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研究生： 余蕙宏
Yu, Hui-Hung
論文名稱： 服用類固醇之全身性紅斑狼瘡患者產生骨鬆性骨折之探討
Osteoporotic Fractures in Systemic Lupus Erythematosus Patients on Glucocorticoids Therapy
指導教授： 高雅慧
Yang, Yeah-Huei Kao
高淑敏
Kao, Shu-Min
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床藥學研究所
Institute of Clinical Pharmacy
論文出版年： 2011
畢業學年度： 99
語文別： 中文
論文頁數： 139
中文關鍵詞： 全身性紅斑狼瘡 、類固醇 、骨質疏鬆症 、骨鬆性骨折
外文關鍵詞： systemic lupus erythematosus, glucocorticoids, osteoporosis, osteoporotic fracture
相關次數： 點閱：124  下載：2 
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    • 研究背景：類固醇為主要治療全身性紅斑狼瘡 (systemic lupus erythematosus，SLE) 之藥物，其使用也與許多副作用相關。這些不良反應在嚴重程度以及出現頻率方面並不一致，但皆被認為與類固醇的使用劑量以及 (或) 時間相關。SLE患者的骨質疏鬆症，可能為原發性或次發性；原發性骨鬆之危險因子包括年齡大於65歲、體重過輕…等；次發性骨鬆之危險因子則包括SLE本身所引起的發炎、治療藥物以及疾病相關的併發症。其中類固醇因廣泛使用在SLE患者，且為次發性骨質疏鬆最常見之原因，故可能是造成SLE患者骨質流失之主因。本研究目的為探討服用類固醇之SLE患者，發生骨鬆性骨折的相關機率，並且進行危險因子的分析。
    研究方法：以在成功大學附設醫院診斷為SLE、確診年齡大於18歲且病史10年以上之患者為觀察對象，進行回溯性世代研究。研究材料為觀察對象之病歷。自患者被診斷為SLE起開始追蹤，觀察終點為骨鬆性骨折發生之際或2010年12月。分組部分，主要分為類固醇連續使用者與間歇使用者。記錄內容包括每位觀察對象之基本資料、有無抽菸飲酒之習慣、診斷當時之臨床表徵、每一筆類固醇處方以及骨鬆性骨折發生時間、位置與後續治療。
    結果：本研究共納入122名觀察對象，平均年齡為34.1歲 (SD = 12.84)，以女性為主 (82.79%)。類固醇的連續使用者，其年齡、類固醇每日劑量與累積劑量、骨質疏鬆症預防藥品的使用以及累積器官傷害，皆與類固醇間歇使用者有顯著差異。骨鬆性骨折的發生率為7.59 / 1,000 人年，平均發生年紀為52.33歲 (SD = 15.20)，且以脊椎壓迫性骨折居多 (75%)。年齡 (HR = 1.18 [1.07-1.29]，p = 0.0005) 為骨鬆性骨折最顯著之危險因子。
    結論：本研究發現接受類固醇治療的SLE患者，其骨鬆性骨折的風險不會顯著地因使用時間以及使用劑量的不同改變。因此，在SLE治療方面，類固醇的使用是必要且具有臨床價值的。基於類固醇在治療上的重要性，應積極鼓勵病人接受類固醇治療；再配合戒除菸酒以及補充適量鈣質、維生素D，患者將可體驗類固醇在治療方面所帶來的益處。

    Background: Glucocorticoids are the mainstay of therapy for SLE. However, numerous adverse effects may result from glucocorticoids use. While complications vary in severity and frequency, they are generally considered to be dependent on the dose and/or duration of glucocorticoids use. The type of osteoporosis in SLE patients could be primary or secondary. The risk factors for developing primary osteoporosis are old age, low body weight...etc; for secondary osteoporosis, the risk factors included inflammation caused by SLE, medications used to treat the disease, and lifestyle restricted by SLE. Because of their extensive use, glucocorticoids are thought to be the most frequent cause of secondary osteoporosis and may be responsible for much of the bone loss in lupus. The objectives of this study were to explore the incidence of osteoporotic fracture in glucocorticoid-treated SLE patients, and to identify the risk factors related to osteoporotic fracture.
    Methods: A retrospective cohort study was performed in patients with SLE. Those diagnosed in National Cheng Kung University Hospital, older than 18 years of age when SLE diagnosed and disease duration more than 10 years were included in this study. Medical records of eligible patients were study materials. Each patient was followed from the day of SLE diagnosis, and the endpoint was the development of osteoporotic fracture or 31 Dec 2010, whichever came first. Data recorded included the baseline characteristics, clinical manifestations at diagnosis, the prescriptions of glucocorticoids and the event of osteoporotic fracture.
    Result: There were 122 eligible patients, with average age of 34.1 years-old (SD =12.84), and most of them were female (82.79%). Patients with continuous glucocorticoids use were significantly older, had received larger daily and cumulated dose of glucocorticoids, and were prescribed more of the osteoporosis-preventing therapy, had greater cumulated organ damage. The incidence of osteoporotic fracture were 7.59 per 1,000 person-years, the average age at the time of fracture was 52.33 years-old (SD = 15.20) and vertebral compression are the most common fractures (75%). Age (HR = 1.18 [1.07-1.29]，p = 0.0005) was the risk factors of osteoporotic fracture.
    Conclusion: This study found that among glucocorticoids-treated SLE patients, the risk of osteoporotic fracture would not vary significantly with different duration and dosage of glucocorticoids. Therefore, glucocorticoids therapy is necessary and clinically valuable for SLE patients. Regarding its crucial role in treatment, patient should be advised to adhere to glucocorticoids. In addition, if patients could undertake activity to prevent possible side effect, such as quitting drinking and smoking, intaking enough calcium and vitamin D, all could benefit from the therapy of glucocorticoids.

    中文摘要 I Abstract III 誌謝 V 目錄 VII 表目錄 XI 圖目錄 XIII 第一篇、類固醇與全身紅斑狼瘡患者發生骨鬆、骨折之探討 1 第一章、研究背景 1 第二章、文獻回顧 2 第一節、全身性紅斑狼瘡 2 一、流行病學 2 二、病因學 3 三、臨床表徵 4 四、診斷 4 五、治療 5 第二節、全身性紅斑狼瘡與骨質流失 11 一、流行病學 11 二、全身性紅斑狼瘡罹患骨質疏鬆之危險因子 12 第三節、全身性紅斑狼瘡與類固醇引發之骨質疏鬆症 18 一、臨床重要性 18 二、類固醇導致骨質疏鬆之機轉 19 三、類固醇在SLE患者骨質疏鬆、骨折事件扮演之角色 23 第三章、研究目的與重要性 37 第四章、研究方法 38 第一節、研究設計 38 一、研究類型 38 二、研究材料與工具 38 三、研究對象與排除條件 38 四、分組 39 五、觀察時間與終點 39 第二節、研究流程 40 第三節、研究名詞、研究變項與操作定義 43 一、排除與納入條件 43 二、病歷資料記錄 44 三、研究結果測量 49 第四節、統計方法 55 一、統計工具 55 二、統計模式設定 55 三、統計資料分析 55 第五章、研究結果 57 第一節、研究對象納入、排除與分組 57 第二節、研究對象基本特徵 59 第三節、類固醇療法與其他全身性紅斑狼瘡治療用藥 64 第四節、骨質疏鬆症預防用藥與骨密度檢查施行概況 68 一、骨質疏鬆預防用藥使用情形 68 二、骨密度檢查施行概況 68 第五節、觀察終點疾病表現、骨鬆性骨折事件與危險因子 71 一、觀察終點疾病表現 71 二、骨鬆性骨折事件 71 三、骨鬆性骨折危險因子分析 76 第六章、研究討論 78 第一節、研究對象納入、排除 78 一、觀察對象之獲取以及研究期間設定 78 二、納入條件與結果之探討 78 三、排除條件與結果之探討 79 第二節、研究對象人口特性與基本特徵分析 81 一、人口特性分析 81 二、研究對象基本資料分析 81 第三節、類固醇療法與其他全身性紅斑狼瘡治療用藥分析 85 一、類固醇療法 85 二、其他治療用藥 86 第四節、骨質疏鬆症預防用藥與骨密度檢查施行概況分析 88 一、骨質疏鬆症預防用藥使用分析 88 二、骨密度檢查施行概況分析 93 第五節、觀察終點疾病表現、骨鬆性骨折事件與危險因子分析 94 一、觀察終點疾病活性分析 94 二、累積器官損傷分析 94 三、死亡率分析 95 四、骨鬆性骨折事件分析 96 五、骨鬆性骨折危險因子分析 98 第六節、研究限制 102 第七章、結論與建議 104 第八章、未來研究方向 105 第二篇、臨床藥事服務-服藥順從度相關調查 106 第一章、緣起 106 第二章、目的 107 第三章、方法 108 第一節、受訪對象 108 第二節、方法與材料 108 第四章、服藥順從度調查結果 111 第一節、問卷填答結果 111 一、受訪對象基本資料 111 二、MARS量表與MASRI-VASDOSE量表 111 三、中藥、保健食品以及成藥服用情形 114 四、用藥副作用之擔憂 114 第二節、順從度不同者各項特徵之比較 116 第五章、討論 120 參考文獻 122 附錄一 134 附錄二 137 附錄三 138 作者簡介 139 表目錄 第一篇、類固醇與全身紅斑狼瘡患者發生骨鬆、骨折之探討 Table 2.1-1全身性紅斑狼瘡類固醇療法 8 Table 2.3-1 Studies about BMD and glucocorticoids therapy in SLE patients 24 Table 2.3-2 Studies about osteoporosis and glucocorticoids therapy in SLE patients 31 Table 2.3-3 Studies about fracture and glucocorticoids therapy in SLE patients 33 Table 4.3-1 1982 ACR Revised Criteria for Classification of SLE 45 Table 4.3-2 1997 Update of 1982 ACR Revised Criteria for Classification of SLE 46 Table 4.3-3 Scoring, variable and definition for SLEDAI 47 Table 4.3-4 The SLICC/ACR damage index (SDI) 50 Table 5.2-1 Baseline characteristics of patients in each group 60 Table 5.2-2 Clinical manifestations and SLEDAI at diagnosis 62 Table 5.3-1 Therapy of glucocorticoids 65 Table 5.3-2 Treatments except glucocorticoids during observation period 66 Table 5.4-1 Osteoporosis preventing therapy 70 Table 5.4-2 Bone mineral density test 70 Table 5.5-1 Disease activity, organ damage and survival state at endpoint 72 Table 5.5-2 The accrual damage at endpoint 73 Table 5.5-3 Osteoporotic fracture and patients' character 75 Table 5.5-4 Risk factors associated with osteoporotic fracture 77 Table 6.4-1 FRAX骨折風險定義 91 Table 6.5-1本研究與台灣地區骨鬆性骨折發生率之比較 97 Table 6.5-2本研究與其他世代研究骨鬆性骨折盛行率之比較 97 第二篇、臨床藥事服務-服藥順從度相關調查 Table 3.2-1 MARS (Modified 8-item Medication Adherence Rating Scale) 110 Table 4.1-1受訪對象基本資料 112 Table 4.1-2 MARS量表以及受訪對象填答結果 113 Table 4.1-3各類藥品MASRI-VASDOSE填答結果 115 Table 4.1-4中藥、保健食品以及成藥服用情形 115 Table 4.2-1類固醇順從度 117 Table 4.2-2 Hydroxychloroquine順從度 118 Table 4.2-3免疫抑制劑順從度 119 圖目錄 第一篇、類固醇與全身紅斑狼瘡患者發生骨鬆、骨折之探討 Figure 2.3-1類固醇導致骨質疏鬆以及骨折之機轉 20 Figure 4.2-1研究流程 42 Figure 5.1-1研究對象納入、排除與分組 58 Figure 5.5-1 Osteoporotic fracture-free analysis 74 Figure 6.2-1觀察對象全身性紅斑狼瘡診斷年份 82 Figure 6.2-2觀察對象診斷年齡以及性別分佈 82 Figure 6.4-1計算服用類固醇之停經後女性及年齡>50歲男性發生骨折的風險 90 Figure 6.4-2 ACR之骨鬆預防建議-停經女性、年齡> 50歲男性 92 Figure 6.4-3 ACR之骨鬆預防建議-未停經女性、年齡< 50歲男性 92

    1. Tutuncu ZN, Kalunian KC. Chapter 2. The Definition and Classification of Systemic Lupus Erythematosus In: Wallace DJH, Bevra Hannahs, ed. Dubois' Lupus Erythematosus, 7th Edition. Philadelphia: Lippincott Williams and Wilkins; 2007.
    2. Pons-Estel GJ, Alarcón GS, Scofield L, Reinlib L, Cooper GS. Understanding the Epidemiology and Progression of Systemic Lupus Erythematosus. Seminars in Arthritis and Rheumatism 2010;39:257-68.
    3. Samanta A, Feehally J, Roy S, Nichol FE, Sheldon PJ, Walls J. High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus. Ann Rheum Dis 1991;50:490-2.
    4. Rus V, Maury EE, Hochberg MC. Chapter 4. The Epidemiology of Systemic Lupus Erythematosus. In: Wallace DJH, Bevra Hannahs, ed. Dubois' Lupus Erythematosus, 7th Edition. Philadelphia: Lippincott Williams and Wilkins; 2007.
    5. Chiu YM, Lai CH. Nationwide population-based epidemiologic study of systemic lupus erythematosus in Taiwan. Lupus 2010;19:1250-5.
    6. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum 2007;56:1251-62.
    7. Hahn BH. Chapter 5. Overview of Pathogenesis of Systemic Lupus Erythematosus. In: Wallace DJH, Bevra Hannahs, ed. Dubois' Lupus Erythematosus, 7th Edition. Philadelphia: Lippincott Williams and Wilkins; 2007.
    8. Lahita RG. Chapter 16. The Clinical Presentation of Systemic Lupus Erythematosus. In: Lahita RG, ed. Systemic Lupus Erythematosus, 4th Edition. Amsterdam: Elsevier Academic Press; 2004:435-48.
    9. Wallace DJ. Chapter 32. The Clinical Presentation of Systemic Lupus Erythematosus. In: Wallace DJH, Bevra Hannahs, ed. Dubois' Lupus Erythematosus, 7th Edition. Philadelphia: Lippincott Williams & Wilkins; 2007.
    10. Michelle P. Chapter 22. Systemic Lupus Erythematosus. In: Imboden JB HD, Stone JH, ed. CURRENT Rheumatology Diagnosis & Treatment, 2nd Edition. United States of America: The McGraw-Hill Companies; 2007.
    11. Dall'Era Maria WD. Chapter 23. Treatment of Systemic Lupus Erythematosus. In: Imboden JB HD, Stone JH, ed. CURRENT Rheumatology Diagnosis & Treatment, 2nd Edition. United States of America: The McGraw-Hill Companies; 2007.
    12. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care & Research 2010;62:1515-26.
    13. Lahita RG. Chapter 44. Nonsteroidal Treatments of Systemic Lupus Erythematosus In: Tsokos GC, Gordon C, Smolen JS, eds. Systemic lupus erythematosus :a companion to Rheumatology, 1st Edition
    Philadelphia: Moseby Elsevier; 2007:483-6.
    14. Al-Maini M, Urowitz M. Chapter 45. Systemic Steroids. In: Tsokos GC, Gordon C, Smolen JS, eds. Systemic lupus erythematosus :a companion to Rheumatology, 1st Edition Philadelphia: Moseby Elsevier; 2007:487-97.
    15. Papadimitraki ED, Boumpas DT. Chapter 46. Cytotoxic Drug Treatment. In: Tsokos GC, Gordon C, Smolen JS, eds. Systemic lupus erythematosus :a companion to Rheumatology, 1st Edition. Philadelphia: Moseby Elsevier; 2007:498-510.
    16. Tassiulas IO, Boumpas DT. Chapter 75. Clinical Features and Treatment of Systemic Lupus Erythematosus. In: Firestein GS, Budd RC, Jr. EDH, McInnes IB, Ruddy S, Sergent JS, eds. Kelley's Textbook of Rheumatology, 8th Edition Philadelphia: Saunders; 2008.
    17. Michalski JP, Kodner C. Systemic lupus erythematosus: safe and effective management in primary care. Prim Care 2010;37:767-78, vii.
    18. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001;285:785-95.
    19. Sen D, Keen RW. Osteoporosis in systemic lupus erythematosus: prevention and treatment. Lupus 2001;10:227-32.
    20. Gordon C. Long-term complications of systemic lupus erythematosus. Rheumatology (Oxford) 2002;41:1095-100.
    21. Alele JD, Kamen DL. The importance of inflammation and vitamin D status in SLE-associated osteoporosis. Autoimmunity Reviews 2010;9:137-9.
    22. Di Munno O, Mazzantini M, Sedie AD, Mosca M, Bombardieri S. Risk factors for osteoporosis in female patients with systemic lupus erythematosus. Lupus 2004;13:724-30.
    23. Swaak AJ, van den Brink HG, Smeenk RJ, et al. Systemic lupus erythematosus: clinical features in patients with a disease duration of over 10 years, first evaluation. Rheumatology (Oxford) 1999;38:953-8.
    24. Ramsey-Goldman R, Dunn JE, Huang CF, et al. Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data. Arthritis Rheum 1999;42:882-90.
    25. Kanis JA, Melton LJ, 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994;9:1137-41.
    26. Lee C, Ramsey-Goldman R. Osteoporosis in systemic lupus erythematosus mechanisms. Rheum Dis Clin North Am 2005;31:363-85, viii.
    27. Lee C, Almagor O, Dunlop DD, et al. Association between African American race/ethnicity and low bone mineral density in women with systemic lupus erythematosus. Arthritis Rheum 2007;57:585-92.
    28. Cunnane G, Lane NE. Steroid-induced osteoporosis in systemic lupus erythematosus. Rheum Dis Clin North Am 2000;26:311-29, vi-vii.
    29. Sambrook PN, Eisman JA, Champion GD, Yeates MG, Pocock NA, Eberl S. Determinants of axial bone loss in rheumatoid arthritis. Arthritis Rheum 1987;30:721-8.
    30. Studnicka-Benke A, Steiner G, Petera P, Smolen JS. Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol 1996;35:1067-74.
    31. Zwerina J, Hayer S, Tohidast-Akrad M, et al. Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum 2004;50:277-90.
    32. Horwood NJ, Kartsogiannis V, Quinn JM, Romas E, Martin TJ, Gillespie MT. Activated T lymphocytes support osteoclast formation in vitro. Biochem Biophys Res Commun 1999;265:144-50.
    33. Lane NE. Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus. Nat Clin Pract Rheumatol 2006;2:562-9.
    34. Malabanan AO, Holick MF. Vitamin D and bone health in postmenopausal women. J Womens Health (Larchmt) 2003;12:151-6.
    35. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477-501.
    36. Lane NE. Vitamin D and systemic lupus erythematosus: bones, muscles, and joints. Curr Rheumatol Rep 2010;12:259-63.
    37. Lakshminarayanan S, Walsh S, Mohanraj M, Rothfield N. Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. J Rheumatol 2001;28:102-8.
    38. Mok CC, Mak A, Ma KM. Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus. Lupus 2005;14:106-12.
    39. O'Leary TJ, Jones G, Yip A, Lohnes D, Cohanim M, Yendt ER. The effects of chloroquine on serum 1,25-dihydroxyvitamin D and calcium metabolism in sarcoidosis. N Engl J Med 1986;315:727-30.
    40. Huisman AM, White KP, Algra A, et al. Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol 2001;28:2535-9.
    41. Mazzantini M, Di Munno O, Incerti-Vecchi L, Pasero G. Vertebral bone mineral density changes in female rheumatoid arthritis patients treated with low-dose methotrexate. Clin Exp Rheumatol 2000;18:327-31.
    42. Arai K, Hanyu T, Sugitani H, et al. Risk factors for vertebral fracture in menopausal or postmenopausal Japanese women with rheumatoid arthritis: a cross-sectional and longitudinal study. J Bone Miner Metab 2006;24:118-24.
    43. Boumpas DT, Austin HA, 3rd, Vaughan EM, Yarboro CH, Klippel JH, Balow JE. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 1993;119:366-9.
    44. Navasa M, Monegal A, Guanabens N, et al. Bone fractures in liver transplant patients. Br J Rheumatol 1994;33:52-5.
    45. Sambrook PN. Cyclosporine and bone mass. Clinical and Experimental Rheumatology 2000;18:S93-S6.
    46. Griffith GC, Nichols G, Asher JD, Flanagan B. Heparin Osteoporosis. JAMA: The Journal of the American Medical Association 1965;193:91-4.
    47. Ruiz-Irastorza G, Khamashta MA, Nelson-Piercy C, Hughes GR. Lupus pregnancy: is heparin a risk factor for osteoporosis? Lupus 2001;10:597-600.
    48. Sanson BJ, Lensing AW, Prins MH, et al. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost 1999;81:668-72.
    49. Ginzler EM, Aranow C. Prevention and treatment of adverse effects of corticosteroids in systemic lupus erythematosus. Baillieres Clin Rheumatol 1998;12:495-510.
    50. Saag KG. Glucocorticoid-induced osteoporosis. Endocrinol Metab Clin North Am 2003;32:135-57, vii.
    51. Lane NE, Lukert B. The science and therapy of glucocorticoid-induced bone loss. Endocrinol Metab Clin North Am 1998;27:465-83.
    52. Pennisi P, Trombetti A, Rizzoli R. Glucocorticoid-induced Osteoporosis and Its Treatment. Clinical Orthopaedics and Related Research 2006;443:39-47.
    53. Garcia-Carrasco M, Mendoza-Pinto C, Escarcega RO, et al. Osteoporosis in patients with systemic lupus erythematosus. Isr Med Assoc J 2009;11:486-91.
    54. Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 2007;18:1319-28.
    55. Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci 2002;966:73-81.
    56. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 1990;112:352-64.
    57. Baylink DJ, Wergedal JE. Bone formation by osteocytes. Am J Physiol 1971;221:669-78.
    58. Canalis E, Bilezikian JP, Angeli A, Giustina A. Perspectives on glucocorticoid-induced osteoporosis. Bone 2004;34:593-8.
    59. Rubin J, Biskobing DM, Jadhav L, et al. Dexamethasone promotes expression of membrane-bound macrophage colony-stimulating factor in murine osteoblast-like cells. Endocrinology 1998;139:1006-12.
    60. Hofbauer LC, Gori F, Riggs BL, et al. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 1999;140:4382-9.
    61. Dovio A, Perazzolo L, Saba L, et al. High-dose glucocorticoids increase serum levels of soluble IL-6 receptor alpha and its ratio to soluble gp130: an additional mechanism for early increased bone resorption. Eur J Endocrinol 2006;154:745-51.
    62. Jia D, O'Brien CA, Stewart SA, Manolagas SC, Weinstein RS. Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density. Endocrinology 2006;147:5592-9.
    63. Canalis E, Centrella M, Burch W, McCarthy TL. Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 1989;83:60-5.
    64. Okazaki R, Riggs BL, Conover CA. Glucocorticoid regulation of insulin-like growth factor-binding protein expression in normal human osteoblast-like cells. Endocrinology 1994;134:126-32.
    65. Sakakura M, Takebe K, Nakagawa S. Inhibition of luteinizing hormone secretion induced by synthetic LRH by long-term treatment with glucocorticoids in human subjects. J Clin Endocrinol Metab 1975;40:774-9.
    66. Hsueh AJ, Erickson GF. Glucocorticoid inhibition of FSH-induced estrogen production in cultured rat granulosa cells. Steroids 1978;32:639-48.
    67. Schaison G, Durand F, Mowszowicz I. Effect of glucocorticoids on plasma testosterone in men. Acta Endocrinol (Copenh) 1978;89:126-31.
    68. MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986;104:648-51.
    69. Goulding A, Gold E. Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta-estradiol. Endocrinology 1988;122:482-7.
    70. Nielsen HK, Thomsen K, Eriksen EF, Charles P, Storm T, Mosekilde L. The effects of high-dose glucocorticoid administration on serum bone gamma carboxyglutamic acid-containing protein, serum alkaline phosphatase and vitamin D metabolites in normal subjects. Bone Miner 1988;4:105-13.
    71. Mok CC, Ying SK, To CH, Ma KM. Bone mineral density and body composition in men with systemic lupus erythematosus: a case control study. Bone 2008;43:327-31.
    72. Bhattoa HP, Bettembuk P, Balogh A, Szegedi G, Kiss E. Bone mineral density in women with systemic lupus erythematosus. Clin Rheumatol 2002;21:135-41.
    73. Chong HC, Chee SS, Goh EM, Chow SK, Yeap SS. Dietary calcium and bone mineral density in premenopausal women with systemic lupus erythematosus. Clin Rheumatol 2007;26:182-5.
    74. Jardinet D, Lefebvre C, Depresseux G, Lambert M, Devogelaer JP, Houssiau FA. Longitudinal analysis of bone mineral density in pre-menopausal female systemic lupus erythematosus patients: deleterious role of glucocorticoid therapy at the lumbar spine. Rheumatology (Oxford) 2000;39:389-92.
    75. Petri M. Musculoskeletal complications of systemic lupus erythematosus in the hopkins lupus cohort: An update. Arthritis & Rheumatism 1995;8:137-45.
    76. Yee CS, Crabtree N, Skan J, et al. Prevalence and predictors of fragility fractures in systemic lupus erythematosus. Ann Rheum Dis 2005;64:111-3.
    77. Gilboe IM, Kvien TK, Haugeberg G, Husby G. Bone mineral density in systemic lupus erythematosus: comparison with rheumatoid arthritis and healthy controls. Ann Rheum Dis 2000;59:110-5.
    78. Hansen M, Halberg P, Kollerup G, et al. Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment. Scand J Rheumatol 1998;27:197-206.
    79. Houssiau FA, Lefebvre C, Depresseux G, Lambert M, Devogelaer JP, Nagant de Deuxchaisnes C. Trabecular and cortical bone loss in systemic lupus erythematosus. Br J Rheumatol 1996;35:244-7.
    80. Pons F, Peris P, Guanabens N, et al. The effect of systemic lupus erythematosus and long-term steroid therapy on bone mass in pre-menopausal women. Br J Rheumatol 1995;34:742-6.
    81. Uaratanawong S, Deesomchoke U, Lertmaharit S, Uaratanawong S. Bone mineral density in premenopausal women with systemic lupus erythematosus. The Journal of Rheumatology 2003;30:2365-8.
    82. Yeap S, Fauzi A, Kong N, et al. Influences on bone mineral density in Malaysian premenopausal systemic lupus erythematosus patients on corticosteroids. Lupus 2009;18:178-81.
    83. Mendoza-Pinto C, Garcia-Carrasco M, Sandoval-Cruz H, et al. Risks factors for low bone mineral density in pre-menopausal Mexican women with systemic lupus erythematosus. Clin Rheumatol 2009;28:65-70.
    84. Almehed K, Forsblad d'Elia H, Kvist G, Ohlsson C, Carlsten H. Prevalence and risk factors of osteoporosis in female SLE patients-extended report. Rheumatology (Oxford) 2007;46:1185-90.
    85. Becker A, Fischer R, Scherbaum WA, Schneider M. Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. Lupus 2001;10:809-14.
    86. Bhattoa HP, Kiss E, Bettembuk P, Balogh A. Bone mineral density, biochemical markers of bone turnover, and hormonal status in men with systemic lupus erythematosus. Rheumatol Int 2001;21:97-102.
    87. Bultink IE, Lems WF, Kostense PJ, Dijkmans BA, Voskuyl AE. Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus. Arthritis Rheum 2005;52:2044-50.
    88. Dhillon VB, Davies MC, Hall ML, et al. Assessment of the effect of oral corticosteroids on bone mineral density in systemic lupus erythematosus: a preliminary study with dual energy x ray absorptiometry. Ann Rheum Dis 1990;49:624-6.
    89. Formiga F, Moga I, Nolla JM, Pac M, Mitjavila F, Roig-Escofet D. Loss of bone mineral density in premenopausal women with systemic lupus erythematosus. Ann Rheum Dis 1995;54:274-6.
    90. Formiga F, Nolla JM, Moga I, Roig-Escofet D. Sequential study of bone mineral density in patients with systemic lupus erythematosus. Ann Rheum Dis 1996;55:857.
    91. Gordon C, Crabtree N, Skan J, Bowman S, D. S. Prevalence and predictors of osteoporotic fractures in patients with systemic lupus erythematosus. Arthritis & Rheumatism 2001;44:S334.
    92. Kalla AA, Fataar AB, Jessop SJ, Bewerunge L. Loss of trabecular bone mineral density in systemic lupus erythematosus. Arthritis Rheum 1993;36:1726-34.
    93. Kipen Y, Buchbinder R, Forbes A, Strauss B, Littlejohn G, Morand E. Prevalence of reduced bone mineral density in systemic lupus erythematosus and the role of steroids. J Rheumatol 1997;24:1922-9.
    94. Li EK, Tam LS, Young RP, Ko GT, Li M, Lau EM. Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus erythematosus treated with corticosteroids. Br J Rheumatol 1998;37:405-10.
    95. Pineau CA, Urowitz MB, Fortin PJ, Ibanez D, Gladman DD. Osteoporosis in systemic lupus erythematosus: factors associated with referral for bone mineral density studies, prevalence of osteoporosis and factors associated with reduced bone density. Lupus 2004;13:436-41.
    96. Sinigaglia L, Varenna M, Binelli L, et al. Determinants of bone mass in systemic lupus erythematosus: a cross sectional study on premenopausal women. J Rheumatol 1999;26:1280-4.
    97. Almehed K, Hetenyi S, Ohlsson C, Carlsten H, Forsblad-d'Elia H. Prevalence and risk factors of vertebral compression fractures in female SLE patients. Arthritis Research & Therapy 2010;12:R153.
    98. Borba VZ, Matos PG, da Silva Viana PR, Fernandes A, Sato EI, Lazaretti-Castro M. High prevalence of vertebral deformity in premenopausal systemic lupus erythematosus patients. Lupus 2005;14:529-33.
    99. LI EK, TAM LS, GRIFFITH JF, et al. High Prevalence of Asymptomatic Vertebral Fractures in Chinese Women with Systemic Lupus Erythematosus. The Journal of Rheumatology 2009;36:1646-52.
    100. Mendoza-Pinto C, Garcia-Carrasco M, Sandoval-Cruz H, et al. Risk factors of vertebral fractures in women with systemic lupus erythematosus. Clin Rheumatol 2009;28:579-85.
    101. LI EK, ZHU TY, TAM L-S, et al. Bone Microarchitecture Assessment by High-Resolution Peripheral Quantitative Computed Tomography in Patients with Systemic Lupus Erythematosus Taking Corticosteroids. The Journal of Rheumatology 2010;37:1473-9.
    102. Lee C, Almagor O, Dunlop DD, Manzi S, Spies S, Ramsey-Goldman R. Self-reported fractures and associated factors in women with systemic lupus erythematosus. The Journal of Rheumatology 2007;34:2018-23.
    103. Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum 2000;43:1801-8.
    104. Chen CJ, Yen JH, Tsai WC, et al. Decreased bone mineral density in premenopausal patients with systemic lupus erythematosus. Kaohsiung J Med Sci 1996;12:567-72.
    105. Buttgereit F, da Silva JA, Boers M, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002;61:718-22.
    106. Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A. The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 2001;12:417-27.
    107. Lilleby V. Review: Bone status in juvenile systemic lupus erythematosus. Lupus 2007;16:580-6.
    108. Kamphuis S, Silverman ED. Prevalence and burden of pediatric-onset systemic lupus erythematosus. Nature Reviews Rheumatology 2010;6:538-46.
    109. Clarke BL, Khosla S. Physiology of bone loss. Radiol Clin North Am 2010;48:483-95.
    110. Korbet SM, Schwartz MM, Evans J, Lewis EJ. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol 2007;18:244-54.
    111. Mok MY, Li WL. Do Asian patients have worse lupus? Lupus 2010;19:1384-90.
    112. Osio-Salido E, Manapat-Reyes H. Epidemiology of systemic lupus erythematosus in Asia. Lupus 2010;19:1365-73.
    113. Lalani S, Pope J, de Leon F, Peschken C. Clinical Features and Prognosis of Late-onset Systemic Lupus Erythematosus: Results from the 1000 Faces of Lupus Study. The Journal of Rheumatology 2009;37:38-44.
    114. Bertoli AM, Alarcón GS, Calvo-Alén J, Fernández M, Vilá LM, Reveille JD. Systemic lupus erythematosus in a multiethnic US cohort: Clinical features, course, and outcome in patients with late-onset disease. Arthritis & Rheumatism 2006;54:1580-7.
    115. Rovenský J, Tuchyňová A. Systemic lupus erythematosus in the elderly. Autoimmunity Reviews 2008;7:235-9.
    116. Appenzeller S, Pereira D, Costallat L. Greater accrual damage in late-onset systemic lupus erythematosus: a long-term follow-up study. Lupus 2008;17:1023-8.
    117. Swaak AJ, van den Brink HG, Smeenk RJ, et al. Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation. Lupus 2001;10:51-8.
    118. Cervera R, Khamashta MA, Font J, et al. Morbidity and Mortality in Systemic Lupus Erythematosus During a 10-Year Period. Medicine 2003;82:299-308.
    119. Badsha H, Edwards CJ. Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Seminars in Arthritis and Rheumatism 2003;32:370-7.
    120. Parker B, Bruce I. High dose methylprednisolone therapy for the treatment of severe systemic lupus erythematosus. Lupus 2007;16:387-93.
    121. American College of Rheumatology task force on Osteoporosis g. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis & Rheumatism 1996;39:1791-801.
    122. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
    123. WHO Fracture Risk Assessment Tool. (Accessed Feb 10, 2011, at http://www.shef.ac.uk/FRAX/.)
    124. Demas KL, Keenan BT, Solomon DH, Yazdany J, Costenbader KH. Osteoporosis and cardiovascular disease care in systemic lupus erythematosus according to new quality indicators. Semin Arthritis Rheum 2010;40:193-200.
    125. Mok CC, Ho CT, Wong RW, Lau CS. Damage accrual in southern Chinese patients with systemic lupus erythematosus. J Rheumatol 2003;30:1513-9.
    126. Kuan W, Li E, Tam LS. Lupus organ damage: what is damaged in Asian patients? Lupus 2010;19:1436-41.
    127. Borchers AT, Keen CL, Shoenfeld Y, Gershwin ME. Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 2004;3:423-53.
    128. 高雅慧, 張家嫺, 林子傑. 國人藥品使用型態分析研究. 九十八年度行政院衛生署補助研究計畫. 2009.
    129. Chambers SA, Allen E, Rahman A, Isenberg D. Damage and mortality in a group of British patients with systemic lupus erythematosus followed up for over 10 years. Rheumatology (Oxford) 2009;48:673-5.
    130. Hahn TJ. Corticosteroid-Induced Osteopenia. Arch Intern Med 1978;138:882-5.
    131. Demartini F, Grokoest AW, Ragan C. PATHOLOGICAL FRACTURES IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH CORTISONE. Journal of the American Medical Association 1952;149:750-2.
    132. Curtiss PH, Clark WS, Herndon CH. VERTEBRAL FRACTURES RESULTING FROM PROLONGED CORTISONE AND CORTICOTROPIN THERAPY. Journal of the American Medical Association 1954;156:467-9.
    133. Adinoff AD, Hollister JR. Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 1983;309:265-8.
    134. Ruegsegger P, Medici TC, Anliker M. Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol 1983;25:615-20.
    135. Robinson RJ, al-Azzawi F, Iqbal SJ, et al. Osteoporosis and determinants of bone density in patients with Crohn's disease. Dig Dis Sci 1998;43:2500-6.
    136. Cohen A, Shane E. Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 2003;14:617-30.
    137. Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 2003;48:3224-9.
    138. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002;13:777-87.
    139. De Vries F, Bracke M, Leufkens HGM, Lammers J-WJ, Cooper C, Van Staa TP. Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis & Rheumatism 2007;56:208-14.
    140. Nilas L, Christiansen C. Bone mass and its relationship to age and the menopause. J Clin Endocrinol Metab 1987;65:697-702.
    141. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353:487-97.
    142. Adler M, Chambers S, Edwards C, Neild G, Isenberg D. An assessment of renal failure in an SLE cohort with special reference to ethnicity, over a 25-year period. Rheumatology (Oxford) 2006;45:1144-7.
    143. Bruce IN, Gladman DD, Urowitz MB. Factors associated with refractory renal disease in patients with systemic lupus erythematosus: the role of patient nonadherence. Arthritis Care Res 2000;13:406-8.
    144. Rojas-Serrano J, Cardiel MH. Lupus patients in an emergency unit. Causes of consultation, hospitalization and outcome. A cohort study. Lupus 2000;9:601-6.
    145. 張峰玉. 全身性紅斑性狼瘡病患服藥遵從行為及其相關因素之研究. 台中縣: 弘光科技大學; 2009.
    146. Koneru S, Shishov M, Ware A, et al. Effectively measuring adherence to medications for systemic lupus erythematosus in a clinical setting. Arthritis Rheum 2007;57:1000-6.
    147. Koneru S, Kocharla L, Higgins GC, et al. Adherence to medications in systemic lupus erythematosus. J Clin Rheumatol 2008;14:195-201.

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