中文摘要

醫療上廣泛使用類固醇治療各種疾病所產生之發炎效應，例如：氣喘、關節炎、紅斑性狼瘡等。雖然類固醇有效消除發炎反應，卻產生代謝障礙、骨質疏鬆，骨壞死等不良副作用。骨壞死主要發生於股骨頭，為破壞性極大危害人體之疾病。美國股骨頭骨壞死每年新增約10,000 ~ 20,000患者且有逐年增加之趨勢，盛行率約佔300,000 ~ 600,000人。調查分析臺灣1996至2004年股骨頭壞死之粗發生率為每十萬人中約13.2人。骨壞死治療方式甚多，但目前臨床治療骨壞死無令人滿意之結果，近年來臨床使用藥物治療骨壞死備受重視，而隨著自然療法盛行，食療亦為治療選擇之一。若能提供早期介入與治療，盼能預防及延緩骨壞死發生與對骨頭侵犯，以期增加個人生活品質與減少社會經濟負擔。本研究目的為探討福善美(Alendronate)、骨穩 (Teriparatide) 及洋蔥(Onion) 應用於類固醇誘發股骨頭骨質改變之影響。

本實驗將滿16周大的50隻S.D雄性大鼠隨機分派6組，在未進行介入之前進行尾部採血。實驗組別分為：1) 8隻健康發育且不接受任何治療之大鼠、2) 7隻只進行每周五天，總路長100公尺並傾斜15度坡度Treadmill負重訓練之大鼠、3) 8隻進行類固醇(Methylprednisolone) 20 毫克/ 公斤 / 天 合併Treadmill負重訓練之大鼠、4) 9隻進行類固醇合併Treadmill負重訓練再注射福善美 0.16毫克/公斤/天 之皮下注射治療之大鼠、5) 9隻進行類固醇合併Treadmill負重訓練再注射骨穩 6.4 微克/公斤/天之皮下注射治療加入每周8克鈣粉之大鼠、6) 9隻進行類固醇合併Treadmill負重訓練再灌食洋蔥 4.8克/公斤/天 治療之大鼠。經過八周的治療介入後，大鼠以心臟採血並犧牲，再進行微電腦斷層掃瞄分析骨量百分比率、骨小樑數量、骨小樑孔隙率、骨小樑厚度和慣性矩，使用 One-way ANOVA 進行六組分析比較，選取α = 0.05。以組織切片觀察脂肪細胞肥大之情況和骨組織之病理變化。血清檢驗血液內三酸甘油脂、膽固醇和鹼性磷酸酶等參數，用以評估福善美、骨穩及洋蔥對於股骨頭骨質代謝與血脂之影響，採取Paired T-test統計分析，選取α = 0.05。
類固醇合併Treadmill負重訓練之大鼠確實導致總骨量減少和骨頭機械強度下降，且血清檢驗鹼性磷酸酶的值顯示骨代謝加快。骨髓腔內出現脂肪細胞肥大情況，若合併Treadmill負重訓練可發現適度運動可增加骨質強度和減少體內血脂堆積。類固醇合併Treadmill負重訓練再加入藥物或食療以福善美和洋蔥對骨質改善效果最顯著，並增加股骨頭骨骺 (Epiphysis) 和幹骺端 (Metaphysis) 之總骨量、骨小樑數量和厚度，減少骨小樑間孔隙率。福善美對於增加股骨頭幹骺端之骨強度效果最佳(p< 0.05)，且對骨質改善情況優於洋蔥，而洋蔥對於增加股骨頭骨骺之骨強度效果最佳(p> 0.05)。骨穩對於骨質與骨強度表現較不顯著。類固醇合併跑步再灌食洋蔥可有效抑制類固醇所導致的脂肪細胞肥大和減少血液中血脂，而藥物福善美和骨穩對脂肪無抑制功效。

本研究結果發現可使用福善美或洋蔥早期預防與治療服用類固醇患者骨質改變之副作用。未來可探討其缺失並發展改良，包括以下幾點：1)延長實驗進行的時間，探討實驗長期作用之效應；2) 增加單獨施打類固醇之組別，以作更確切之實驗對照；3) 將藥物治療與食療合併，探討是否能有更好之療效。

Abstract

Medical widespread use steroid in anti-inflammation of various diseases. for example: Asthma, Arthritis and Systemic lupus erythematosus etc. Although steroid eliminate anti-inflammation, but it may product metabolic disorders, osteoporosis and osteonecrosis etc. Osteonecrosis occurs mainly in the femoral head and as a disease which devastating harm to human. The incidence of femoral head osteonecrosis between 10,000 ~ 20,000 patients, and the prevalence of femoral head osteonecrosis about 300,000 ~ 600,000 patients in the U.S. Survey in Taiwan form 1996 to 2004, the incidence of osteonecrosis of the crude of about 13.2 per 100,000 people. Osteonecrosis has many treatment methods, but it is no satisfactory output. In recent years, the clinical focus on treatment osteonecrosis by using drugs, and as the popularity of nature therapies , the diet will be one of the options in treatment osteonecrosis .If it could provide early intervention and treatment , it may prevention violate bone and delay the occurrence ratio of osteonecrosis. Increase quality of life of human beings and reduce social and economic burden .The purpose of this study is investigating the Effect of Alendronate, Teriparatide and onion on Steroid-induced Femoral Head Trabecular Architecture Using Animal Model.

In this study, 50 male 16-week-old S.D. rats were assigned to six groups randomly and collected tail blood before intervention. The experimental group is divided into : 1) Eight healthy rats；2) Seven healthy rats with tilt 15 degrees slope and 100 meters length road treadmill training；3) Eight rats with steroids (Methylprednisolone) injection 20 mg/kg/ day with treadmill training；4) Nine rats with steroids injection with treadmill training combine Alendronate injection 0.16 mg/kg/day ；5) Nine rats with steroids injection with treadmill training combine Teriparatide injection 0.64 μg/kg /day and Ca 8 g/week；6) Nine rats with steroids injection with treadmill training combine Onion feeding 4.8g/kg/day. After eight weeks treatment, the rats were sacrificed and collected heart blood. Micro Computed Tomography systems scan and analysis Percent bone volume, Trabecular number, Trabecular separation, Trabecular thickness and Mean polar moment of inertia. Using One-way ANOVA analysis and comparison of six groups, select α=0.05. Tissue section observed the hypertrophy of fat cells and pathological changes of bone tissue. Serums examine triglycerides, cholesterol and alkaline phosphatase to assess the bone metabolism and lipids which effect by Alendronate, Teriparatide and onion. Using Paired T-test statistical analysis and select α = 0.05.

Steroids combined Treadmill groups indeed lead to decreased the total bone mass and bone mechanical strength. The value of serum alkaline phosphatase shows bone metabolism ratio to speed up. The bone marrow cavity appears fat cell hypertrophy, if steroid combined moderate exercise and it could increase the bone strength and reduce the lipids accumulation. Alendronate and Onion have positive in improving metabolic bone diseases, and increase total bone percent, trabecular numbers, trabecular thickness and decrease trabecular separation in epiphysis and metaphysis of femoral head. For the purposes of improving bone strength, Alendronate has most effect in meatphysis (p<0.05), and Onion has most effect in epiphysis (p>0.05) than other groups. Teriparatide treatment has poor performance in bone strength and bone percent. Steroids combined treadmill training with feeding onion can inhibit steroid-induced fat cell hypertrophy and reduce blood lipids, and both of the Alendronate and Teripraratide cannot suppress fat or lipids.

The study found that Alendronate and onion can use to prevention and treatment steroid-induced side effects of bone loss. In the future work, the missing can be improved and modified, include the following：1) Extend the experiments time and explore the effect of long-term experimental；2) Add steroids only group for more precise control of experimental；3) Combine drugs with diet treatment and expect to achieve the better effect.

參考資料
1. Luigi Gennari , J.P.B., Glucocorticoid-induced osteoporosis: hope on the HORIZON-COMMENT once yearly infusion therapy better than once weekly. The Lancet, 2009. 373(9671): p. 1225-1226.
2. Oinuma, K., Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Annals of the Rheumatic Diseases, 2001. 60(12): p. 1145-1148.
3. Carlos J. Lavernia, M., Rafael J. Sierra, MD, and Francisco R. Grieco, MD, Osteonecrosis of the femoral head. J Am Acad Orthop Surg, 1999. 7: p. 250-261.
4. Agarwala, S., Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study. Rheumatology, 2005. 44(3): p. 352-359.
5. H Hanumanthappa, R.R., Corticosteroid - Induced Avascular Necrosis of Head of Femur in a Patient with Pemphigus Vulgaris. 2000. 66(3): p. 147-148.
6. Andrea Giustina, M., Alberto Angeli, MD , Ernesto Canalis,MD , Filippo Manelli, MD, Glucocorticoid-Induced Osteoporosis. Vol. 30. 2002: Karger.
7. DONN MARCINIAK, M., CHRISTOPHER FUREY, MD, AND JOHN W. SHAFFER, MD, <Osteonecrosis of the Femoral Head.pdf>. The Journal of Bone and Joint Surgery, 2005. 87-A(4).
8. Mont, M.A., Nontraumatic Osteonecrosis of the Femoral Head: Ten Years Later. The Journal of Bone and Joint Surgery, 2006. 88(5): p. 1117-1132.
9. Marker, D.R., et al., Treatment of Early Stage Osteonecrosis of the Femoral Head. The Journal of Bone and Joint Surgery, 2008. 90(Supplement 4): p. 175-187.
10. Weinstein, R.S., Apoptosis of Osteocytes in Glucocorticoid-Induced Osteonecrosis of the Hip. Journal of Clinical Endocrinology & Metabolism, 2000. 85(8): p. 2907-2912.
11. Michael R Aiello, M., Radiologist, St Elizabeth Medical Center, Utica, NY <Avascular Necrosis, Femoral Head.pdf>. 2009.
12. Chen, W., et al., Autosomal Dominant Avascular Necrosis of Femoral Head in Two Taiwanese Pedigrees and Linkage to Chromosome 12q13. The American Journal of Human Genetics, 2004. 75(2): p. 310-317.
13. Lai, K.A., The Use of Alendronate to Prevent Early Collapse of the Femoral Head in Patients with Nontraumatic Osteonecrosis. A Randomized Clinical Study. The Journal of Bone and Joint Surgery, 2005. 87(10): p. 2155-2159.
14. Bulletin, S., Taiwan Team Discovers Gene for Inherited Form of Osteonecrosis. National Science Council, 2005. 37(8).
15. Nobuhiko Sugano 1 , T.A., Kenji Ohzono 3 , Toshikazu Kubo 4 , Takao Hotokebuchi 5 , and a.K. Takaoka, <The 2001 revised criteria for diagnosis, classification, and staging of.pdf>. journal of Orthopaedic Science, 2002. 7: p. 601-605.
16. Powell, C., et al., Steroid induced osteonecrosis: An analysis of steroid dosing risk. Autoimmunity Reviews, 2010. 9(11): p. 721-743.
17. Yu-Fen Liu, P.D., Wei-Ming Chen, M.D., Yung-Feng Lin, M.S., and M.D. Ruei-Cheng Yang, Ming-Wei Lin, Ph.D., Ling-Hui Li, Ph.D., <Type II Collagen Gene Variants and Inherited.pdf>. N Engl J Med, 2005. 352: p. 2294-301.
18. Hofstaetter, J.G., et al., The effects of alendronate in the treatment of experimental osteonecrosis of the hip in adult rabbits. Osteoarthritis and Cartilage, 2009. 17(3): p. 362-370.
19. Zaidi, M., et al., ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proceedings of the National Academy of Sciences, 2010. 107(19): p. 8782-8787.
20. Society, B.a.T., Glucocorticoid-induced osteoporosis:guidelines for prevention and treatment. 2002: Royal College of Physicians.
21. 呂宗學, 賴., 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, 醫學系公共衛生學科暨公共衛生研究所.
22. Hirota Y, H.T., Sugioka Y. ,, Idiopathic osteonecro-sis of the femoral head: nationwide epidemiologic studies in Japan. Osteonecrosis—etiology, diagnosis, and treatment. 1997: American Academy of Orthopaedic Surgeons. .
23. Soen, S. and Y. Tanaka, Glucocorticoid-induced osteoporosis: skeletal manifestations of glucocorticoid use and 2004 Japanese Society for Bone and Mineral Research-proposed guidelines for its management. Modern Rheumatology, 2005. 15(3): p. 163-168.
24. Abdulaziz M. AL-BAHLOOL, D.A.B., Mir SADAT-ALI, Outcome of traumatic hip dislocation. Abdulaziz M. AL-BAHLOOL, Dalal A. BUBSHAIT, Mir SADAT-ALI, 2009. 15(5).
25. McKay, W.F., Implant depots to deliver growth factors to treat avascular necrosis. 2007.
26. Ramachandran, M., et al., Intravenous Bisphosphonate Therapy for Traumatic Osteonecrosis of the Femoral Head in Adolescents. The Journal of Bone and Joint Surgery, 2007. 89(8): p. 1727-1734.
27. A. L. Boskey, P.D., C. L. Raggio, M. D., P. G. Bullough, M. D., , Changes in the Bone Tissue Lipids in Persons with Steroid- and Alcohol - induced Osteonecrosis. Clinical Orthopaedics & Related Research, 1983. 172: p. 289-295.
28. Hungerford, M.M.a.D., Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am., 1995. 77: p. 459-474.
29. Wang GJ, C.Q., Balian G., The pathogenesis and prevention of steroid-induced osteonecrosis. Clin Orthop Relat Res., 2000(370): p. 295-310.
30. Boss, J.H. and I. Misselevich, Osteonecrosis of the Femoral Head of Laboratory Animals: The Lessons Learned from a Comparative Study of Osteonecrosis in Man and Experimental Animals. Veterinary Pathology, 2003. 40(4): p. 345-354.
31. Kim, H.K.W., Introduction to osteonecrosis of the femoral head (OFH) and osteonecrosis of the jaw (ONJ). J Musculoskelet Neuronal Interact, 2007. 7(4): p. 350-353.
32. Aspenberg, J.Å.a.P., Systemic alendronate prevents resorption of necrotic bone during revascularization.A bone chamber study in rats. BMC Musculoskeletal Disorders, 2002. 3(19).
33. Jager, M., et al., Rationale for PGI2 in bone marrow edema - from theory to application. Arthritis Research & Therapy, 2008. 10(5): p. R120.
34. Canlon, B., et al., Glucocorticoid receptors modulate auditory sensitivity to acoustic trauma. Hearing Research, 2007. 226(1-2): p. 61-69.
35. 林興中, 骨質疏鬆症之成因, in 臺灣醫界. 1995: 臺灣. p. 34-38.
36. Alesci, S., et al., Glucocorticoid-Induced Osteoporosis: From Basic Mechanisms to Clinical Aspects. Neuroimmunomodulation, 2005. 12(1): p. 1-19.
37. Turk Rhen, P.D., and John A. Cidlowski, Ph.D., <Antiinflammatory Action of Glucocorticoids —New Mechanisms for Old Drugs .pdf>. The new england journal of medicine, 2005. 353: p. 1711-23.
38. Alessandra Bitto 1 , M.F.P., PhD; Bruce Burnett 2 , PhD; Robert Levy 2 , MD; Vincenzo Di Stefano 1 , MD; Mary Ann Armbruster 2 , PhD; Herbert Marini 3 , MD; Letteria Minutoli 1 , MD; Domenica Altavilla 1 , PhD and FrancescoSquadrito 1* , MD. , <PROTECTIVE EFFECT OF GENISTEIN AGLYCONE ON THE .pdf>. 2009.
39. http://retina.umh.es/docencia/confsvivos/temas/apoptosis/apoptosis.html.
40. COOPER, M.S., <Sensitivity of bone to glucocorticoids.pdf>. Clinical Science, 2004. 107: p. 111-123.
41. GORO MOTOMURA, T.Y., TAKAHIKO IRISA, KEITA MIYANISHI, KENJIRO NISHIDA, and a.Y. IWAMOTO, Dose Effects of Corticosteroids on the Development of Osteonecrosis in Rabbits. The Journal of Rheumatology, 2008. 35: p. 2395-2399.
42. Koo KH, K.R., Kim YS, Ahn IO, Cho SH, Song HR, Park YS, Kim H, Wang GJ, Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin Rheumatol, 2002. 21(299-303).
43. KYUNG-HOI KOO, R.K., GYUNG-HYUCK KO, HAE-RYONG SONG, SOON-TAEK JEONG, and S.-H. CHO, <PREVENTING COLLAPSE IN EARLY OSTEONECROSIS OF THE FEMORAL HEAD.pdf>. The Journal of Bone and Joint Surgery, 1995. 77-B: p. 870-4.
44. Mavrokokki T, C.A., Nature and frequency of bisphosphonate- associated osteonecrosis of the jaws in Australia. iNT J Oral Maxillofac Surg, 2007. 65: p. 415-23.
45. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Whitehouse Station, NJ 08889, USA 2010.
46. Kim T. Brixen 1 , P.M.C., Charlotte Ejersted 1 and Bente Lomholt Langdahl 3, Teriparatide (Biosynthetic Human Parathyroid Hormone 1–34) A New Paradigm in the Treatment of Osteoporosis. Basic & Clinical Pharmacology & Toxicology, 2004. 94: p. 260-270.
47. 健康企劃部, 洋蔥的妙用與療法. 2004, 臺灣: 智慧大學出版有限公司.
48. Evans and K., Alendronate affects long bone length and growth plate morphology in the oim mouse model for Osteogenesis Imperfecta. Bone, 2003. 32(3): p. 268-274.
49. Iwata, K., et al., Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia. Bone, 2006. 39(5): p. 1053-1058.
50. J. E. FISHER*†, M.J.R., J. M. HALASY†, S. P. LUCKMAN‡, D. E. HUGHES§, P. J. MASARACHIA†, and R.G.G.R. G. WESOLOWSKI†, G. A. RODAN†, AND A. A. RESZKA†¶, Alendronate mechanism of action geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. The National Academy of Sciences, 1999. 96: p. 133-138.
51. Im, G.-I., et al., Osteoblast proliferation and maturation by bisphosphonates. Biomaterials, 2004. 25(18): p. 4105-4115.
52. Downs, R.W., Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women. Journal of Clinical Endocrinology & Metabolism, 2000. 85(5): p. 1783-1788.
53. Hwang, J.-S., et al., The effects of weekly alendronate therapy in Taiwanese males with osteoporosis. Journal of Bone and Mineral Metabolism, 2009. 28(3): p. 328-333.
54. S. Agarwala, S. Shah, and V.R. Joshi, The use of alendronate in the treatment of avascular necrosis of the femoral head. J Bone Joint Surg 2009. 91-B: p. 1013-18.
55. Ma, Y.L., et al., Teriparatide Increases Bone Formation in Modeling and Remodeling Osteons and Enhances IGF-II Immunoreactivity in Postmenopausal Women With Osteoporosis. JOURNAL OF BONE AND MINERAL RESEARCH, 2006. 21(6): p. 855-864.
56. S.A.S, L.F. (2009) 骨 穩 ® 注射液 [ FORTEO ® For Injection].
57. 陳燕惠, 台大藥事通訊. Vol. 27. 2006, 臺灣: 國立台灣大學醫學院附設醫院藥劑部.
58. S.A.S, L.F. (2009) FORTEO®骨穩注射筆使用手冊.
59. 陳青青, 低劑量間斷性注射副甲狀腺素對大白鼠顱顏骨缺損癒合的影響. 2007, 國立陽明大學 臨床牙醫學研究所 牙周病學組: 台北.
60. F. Cosman, R.L., Is Parathyroid Hormone a Therapeutic Option for Osteoporosis-A Review of the Clinical Evidence. 1998.
61. Dempster DW, Z.H., Cosman F, Nieves J, Adachi JD, Fraher LJ, Watson PH, Lindsay R, Hodsman AB, PTH treatment directly stimulates bone formation in cancellous and cortical bone in humans. J Bone Miner Res 2001. 16.
62. Locklin, R.M., et al., Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. Journal of Cellular Biochemistry, 2003. 89(1): p. 180-190.
63. Vogel M, H.R., Delling G., Morphologic study of iliac crest spongiosa in patients with osteoporosis treated with combination therapy of pulsatile administration of parathyroid hormone (1-38 hPTH) and sequential addition of calcitonin nasal spray. 1990. 85(2): p. 82-6.
64. M. LI, L.M.O.S.E.K.I.L.D.E., C. H. S O G A A R D , J. S. T H O M S E N and T. J. W R O N S K I Parathyroid Hormone Monotherapy and Cotherapy with Antiresorptive Agents Restore Vertebral Bone Mass and Strength in Aged Ovariectomized Rats. Bone, 1995. 16(6): p. 629-35.
65. Mosekilde L, S.C., McOsker JE, Wronski TJ, PTH has a more pronounced effect on vertebral bone mass and biomechanical competence than antiresorptive agents (estrogen and bisphosphonate)--assessed in sexually mature, ovariectomized rats. Bone, 1994. 15(4): p. 401-8.
66. L Mosekilde, C.D.a.J.G., The effect on vertebral bone mass and strength of long term treatment with antiresorptive agents (estrogen and calcitonin), human parathyroid hormone-(1-38), and combination therapy, assessed in aged ovariectomized rats. Endocrinology, 1994. 134(5): p. 2126-2134.
67. 黃滄海 1, R.C.M.湯.陳.張.黃.賴.林.楊.楊., 洋蔥增補飲食可減少大鼠去除卵巢後之骨質流失. 成大研發快訊 2009. 42(6): p. 1154-1163.
68. Marie-Noëlle Horcajada-Molteni, et al., Rutin Inhibits Ovariectomy-Induced Osteopenia in Rats. Journal of Bone and Mineral Research, 2000. 15(11): p. 2251–2258.
69. LI, R.C.M.A.F., Nutrition: Effect of vegetables on bone metabolism. Nature, 1999. 401: p. 343 - 344.
70. ROMAN C. MU¨ HLBAUER, A.L., and ANDREAS REINLI, Onion and a Mixture of Vegetables, Salads, and Herbs Affect Bone Resorption in the Rat by a Mechanism Independent of Their Base Excess. JOURNAL OF BONE AND MINERAL RESEARCH, 2002. 17: p. 1230 –1236.
71. Tang, C.H., et al., Water solution of onion crude powder inhibits RANKL-induced osteoclastogenesis through ERK, p38 and NF-κB pathways. Osteoporosis International, 2008. 20(1): p. 93-103.
72. James D O’Reilly, A.I.M., Gareth T McAnlis, Ian S Young, Barry Halliwell, Tom AB Sanders, and Helen Wiseman, Consumption of flavonoids in onions and black tea lack of effect on F 2 -isoprostanes and autoantibodies to oxidized LDL in healthy humans. American Society for Clinical Nutrition, 2001. 73: p. 1040-4.
73. Nuutila, A., Comparison of antioxidant activities of onion and garlic extracts by inhibition of lipid peroxidation and radical scavenging activity. Food Chemistry, 2003. 81(4): p. 485-493.
74. Notoya, M., Quercetin, a flavonoid, inhibits the proliferation, differentiation, and mineralization of osteoblasts in vitro. European Journal of Pharmacology, 2004. 485(1-3): p. 89-96.
75. http://www.rci.rutgers.edu/~uzwiak/AnatPhys/APFallLect8.html.
76. Elaine N. mARIEB , J.M., Human Anatomy, ed. 3. 2006.
77. Keith L.Moore, A.M.R.A., Moore & Agur essential clinical anatomy. 3 ed. 2003.
78. ANNE M.R. AGUR , A.F.D., Grant's Atlas of Anatomy. 11 ed. 2005.
79. Salvatore Alesci, M.U.D.M., Ioannis Ilias, Philip W. Gold, George P. Chrousos, Glucocorticoid-Induced Osteoporosis:From Basic Mechanisms to Clinical Aspects. Neuroimmunomodulation, 2005. 12: p. 1-19.
80. O. BAROU, S.M., 1 L. VICO, 1 G. BOIVIN, 2 C. ALEXANDRE, 1 and M. H. LAFAGE-PROUST 1, Relationships Between Trabecular Bone Remodeling and Bone Vascularization A Quantitative Study. Bone, 2002. 30: p. 604-612.
81. A Patient's Guide to Slipped Capital Femoral Epiphysis
82. Kevin D. Plancher, M., MS and Afshin Razi, BA, <Management of osteonecrosis of the femoral head.pdf>. 1997. 28(3).
83. Manolagas SC, J.R., Bone marrow, cytokines, and bone remodeling: Emerging insights into the pathophysiology of osteoporosis. . N Engl J Med, 1995. 332: p. 305-311.
84. AM, P., Osteonal and hemi-osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem, 1994. 55: p. 273-286.
85. WEINSTEIN, S.C.M.a.R.S., New Developments in the Pathogenesis and Treatment of Steroid-Induced Osteoporosis. JOURNAL OF BONE AND MINERAL RESEARCH, 1999. 14(7).
86. Williams, A.I.G.M.S.C.J.D.B.G.R., Bone Signaling Pathways and Treatment of Osteoporosis. Expert Rev Endocrinol 2009. 4(6): p. 639-650.
87. 廖二元, 內分泌學-第2版(上下冊), ed. 人民衛生出版社. 2007.
88. Roach, H.I., et al., Temporal Analysis of Rat Growth Plates: Cessation of Growth with Age Despite Presence of a Physis. Journal of Histochemistry & Cytochemistry, 2003. 51(3): p. 373-383.
89. J. IWAMOTO, 3 J. K. YEH, 1,2 and J. F. ALOIA 1,2, Differential Effect of Treadmill Exercise on Three Cancellous Bone Sites in the Young Growing Rat. Bone 1999. 24: p. 163-169.
90. Iwamoto, J., et al., Effects of treadmill exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. Journal of Bone and Mineral Metabolism, 2004. 22(1): p. 26-31.
91. Novelline, R., Squire's Fundamentals of Radiology. 5th edition ed, ed. H.U. Press. 1997.
92. Oxford English Dictionary. 2nd ed, ed. O.U. Press. 1989.
93. Dendy, P.B.H., Physics for Diagnostic Radiology. 1999, USA.
94. MCT, An introduction to MICRO CT SCAN okt., 2008.
95. Hofstaetter, J.G., et al., Changes in Bone Microarchitecture and Bone Mineral Density following Experimental Osteonecrosis of the Hip in Rabbits. Cells Tissues Organs, 2006. 184(3-4): p. 138-147.
96. 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 2009.
97. Eastell, R., et al., Bone formation markers in patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate☆. Bone, 2010. 46(4): p. 929-934.
98. 史 中 , 夏., 移植骨生成細胞預防年齡增長後骨質流失效果及機轉的骨組織形學研究. Chin J Oral Maxillofac Surg 2004. 15(1-6).
99. Yasmeen Agosti , P.D., MedMaps for Pathophysiology. 2009: Lippincott Williams & Wikins.