隨著醫療科技的進步，人類壽命延長，老年人及婦女在經歷更年期停經後，骨質密度快速下降，導致骨質疏鬆症罹患率升高。全球超過五十歲以上的女性約有1/3罹患骨質疏鬆症，男性為1/5。在台灣，19.8%的65歲以上婦女至少發生一個以上之脊椎體壓迫性骨折；男性則為12.5%。傳統治療骨質疏鬆症的方法為服用鈣片、荷爾蒙或藥物，但大部分藥物易產生副作用，造成體內器官負擔及不舒服感，亦或是副作用少卻價格昂貴。因此發展使用外在的物理性刺激治療骨質疏鬆症將成為趨勢。美國食品藥物管理局核准的脈衝式電磁場，每天需配戴六至八小時不等，長時間配戴並不符合病患期望。本研究目的為探討物理性單脈衝高能量磁場於卵巢切除誘發骨質疏鬆動物模型的骨質效應。

本實驗使用24 隻大鼠隨機分組：Group 1 為Control 組，8 隻健康發育的大鼠，不進行磁刺激治療；剩下16隻大鼠進行雙側卵巢切除手術誘發仿婦女停經後骨質疏鬆，再隨機分為兩組：Group 2 將8 隻施行雙側卵巢切除誘發骨質疏鬆的大鼠，不進行磁刺激治療，為non-treatment 組；Group 3 有8 隻施行雙側卵巢切除誘發骨質疏鬆的大鼠，進行8 週單一脈衝式電磁場(SPEMF)刺激，命名為SPEMF 組。16週大的大鼠使用micro-CT量測三組的骨形態參數值，並在第32週以微電腦斷層掃描確定卵巢切除有誘發骨質疏鬆的現象。在磁刺激治療進行的八週後使用微電腦斷層掃描攝影大鼠腰椎第五節的活體影像。三組活體所得到的骨形態參數：骨體積百分比、骨小樑厚度、骨小樑間距、骨小樑數量、以及轉動慣量，個別使用One-way ANOVA進行基線、卵巢切除後及治療後的分析比較，選取α=0.05。三組老鼠經過八週後，將老鼠犧牲取出第五節腰椎作組織切片觀察。

初始的骨型態學參數值之平均值及標準差，三組間各骨型態參數無顯著差異。Osteoporosis 組的16隻大鼠測量初始骨小樑參數後將其雙側卵巢切除，經過16週後，各參數顯示骨小樑有減少的情形，表示卵巢切除後32週成功誘發骨質疏鬆。在骨體積百分比、骨小樑厚度、骨小樑間距、骨小樑數量及轉動慣量，control組均顯現出骨量及強度增加的趨勢，除了骨小樑數量外，在40週的參數均與16週有顯著差異；non-treatment組均顯現出骨量及強度減弱的趨勢，除了轉動慣量外，在40週的參數均與16週有顯著差異；SPEMF組在卵巢切除後有顯現出骨量及強度減弱的趨勢，除了骨小樑厚度外，在32週的參數均與16週有顯著差異，在磁刺激治療後均有顯現出骨量及強度增加的趨勢，所有的參數在40週均與32週有顯著差異。在本實驗中，磁場刺激對於骨量及強度的增加有顯著的功效。

本研究應用脈衝式電磁場系統於雙側卵巢切除誘發骨質疏鬆大鼠，經由微電腦斷層攝影掃描量化骨質及強度，結果顯示磁場刺激可促進骨質疏鬆老鼠的腰椎椎體骨質修復。未來可繼續探討其缺失並發展改良，包括以下幾點：利用不同的磁場強度對於骨質的增生進行探討與分析。探討磁場刺激對於骨以外的組織(如：韌帶、血管)以及臟器(如：肝、腎)是否有鈣化等不良影響進行研究分析。

The human life expectancy due to advanced technological development has led to a dramatic increasing incidence and prevalence of osteoporosis recently. In the worldwide, 1/3 of the female population with above 50 years old suffer from osteoporosis, the prevalence was about 1/5 for the male with ages above 50 years old. In Taiwan, 19.8% of compression fracture at vertebral body due to osteoporosis in woman over 65 years old. The conventional treatment for osteoporosis were taking calcium, hormone or drug medication, but these medication were either high cost or often producing side effects on the user. The physical stimulation was likely to enhance the bone formation. The treatment duration of pulsed electromagnetic field approved by FDA was about 6~8 hours per day. It’s too long time to inconvenience for patients. This study was to investigate the effect of the single pulsed electromagnetic field (SPEMF) on osteoporosis in bilateral ovariectomy animal models.

Total of 24 S.D. rats were randomly assigned to 3 groups including: control group with 8 normal health rats, without SPEMF stimulation. The other 16 rats induced osteoporosis after bilateral ovariectomy then randomly assigned to 2 groups: non-treatment group with 8 osteoporosis rats without SPEMF stimulation, and SPEMF group with 8 osteoporosis rats with 8 weeks SPEMF stimulation. 3 groups of 16 weeks old rats were scanning by micro-CT to get baseline data. Scanning by micro-CT to make sure rats was induced osteoporosis after bilateral ovariectomy at 32 weeks old. Use micro-CT to investigate the effect of SPEMF on L5 after 8 weeks stimulation. To get percent bone volume, trabecular thickness, trabecular separation, trabecular number, and polar moment of inertia. One-way ANOVA was used to analyze the bone parameter and compare all 3 different time with α=0.05. The rats of all groups were sacrificed and analysis the bone morphology.
There were no significant difference among the three groups in the standard deviation and mean of the initial bone parameters. After measuring initial parameter, 16 rats did bilateral ovariectomy as osteoporosis group. 16 weeks after bilateral ovariectomy, there was significantly reduced in each bone parameters. So we can make sure that is successful induced osteoporosis after bilateral ovariectomy. Control group was showing increasing trend in bone mass and strength by increasing in percent bone volume, trabecular thickness, trabecular separation, trabecular number, and polar moment of inertia. In addition to trabecular number, the parameters of 40 weeks and 16 weeks were significant differences. Non-treatment group was showing decreasing trend in bone mass and strength. In addition to polar moment of inertia, the parameters of 40 weeks and 16 weeks were significant differences. SPEMF group was showing decreasing trend in bone mass and strength after bilateral ovariectomy, and increasing after 8 weeks SPEMF stimulation. All the bone parameters were significant differences after 8 weeks SPEMF stimulation. In this study, there was a significant effect with SPEMF to increase in bone mass and strength.

The findings of this study are that the SPEMF stimulation is likely to improve bone mass and strength in L5 vertebral body for osteoporosis rats induced by bilateral ovariectomy measuring by micro-CT. Future research is recommended to include the following: to investigate the effect on bone mass and strength by using different doses; to investigate the effect on different tissues (likes ligament and blood vessel) and organs (likes liver and kidney).

[1] International Orienteering Federation, IOF
[2]中華民國骨質疏鬆症學會(Taiwanese Osteoporosis Association, TOA)
[3]骨質疏鬆症之成因。高雄榮總新陳代謝科主治醫師林興中臺灣醫界1995；38: 34-38
[4] Elaine N. Maried et al., “Human anatomy, 4th edition”, 2005
[5] 洪世彥，“脈衝磁場刺激研發及對骨髓間葉幹細胞之骨化效應”，國立成功大學醫學工程研究所碩士論文，台南，2007
[6] Kanis JA , “Osteoporosis”, Blackwell Science Ltd., Oxford., 1994
[7] 胡明一等編譯，“人體解剖學”，藝軒圖書出版社，台灣，1998
[8] 林興中，“骨質疏鬆症之成因”，台灣醫界，高雄榮總， 38:34-38, 1995
[9] 輔仁大學體育教育學系
[10] Om P. Gandhi, “Biological Effects and Medical Applications of Electromagnetic Energy”, ISBN: 75-140, 1990
[11] 世界衛生組織國際電磁場計畫( http://www.who.int/peh-emf )
[12] C.T. Brighton, E. Okereke, S.R. Pollack, and C.C. Clark, “In vitro bone – cell response to a Capacitively coupled electrical field”, Clinical Orthopedics and Related Research, 85: 255-256, 1992.
[13] http://www.niea.gov.tw/analysis/publish/month/44/44th4-2.htm
[14] L Potenza, L Ubaldi, R De Sanctis, R De Bellis, L Cucchiarini, M Dachà, “Effects of a static magnetic field on cell growth and gene expression in Escherichia coli”, Mutation Research 561:53-62, 2004
[15] Harvey N. Mayrovitz, Edye E. Groseclose, “Effects of a static magnetic field of either polarity on skin microcirculation”, Micro-vascular Research 69: 24-27, 2005

[16] Berna Okudan, Ali Ü mit Keskin, Mustafa Asim Aydin, Gökhan Cesur, Selçuk Ç ömlekçi, Harun Süslü, “DEXA analysis on the bones of rats exposed in utero and neonatally to static and 50 Hz electric fields”, Bioelectromagnetics, 27-7: 589-592, 2006
[17] Takehisa Nakahara, PhD, Hiroko Yaguchi, PhD2, Masami Yoshida, BSci and Junji Miyakoshi, PhD, “Effects of exposure of CHO-K1 cells to a 10-T static magnetic field”, Radiology, 224-3:817-822, 2002
[18] Ilka B. Schiffer, Wolfgang G. Schreiber, Robert Graf, Elke M. Schreiber, Detlev Jung, Dirk M. Rose, Manfred Hehn, Susanne Gebhard, Jens Sagemüller, Hans W. Spieß, Franz Oesch, Manfred Thelen, Jan G. Hengstler, “No Influence of Magnetic Fields on Cell Cycle Progression Using Conditions Relevant for Patients during MRI”, Bioelectromagnetics, 24:241-250, 2003
[19] “WHO health risk assessment process for static fields”, Progress in Biophysics and Molecular Biology, 87:355-363, 2005
[20] Frank G. Shellock, PhD and John V. Crues, MD, “MR procedures: biologic effects, safety, and patient care”, Radiology, 232-3:635-652, 2004
[21] “Mechanical and electrical intractions in bone remodeling.” Bioelectromanetics. 1997; 18(3): 193-202. Review.
[22] “On the pirzoelectric effect of bone.” 1957; J. Phys. Soc. Japan 12, 1158-1162.
[23] C.A.L. Bassett, R.J. Pawluk, and A.A. Pilla, “Augmentation of bone repair by inductively-coupled electromagnetic fields”, Science, 184:575-577, 1974
[24] C.A.L. Bassett, R.J. Pawluk, and R.O. Becker, “Effect of electrical current on bone in vivo”, Nature, 204:652-655, 1964
[25] C. A. L. Bassett, R. J. Pawluk, A. A. Pilla, “Acceleration of fracture repair by electromagnetic fields A surgically noninvasive method”, Ann N Y Acad Sci, 238:242-262, 1974
[26] Sakai Y, Patterson TE, Ibiwoye MO, Midura RJ, Zborowski M, Grabiner MD, Wolfman A., “Exposure of mouse preosteoblasts to pulsed electromagnetic fields reduces the amount of mature, type I collagen in the extracellular matrix”, J Orthop Res 24: 242-53, 2006
[27] Pericles Diniz, Kenji Shomura, Kazuhisa Soejima, Gakuji Ito, “Effects of pulsed electromagnetic field stimulation on bone tissue like formation and dependent on the maturation stages of the osteoblasts”, Bioelectromagnetics 23:398-405, 2002
[28] V. Sollazzo, L. Massari, and F. Pezzetti, “Effect of low-frequency pulsed electromagnetic fields on human osteoblast-like cells in vitro”, Electro-and Magnetobiolog, 15-1: 75-83, 1996
[29] M. Simko, R. Kriehuber, D.G. Weiss, and R.A. Luben, “Effects of 50 Hz EMF exposure on micronucleus formation and apoptosis in transformed and non-transformed human cell lines”, Bioelectromagnetics, 19: 85-91, 1988
[30] C.H. Lohmann, Z. Schwartz, Y. Liu, H. Guerkov, D.D. Dean, B. Simon, and B.D. Boyan, “Pulsed Electromagnetic Field Stimulation of MG-63 Osteoblast-like Cells Affects Differentiation and Local Factor Production”, Journal of Orthopaedic Research, 18:637-646, 2000.
[31] K.J. McLeod, and L. Collazo, “Suppression of a differentiation response in MC-3T3-E1 Osteoblast-like cells by sustained, low-level, 30 Hz magnetic-field exposure”, Radiation Research, 153:706-714, 2000
[32] M.A.V. Molen, H.J. Donahue, C.T. Rubin, and K.J. McLeod, “Osteoblastic networks with deficient coupling : Differential effects of magnetic and electric field exposure”, Bone, 27-2:227-231, 2000
[33] Gwynne Hannay, David Leavesley, and Mark Pearcy, “Timing of pulsed electromagnetic field stimulation does not affect the promotion of bone cell development”, Bioelectromagnetics, 26:670-676 , 2005
[34] S. Mishima, “The effect of long-time P.E.M.F. stimulation on experimental oseoporosis of rats”, Journal of University of Occupational and Environmental, 10-1: 31-45, 1988
[35] C.T. Rubin, K.J. McLeod, and L.E. Lanyon, “Prevention of osteoporosis by pulsed electromagnetic fields”, Journal of Bone and Joint Surgery, 71:411-417, 1989
[36] T.M. Skerry, M.J. Pead, and L.E. Lanyon, “Modulation of bone loss during disuse by pulsed electromagnetic fields”, Journal and Orthopaedic Research, 9:600-608, 1991
[37] C.A.L. Bassett, M.G. Valdes, and E. Hernandez, “Modification of fracture repair with selected pulsing electromagnetic fields”, Journal of Bone and Joint Surgery, 64-A-6: 888-895, 1982
[38] K.J. McLeod, and C.T. Rubin, “The effect of low frequency electrical fields on osteogenesis”, Journal of Bone and Joint Surgery, 74-6:920-929, 1992
[39] K.J. McLeod, and C.T. Rubin, “The effect of low frequency electrical fields on osteogenesis”, Journal of Bone and Joint Surgery, 74-6:920-929, 1992
[40] T.T. Yamamoto, M. Kawakami, and M. Sakuda, “Effect of a pulsing electromagnetic field on demineralized bone-matrix-induced bone formation in a bony defect in the premaxilla of rats”, Journal of Dental Research, 71-12:1920-1925, 1992
[41] P.S. Landry, K.K. Sadasivan, A.A. Marino, and J.A. Albright, “Electromagnetic fields can affect osteogenesis by increasing the rate of differentiation”, Clinical Orthopaedics and Related Research, 338：262-270, 1997
[42] Micro-CT 原理及應用(http://www.szsbetter.com/ft/2.html)
[43] 林景福，“電腦斷層攝影入門”，合記，1990。
[44] 李亞倫，“Micro-CT 影像評估系統”，第三屆國際醫學影像暨放射科學研討會，2007
[45] 莊克士，“醫學影像物理學”，合記，1998
[46] The manual of Skyscan 1076, Skyscan
[47]張昱婷，“探討物理性刺激對於骨質疏鬆症之影響”，國立成功大學醫學工程研究所碩士論文，台南，2007
[48]林摯鈞，“電磁場刺激對於人類間葉幹細胞之增值與骨分化作用之探討”，高雄醫學大學生理及分子醫學研究所碩士論文，高雄，2007