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研究生: 陳柏霖
Chen, Po-Lin
論文名稱: 探討物理性刺激應用於類固醇誘發股骨頭骨質改變之影響
Investigate the Effect of Physical Stimulation on Steroid-induced Femoral Head Trabecular Architecture Using Animal Model
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: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 87
中文關鍵詞: 電磁場刺激單一脈衝式電磁場高壓氧治療微電腦斷層掃描股骨頭壞死骨壞死骨質改變動物模型
外文關鍵詞: electromagnetic field, high magnetic single pulsed electromagnetic field, hyperbaric oxygen therapy, micro ct, osteonecrosis of femoral head, ONFH, osteonecrosis, AVN, Ischemic necrosis of femoral head, animal model
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  • 隨著醫療進步使得皮質類固醇(corticosteroid)已被廣泛運用在器官移植、急性發炎及免疫系統相關疾病的臨床治療上。現今美國有超過三千萬人的治療方案中需使用糖化皮質類固醇(glucocorticoid) [1]。儘管皮質類固醇在臨床治療上有非凡貢獻,但卻使患者暴露在罹患股骨頭壞死的風險下。學者Koo指出,長期服用類固醇患者約有5% ~ 40%會形成不同程度的股骨頭壞死 [2]。在台灣約有47%人工髖關節置換手術的主診斷為股骨頭壞死 [3],而造成每年高達8.5億台幣的花費。現今股骨頭壞死的治療方式以手術的核心減壓術最為常見且妥當,但僅對於股骨頭壞死初期具有療效。而非手術的治療方式尚無較合適且具有療效的方法,因此發展使用物理性刺激達到預防或早期治療股骨頭壞死將成為趨勢。在尚未形成股骨頭壞死之前,其主要原因可能與類固醇誘發股骨頭骨質改變有關。因此本研究目的為探討物理性刺激於類固醇誘發股骨頭骨質改變之效應。本實驗之特定目標為應用類固醇誘發股骨頭骨質改變之大白鼠動物模型,探討電磁場刺激及高壓氧治療對於股骨頭骨質改變之影響。

    本實驗使用48隻十六週大白鼠,分為控制組、跑步組、誘發組、高壓氧治療組、電磁場刺激組及合併治療組。健康大白鼠隨機分配為控制組及跑步組;利用注射糖皮質類固醇及負重訓練誘發股骨頭骨質改變之大白鼠,分別應用高壓氧治療、單一脈衝式電磁場及電磁場合併高壓氧治療三種方式,分別命名為高壓氧治療組、電磁場刺激組及合併治療組。在八週結束後犧牲大白鼠,並使用微電腦斷層(micro-CT)及蘇木紫與伊紅染色(H&E stain)獲取股骨頭之骨骺及幹骺端之骨形態學與組織學參數,以探討兩種不同的物理性刺激對於類固醇誘發股骨頭骨質改變之影響。骨型態學參數包含骨體積百分比、骨小樑厚度、骨小樑數量、骨小樑間隙及極慣性矩;組織學參數包括骨細胞死亡情況及脂肪細胞數量與體積大小。
    組織學切片結果顯示:藉由類固醇注射及負重訓練的方式大白鼠之骨骺處脂肪細胞有明顯體積增大與數量增加的趨勢,儘管沒有骨細胞死亡之組織學特徵,但幹骺端的骨小樑數量也有減少之趨勢。高壓氧治療有助於避免骨骺處及幹骺端之脂肪細胞增生及肥大。電磁場刺激則是有助於增加幹骺端之骨小樑厚度及數量之趨勢,但對於抑制脂肪細胞肥大和增生卻無正面療效。

    骨骺處之骨型態學結果顯示:誘發組之骨骺處骨小樑厚度小於控制組,並達統計差異 (p<0.05)。經過八週的類固醇注射及負重訓練使得大白鼠股骨頭骨骺處的骨質產生改變。高壓氧治療組在骨骺處之骨小樑厚度明顯小於控制組,達到統計差異 (p<0.05)。因此高壓氧治療對於類固醇誘發股骨頭骨質改變的大白鼠動物模型並沒有正面的療效。電磁場刺激組在骨骺處之骨組織百分比及骨小樑數量較誘發組高,且有統計上的差異 (p<0.05)。

    幹骺端之骨型態學結果顯示:誘發組之幹骺端骨組織百分比與骨小樑厚度和控制組之間相差無異,但骨小樑數量高於控制組,並達統計差異 (p<0.05)。高壓氧治療組之幹骺端骨組織百分比、骨小樑數量及骨小樑間隙和誘發組無統計差異 (p>0.05),但骨小樑厚度則高於誘發組,並具統計差異 (p<0.05)。電磁場刺激組之幹骺端骨小樑厚度高於誘發組,並具統計差異 (p<0.05),儘管骨小樑數量及骨組織百分比高於誘發組但無差異。

    高壓氧治療對於類固醇誘發股骨頭骨質改變之大白鼠的骨骺處無明顯改善骨質之效果,但卻有提高幹骺端之骨小樑厚度及避免脂肪細胞肥大與增生的效果。單一脈衝式電磁場刺激對於類固醇誘發股骨頭骨質改變之大白鼠確實達到改善骨質之效果,使得骨骺及幹骺端之骨小樑數量均有明顯的增加,並達統計上差異 (p<0.05)。單一脈衝式電磁場未來具有發展成為較佳的預防或治療初期股骨頭壞死之非手術治療方法。

    The corticosteroid has been widely used in organ transplantation, acute inflammation and immune system related diseases. Currently, more than 30 million Americans require glucocorticoid (GC) drugs as part of their treatment regime [1]. The corticosteroid in clinical treatment has extraordinary contributions, but patients exposed to the risk of osteonecrosis. Osteonecrosis of the femoral head occurs in 5 – 40% of patients treated with long-term steroids [2]. About 47% total hip replacement patient were caused by osteonecrosis in Taiwan [3], and cost NT 85 million for total hip replacement .
    One of the treatments of osteonecrosis was core decompression surgery, and that was most common and appropriate. Core decompression surgery only has effect for early osteonecrosis patients. There is no appropriately treatment for non-surgical treatments. Using physical stimulation to prevent osteonecrosis that are will be future. The femoral head trabecular architecture was changed before osteonecrosis. Purpose of this study is investigating the effect of physical stimulation on steroid-induced femoral head trabecular architecture. Specific aim is investigating the effect of high magnetic single pulsed electromagnetic field (SPEMF) and hyperbaric oxygen therapy (HBO) on steroid-induced femoral head trabecular architecture using animal model.

    16-weeks-old S.D. rats were randomly assigned 6 groups including control group (C), treadmill group (T), positive control group (P), HBO group (H), SPEMF group (S) and HBO&SPEMF group (M). There are 8 normal rats in C group; 8 normal rats with treadmill training in T group. 32 rats was treat steroids and treadmill training was gave four treatments (no treatment, HBO, SPEMF and HBO&SPEMF). After 8 weeks, the rats were sacrificed and femur were took out for micro-CT scanning epiphysis and metaphysis to measure percent of bone volume, trabecular thickness, trabecular separation, and trabecular number. And on the other hand, using biopsy and H&E stain to observe epiphysis and metaphysis of the femoral head.

    Results of histology show that rats treat steroids and treadmill training make hypertrophy and hyperplasia of fat cells on epiphysis, but osteocyte was still alive. HBO therapy was prevent hypertrophy and hyperplasia of fat cells on epiphysis and SPEMF made trabecular thickness and number increase.

    Results of morphology on epiphysis show that P group was less than C group in trabecular thickness on epiphysis; H group was less than C group in trabecular thickness on epiphysis; percent of bone volume and trabecular number of SPEMF group were large than P group.

    Results of morphology on metaphysis show that percent of bone volume and trabecular thickness of P group was similar C group, but trabecular number of P group was higher than C group; the percent of bone volume, trabecular number and trabecular separation of HBO group was similar C group, but trabecular thickness of HBO group was higher than P group; trabecular thickness of SPEMF group was higher than P group.

    HBO therapy was no effect on steroid-induced femoral head trabecular architecture, but HBO therapy was prevent that hypertrophy and hyperplasia of fat cells. SPEMF stimulation make trabecular thickness higher on epiphysis and metaphysis. SPEMF was one of non-surgical treatments in the future.

    目錄 中文摘要 ............................................ I 英文摘要 ........................................... III 致謝 ........................................... V 目錄 ............................................... VII 表目錄 .............................................. IX 圖目錄 ............................................. X 第一章 緒論 ........................................ 1 1.1 骨壞死 ....................................... 2 1.1.1 股骨頭壞死之盛行率及發生率 ..................... 3 1.1.2 股骨頭壞死之病因學 ......................... 4 1.1.3 股骨頭壞死之臨床診斷及治療方式 ................. 10 1.2 股骨的功能性解剖及骨骼之生理機轉 .................... 14 1.3 股骨頭壞死動物模型 ......................... 20 1.4 物理性刺激應用於預防或治療股骨頭壞死 ............ 21 1.4.1電磁場之基礎理論及電磁刺激之生物效應................... 21 1.4.2高壓氧治療之基礎理論及骨質的生成效應................ 23 1.4.3電磁場刺激及高壓氧治療於股骨頭壞死之文獻探討 ........... 25 1.5 骨質之定量及定性分析 ......................... 29 1.5.1微電腦斷層掃描之原理及骨質診斷評估 .................. 29 1.5.2組織切片及染色 ................................ 31 1.6 研究動機與目的 ........................ 31 第二章 材料與方法.......................................... 32 2.1 單一脈衝電磁場及高壓氧於類固醇誘發股骨頭骨質之影響 ........ 33 2.1.1 動物模型 .......................................... 33 2.1.2 儀器設備 .......................................... 34 2.1.3 實驗設計與流程 ................................ 38 2.1.4 資料分析 ......................................... 43 第三章 結果與討論..................................... 44 3.1 物理性刺激對於骨質改變之效應 ......................... 44 3.1.1 物理性刺激對於股骨頭組織學之改變 ..................... 45 3.1.2 物理性刺激對於骨型態學之改變 .................. 55 3.1.3 物理性刺激對於骨型態學參數改變之討論 ............ 67 第四章 結論 ..................................... 70 4.1 結論 ........................................ 70 4.2 未來展望 ................................ 71 參考文獻 .......................................... 72 附錄A ............................................... 76

    1. Kerachian, M.A., C. Seguin, and E.J. Harvey, Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J Steroid Biochem Mol Biol, 2009. 114(3-5): p. 121-8.
    2. Koo, K.H., et al., Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin Rheumatol, 2002. 21(4): p. 299-303.
    3. Lu, T.-H., 呂宗學, and 賴國安, 95年度股骨頭壞死與人工髖關節置換手術流行病學調查計畫. 2006.
    4. Fukushima, W., et al., Nationwide Epidemiologic Survey of Idiopathic Osteonecrosis of the Femoral Head. Clin Orthop Relat Res, 2010.
    5. Nixon, J.E., Avascular necrosis of bone: a review. J R Soc Med, 1983. 76(8): p. 681-92.
    6. McCarthy, E.F., Aseptic necrosis of bone. An historic perspective. Clin Orthop Relat Res, 1982(168): p. 216-21.
    7. Sugano, N., et al., The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head. J Orthop Sci, 2002. 7(5): p. 601-5.
    8. Assouline-Dayan, Y., et al., Pathogenesis and natural history of osteonecrosis. Seminars in Arthritis and Rheumatism, 2002. 32(2): p. 94-124.
    9. Richard P. J. B. Weller, J.A.A.H., Mark Dahl, Clinical Dermatology. 2008: John Wiley and Sons.
    10. Symptomatic multifocal osteonecrosis. A multicenter study. Collaborative Osteonecrosis Group. Clin Orthop Relat Res, 1999(369): p. 312-26.
    11. Kelman, G.J., et al., Steroid-related osteonecrosis of the knee. Two case reports and a literature review. Clin Orthop Relat Res, 1990(257): p. 171-6.
    12. Drury, P. and D.J. Sartoris, Osteonecrosis in the foot. J Foot Surg, 1991. 30(5): p. 477-83.
    13. Ferlic, D.C. and P. Morin, Idiopathic avascular necrosis of the scaphoid: Preiser's disease? J Hand Surg Am, 1989. 14(1): p. 13-6.
    14. Laloux, P., et al., Spinal cord compression secondary to vertebral aseptic osteonecrosis. Spine (Phila Pa 1976), 1991. 16(4): p. 480-1.
    15. Chandler , F.A. and L.F. Peltier, Coronary Disease of the Hip. Clinical Orthopaedics and Related Research, 2001. 386: p. 7-10.
    16. Mont, M.A., L.C. Jones, and D.S. Hungerford, Nontraumatic osteonecrosis of the femoral head: Ten years later. Journal of Bone and Joint Surgery-American Volume, 2006. 88A(5): p. 1117-1132.
    17. Sakamoto, M., et al., Osteonecrosis of the femoral head - A prospective study with MRI. Journal of Bone and Joint Surgery-British Volume, 1997. 79B(2): p. 213-219.
    18. Inoue, S., et al., Risk factors for nontraumatic osteonecrosis of the femoral head after renal transplantation. J Orthop Sci, 2003. 8(6): p. 751-6.
    19. Griffith, J.F., et al., Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids. Radiology, 2005. 235(1): p. 168-75.
    20. Nagasawa, K., et al., Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI. Lupus, 2005. 14(5): p. 385-90.
    21. Lieberman, J.R., et al., Osteonecrosis of the Hip: Management in the Twenty-first Century. J Bone Joint Surg Am, 2002. 84(5): p. 834-853.
    22. Mont, M.A. and D.S. Hungerford, Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am, 1995. 77(3): p. 459-74.
    23. Callaghan, J., A. Rosenberg, and H. Rubash, The adult hip. 2007: Lippincott Williams & Wilkins.
    24. Hirota Y, H.T., Sugioka Y. , Idiopathic osteonecro-sis of the femoral head: nationwide epidemiologic studies in Japan. Osteonecrosis—etiology, diagnosis, and treatment. 1st ed., ed. J. JP. 1997, Chicago: American Academy of Orthopaedic Surgeons. 51.
    25. Fukushima, W., et al., Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res, 2010. 468(10): p. 2715-24.
    26. Kang, J.S., et al., Prevalence of Osteonecrosis of the Femoral Head A Nationwide Epidemiologic Analysis in Korea. Journal of Arthroplasty, 2009. 24(8): p. 1178-1183.
    27. Parsons, S.J. and N. Steele, Osteonecrosis of the femoral head: Part 1--Aetiology, pathogenesis, investigation, classification. Current Orthopaedics, done 2007. 21(6): p. 457-463.
    28. RK., A., Osteonecrosis: etiology, pathophysiology and diagnosis. The adult hip., ed. C. JJ. 1998, Philadelphia: Lippincott-Ravin. 451–66.
    29. O'Brien, C.A., et al., Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology, 2004. 145(4): p. 1835-41.
    30. Gautier, E., et al., Anatomy of the medial femoral circumflex artery and its surgical implications. J Bone Joint Surg Br, 2000. 82(5): p. 679-83.
    31. Lowell, J.D., Results and complications of femoral neck fractures. Clin Orthop Relat Res, 1980(152): p. 162-72.
    32. Cruess, R.L., Steroid-induced osteonecrosis. J R Coll Surg Edinb, 1981. 26(2): p. 69-77.
    33. Netter's人體解剖學圖譜. 2002: 合記圖書出版社.
    34. 劉郁芬, 原發性股骨頭缺血性壞死之分子遺傳學研究. 2004.
    35. Assouline-Dayan, Y., et al., Pathogenesis and natural history of osteonecrosis. Seminars in Arthritis and Rheumatism, done 2002. 32(2): p. 94-124.
    36. Felson, D.T. and J.J. Anderson, Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. Lancet, 1987. 1(8538): p. 902-6.
    37. Zizic, T.M., et al., Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosus. Am J Med, 1985. 79(5): p. 596-604.
    38. Vakil, N. and M. Sparberg, Steroid-related osteonecrosis in inflammatory bowel disease. Gastroenterology, 1989. 96(1): p. 62-7.
    39. Motomura, G., et al., Dose Effects of Corticosteroids on the Development of Osteonecrosis in Rabbits. Journal of Rheumatology, 2008. 35(12): p. 2395-2399.
    40. Li, X., et al., Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos Int, 2005. 16(1): p. 101-8.
    41. Fink, B., et al., Early detection of avascular necrosis of the femoral head following renal transplantation. Arch Orthop Trauma Surg, 1997. 116(3): p. 151-6.
    42. Chernetsky, S.G., et al., Pathologic features in steroid and nonsteroid associated osteonecrosis. Clin Orthop Relat Res, 1999(368): p. 149-61.
    43. Hirota, Y., et al., Association of Alcohol Intake, Cigarette Smoking, and Occupational Status with the Risk of Idiopathic Osteonecrosis of the Femoral Head. Am. J. Epidemiol., 1993. 137(5): p. 530-538.
    44. Matsuo, K., et al., Influence of alcohol intake, cigarette smoking, and occupational status on idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res, 1988(234): p. 115-23.
    45. Jones, L.C., et al., Procoagulants and osteonecrosis. J Rheumatol, 2003. 30(4): p. 783-91.
    46. Glueck, C., R. Freiberg, and P. Wang, Heritable Thrombophilia-Hypofibrinolysis and Osteonecrosis of the Femoral Head. Clinical Orthopaedics and Related Research®, 2008. 466(5): p. 1034-1040.
    47. Glueck, C.J., R.A. Freiberg, and P. Wang, Role of thrombosis in osteonecrosis. Curr Hematol Rep, 2003. 2(5): p. 417-22.
    48. JONES, J.P.J., Intravascular Coagulation and Osteonecrosis. Clinical Orthopaedics and Related Research, 1992. 277: p. 41-53.
    49. Steinberg, D.R., et al., Determining Lesion Size in Osteonecrosis of the Femoral Head. J Bone Joint Surg Am, 2006. 88(suppl_3): p. 27-34.
    50. Scheiber, C., et al., The pitfalls of planar three-phase bone scintigraphy in nontraumatic hip avascular osteonecrosis. Clin Nucl Med, 1999. 24(7): p. 488-94.
    51. Arlet J, F.R., Forage-biopsie de la tete femorale dans l0osteonecrose primative. Observations histo-pathologiques portant sur huit forages. Rev Rhumat, 1964. 31: p. 257-64.
    52. Ficat RP, A.J., Ischaemia and necrosis of bone., ed. H. DS. 1980, Baltimore: Williams and Wilkins.
    53. Ficat, R.P., Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. J Bone Joint Surg Br, 1985. 67(1): p. 3-9.
    54. Steinberg, M.E., G.D. Hayken, and D.R. Steinberg, A QUANTITATIVE SYSTEM FOR STAGING AVASCULAR NECROSIS. Journal of Bone and Joint Surgery-British Volume, 1995. 77B(1): p. 34-41.
    55. ME., S., Recent advances in the management of osteonecrosis of the hip. Semin Arthroplasty, 1998(9): p. 181-3.
    56. Stein, G.S., et al., Transcriptional control of osteoblast growth and differentiation. Physiol. Rev., 1996. 76(2): p. 593-629.
    57. Hill, P.A., Bone remodelling. Br J Orthod, 1998. 25(2): p. 101-7.
    58. Wang, G.J., Q. Cui, and G. Balian, The Nicolas Andry award. The pathogenesis and prevention of steroid-induced osteonecrosis. Clin Orthop Relat Res, 2000(370): p. 295-310.
    59. Conzemius, M.G., et al., A new animal model of femoral head osteonecrosis: one that progresses to human-like mechanical failure. Journal of Orthopaedic Research, 2002. 20(2): p. 303-309.
    60. Yamamoto, T., et al., Effects of pulse methylprednisolone on bone and marrow tissues - Corticosteroid-induced osteonecrosis in rabbits. Arthritis and Rheumatism, 1997. 40(11): p. 2055-2064.
    61. Bekler, H., et al., [The effect of steroid use on the pathogenesis of avascular necrosis of the femoral head: an animal model]. Acta Orthop Traumatol Turc, 2007. 41(1): p. 58-63.
    62. Hampson, Hyperbaric oxygen therapy: 1999 Committe report. 1999, Kensington: Undersea and Hyperbaric Medical Society.
    63. Gill, A.L. and C.N.A. Bell, Hyperbaric oxygen: its uses, mechanisms of action and outcomes. QJM, 2004. 97(7): p. 385-395.
    64. Jones, L.C. and D.S. Hungerford, Osteonecrosis: etiology, diagnosis, and treatment. Current Opinion in Rheumatology, done 2004. 16(4): p. 443-449.
    65. Reis, N.D., et al., Hyperbaric oxygen therapy as a treatment for stage-I avascular necrosis of the femoral head. Journal of Bone and Joint Surgery-British Volume, 2003. 85B(3): p. 371-375.
    66. Peskin, B., et al., Effects of non-weight bearing and hyperbaric oxygen therapy in vascular deprivation-induced osteonecrosis of the rat femoral head. Undersea & Hyperbaric Medicine, 2001. 28(4): p. 187-194.
    67. Sen, R., Management of avascular necrosis of femoral head at pre-collapse stage. Vol. 43. 2009. 6-16.
    68. Aaron, R.K., et al., The conservative treatment of osteonecrosis of the femoral head. A comparison of core decompression and pulsing electromagnetic fields. Clin Orthop Relat Res, 1989(249): p. 209-18.
    69. Hinsenkamp, M., J.P. Hauzeur, and S. Sintzoff Jr, Preliminary results in electromagnetic field treatment of osteonecrosis. Bioelectrochemistry and Bioenergetics, 1993. 30: p. 229-235.
    70. Massari, L., et al., Biophysical stimulation with pulsed electromagnetic fields in osteonecrosis of the femoral head. Journal of Bone and Joint Surgery-American Volume, 2006. 88A: p. 56-60.
    71. Ishida, M., et al., Electromagnetic fields - A novel prophylaxis for steroid-induced osteonecrosis. Clinical Orthopaedics and Related Research, done 2008 466(5): p. 1068-1073.
    72. Pan, X., et al., Study of rotating permanent magnetic field to treat steroid-induced osteonecrosis of femoral head. Int Orthop, 2009. 33(3): p. 617-23.
    73. Ditri, L., et al., Femoral Head Necrosis, in Handbook on Hyperbaric Medicine, D. Mathieu, Editor. 2006, Springer Netherlands. p. 547-552.
    74. Levin, D., et al., Treatment of Experimental Avascular Necrosis of the Femoral Head with Hyperbaric Oxygen in Rats: Histological Evaluation of the Femoral Heads during the Early Phase of the Reparative Process. Experimental and Molecular Pathology, 1999. 67(2): p. 99-108.
    75. Enrico, M.C., et al., Hyperbaric Oxygen Therapy in Femoral Head Necrosis. The Journal of Arthroplasty, 2010. 25(6): p. 118-123.
    76. WANG, et al., Treatment for osteonecrosis of the femoral head : Comparison of extracorporeal shock waves with core decompression and bone-grafting. Vol. 87A. 2005, Boston, MA, ETATS-UNIS: Journal of Bone and Joint Surgery Incorporated. 8.
    77. Wang, C.J., et al., Extracorporeal shockwave therapy shows regeneration in hip necrosis. Rheumatology, 2008. 47(4): p. 542-546.
    78. 莊克士, 醫學影像物理學. 1998: 合記圖書出版社.
    79. Kimura, E., et al., Effects of bisphosphonate on the mandible of rats in the growing phase with steroid-induced osteoporosis. Oral Diseases, 2007. 13(6): p. 544-549.
    80. 張昱婷, 探討物理性刺激對於骨質疏鬆症之影響. 2009.
    81. 林摯鈞, 電磁場刺激對於人類間葉幹細胞之增殖與骨分化作用之探討, in Effect of electromagnetic field stimulation on proliferation and osteogenic differentiation of human mesenchymal stem cells. 2007, 高雄醫學大學.

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