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系統識別號 U0026-0207201319191700
論文名稱(中文) 骨質疏鬆藥物於台灣使用之療效與安全性之探討
論文名稱(英文) Investigation on Effectiveness and Safety of Osteoporosis Drugs in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 101
學期 2
出版年 102
研究生(中文) 林子傑
研究生(英文) Tzu-Chieh Lin
學號 TB8971044
學位類別 博士
語文別 英文
論文頁數 130頁
口試委員 指導教授-高雅慧
口試委員-楊俊佑
口試委員-張志欽
口試委員-李中一
口試委員-林素真
口試委員-邵文逸
中文關鍵字 骨質疏鬆症  服藥順從度  相對療效  靜脈栓塞  下顎骨壞死 
英文關鍵字 osteoporosis  compliance  relative effectiveness  VTE  ONJ 
學科別分類
中文摘要 研究背景:
骨質疏鬆症引起之骨鬆骨折及其併發症常見於老年人,不但影響生活品質,亦可能增加日後骨折再發甚至死亡的風險。臨床上有許多骨質疏鬆藥品(例如: 雙磷酸鹽類藥物、raloxifene及calcitonin)可降低已發生骨鬆骨折之病患再發的風險。但是,近幾年的研究也發現,發生骨鬆骨折之病患若屬用藥順從度不佳者,發生骨折的風險顯著高於用藥順從度較佳的病患;並且,用藥順從度必須達到一定的程度才有治療效果。值得注意的是,雙磷酸鹽類藥物在曾經發生骨鬆骨折的病患中預防骨折再發的效果雖然優於他類藥品,但是,osteonecrosis of the jaw (ONJ)與靜脈栓塞的案例自2002年起出現於使用雙磷酸鹽類藥物之通報而廣受注意,近年來亦陸續有研究探討使用雙磷酸鹽類藥物與發生ONJ與靜脈栓塞之相關性。骨質疏鬆症是老年族群不容忽視的醫療議題,惟國內相關研究仍然闕如。

研究目的:
應用國內全民健康保險資料庫,探討國人發生骨鬆骨折族群之基本特質、用藥持續性及順從度,探討病患用藥順從度與骨折再發風險之相關性,骨質疏鬆藥品降低骨折再發風險之相對療效以及長期使用雙磷酸鹽類藥物與發生ONJ與靜脈栓塞之相關性。

研究方法:
採用回溯性世代研究法(retrospective cohort study),由2003至2006年20歲以上曾經發生過骨鬆骨折的病患中,自第一次開始使用骨質疏鬆藥品 (alendronate, raloxifene或calcitonin)的時間點,往後追蹤。評估病人開始使用藥品前一年的基本特質、開始使用骨質疏鬆藥品後一年內之用藥持續性及順從度。髖關節與非脊椎骨折再發為探討順從度影響與藥品相對療效之主要臨床成果。而ONJ與靜脈栓塞則為探討骨鬆藥品安全性時之主要研究目標。於探討病患順從度之好壞對於未來髖關節骨折再發風險影響、骨鬆藥品相對療效與安全性時,本研究利用多變項Cox regression控制相關之共變數、評估相對危險比及描繪校正後之存活曲線。本研究亦會利用傾向分數 (propensity score),以及一系列之敏感度測試來確認研究之可信度。所有資料處理及統計皆使用SAS 9.2版統計軟體。

結果:
本研究首先發現,台灣新發生骨鬆骨折之病患,於開始治療後一年內之順從度不佳。儘管如此,順從度高者相較與順從度低者,仍可有70%較低髖關節骨折再發之風險 (adjusted HR, 0.30; 95%CI:0.22-0.42)。此外,於骨鬆藥品中,raloxifene與calcitonin相較於alendronate使用者,皆有顯著較高之非脊椎骨折發生風險 (adjusted HR for raloxifene: 1.31, 95%CI, 1.14-1.51; adjusted HR for calcitonin: 1.47, 95%CI, 1.29-1.67). 不過,本研究發現,alendronate使用者相較於raloxifene或calcitonin使用者,並不會增加ONJ會靜脈栓塞之風險。

結論:
本研究發現,台灣骨鬆族群於新發生骨鬆骨折後第一年之服藥順從度不佳。不過,順從度佳者仍然有較低之骨鬆骨折再發風險。Alendronate為骨鬆藥品中療效較佳,且相較於他類骨鬆藥品無較高之ONJ與靜脈栓塞發生風險。因此,衛生主管機關與醫療人員應致力於增加病患之服藥順從度,降低未來骨鬆骨折再發之機會。
英文摘要 Background:
Osteoporotic fractures and their complications are serious problems for the elderly, due to their deleterious effects on quality of life and increased future fracture even mortality risk. Although there are effective treatments for preventing osteoporotic fractures, including bisphosphonates, raloxifene and calcitonin, the persistence and compliance of patients taking these drugs are suboptimal as reported in the literature. The fracture risks of poor compliant patients were significantly higher than compliant patients; furthermore, the compliance should be kept in certain level for the pharmacological agents to be effective. While bisphosphonates have demonstrated the superiority to the other osteoporotic regimen in patients with established osteoporotic fractures, cases of osteonecrosis of the jaw (ONJ) and venous thromboembolism (VTE) after using bisphosphonates since 2002 have drawn much attention. A few pilot studies regarding to the association between use of bisphosphonates and ONJ/VTE have been conducted in these years. Given osteoporosis and its complications are highly concerned, the effectiveness and risk of the osteoporotic treatment remains unknown in Taiwan.

Objective:
By using National Health Insurance Research Database, we will describe the baseline characteristics and compliance of osteoporotic therapy in patients with new osteoporotic fractures in Taiwan. Regarding to outcome evaluation, we will analyze the association between patients' compliance and risk of fracture. This study also aims to investigate the comparative effectiveness of pharmacological agents in preventing osteoporotic fractures and the association between use of bisphosphonates and ONJ risk. Finally, the safety of bisphosphonates, in terms of the risk of ONJ/VTE was investigated as well.

Method:
From 2003-2006, Enrollees in the National Health Insurance Research Database (NHIRD) aged above 50 years, with vertebral/hip fracture and new to osteoporosis therapy were recruited. Patients had Paget’s disease or cancer during baseline period were excluded. Patients were classified into alendronate or calcitonin/raloxifene (control) group according to the exposure after follow-up. The impact of patient adherence on secondary hip fracture risk, the relative effectiveness of osteoporosis drugs and the safety of bisphosphonates were estimated by using Cox modeling to correct effects of covariates and their correlation with outcomes, estimate hazard ratio and plot corrected survival curves. Results were examined in series sensitivity analyses, including different cumulative doses group. SAS 9.2 will be used for data management and statistical purpose.

Results:
We found only 38% of the study population remained compliant during the first year of treatment. Over the 4-year follow-up period, the risk of hip fracture among the compliant patients was 70% lower than in non-compliant patients (adjusted HR, 0.30). As for the relative effectiveness, the fracture rates were highest in calcitonin recipients (4.57/100 person-years), followed by raloxifene and alendronate. Results from Cox analyses showed raloxifene (HR, 1.47; 95%CI, 1.29-1.67) and calcitonin (HR, 1.51; 95%CI, 1.29-1.75) had higher non-vertebral fracture risk as compared with alendronate. We also did not observe higher incidence and risk of ONJ/VTE for alendronate recipients, as compared with raloxifene/calcitonin recipients.

Conclusion:
The compliance of osteoporosis population in Taiwan is suboptimal. The effectiveness of alendronate in Taiwan is best within drug classes, and the potential risks for serious adverse events (ONJ, VTE) were low. Efforts and policies should be implanted to osteoporosis patients by the regulatory agencies and healthcare professionals to improve their compliance.
論文目次 Part I. Introduction 1
1. Introduction to Osteoporosis 1
1.1 Pathology and risk factors for osteoporosis 2
1.2 Diagnosis of osteoporosis 4
2. Pharmacological Treatments for Osteoporosis 9
2.1 Mechanism of action of osteoporosis drugs 9
2.2 Clinical efficacies of the osteoporosis drugs 12
3. Statement of the Research Questions 16
4. Specific Aims 18
5. Significance 19
Part II. Compliance with Alendronae and Its Impact on Hip Fracture Risk among Established Osteoporosis Patients in Taiwan 20
1. Literature review 20
1.1 Researches using health insurance database to assess patients compliance to osteoporosis drugs and its impact on fracture risk 21
2. Methods 24
2.1 Data Source 24
2.2 Study Design and Population 24
2.3 Compliance with Alendronate 25
2.4 Covariates and Outcomes 26
2.5 Statistical Analysis 26
3. Results 28
3.1 1st Year Compliance and Cohort Characteristics 28
3.2 The Impacts of Compliance on the Incident Hip Fracture Risk 29
4. Discussion 32
5. Strength and limitations 37
6. Conclusion and Clinical Implications 39
Part III. The Relative Effectiveness of Osteoporosis Drugs in Preventing Secondary Non-vertebral fractures in Taiwan 47
1. Literature review 47
1.1 Current evidences from clinical trials 47
1.2 Current evidences from observational studies 48
2. Methods 51
2.1 Data source 51
2.2 Study design and population 51
2.3 Exposure to osteoporosis drugs 52
2.4 Outcomes and Covariates 52
2.5 Statistical analysis 53
3. Results 55
3.1 Baseline Characteristics of Osteoporosis drug users 55
3.2 Fracture Rates and Relative Effectiveness of Osteoporosis drugs 55
4. Discussion 57
5. Strength and Limitation 61
6. Conclusion and clinical implication 63
Part IV. Incidence and Risk of Osteonecrosis of the Jaw among the Taiwan Osteoporosis Population 71
1. Literature review 71
1.1 Introduction to ONJ 71
1.2 Incidence of ONJ and methodological challenges 72
2. Methods 74
2.1 Data source 74
2.2 Study design and population 74
2.3 Exposure to osteoporosis drugs 75
2.4 Covariates and Outcomes 75
2.5 Statistical analysis 76
3. Results 78
3.1 Baseline Characteristics 78
3.2 Risk and Incidence of possible ONJ 79
3.3 Sensitivity analysis 80
4. Discussion 81
5. Strength and limitations 85
6. Conclusion and clinical implications 87
Part V. Incidence and Risk of Venous Thromboembolism among Taiwan Osteoporotic Fracture Population 94
1. Literature review 94
1.1 Potential adverse cardiovascular events associated with the osteoporosis drugs 94
1.2 Risk of VTE in the bisphosphonates and raloxifene 95
2. Methods 97
2.1 Data source 97
2.2 Study design and population 97
2.3 Exposure to osteoporosis drugs 98
2.4 Outcomes and Covariates 98
2.5 Statistical analysis 100
3. Results 102
3.1 Baseline Characteristics of Osteoporosis drug users 102
3.2 Incidence and risk of VTE for alendronate or raloxifene compared with calcitonin 103
4. Discussion 105
5. Strength and limitations 108
6. Conclusion and clinical implications 110
Part VI. Summary 117
Part VII. Reference 119
參考文獻 1. National Osteoporosis Foundation: Clinician's Guide to Prevention and Treatment of Osteoporosis. (National Osteoporosis Foundation, Washington,DC, 2010), 2010.
2. Colón-Emeric C, K.M., Pieper C, et al, The contribution of hip fracture to risk of subsequent fracture: Data from two longitudinal studies. Osteoporos Int, 2003. 14: p. 879-883.
3. National Osteoporosis Foundation, America’s Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation. Washington, DC: National Osteoporosis Foundation. 2002.
4. US Department of Health and Human Services, Office of the Surgeon General, Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General. 2004.
5. Khosla, S. and B.L. Riggs, Pathophysiology of age-related bone loss and osteoporosis. Endocrinology & Metabolism Clinics of North America. 34(4): p. 1015-30.
6. Organization, W.H., Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical Report Series 843. WHO, Geneva, 1994.
7. Kanis JA, B.F., De Laet C, Johansson H, Johnell O, Jonsson B et al, Assessment of fracture risk. Osteoporos Int, 2005. 16: p. 581-589.
8. Amir Qaseem, M., PhD, MHA, Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med, 2008. 149: p. 404-415.
9. Group, K.J.o.b.o.t.W.H.O.S., Assessment of Osteoporosis at the Primary Health Care Level. 2008 Technical
Report. University of Sheffield, UK: WHO Collaborating Center, 2008.
10. Kanis, J.A., et al., Perspective - the Diagnosis of Osteoporosis. Journal of Bone and Mineral Research, 1994. 9(8): p. 1137-1141.
11. 中華民國骨質疏鬆學會, Taiwanese Guidelines for the Prevention and Treatment of Osteoporosis . http://www.toa1997.org.tw/files/Taiwanese%20Guidelines%20for%20the%20Prevention%20and%20Treatment%20of%20Osteoporosis.pdf Assessed online 2013.4.19.
12. Kanis, J.A., et al., European guidance for the diagnosis and management of osteoporosis in postmenopausal women. [Review] [166 refs]. Osteoporosis International, 2008. 19(4): p. 399-428.
13. Okazaki, R., et al., Estrogen promotes early osteoblast differentiation and inhibits adipocyte differentiation in mouse bone marrow stromal cell lines that express estrogen receptor (ER) alpha or beta. Endocrinology, 2002. 143(6): p. 2349-2356.
14. Lindsay, R., et al., Prevention of Spinal Osteoporosis in Oophorectomized Women. Lancet, 1980. 2(8205): p. 1151-1154.
15. Reid, I.R., et al., A comparison of the effects of raloxifene and conjugated equine estrogen on bone and lipids in healthy postmenopausal women. Archives of Internal Medicine, 2004. 164(8): p. 871-879.
16. Reginster, J.Y., Effect of Calcitonin on Bone Mass and Fracture Rates. American Journal of Medicine, 1991. 91: p. S19-S22.
17. Plosker, G.L. and D. McTavish, Intranasal salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis. Drugs Aging, 1996. 8(5): p. 378-400.
18. Geusens, P.P., et al., Drug Insight: choosing a drug treatment strategy for women with osteoporosis-an evidence--based clinical perspective. [Review] [62 refs]. Nature Clinical Practice Rheumatology, 2008. 4(5): p. 240-8.
19. 中央健康保險局, 全民健康保險藥品給付規定. 2008.
20. Black DM, C.S., Karpf DB, Cauley JA, Thompson DE, Nevitt MC et al, Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet, 1996. 348: p. 1535-1541.
21. Harris ST, W.N., Genant HK, McKeever CD, Hangartner T, Keller M et al, Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. JAMA, 1999. 282: p. 1344-1352.
22. Black, D.M., et al., Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.[see comment]. New England Journal of Medicine, 2007. 356(18): p. 1809-22.
23. Chesnut IC, S.A., Christiansen C, Recker R, Stakkestad JA, Hoiseth A et al, Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res, 2004. 19: p. 1241-1249.
24. 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.
25. Ettinger B, B.D., Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK et al, Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA. 282: p. 637-645.
26. Neer RM, A.C., Zanchetta JR, Prince R, Gaich GA, Reginster JY et al, Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med, 2001. 344: p. 1434–1441.
27. Cherry N, G.K., Hannaford P, Heagerty A, Khan MA, Kitchener H, et al. ESPRIT team, Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial. Lancet, 2002. 360: p. 2001-2008.
28. Hulley S, G.D., Bush T, Furberg C, Herrington D, Riggs B, et al, Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA, 1998. 280: p. 605-13.
29. National Osteoporosis Foundation, America’s Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation. Washington, DC: National Osteoporosis Foundation. 2002.
30. Burge R, D.-H.B., Solomon DH, Wong JB, King A, Tosteson A, Incidence and economic burden of osteoporosis-related fractures in the United States. J Bone Miner Res, 2007. 22(3): p. 465-475.
31. Klotzbuecher CM, R.P., Landsman PB, Abbot TA, Berger M, Patients with prior fractures have increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res, 2000. 15: p. 721-727.
32. McClung MR, G.P., Miller PD, Zippel H, Bensen WG, Roux C et al, Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med, 2001. 344: p. 333-340.
33. Cramer, J.A., et al., A systematic review of persistence and compliance with bisphosphonates for osteoporosis. [Review] [34 refs]. Osteoporosis International, 2007. 18(8): p. 1023-31.
34. Caro, J.J., et al., The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporosis International, 2004. 15(12): p. 1003-8.
35. Caro JJ, I.K., Huybrechts KF et al, The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int, 2004. 15: p. 1003–1008.
36. Huybrechts KF, I.K., Caro JJ, Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone, 2006. 38: p. 922–928.
37. Siris, E.S., et al., Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases.[see comment]. Mayo Clinic Proceedings, 2006. 81(8): p. 1013-22.
38. Kothawala, P., et al., Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. [Review] [57 refs]. Mayo Clinic Proceedings, 2007. 82(12): p. 1493-501.
39. Solomon, D.H., et al., Compliance with osteoporosis medications. Archives of Internal Medicine, 2005. 165(20): p. 2414-9.
40. Blouin, J., et al., Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women. British Journal of Clinical Pharmacology, 2008. 66(1): p. 117-27.
41. Cotte, F.E., F. Mercier, and G. De Pouvourville, Relationship between compliance and persistence with osteoporosis medications and fracture risk in primary health care in France: a retrospective case-control analysis. Clinical Therapeutics, 2008. 30(12): p. 2410-22.
42. Gallagher, A.M., et al., Fracture outcomes related to persistence and compliance with oral bisphosphonates. Journal of Bone & Mineral Research, 2008. 23(10): p. 1569-75.
43. Rabenda, V., et al., Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. Osteoporosis International, 2008. 19(6): p. 811-8.
44. NHIRD, National Health Insurance Research Database, Taiwan.
http://www.nhri.org.tw/nhird/en/index.htm.
45. McCombs, J.S., et al., Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas, 2004. 48(3): p. 271-87.
46. Brankin E, W.M., Lynch NO, The impact of dosing frequency on compliance and persistence with bisphosphonates among postmenopausal women in the UK: evidence from three databases. Curr Med Res Opin, 2006. 22: p. 1249-1258.
47. Huybrechts KF, I.K., Caro JJ, Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone, 2006. 38: p. 922-928.
48. Cadarette, S.M., et al., Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture.[see comment][summary for patients in Ann Intern Med. 2008 May 6;148(9):I28; PMID: 18458273]. Annals of Internal Medicine, 2008. 148(9): p. 637-46.
49. Morin, S., et al., Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures. Osteoporosis International, 2007. 18(12): p. 1625-32.
50. Pinheiro, M.M., et al., Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS). Osteoporosis International, 2009. 20(3): p. 399-408.
51. Chang, C.M., et al., Benzodiazepine and risk of hip fractures in older people: a nested case-control study in Taiwan. American Journal of Geriatric Psychiatry, 2008. 16(8): p. 686-92.
52. Wagner, A.K., et al., Benzodiazepine use and hip fractures in the elderly: who is at greatest risk? Archives of Internal Medicine, 2004. 164(14): p. 1567-72.
53. Takkouche, B., et al., Psychotropic medications and the risk of fracture: a meta-analysis. Drug Safety, 2007. 30(2): p. 171-84.
54. Weycker, D., et al., Compliance with osteoporosis drug therapy and risk of fracture. Osteoporosis International, 2007. 18(3): p. 271-7.
55. Black, D.M., et al., Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet, 1996. 348(9041): p. 1535-41.
56. Curtis, J.R., et al., Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users. Journal of Bone & Mineral Research, 2008. 23(9): p. 1435-41.
57. Rosen, C.J., et al., Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study.[see comment]. Journal of Bone & Mineral Research, 2005. 20(1): p. 141-51.
58. Bonnick, S., et al., Comparison of weekly treatment of postmenopausal osteoporosis with alendronate versus risedronate over two years.[see comment][erratum appears in J Clin Endocrinol Metab. 2007 Aug;92(8):3032]. Journal of Clinical Endocrinology & Metabolism, 2006. 91(7): p. 2631-7.
59. Recker, R.R., et al., Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass. Bone, 2007. 40(4): p. 843-51.
60. Luckey, M., et al., Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the treatment of postmenopausal osteoporosis. Menopause, 2004. 11(4): p. 405-15.
61. Seeman, E., Is a change in bone mineral density a sensitive and specific surrogate of anti-fracture efficacy?. [Review] [53 refs]. Bone, 2007. 41(3): p. 308-17.
62. Watts, N.B., et al., Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in BMD. Journal of Bone & Mineral Research, 2005. 20(12): p. 2097-104.
63. Silverman, S.L., et al., Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study.[see comment]. Osteoporosis International, 2007. 18(1): p. 25-34.
64. Watts, N.B., et al., Comparison of risedronate to alendronate and calcitonin for early reduction of nonvertebral fracture risk: results from a managed care administrative claims database. J Manag Care Pharm, 2004. 10(2): p. 142-51.
65. Avorn, J., Debate about funding comparative-effectiveness research. New England Journal of Medicine, 2009. 360(19): p. 1927-9.
66. Lin, T.C., et al., Alendronate Adherence and Its Impact on Hip-Fracture Risk in Patients With Established Osteoporosis in Taiwan. Clinical Pharmacology & Therapeutics, 2011. 90(1): p. 109-116.
67. Parsons, L.S., Reducing Bias in a Propensity Score Matched-Pair Sample Using Greedy Matching Techniques. http://www2.sas.com/proceedings/sugi26/p214-26.pdf. Assessed Jan. 4th, 2011.
68. MacLean, C., et al., Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Annals of Internal Medicine, 2008. 148(3): p. 197-213.
69. Ettinger, B., et al., Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA, 1999. 282(7): p. 637-45.
70. Delmas, P.D., et al., Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone, 2003. 33(4): p. 522-32.
71. Murad, M.H., et al., Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. Journal of Clinical Endocrinology & Metabolism, 2012. 97(6): p. 1871-80.
72. Chesnut, C.H., 3rd, et al., A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med, 2000. 109(4): p. 267-76.
73. Watts, N.B., et al., Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: Reduction in risk of nonvertebral fracture is not related to change in BMD. Journal of Bone and Mineral Research, 2005. 20(12): p. 2097-2104.
74. Seeman, E., Is a change in bone mineral density a sensitive and specific surrogate of anti-fracture efficacy? Bone, 2007. 41(3): p. 308-317.
75. Horwitz, R.I., et al., Treatment adherence and risk of death after a myocardial infarction. Lancet, 1990. 336(8714): p. 542-5.
76. Padula, A.M., et al., Placebo adherence and mortality in the heart and estrogen/progestin replacement study. Am J Med, 2012. 125(8): p. 804-10.
77. Granger, B.B., et al., Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial. Lancet, 2005. 366(9502): p. 2005-11.
78. Glynn, R.J., S. Schneeweiss, and T. Sturmer, Indications for propensity scores and review of their use in pharmacoepidemiology. Basic & Clinical Pharmacology & Toxicology, 2006. 98(3): p. 253-9.
79. Schneeweiss, S., et al., High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology, 2009. 20(4): p. 512-22.
80. The European Medicines Agency, European Medicines Agency recommends limiting long-term use of calcitonin medicines. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/public_health_alerts/2012/07/human_pha_detail_000065.jsp&mid=WC0b01ac058001d126 assessed online 2012/9/5, 2012.
81. Adomaityte, J., M. Farooq, and R. Qayyum, Effect of raloxifene therapy on venous thromboembolism in postmenopausal women. A meta-analysis. Thromb Haemost, 2008. 99(2): p. 338-42.
82. Barrett-Connor, E., et al., Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med, 2006. 355(2): p. 125-37.
83. Abrahamsen, B., Adverse effects of bisphosphonates. Calcified Tissue International, 2010. 86(6): p. 421-35.
84. Silverman, S.L. and R. Landesberg, Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. [Review] [60 refs]. American Journal of Medicine, 2009. 122(2 Suppl): p. S33-45.
85. Khan, A.A., et al., Bisphosphonate associated osteonecrosis of the jaw. [Review] [95 refs]. Journal of Rheumatology, 2009. 36(3): p. 478-90.
86. Marx, R.E., Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg, 2003. 61(9): p. 1115-7.
87. Ruggiero, S.L., et al., Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. Journal of Oral and Maxillofacial Surgery, 2004. 62(5): p. 527-534.
88. Marx, R.E., et al., Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. Journal of Oral and Maxillofacial Surgery, 2005. 63(11): p. 1567-1575.
89. Woo, S.B., J.W. Hellstein, and J.R. Kalmar, Systematic review: bisphosphonates and osteonecrosis of the jaws (vol 144, pg 753, 2006). Annals of Internal Medicine, 2006. 145(3): p. 235-235.
90. Reid, I.R., Osteonecrosis of the jaw: who gets it, and why?. [Review] [65 refs]. Bone, 2009. 44(1): p. 4-10.
91. Hoff, A.O., et al., Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. Journal of Bone and Mineral Research, 2008. 23(6): p. 826-836.
92. Heckbert, S.R., et al., Use of alendronate and risk of incident atrial fibrillation in women.[see comment]. Archives of Internal Medicine, 2008. 168(8): p. 826-31.
93. Edwards, B.J., et al., Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. [Review] [69 refs]. Lancet Oncology, 2008. 9(12): p. 1166-72.
94. Felsenberg D, H.m.B., Amling M, Bisphosphonattherapie assoziierte. Kiefernekrosen Deutsches Arzteblatt, 2006. 46: p. A3078–80.
95. Solomon, D.H., et al., Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int, 2013. 24(1): p. 237-44.
96. Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, A.A.o.O. and S. Maxillofacial, American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. Journal of Oral & Maxillofacial Surgery, 2007. 65(3): p. 369-76.
97. Wilkinson, G.S., et al., Intravenous bisphosphonate therapy and inflammatory conditions or surgery of the jaw: a population-based analysis.[see comment]. Journal of the National Cancer Institute, 2007. 99(13): p. 1016-24.
98. Cartsos VM, Z.S., Zavras AI, Bisphosponate use and the risk of adverse jaw outcomes. J Am Dent Assoc, 2008. 139: p. 23-30.
99. Pazianas, M., W.A. Blumentals, and P.D. Miller, Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporosis International, 2008. 19(6): p. 773-9.
100. Lin, T.C., et al., Alendronate adherence and its impact on hip-fracture risk in patients with established osteoporosis in taiwan. Clin Pharmacol Ther, 2011. 90(1): p. 109-16.
101. Hess, L.M., et al., Factors associated with osteonecrosis of the jaw among bisphosphonate users. [Review] [57 refs]. American Journal of Medicine, 2008. 121(6): p. 475-483.
102. Lo, J.C., et al., Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. Journal of Oral & Maxillofacial Surgery, 2010. 68(2): p. 243-53.
103. Tennis, P., et al., Incidence of osteonecrosis of the jaw among users of bisphosphonates with selected cancers or osteoporosis. Pharmacoepidemiology & Drug Safety, 2012. 21(8): p. 810-7.
104. Van den Wyngaert, T., M.T. Huizing, and J.B. Vermorken, Osteonecrosis of the jaw related to the use of bisphosphonates. [Review] [60 refs]. Current Opinion in Oncology, 2007. 19(4): p. 315-22.
105. Hong, J.W., et al., Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia. Osteoporos Int, 2010. 21(5): p. 847-53.
106. King, A.E. and E.M. Umland, Osteonecrosis of the jaw in patients receiving intravenous or oral bisphosphonates. [Review] [71 refs]. Pharmacotherapy, 2008. 28(5): p. 667-77.
107. Fellows, J.L., et al., ONJ in two dental practice-based research network regions. J Dent Res, 2011. 90(4): p. 433-8.
108. Baillargeon, J., et al., Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous bisphosphonates. Ann Pharmacother, 2011. 45(10): p. 1199-206.
109. Zavras, A.I. and S. Zhu, Bisphosphonates are associated with increased risk for jaw surgery in medical claims data: is it osteonecrosis?[see comment]. Journal of Oral & Maxillofacial Surgery, 2006. 64(6): p. 917-23.
110. American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws. Journal of Oral and Maxillofacial Surgery, 2007. 65(3): p. 369-376.
111. Rosendaal, F.R., V.A.N.H.V. A, and C.J. Doggen, Venous thrombosis in the elderly. J Thromb Haemost, 2007. 5 Suppl 1: p. 310-7.
112. Guessous, I., et al., Osteoporotic fracture risk in elderly women: estimation with quantitative heel US and clinical risk factors. Radiology, 2008. 248(1): p. 179-84.
113. Hans, D., et al., Assessment of the 10-year probability of osteoporotic hip fracture combining clinical risk factors and heel bone ultrasound: the EPISEM prospective cohort of 12,958 elderly women. J Bone Miner Res, 2008. 23(7): p. 1045-51.
114. Cheung, A.M. and A.S. Detsky, Osteoporosis and fractures: missing the bridge? JAMA, 2008. 299(12): p. 1468-70.
115. Breart, G., et al., Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database. Osteoporosis International, 2010. 21(7): p. 1181-7.
116. Black, D.M., et al., Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med, 2007. 356(18): p. 1809-22.
117. Sorensen, H.T., et al., Use of bisphosphonates among women and risk of atrial-fibrillation and flutter: population based case-control study. British Medical Journal, 2008. 336(7648): p. 813-816.
118. Grosso, A., et al., Oral Bisphosphonates and Risk of Atrial Fibrillation and Flutter in Women: A Self-Controlled Case-Series Safety Analysis. Plos One, 2009. 4(3).
119. Weng-Foung Huang, P., 1 Yi-Wen Tsai, PhD,1,2 Yu-Wen Wen, PhD,2 Fei-Yuan Hsiao, PhD,3 Ken N. Kuo, MD,2 and Chia-Rung Tsai, MS2, Osteoporosis treatment and atrial fibrillation: alendronate versus raloxifene. Menopause, 2009. 17(1).
120. Abrahamsen, B., P. Eiken, and K. Brixen, Atrial fibrillation in fracture patients treated with oral bisphosphonates. Journal of Internal Medicine, 2009. 265(5): p. 581-92.
121. Adami, S. and N. Zamberlan, Adverse effects of bisphosphonates - A comparative review. Drug Safety, 1996. 14(3): p. 158-170.
122. Diel, I.J., R. Bergner, and K.A. Grotz, Adverse effects of bisphosphonates: current issues. J Support Oncol, 2007. 5(10): p. 475-82.
123. Lamberg, A.L., et al., Use of oral bisphosphonates and risk of venous thromboembolism: a population-based case-control study. Osteoporos Int, 2010. 21(11): p. 1911-7.
124. Vestergaard, P., et al., Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism. Osteoporosis International, 2010. 21(9): p. 1591-7.
125. Lee, C.H., et al., Incidence and cumulative recurrence rates of venous thromboembolism in the Taiwanese population. J Thromb Haemost, 2010. 8(7): p. 1515-23.
126. Lee, C.H., et al., Universal pharmacological thromboprophylaxis for total knee arthroplasty may not be necessary in low-risk populations: a nationwide study in Taiwan. J Thromb Haemost, 2012. 10(1): p. 56-63.
127. Spencer, F.A., et al., The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. Journal of General Internal Medicine, 2006. 21(7): p. 722-7.
128. Schneeweiss, S., et al., Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development. Clinical Pharmacology & Therapeutics, 2011. 90(6): p. 777-90.
129. Sturmer, T., et al., A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods. Journal of Clinical Epidemiology, 2006. 59(5): p. 437-47.
130. Delmas, P.D., et al., Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab, 2002. 87(8): p. 3609-17.
131. Kung, A.W., et al., Efficacy and safety of raloxifene 60 milligrams/day in postmenopausal Asian women. J Clin Endocrinol Metab, 2003. 88(7): p. 3130-6.

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