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研究生: 張昱婷
Chang, Yu-Ting
論文名稱: 探討物理性刺激對於骨質疏鬆症之影響
Investigate the Effect of Physical Stimulation on Osteoporosis Using Animal Models
指導教授: 鍾高基
Chung, Kao-Chi
學位類別: 碩士
Master
系所名稱: 工學院 - 醫學工程研究所
Institute of Biomedical Engineering
論文出版年: 2009
畢業學年度: 97
語文別: 中文
論文頁數: 114
中文關鍵詞: 單一脈衝式電磁場連續脈衝式電磁場全身性振動骨質疏鬆
外文關鍵詞: HMSP-EMF, PEMF, Osteoporosis, Whole body vibration
相關次數: 點閱:112下載:4
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  • 隨著時代與科技的進步,國民的生活習慣日趨改變,導致骨質疏鬆症罹患率升高。全球超過50歲以上的女性罹患骨質疏鬆症的機率為1/3,男性為1/5。在台灣,超過60歲的女性罹患骨質疏鬆症的比例超過16% [1]。治療骨質疏鬆症的方法多為服用鈣片、賀爾蒙或藥物,但藥物易產生副作用或是價格昂貴。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。本研究目的為探討物理性刺激對於骨質疏鬆的效應。本實驗之特定目標:1) 應用骨質疏鬆SD rats模型,探討振動刺激對於骨質的影響;2) 應用骨質疏鬆BALB/C mice模型,探討兩種不同磁刺激對於骨質的影響。

    實驗主要分為振動刺激與磁刺激兩部份:Phase A - 32隻八週大的SD rats,隨機分為四組:control組有8隻健康之大鼠;normal + WBV組8隻健康大鼠使用WBV刺激;osteoporosis組有8隻骨質疏鬆症大鼠及osteoporosis + WBV組使用WBV刺激8隻骨質疏鬆症大鼠。應用0.26 ~ 0.73G之全身性振動儀於骨質疏鬆SD rats模型,實驗進行時間為4星期,將大鼠犧牲取出脛骨,使用微電腦斷層攝影掃描脛骨頭,並計算骨密度、骨髓腔內骨頭體積百分比、骨小樑厚度、骨小樑間距、骨小樑數量等五種骨型態學參數,使用one-way ANOVA進行四組分析比較,選取α=0.05。Phase B - 37隻八週大的BALB/C mice,隨機分為六組:Control組有6隻健康小鼠;Normal + PEMF組有6隻健康小鼠,進行連續脈衝式電磁場(PEMF)刺激;Normal + HMSP-EMF組有5隻健康小鼠,進行單一脈衝式電磁場(HMSP-EMF)刺激;Osteoporosis組有6隻骨質疏鬆小鼠; Osteoporosis + PEMF組有7隻骨質疏鬆小鼠,使用PEMF刺激; Osteoporosis + PEMF組有7隻骨質疏鬆小鼠,使用HMSP-EMF刺激。應用PEMF與HMSP-EMF於骨質疏鬆小鼠模型,在磁刺激4, 6, 8, 10, 12星期時,使用micro-CT活體掃描脛骨頭計算分析,使用Two - way ANOVA進行磁刺激方式與刺激時間的分析比較,選取α=0.05;12星期後將小鼠犧牲取出脛骨頭,使用微電腦斷層攝影掃描脛骨頭,並計算分析骨密度、骨髓腔內骨頭體積百分比、骨小樑厚度、骨小樑間距、骨小樑數量等五種骨型態學參數,使用one-way ANOVA進行六組分析比較,選取α=0.05。

    Phase A的結果顯示結果顯示:Control組、Normal + WBV組的BMD、骨頭體積百分比及骨小樑間距在統計上比Osteoporosis組、Osteoporosis + WBV組有顯著差異。Osteoporosis + WBV組與Osteoporosis組比較結果顯示:BMD、骨頭體積百分比有增加的趨勢,在統計上沒有顯著的差異。未來實驗將延長刺激時間並減少振動頻率,相信必能改善骨質流失的現象。

    Phase B的結果顯示Osteoporosis + PEMF組及Osteoporosis + HMSP-EMF組的骨質密度在統計上顯著大於Osteoporosis組(p<0.05);使用磁刺激6, 8, 10, 12週的小鼠其骨質密度在統計上顯著大於治療0, 4週(p<0.05)。使用單一脈衝式電磁場刺激6週後骨質已有顯著的增生,長時間使用也可維持其骨質密度。小鼠犧牲後所得到的五個型態學參數結果顯示:Osteoporosis + HMSP-EMF組的骨質密度、骨頭體積百分比與骨小樑數量在統計上有顯著大於Osteoporosis組(p<0.05);Osteoporosis + PEMF組與Osteoporosis組的骨小樑厚度在統計上顯著小於Normal + HMSP-EMF組與Control組(p<0.05)。Osteoporosis + PEMF組與Osteoporosis組的骨小樑間隙在統計上顯著大於Normal + PEMF組及Control組(p<0.05)。單一脈衝式電磁場刺激時間一天僅須3分鐘,6週後有改善骨質流失的效果;連續脈衝式電磁場一天需要進行8小時的刺激,治療時間須長達12星期,治療效果有限。

    本研究發現HMSP-EMF刺激可促進骨質疏鬆症的治療效果。未來可探討其缺失並發展改良,包括以下幾點:Phase A - 利用不同的頻率強度對於骨質的增生進行探討與分析,並延長實驗刺激的時間,以得到最佳療效。Phase B - 設計不同的骨質疏鬆動物模型(例如:脊椎等部位損傷),應用脈衝式電磁場於各不同型態之骨質疏鬆模型進行探討與分析。

    The change of human living style 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, 56% of the female with above 60 years old suffer from osteoporosis [1]. The conventional treatment for osteoporosis were to take calcium, hormone or drug medication, but these medication were either high cost or often producing side effects on the user. The physical stimulation including ultrasound, electrical, electromagnetic field, and vibration and so on were likely to enhance the bone formation. This study was to investigate the effect of physical stimulation on osteoporosis in osteoporotic animal models. More specifically, the research aims were to: 1) investigate the effect of whole body vibration (WBV) on osteoporotic SD rats model, and 2) investigate the effect of pulsed electromagnetic field (PEMF) and high magnetic single pulsed electromagnetic field (HMSP-EMF) on osteoporotic BALB/C mice model.

    The experiment was divided into two phases: Phase A – a total of 32 SD rats with 8 weeks old were randomly assigned to 4 groups including: control group with 8 normal rats, normal + WBV group with 8 normal rats plus WBV, osteoporosis group with 8 osteoporotic rats, and osteoporosis + WBV group with 8 osteoporotic rats plus WBV. The dosage of WBV was increased from 0.26G to 0.73G for 4 weeks. After 4 weeks, the rats of all groups were sacrificed and the tibia were took out for micro-CT scanning to measure bone mineral density (BMD), percent bone volume, trabecular thickness, trabecular separation, and trabecular number. One-way ANOVA was used to analyze the bone parameter and compare all 4 groups with α=0.05. Phase B – a total of 37 BALB/B mice with 8 weeks old were randomly assigned to 6 groups including: control group with 6 normal mice, normal + PEMF group with 6 normal mice plus PEMF, normal + HMSP-EMF group with 5 normal mice plus HMSP-EMF, osteoporosis group with 6 osteoporotic mice, osteoporosis + PEMF group with 7 osteoporotic mice plus PEMF, osteoporosis + HMSP-EMF group with 7 osteoporotic mice plus HMSP-EMF. The dosage of PEMF was 1.8 mT and the dosage of HMSP-EMF was 0.8 T for 12 weeks stimulation. On 4, 6, 8, 10, 12 weeks, all 6 groups were scanned by micro-CT to measure the BMD of tibia. Two-way ANOVA was used to analyze the treatment type and treatment time on the BMD with α=0.05. After 12 weeks, the mice of all groups were sacrificed and the tibia of all mice were took out for micro-CT scanning to measure BMD, percent bone volume, trabecular thickness, trabecular separation, and trabecular number. One-way ANOVA was used to analyze the bone parameter and compare all 6 groups with α=0.05.

    The results of Phase A show the BMD and percent bone volume of control and normal + WBV groups are significantly large than those of osteoporosis and osteoporosis + WBV groups. To compare the osteoporosis group, the BMD and percent bone volume of osteoporosis + WBV group have an increasing tendency, but no significantly difference. The insignificant improvement of bone mass is probably due to only 4 weeks vibration training. Future study will increase the vibration training time and decrease training gravity for improved osteoporosis treatment.

    The results of Phase B show that the BMD of osteoporosis + PEMF and osteoporosis + HMSP-EMF groups is significantly large than that of osteoporosis group (p<0.05); the BMD of both groups treated at 6, 8, 10, 12 weeks is significantly large than that of both groups treated at 0, 4 weeks (p<0.05). The HMSP-EMF treatment shows that the BMD of osteoporotic mice has significantly improved on 6 weeks treatment and then maintain the same quality after later treatment. The BMD, percent bone volume, and trabecular number of osteoporosis + HMSP-EMF group are significantly large than those of osteoporosis group after scarification (p<0.05); the trabecular thickness of osteoporosis + PEMF and osteoporosis groups is significantly smaller than that of normal + HMSP-EMF and control groups (p<0.05); the trabecular separation of osteoporosis + PEMF and osteoporosis groups is significantly large than that of normal + PEMF and control groups (p<0.05). The efficacy of HMSP-EMF stimulation is validated through 3 minutes stimulation per day to improve the bone quality after 6 weeks treatment. In contrast, the application of PEMF is limited by 8 hours stimulation per day for 12 weeks.

    The findings of this study are that the HMSP-EMF stimulation is likely to improve bone mass for osteoporosis treatment. Future research is recommended to include the following: Phase A – to investigate different frequencies and amplitude and treatment duration on bone quality for osteoporotic animal model; Phase B – to design different osteoporotic animal models, such as spinal cord injury, in order to study the treatment effect of different EMF on bone quality.

    中文摘要I AbstractIII 誌謝V 目錄VII 表目錄X 圖目錄XII 第一章 緒論1 1.1 骨質疏鬆症2 1.1.1 全球骨質疏鬆症的盛行率2 1.1.2 骨質疏鬆症病因學4 1.1.3 骨質疏鬆症臨床診斷與治療方式6 1.2 骨的功能性解剖及生理機轉8 1.3 磁刺激對於骨質的物理效應16 1.3.1 磁的基礎理論16 1.3.2 電磁波的物理特性19 1.3.3 磁刺激的生物效應21 1.3.4 磁刺激應用於生物效應的文獻探討23 1.4 振動刺激對於骨質的物理效應26 1.4.1 振動刺激的基礎理論26 1.4.2 振動刺激應用於骨頭的文獻探討28 1.5 微電腦斷層掃描29 1.5.1 微電腦斷層的原理30 1.5.2 微電腦斷層掃描應用骨質型態之診斷評估31 1.6 研究動機與目的32 第二章 系統設計與材料方法33 2.1振動刺激對於骨質的影響34 2.1.1 動物模型34 2.1.2 儀器設備34 2.1.3 實驗設計與實驗流程36 2.1.4 統計分析37 2.2磁刺激對於骨質的影響38 2.2.1 動物模型38 2.2.2 儀器設備39 2.2.3 實驗設計與實驗流程42 2.2.4 統計分析45 第三章 結果與討論46 3.1全身性振動系統刺激骨質增生的效應46 3.1.1全身性振動刺激對於骨質密度改變的結果48 3.1.2全身性振動刺激對於骨頭體積百分比改變的結果49 3.1.3 全身性振動刺激對於骨小樑間隙改變的結果50 3.1.4全身性振動刺激對於骨小樑間隙改變的結果51 3.1.5全身性振動刺激對於骨小樑數量改變的結果52 3.1.6 全身性振動刺激對於骨質改變結果之討論53 3.2電磁場系統刺激骨質增生的效應54 3.2.1磁刺激及刺激時間對於骨質密度改變之結果55 3.2.2 磁刺激與刺激時間對於骨質密度改變之討論58 3.2.3 小鼠犧牲後觀察磁刺激對於骨質密度改變的結果59 3.2.4 磁刺激對於骨質改變結果之討論66 3.2.5 微電腦斷層掃描影像與傳統切片圖片之比較66 第四章 結論67 4.1 結論67 4.2 未來展望68 附錄69 附錄A….69 附錄B74 附錄C75 參考文獻83

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