue morphology and metabolism. Sports Medicine, 2(3), 223-233.
Tsuang, Y.-H., Chen, L.-T., Chiang, C.-J., Wu, L.-C., Chiang, Y.-F., Chen, P.-Y., . . . Wang, C.-C. (2008). Isoflavones prevent bone loss following ovariectomy in young adult rats. Journal of Orthopaedic Surgery and Research, 3(1), 12.
Vainionpää, A., Korpelainen, R., Leppäluoto, J., & Jämsä, T. (2005). Effects of high-impact exercise on bone mineral density: a randomized controlled trial in premenopausal women. Osteoporosis International, 16(2), 191-197.
Villareal, D. T., Fontana, L., Weiss, E. P., Racette, S. B., Steger-May, K., Schechtman, K. B., . . . Holloszy, J. O. (2006). Bone mineral density response to caloric restriction–induced weight loss or exercise-induced weight loss: a randomized controlled trial. Archives of Internal Medicine, 166(22), 2502-2510.
Väänänen, H. K., & Härkönen, P. L. (1996). Estrogen and bone metabolism. Maturitas, 23, 65-69.
Weindruch, R. (1996). The retardation of aging by caloric restriction: studies in rodents and primates. Toxicologic Pathology, 24(6), 742-745.
Weise, M., De-Levi, S., Barnes, K. M., Gafni, R. I., Abad, V., & Baron, J. (2001). Effects of estrogen on growth plate senescence and epiphyseal fusion. Proceedings of the National Academy of Sciences, 98(12), 6871-6876.
Welsh, L., & Rutherford, O. M. (1996). Hip bone mineral density is improved by high-impact aerobic exercise in postmenopausal women and men over 50 years. European Journal of Applied Physiology and Occupational Physiology, 74(6), 511-517.
Wieczorek-Baranowska, A., Nowak, A., & Pilaczyńska-Szcześniak, Ł. (2012). Osteocalcin and glucose metabolism in postmenopausal women subjected to aerobic training program for 8 weeks. Metabolism, 61(4), 542-545.
Wood, P. D., Stefanick, M. L., Dreon, D. M., Frey-Hewitt, B., Garay, S. C., Williams, P. T., . . . Vranizan, K. M. (1988). Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. New England Journal of Medicine, 319(18), 1173-1179.
Yamazaki, S., Ichimura, S., Iwamoto, J., Takeda, T., & Toyama, Y. (2004). Effect of walking exercise on bone metabolism in postmenopausal women with osteopenia/osteoporosis. Journal of Bone and Mineral Research, 22(5), 500-508.