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Osteoporosis guideline2010

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Utai Sukviwatsirikul
Utai Sukviwatsirikul

แนวทางเวชปฏิบัติเรื่องโรคกระดูกพรุน http://www.tmsociety.or.th/ckfinder/userfiles/files/guideline2010.pdf

Salud y medicina
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Definition, epidemiology, burden and etiology of osteoporosis .....1 I-1 I-2 Definition and concept ............................................................................................................1 Epidemiology of osteoporosis and osteoporotic fractures ....................................................1 2.1 ก (Worldwide epidemiology) ...............................................................1 2.2 (Epidemiology in Asia and Thailand)........2 I-3 Burden and impact of osteoporosis and osteoporotic fractures ...........................................2 3.1 ก ก กก ก ก ก ก ก ก ก (Osteoporosis related mortality and morbidity) .................................................................................................3 3.2 ก ก ก ก ก ก F (Health economic aspect of osteoporotic fractures) ...................................................................................3 I-4 Pathogenesis and etiology .....................................................................................................4 4.1 ก (Pathogenesis) ...........................................................................................4 ก F ......................................................................................................................................5 Diagnosis and bone mass assessment in osteoporosis .................8 II-1 History, physical examination and differential diagnosis .......................................................8 1.1 ก ก ก ก (Classification of osteoporosis) .........................8 II-2 Risk factors for osteoporosis and osteoporotic fractures ......................................................9 2.1 ˆ ก ก ก ก ก ก ก ก (Risk factors of osteoporosis and osteoporotic fracture) ........................................................................9 2.2 ก ˆ ก ก ก ก ก ก ก ก F FRAXTM Fก ก (Risk assessment of osteoporotic fracture using WHO-FRAXTM) 9 II-3 Laboratory investigations and bone strength assessments ................................................11 3.1 ก F ก (Laboratory investigation) ................................................11 3.2 ก ก F ก ก (Bone strength assessment) ............................11 II-4 Diagnostic criteria for osteoporosis ......................................................................................12 4.1 ก F ก ก (Measurement of bone density) ..................................12 4.2 ก ก F ก ก (Biochemical markers of bone turnover) .......................................................................................................................13 4.3 ก ก (Screening) .......................................................................................14 ก 2.1 ...................................................................................................................................15 OSTA (Osteoporosis Self-Assessment Tool for Asians) ...................................................15 Khon Kaen Osteoporosis study score (KKOS) ..................................................................16 ก 2.2 ...................................................................................................................................18 ก ก ก ก ก ก F ก QUS ...........................................................................................................18 ก F ....................................................................................................................................19
Prevention of osteoporosis and prevention of falls .......................21 III-1 Strategies to maximize peak bone mass ............................................................................21 III-2 Strategies to prevent bone loss ...........................................................................................21 ก F F (Hormone replacement therapy) .....................................................22 III-3 Nutritional aspect in osteoporosis ........................................................................................22 (Calcium) .............................................................................................................22 (Vitamin D) ............................................................................................................26 (Vitamin K) ...........................................................................................................27 III-4 Life style modification and prevention of fall .......................................................................28 4.1 ก ก Fก ˈ ก ก ............................................28 4.2 ก ˂ ก ก ก F F ˁ ก ก ................................................................29 ก 3.1 Falls Risk Assessment tool ............................................................................32 ก 3.2 ก กก ก ˂ ก ก ก ....................................................33 ก กก ก F ก ก ก ก ก ก ..........................................33 ก ˂ ก ก กF ก ก ก ก ก ......................................................................34 ก F ....................................................................................................................................34 Treatment of osteoporosis ................................................................38 IV-1 Goal of osteoporosis treatment ............................................................................................38 1.1 ก ˂ ก ก ก ก ก .........................................................38 1.2 F ก ก ก ก ......................................................................38 1.3 ก Fก ก ก ก F ก Fก F F International Osteoporosis Foundation National Osteoporosis Foundation 38 1.4 ก Fก ก ก ก F ก Fก F F ก ก F ....................................................................39 IV-2 Pharmacotherapy for osteoporosis ......................................................................................40 2.1 ก ก ก (Inhibitors of bone resorption) ..............................................41 2.2 ก F ก F ก ก F (Stimulators of bone formation) ....................................42 2.3 ก (mixed action agents) ............................................................43 IV-3 Alternative therapy and non-pharmacological treatment .....................................................44 3.1 Hip protector .................................................................................................................44 IV-4 Potential adverse events, prerequisites and contraindications in using anti-osteoporotic agents ..................................................................................................................................44 4.1 F F F F ก F ก ก ก ..........................44 IV-5 Monitoring treatment and duration of treatment ..................................................................47 5.1 ก ก ก ...............................................................................47 5.2 ก ก ........................................................................................................48 ก F ....................................................................................................................................54 Glucocorticoid-induced osteoporosis (GIO) ...................................62
V-1 Introduction and epidemiology .............................................................................................62 1.1 ............................................................................................................................62 1.2 ...................................................................................................................62 V-2 Pathophysiology and risk assessment .................................................................................62 2.1 ก กก ก ...........................................................................................................62 2.2 ˆ .....................................................................................................................63 V-3 Diagnosis ..............................................................................................................................63 V-4 Prevention and treatment .....................................................................................................63 4.1 ก ˂ ก ก ก ก ก กก F ก F F ..........63 V-5 Monitoring treatment ............................................................................................................64 5.1 ก ก ก .................................................................................................64 ก F ....................................................................................................................................65 Osteoporosis in men ..........................................................................68 VI-1 Introduction and epidemiology .............................................................................................68 1.1 ก ..............................................................................................68 1.2 ...................................................................................................................68 1.3. ˆ .....................................................................................................................69 VI-2 Assessment and diagnosis ..................................................................................................69 2.1 ก ....................................................................................................................69 2.2 ก F ก ก ..............................................................................69 VI-3 Prevention .............................................................................................................................70 3.1 ก ˂ ก ก ก F ................................................................................70 VI-4 Treatment and follow-up ......................................................................................................71 4.1 ก ก ก ก F .......................................................................71 4.2 ก ก ก ..................................................................................................71 ก F ....................................................................................................................................72
1 Definition, epidemiology, burden and etiology of osteoporosis I-1 Definition and concept ʾ . . 2543 National Institute of Health F ก (1) F ˈ ก ก กF ก ก (bone strength) F ก ก ก กF ก ก ก F 2 F ก (bone density) ก ก (bone quality) ก ก F F F ก ก I-2 Epidemiology of osteoporosis and osteoporotic fractures 2.1 ก (Worldwide epidemiology) ʾ . . 2536 F กก (2) ก (WHO) F ก fractures) 1.3 F F ʾ 25% ˈ ก ก ก ก (hip fractures) ก ก F ก F 30% F Consensus Development Conference ก F F ก ก ก ก ก ก ก (osteoporotic 50% ˈ ก ก ก (vertebral fractures) ก 25% ˈ ก ก ก ก F ก ก F 50 ʾ ˈ ก ก กก ก National Health and Nutrition Survey (NHANES III) ก ʾ . . 2540 F ก F F ก 13-18% ˈ ก ก (osteoporosis) ก 27-50% F ก ก (osteopenia) ก ก ก ก F F ก F ก FF F กF F ก Fก กก F 80 ʾ F ˈ ก ก 70% (3) F ก ก ก F ก F (incidence) F กF F F F F F (adolescence) ก (middle life) ก F ก ก (working) ก (lifestyle) F กก F ก ก ก ก FF ˈ ก ก ก ก (high-energy trauma) F F 40-50 ʾ ก ก ก F ก ก ก ก F ก F ก ก ก F F ก ก ก ก F ก ก ก (4) ก ก ก F ก F ก ก ก F ˈ ก F (low-energy trauma) ก ก ก กก ก (osteoporotic fractures) ก (4) ก ก ก F ˁ ก ก ก ก ʾ 500,000 ก กก F 10 F FF F ก กก F 70 ʾ (4) ก ก ก F F F ก Fก ก ก ก ก ก F (Caucasian) F ʾ 737 F 100,000 F F F (5) ʾ 280 F 100,000 F ʽ F
2 2.2 (Epidemiology in Asia and Thailand) ก F F 76.3 ʾ F F ก 2541(7) . . 2544(8) ก FF F F F F 40 ʾ 11-13% ˈ ก ʾ . . 2551 (life expectancy) ก 69.5 ʾ F ก ก (prevalence) ก ก F F กก F F ก ก ʾ . . F F F ก Fก ก ก Fก ก F F ก ก Fก ก F 2.5 F F ก ก ก F (T-score ≤ -2.5) F 19-21% F ˈ ก ก ก ก F (lumbar spine osteoporosis) ก ก ก ก (femoral neck osteoporosis) (6) ʾ . . 2540-2541(9) ก F ก F 50 ʾ ʾ 162 F 100,000 851 F 100,000 ก ก 75 ʾ F ก F 50 ʾ ก F ก ก ก ก ʾ 269 ˈ ʾ 1,011 F 100,000 F กก F 75 ʾ กF ก ก ก F ก ก F ก ก Fก ก ก ก ก ก F Fก ก ก ก ก ก F F ก (Hong Kong Chinese) 179 F 100,000 ʾ . . 2508 ˈ ʾ 389 F 100,000 (10) กF F กก ˁ ( . . 2545) ก ก ก ก ʾ 92,400 5 ʾกF F ˈ ʾ 117,900 (11) ʾ . . 2050 ก 40 ก F ʾ F F ก ก ก ก ก ก กF 6 F 3 F ก F ก ก ก ก ก ˈ ʾ ก F 100,000 ก F ก ก F F F F ก ก ก ก F ก ʾ ʾ . . 2528 ก ก F ก ก F FF ก ก (10) F F I-3 Burden and impact of osteoporosis and osteoporotic fractures F ก 1. ก ก ก กF ก F 2. ก ก ก ก ˈ ก fractures ก ก ˈ ก ก ก ก ก FF ก F ก ก F ก ก ก F ก ก F ก F ˈ F ก ก กก ˈ กF F ก (burden) F ก F clinical consequence F ก F ˈ 2ก (low-energy trauma) F ก ก ก ก กก กF ก ก F ก F ˈ F ก F ก ก ก กก กF ก ก F ก ก ก ก ก ก ก (impact) ก กF ก ก osteoporotic ก ก ก ก ก
3 3.1 ก ก กก ก ก ก ก ก (Osteoporosis related mortality and morbidity) 1. ก ก ก 2. 3. 4. 5. 6. ก ก ก ก ก ก ก ก (osteoporotic vertebral fractures) ก ก กก ก ก F F ˈ F 40% F ก ก ก F F F F ˈ ก ก ก ก ก ก ก F ก F ก F ก F F F F ก ก ก ก ก ก ก (12) (13) ˁ (morbidity) ก (mortality) กก F F F ก ก ก F F ˁ ก (height loss) F (kyphosis) (scoliosis) F ก F F ก กก ก ก ก ก ก ก ก ก ก (functional disability) ก F F ก ก ก F ก F ก morbidity mortality ก F (12-14) ก ก ก ก F ก ก ก ก F (14) ก ก ก ก (hip fractures) ˈ ก ก ก ก ก ก ˆ ก ก ก ก ก ก ก F ก ก ก ก ก F ก ก F FF ก ก ก ก ก กก กก F ก ก ก ก F F F ก F ก F ˁ F F ก ก F F ก F F (15F ก ก ก ก ˁ ก ก ก ก 16) ก 20% 1 ʾ ก ก ก F F 30% ก ก (permanent disability) F F ก ก F F (nursing home) 40% F F F ก F F F F F 80% F ก F F F F กF ก ก ก ก ก ก ก ก ก กก ก F(17) F 2.1% F ก กก ก ก ก 3 ,6 1 ʾ F ก 9%, 12% 17% ก ก ก ก (18) ก ก ก ก F F F ˁ (22%) F F 23% F F wheel chair ก F ก ก F ˁ F F F ก F ก ก F F 11% F F 10% F F F 22% F F ก F 5% F F ก 3.2 ก ก ก ก ก ก F (Health economic aspect of osteoporotic fractures) 1. ก ก International Osteoporosis Foundation (IOF) F ก ก ก ก ก ก ก (osteoporotic fractures) FF ก ก ก ก ก ก ก ก ʾ 25 F (19) F FF (cost) F ก F
4 ก 2. F ก (20) ʾ 1.8 F F ก ก ʾ . . 1995(21) F ʾ 17 F F ก ˆ ก ก ก ก ก F F ˁ ก ก ก ก ก ก ก ก National Osteoporosis Foundation (NOF) FF ก ก ก ก ก ก ก ก F F F F F ก 120,000 F ʾ (22) F FF ก I-4 Pathogenesis and etiology 4.1 ก 1. ก (Pathogenesis) ก ก กก ก ก ก ก 2 ก F ก ก F F กF ˈ ก ก ก กก F ก F F กก ก ก ก กก F ก ก กก F ก ก ก F ก ก ก ก ก ก ก F F F กF ก ก (peak bone mass) ก ก (8) ก F F 30-34 ʾ ก ก F ก ก ก ก F ก ก F 40-45 ʾ ก ก ก ก กก F ก F ก ก F ก ก F F ก F F F ก ก ก (rate of bone loss) F ก FF ก ก ก ก F F F ก กก ก F F F ก ก ก ก กF ก ก ก ก ก ก F ก ก ก ก ก ก F F Fก Fก ก ก ก F 2. ˆ F ก ก F กF F ก ก ก F กF F ก F F ก ก (23-25) Fก ก ก ก กก ก ก ก (26,27) F F ก ก ก ก F F (28,29) (30) ก ก ก ก F F ก ก 3. ก ก ก F ก F F 10 ʾ ก ก F postmenopausal bone loss ก ก ก ʾ 3-5% ˈ กก F F F F ก ก(osteoclast) ก F ก F ก ก ก กก F ก F ก ก ก ก ก F (cancellous or trabecular bone) กก F ก ก (cortical bone) ก ก ก ก ก ก ก F ก ก กF F ก ก F ก F ก ก F F ก ก F (31) ก ก ก ก F ก F ก ก ก ก ก F F ก F 4. ก ก ก F ก กF F ʾ 1-2% F F F F 40-50 ʾ F F F ( F >70 ʾ) F ก ก ก กก F F ก ก
5 (osteoblast) ก ก ก F age-related bone loss 5. ก F ก ก ก ก ก ก F 65 ʾ F F ก ก ก ก ก ก ˈ exponential ก 6. ˆ Fก ก ก F กF ก F ก F F F F F F กก F ˈ ก ก F 7. ก ก ก ก ก ก ก ก กก ก F ˆ ก F ก ก F (factors reflexes F ก coordination ก F ก ก ก F F ก ก ก กก ก F ก ก ก ก ก ก ก ก ก ก ก F ก F 70-75 ʾ ก ก F F Fก F ก F F ˈ F ก ก ก F F (32) of fall) F กF ก postural fat padding ก ก F F ก F ก กก ˂ ก ก F ก F F 1. Osteoporosis prevention, diagnosis and therapy. NIH consensus statements 2000; 17: 1-36. 2. Consensus Development Conference: prophylaxis and treatment of osteoporosis. Am J Med 1991;90:107-10. 3. Johnell O. The socioeconomic burden of fracture: today and in the 21st century. Am J Med 1997;103(suppl 2A):S20-5. 4. Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL. How many women have osteoporosis? J Bone Miner Res 1992;7(9):1005-10. 5. Maggi S, Kelsey JL, Litvak J, Heyse SP. Incidence of hip fractures in elderly; a crossnational analysis. Osteoporosis Int 1991;1:232-41. 6. Mahidol Population Gazette. Institute of Population and Social Research, Mahidol University, 2008. 7. Taechakraichana N, Angkawanich P, Panyakhamlerd K, Limpaphayom K. Postmenopausal osteoporosis: what is the real magnitude of problem? J Med Assoc Thai 1998;81:397-401. 8. Limpaphayom K, Taechakraichana N, Jaisamrarn U, Bunyavejchevin S, Chaikittisilpa S, Poshyachinda M, et al. Prevalence of osteopenia and osteoporosis in Thai women. Menopause 2001;8:65-9. 9. Lau EM, Lee JK, Suriyawongpaisal P, Saw SM, Das De S, Khir A, et al. The incidence of hip fracture in four Asian Countries: the Asian Osteoporosis Study (AOS). Osteoporosis Int 2001;12:239-43.
6 10. Lau EM, The epidemiology of osteoporosis in Asia. In: Lau EM, Ho SC, Leung S, Woo J, (eds). Osteoporosis in Asia: crossing the frontiers. Singapore World Scientific, 1997:1-20. 11. Orimo H, Nakamura T, Fukunaga M. The Japanese guidelines for prevention and treatment of osteoporosis. (Translated abridged edition). Life Science Publishing, 2006:5. 12. Nevitt MC, Ettinger B, Black DM, et al. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 1998; 128:793-800. 13. Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR, for the Study of Osteoporotic Fractures Research Group. Vertebral fractures and mortality in older women; a prospective study. Arch Intern Med 1999;159:1215-20. 14. Pongchaiyakul C, Nguyen ND, Jones G, Center JR, Eisman JA, Nguyen TV. Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J Bone Miner Res 2005;20:1349-55. 15. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999;353:878-82. 16. Scaf-Klomp W, van Sonderen E, Sanderman R, Ormel J, Kempen GI. Recovery of physical function after limb injuries in independent older people living at home. Aging 2001;30:213-9. 17. Chariyalertsak S, Suriyawongpaisal P, Thakkinstain A. Mortality after hip fracture in Thailand. Int Orthop 2001;25:294-7. 18. Suriwongpaisal P, Chariyalertsak S, Wanvarie S. Quality of life and functional status of patients with hip fractures in Thailand. Southeast Asian J Trop Med Public Health 2003;34:427-32. 19. European Union Osteoporosis Consultation Panel. Osteoporosis in the European Community: Action plan, 2003. 20. Burge RT, Worley D, Johansen A, Bhattacharyya S, Bose U. The cost of osteoporotic fractures in the UK: projections for 2000-2020. J Med Econ 2001;4:51-62. 21. Ray NF, Chan JK, Thamler M, Melton LJ-III. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 1997;12:24-35. 22. Woratanarat P, Wajanavisit W, Lertbusayanukul C, Loahacharoensombat W, Ongphiphatanakul B. Cost analysis of osteoporotic hip fracture. J Med Assoc Thai 2005; 88(5):S96-104. 23. Krall EA, Dawson-Hughes B. Heritable and life style determinants of bone mineral density. J Bone Miner Res 1993;8(1):1-9. 24. Brown MA, Haughton MA, Grant SF, Gunnell AS, Henderson NK, Eisman JA. Genetic control of bone density and turnover: role of the collagen 1alpha1, estrogen receptor, and vitamin D receptor genes. J Bone Miner Res 2001;16(4):758-64. 25. Ralston SH. Genetics of osteoporosis. Rev Endocr Metab Disord 2001;2(1):13-21.
7 26. Taaffe DR, Robinson TL, Snow CM, Marcus R. High-impact exercise promotes bone gain in well-trained female athletes. J Bone Miner Res 1997;12(2):255-60. 27. Kemper HC, Twisk JW, van Mechelen W, Post GB, Roos JC, Lips P. A fifteen-year longitudinal study in young adults on the relation of physical activity and fitness with the development of the bone mass: The Amsterdam Growth And Health Longitudinal Study. Bone 2000;27(6):847-53. 28. Matkovic V, Fontana D, Tominac C, Goel P, Chesnut CH, 3rd. Factors that influence peak bone mass formation: a study of calcium balance and the inheritance of bone mass in adolescent females. Am J Clin Nutr 1990;52(5):878-88. 29. Johnston CC Jr, Miller JZ, Slemenda CW, Reister TK, Hui S, Christian JC, et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med 1992;327(2):82-7. 30. Välimäki MJ, Kärkkäinen M, Lamberg-Allardt C, Laitinen K, Alhava E, Heikkinen J, et al. Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. Cardiovascular Risk in Young Finns Study Group. BMJ 1994;309:230-5. 31. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996; 11(3):337-49. 32. Bouxsein ML, Myers ER, Hayes WC. Biomechanics of age-related fractures. In Marcus R, Feldmen D, Kelsey J. (eds). Osteoporosis. Academic Press 1996, San Diego, CA.
8 Diagnosis and bone mass assessment in osteoporosis II-1 History, physical examination and differential diagnosis 1.1 ก ก ก ก (Classification of osteoporosis) (1) ก ก 1. ก ก 2. ก ก ก F ก ก ก ก ˈ ˆ กก (Primary osteoporosis) F F ˈ (postmenopausal osteoporosis) ก ก F ˈ ก (age-related senile osteoporosis) ก F F F ก ก F F ก F F ก ก ก (Secondary osteoporosis) F ก ก ก F ˈ 2.1 1. − − − − ก F F F Cushing s syndrome hypogonadism F F ˈ F ก F F 2. 3. − ก F F − F ก (heparin, warfarin) − ก ก F กF phenytoin, phenobarbital − ก F ก ก ก − − − ก (malabsorption) F − F ก F 4. − − − multiple myeloma osteogenesis imperfecta ก 2.1
9 II-2 Risk factors for osteoporosis and osteoporotic fractures 2.1 ˆ ก ก ก ก ก ก ก ก (Risk factors of osteoporosis and osteoporotic fracture) ก ก ˆ ก ก F ก F F F F ก ก (bone densitometer) ก (risk assessment) ˈ F FF ก ก ก ก ก ก F ˈ ˆ ก ˆ 1. 2. 3. 4. Fก ก F ก ก ก F ก ก ก ก F F ก ก F ก Fก ก F (2) ก กF ก ก ก ก ก ˆ F F F (Non-modifiable risk factors) ( F 65 ʾ F ) F กF 5. 6. 7. F ก F ก F F ก F กF ก ˈ ก ก ˈ ก F 19 กก./ . F (estrogen deficiency) กF F F gonadotropin releasing hormone (GnRH) analogue F ก F F (Modifiable risk factors) F (inadequate calcium intake) ก (sedentary lifestyle) F F ˈ ก F ก ก (small body build) F ˈ ก ก ก ก ก ก ก ก (fragility fracture) ก ก ก ˆ 1. 2. 3. 4. 5. 6. 7. 45 ʾ (early menopause) F ก กก กก ก F ก ˈ 8. Fก 2.2 ก ก F (propensity to falls) F ก ˆ ก ก ก ก ก ก F ก (impaired vision) ก F FRAXTM Fก ก (Risk assessment of osteoporotic fracture using WHO-FRAXTM) WHO(3) F ก ก ˆ ก ก meta-analysis population-based cohorts ก ˆ ก ก ก ก
10 1. Independent F BMD 2. ก ก 3. adjusts 4. F 5. กก ก F ก , F ก F ˈ ˆ ก ก ก F F F F F F F( ก F F ˆ 9 ˆ F F F ก ก (bone mass density, BMD) F femoral neck BMD ˈ ก F F F (BMI) F ˆ F ˈ F BMD/BMI F F F กก ˈ ˆ F modifiable) F 2.2 F F F BMD F F F F body mass index กF F (yes/no) ก F 2.2 ˆ WHO F FRAXTM Age (yr) BMD(FN) / BMI (T-score or kg/M2) A prior fragility fracture (yes/no) Parental history of hip fracture (yes/no) Current tobacco smoking (yes/no) Ever long-term use of oral glucocorticoids (yes/no) Rheumatoid arthritis (yes/no) Other causes of secondary osteoporosis (yes/no) Daily alcohol consumption of three or more units daily (yes/no) BMD(FN) = femoral neck bone mass density, BMI = bone mass density WHO task force conference held in Brussels, Belgium in May 2004 F กก F ˈ ก ก ˈ F ˈ ก ก ก ก 10 ʾ (10-year probability of fracture) TM F ก FRAX F F F internet http://www.shef.ac.uk/FRAX(4) F TM 10-year probability ก F F website ก FRAX F ก ˁ US-Asian F F ˈ 2 10-year probability of hip fracture 10-year probability of other major osteoporotic fractures F F F ˁ F ก ก F (therapeutic threshold) F ก ˆ F F ˁ F fracture BMD F กF -2.5 Fก F 10-year probability of fracture ˈ ก F F ก F F F ˁ 10-year probability of hip fracture ≥ 3% 10-year probability of other major osteoporotic (5) fractures ≥ 20% ก F ก F ˆ ˆ F ก F F F ก ก F FRAXTM F F ก ก ก ก FRAX TM FRAX ก F F F กF US-Asian Japan F ก ก Asia F F
11 ก F ก ก ก ก F ก Fก ก F NOF 10-year probability of hip fracture ≥ 3% osteoporotic fractures ≥ 20% ก F ก F F ก ก F F F F 10-year probability of other major II-3 Laboratory investigation and bone strength assessments 3.1 ก F F 1. 2. 3. − − − − − 3.2 ก ก ก ก 1. 2. 3. 4. ก ก (Laboratory investigation) ก F ก ก ก ก ก ก ก ก ก ก F F ก Complete blood count (CBC) Serum calcium, phosphate, albumin liver transaminases Serum alkaline phosphatase Renal function (blood urea nitrogen and creatinine) Plain x-rays F ก ก F ก F F (lateral thoraco-lumbar spine) ก ก ก F F (antero-posterior hip) F F F ก ก ก กF ก ก (Bone strength assessment) ก F ก กก ก ˆ ก ก ก (bone mass) ก ก (bone quality) ˆ F F F ก F F F ก F ก กF ก ก Fก F ก ก ˈ ก ก F plain x-ray F F กก ก ก F ก x-ray F ก ก ก F F ก ก F กก F 30% ก F ก F Semi-quantitative method ก plain film x-ray F Singh s index ˈ F F ก F F ก intra-observer inter-observer variation ก F F F Bone mass measurements WHO ก F ˈ ก ก ก ก axial dual-energy x-ray absorptiometry (axial DXA) F Bone mass measurements F F quantitative ultrasonography (QUS) peripheral DXA (pDXA) F F ก F axial DXA ก ก ก F F ก F ก F F ก ก ก F axial DXA ก
12 II-4 Diagnostic criteria for osteoporosis 4.1 ก F ก F ก ก (Measurement of bone density) ก (Bone mass density, BMD) F F F Dual Energy X-ray Absorptiometry ก ก ก ก Fก 2.3 ก Fก F BMD กF F ก -2.5 F F ก ก ก ก ก ก 1.4 - 2.6 F ก 1 F F 2.3 ก ก ก ก ก ก (normal) ก ก F F BMD F F ก -1 F F ก ก (osteoporosis) ก ก (severe/established osteoporosis) F F Caucasian) ก F Fก ก ก ก F F F ก ก F กก F ก F Fก ก F กก F ก ก ก F F ก ก ก F (female reference) ก F F F F F (fragility fracture) F ก ก F (lumbar spine ก F axial DXA F ˈ F ก ก ก F axial DXA F F ก F ก DXA F F F ก ก ก F ก (Asian female reference) ก F ก ก ก F Fก F F F F (8) F F ก 2.3) F F ก F F ก BMD ก L-spine) ก ก ก (hip) F (peripheral DXA) ก F F ˁ F F ก F ก F (T-score ≥ -1) F ก ก ก F -1 F F -2.5 F F F ( -2.5 < T-score < -1) F ก ก กF F ก -2.5 ก F ก ก (T-score ≤ -2.5) F ก ก กF F ก -2.5 ก F ก ก (T-score ≤ -2.5) F ก ก ก ก ก (osteopenia) F F F F F ก ก(6,7) Fก ก FF F (male reference) ˈ Fก F ˈ F ˁ F F ก ก F ( (reference young adult mean) ก กF ก ก F( F F F
13 F F 1. 2. ก F F F 65 ʾ ก F 65 ʾ F 1 F − กF − 4. 5. 6. กF ˆ 45 ʾ (early menopause) F กF 1 ʾ ก F ก F ก F ˈ กF 3 ) ก ก F F ก (estrogen deficiency) กF F F ( F F F F F F 7.5 ก. F ˈ ก ก F ก F ก F 19 กก./ . ก ก ก ก กก F ก F (radiographic osteopenia and / or vertebral deformity by x-ray) ก ก ก ก F F F กF กก ก F OSTA score(10), KKOS score(11) nomogram กก F 0.3 F ( ก 2.2) ( OSTA; Osteoporosis Self Assessment Tool for Asians, KKOS; Khon Kaen Osteoporosis Study score) − − 3. F F − axial DXA(9) F 70 ʾ F ก F 70 ʾ BMD F Quantitative Ultrasound (QUS) QUS ก ก F QUS F QUS F F ก OSTA(10) ก F QUS F ก F (13) F ก ก 4.2 ก (sensitivity) KKOS(11) ก F ก ก F 16) ก F ก F F ก ก F F ก ก F ก ก 3 ก F ก ก F ก ˆ F F ก BMD ก F F ก 1 ʾ F ก F F ก ก (12) ก ก F ก (nomogram) F F ก ก ก ก ก F ก (Biochemical markers of bone turnover) ก F (specificity) ก ก ก ก ก ก ก F F F ก ก ก ก ก ก ก ก (17) F ก ก F ก F ก ก F(14F F F telopeptide (NTx) ก ก ก F กF urinary deoxypyridinoline (DPD), urinary Nserum C-telopeptide (CTx) F ก F ก ก F กF bone
14 specific alkaline phosphatase (BSAP), osteocalcin, C-terminal propeptide of type 1 procollagen (P1CP) N-terminal propeptide of type 1 procollagen (P1NP)(18) 4.3 ก ก ก ก F F ก BMD F F F( (Screening) ก ก F ก F F FF ก 2.1) F axial DXA F ˆ ก F F F ก F ก F KKOS(11) (10) OSTA ก ก ก ก
15 ก 2.1 OSTA (Osteoporosis Self-Assessment Tool for Asians) ก ก ก OSTA index F F F ˈ ʾ OSTA F ก 0.2 X ( ก F F ˈ ก ก F ก F -4 F -4 -1 F -1 ก ก- ) F F F
16 Khon Kaen Osteoporosis study score (KKOS)(13) Age (y) Score Weight (kg) Score < 45 45 - 49 50 - 54 55 - 59 60 - 64 65 - 69 70 - 74 75 - 79 80 - 84 85 89 > 90 + 7.5 + 6.0 + 4.5 + 3.0 + 1.5 0 - 1.5 - 3.0 - 4.5 - 6.0 - 7.5 < 30 30 - 34 35 - 39 40 - 44 45 - 49 50 - 54 55 - 59 60 - 64 65 - 69 70 - 74 75 - 79 80 - 84 85 - 89 > 90 - 14 - 12 - 10 -8 -6 -4 -2 0 +2 +4 +6 +8 + 10 + 12 ก KKOS F KKOS < -1 : KKOS > -1 : F ก ก ก ก ก ( ʾ) ก ก ก (ก ก ) กก ก ก F ก 52 ʾ, ก 48 ก ก KKOS = (+ 4.5) + (- 6) = - 1.5 ..=.. ก 20% ก ก F 80% F กF KKOS F กF ก ก ก ก 21-79% F กF ก F ก ก F กF
17 ก (probability) ก ก ก ก F KKOS
18 ก 2.2 ก ก ก ก ก ก F QUS(15) ก ก 1. 2. 3. 4. 5. ก F ก F ก F กก ก (point) กก ก ก (point) ก ก QUS ก (point) 3 ก (total points) ก F กก (total points) ก osteoporosis) 6. ก ก ก ก ก F 0.3 ก ก F BMD F ก ก (risk of ˈ กF ก ก F F 193 ( F F ก 0.5 ( 70 ʾ ก 50 ก ก ก F 4) ก ก ก 1-3 ก F กก F QUS T-score -3 SD 48, 67 193 78 ก Fก ก ก 5) : F ก ก 70 ʾ 50 ก 50 ก ก QUS T-score -3 SD 100
19 ก F 1. Greenspan SL, Luckey MM. Evaluation of postmenopausal osteoporosis. In : Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th ed. Lippincott Raven Press; New York, NY, USA, 2006, pp.268-72. 2. Riggs BL, Melton LJ. Evidence for two distinct syndromes of involutional osteoporosis. Am J Med 1983;75:899-901. 3. Kanis JA, Black D, Cooper C, et al. on behalf of the IOF and the NOF USA. A new approach to the development of assessment guidelines for osteoporosis. Osteoporosis Int 2002;13:527-36. 4. FRAX-WHO fracture risk assessment tool, http://www.shef.ac.th/FRAX 5. NOF(National Osteoporosis Foundation). Clinician Guide for Prevention and Treatment of Osteoporosis 2008. 6. Gallagher JC. The pathogenesis of osteoporosis. Bone Miner 1990;9(3):215-27. 7. National Osteoporosis Foundation. Osteoporosis: review of the evidence for prevention, diagnosis, and treatment and cost-effectiveness analysis. Osteoporosis Int 1998; 8 (Suppl 4):S1-80. 8. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. No. 843 of Technical Reports Series. Geneva: 1994. 9. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994 ;9:1137-41. 10. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312(7041):1254-9. 11. WHO.1994. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical report series 843. Geneva: WHO 12. Koh LK, Sedrine WB, Torralba TP, Kung A, Fujiwara S, Chan SP, et al. A simple tool to identify asian women at increased risk of osteoporosis. Osteoporosis Int 2001;12:699-705. 13. Pongchaiyakul C, Nguyen ND, Pongchaiyakul C, Nguyen TV. Development and validation of a new clinical risk index for prediction of osteoporosis in Thai women. J Med Assoc Thai 2004;87:910-6. 14. Pongchaiyakul C, Panichkul S, Songpatanasilp T. Combined clinical risk indices with quantitative ultrasound calcaneus measurement for identifying osteoporosis in Thai postmenopausal women. J Med Assoc Thai 2007;90(10):2016-23. 15. Pongchaiyakul C, Panichkul S, Songpatanasilp T, Nguyen TV. A nomogram for predicting osteoporosis risk based on age, weight and quantitative ultrasound measurement. Osteoporos Int 2007;18(4):525-31. 16. Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A, et al. Biochemical Markers of Bone Metabolism and Prediction of Fracture in Elderly Women. J Bone Miner Res 2004;19(3):386-93.
20 17. Riis BJ, Hansen MA, Jensen AM, Overgaard K, Christiansen C. Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15 year follow-up study. Bone 1996;19(1):9-12. 18. Riggs B, Melton LJ, O Fallon WM. Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone 1996;18:197S-201S.
21 Prevention of osteoporosis and falls ก ˂ ก ก ก ก ˂ ก F F ก ก F ˈ ก ก ˆ ก F ก ˂ ก ก ก F ก F F (nonpharmacologic strategy) F F F กก F ก ˂ ก F ก F ˈ F F ˈ ก F F ก ก ก ˂ ก ก ก ก F F กก F 50 ʾ III-1 Strategies to maximize peak bone mass ก F Fก 1. ก F ก ก (peak bone mass) F F F ก (weight bearing exercises) ก ก F กก ก ก (resistive exercises) 2. ก 3. ก 4. ก 4.1. 4.2. 4.3. 4.4. 5. 6. 7. 8. Fก F ก F F ก ก ก F ก ก กก ก F F F F กF F ก F ก F กก ก F ก ˈ ˆ ˈ ˆ ก F ก (physical activities) F ก ก F ก ก ก F F 20-23 กก./ . III-2 Strategies to prevent bone loss กF ก F 1. 2. ก ก ก 2.1. 2.2. ก F ก F ก ก F ก F ก ก (rate of bone formation) F ก ก (rate of bone resorption) กF ก F F กF ก ก ก F F F (non-pharmacological management) ˈ F III-1 F (pharmacological management) ก F ก F F กF F ก ˈ ก ก F ก F กF F
22 ก F F (Hormone replacement therapy) 1. ก ก F (estrogen therapy, ET) F (hormone [replacement] therapy, H[R]T) ก ก F F ก F F ˈ F ก ก F F F ก F F F ˂ ก ก ก (1-6) ก F F F F ก F F F F ˂ ก ก 2. ก ก F Women Health Initiative (WHI) study(7) F ก F F ˈ conjugated equine estrogen (CEE) F ก medroxy progesterone acetate (MPA) ˈ 5 ʾ F ก F ก ก ก ก ก ก ก ก ก F 34% ก ก ก ก F 23% 3. ก WHI study F ก F F F F ก F Fก ก F ก F F WHI F ก F ก F F (CEE F ก MPA) F F ก F 10 ʾ ก ก F F ˈ ก F F ก ˈ 7.1 ʾ ก F ก ก F F กF F F F F F F ก F F ก ก ก CEE MPA F F F ก Fก F F / F ก F F ก Fก ก F F F ˈ (8, 9) 4. ก F F ˈ F ก F F ก ก ก ก F F F F F (9) ก F F F 5. ก F Fก ก ก ก ʾ 3% 6% F F ก F F F ก ก ก ก ก ก F (catch-up phenomenon) ก F ก ก ก Fก F F F F (10) ʾ F F F F F F F III-3 Nutritional aspect in osteoporosis Fก F ก F F F กF F ก ก F กF ก ก ก NIH ก F ˈ F (Calcium) 3.1 (11) F ก F
23 3.1 F a Health Consensus Panel ก F Infant Birth- 6 months 6 months- 1 year Children 1-5 years 6-10 years Adolescents/young adults 11-24 years Men 25-50 years Over 65 years Women 25-50 years Over 50 years (postmenopausal) − On estrogen − Not on estrogen Over 65 years Pregnant and nursing F กF National Institutes of Optimal calcium intake (mg/day) 400 600 800 800-1200 1200-1500 1000 1500 1000 1000 1500 1500 1200-1500 ก ก a NIH Consensus Development Panel on Optimal Calcium Intake: Optimal Calcium Intake. JAMA 272:1942-1948; 1994. ก F กF ʾ . . 2545 3.2 F
24 3.2 F F กF ก . . 2545 ก F F ก 0-5 6-11 1-3 ʾ 800 9-18 ʾ 1,000 19-50 ʾ 800 กก F 50 ʾ 1,000 F F F F∗ F ∗ ก ∗∗∗ ก 800 F F ˈ F F F F 1 กF 1 ก F (200 ก ก ก 2545:16-23 ก 230 ) ก . ˁ : F F 702 ก. F ก ˈ F F ก Fก ก F balance study(12) ก 842 ก. F F F F F ก . ก ก F ก. F F กก 788 800 ∗ F ∗∗ ก ) 210 270 500 4-8 ʾ ก ( F F F ก F F ก F F ก 20% 946 ˈ ก. ก ˈ F ˈ Fก ก F ก ก ˆ ก F F F ก F กก ˈ ก FF F ก 3.3 ก ˆ ก
25 3. 3 ( ก.) , กF , กF F กF ก ʽ ก F ก F ˈ F กF F กก , F F ก ก ˆก ก F ก . F 240 150 145 167 156 76 52 106 78 63 30 116 97 240 245 125 469 429 230 49 299 76 17 200 (1 ก F ) 150 (1 ก F ) 1 F F ( ) 1 2 F ( ) 1/2 F ( ) 10 ก 1 1 1 1 1 1 1 กF 10 10 1 10 ˆก 1 1 1 1 4 F F F F .
26 (Vitamin D) 1. 2. 3. 4. 5. ˈ F F F ก F ก ก F ก F ก ก ก F F ก parathyroid hormone ก F ก ก ก F F ก ก ก ก ก F Fก ก ก ก F ก ก ก ก F ก ก (bone formation and mineralization) F F ก กก F กก ก F F F (ultraviolet B, UVB) F F ก F กF ˈ F F F ก ก F Fก ก F F ergocalciferol ( ก ) cholecalciferol ( ก ) F ˈ F F F ก OH group ก OH F 25 ก ˈ 25-hydroxyvitamin D (25(OH)D calcidiol vitamin D2)ก ก ก OH F 1 ก ˈ 1,25-dihydroxyvitamin D (1,25(OH)2D calcitriol vitamin D3) ˈ (active form) ก ก ก F F ก F F กF − ก F 7-dehydrocholesterol ˈ F 3 F F F F − ก ก F F F F ( F F F ก F F F ) − ก Fก F 1,25(OH)2D − ก F F ก ก F F F F F F ก F secondary hyperparathyroidism ก ก ก ก ก ก (13,14) F F F กก ก F F ก 400-800 IU ˈ F ก ˂ ก ก
27 3.4 Food International Units (IU) per serving 1,360 360 345 200 250 98 Cod liver oil, 1 Tablespoon Salmon, cooked, 3 ounces Mackerel, cooked, 3 ounces Tuna fish, canned in oil, 3 ounces Sardines, canned in oil, drained, 1 ounces Milk, nonfat, reduced fat, and whole, vitamin D fortified, 1 cup Margarine, fortified, 1 Tablespoon 60 Pudding, prepared from mix and made with vitamin D 50 fortified milk, cup Ready-to-eat cereals fortified with 10% of the DV for vitamin 40 D, 1 cup servings (servings vary according to the brand) Egg, 1 whole (vitamin D is found in egg yolk) 20 Liver, beef, cooked, 3 ounces 15 Cheese, Swiss, 1 ounce 12 Percent DV* 340 90 90 50 70 25 15 10 10 6 4 4 * DV = daily value. DVs are reference numbers developed by the Food and Drug Administration (FDA) to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for vitamin D is 400 IU (10 µg) for adults. Most food labels do not list vitamin D content unless a food has been fortified with this nutrient. ก ก http://www.usda.gov/cnpp/pyramid2.htm. (Vitamin K) 1. 2. 3. 4. 5. -1 (phylloquinone) ˈ ก -2 (menaquinone) ˈ F F F F ก F phylloquinones phylloquinone ˈ F ก chloroplasts normal flora F F spore-forming Actinomyces spp. F menaquinones F ก F F F ก F F F menaquinone F Fก ˈ passive diffusion ก F F F ก F F ก ก (osteoblast) F collagen matrix osteocalcin ˈ non-collagen matrix osteocalcin F ก F F ˈ osteocalcin F ก ˈ undercarboxylated osteocalcin (ucOC) ก ucOC ก carboxylated F ˈ mature osteocalcin carboxylated osteocalcin (Gla protein) ก F F osteocalcin ก F ˈ F ก ก ก ก F ก ก
28 F ก ucOC ก F ˈ F Fก F F ก F ก F ก ก Fก ก ucOC Fก ก ก ก 6. ก ก ucOC 2.314 ng/mL ˈ (15) F F F ก ก ก ก 2.314 ng/mL) 39.1% F ucOC ก F 2.314 ultradistal radius distal 1/3 of radius 25(OH)D ucOC ก F (p<0.05) 7. F F6 ʾ ก ก ก F ก ก 80 µg F กF 2 ก. F ก ( ˈ กก.) 8. F กF ก ก ก ก ก F F ˈ ก ก F กF F ˈ ก F 3.5 ก ก กF F ก ( ng/mL กF F (mcg/100 g) 817 400 231 205 147 193 141 775 III-4 Life style modification and prevention of falls 4.1 ก ก ก − − − − − − − ก ก F ก F ก ก ก ˈ ก ก F F F ก ก F กก ก F ก ˈ ˆ ˈ ˆ ก (physical activities) F ก ก F ก ก ucOC > F ก ก (Thai RDI) . . 2538 ก 70-140 ก. ก F ก F ก F (Kale) ก (Spinach) ก (Endive) Broccoli ก (Cabbage) Soybean oil Rapeseed oil F (Regular natto) F F F F F F
29 4.2 ก F ˆ ˆ ก ก F F ˁ F ˂ ก ก ก ก F ˁ ก ก ก ก ก ก FF ก ก ก F F ก ก ก ก ก F F ก กก ก Fก ก F F F ʾ F กก F 65 (16) F กก F 80 ʾ ก F กF F ก F ก F 3 F ก ก F กF ก F กF ก (17) กก F 40% F ก F กก F 1 F ʾ F ก กF F ก กF ˈ F F F กก F 5 F F ˁ F F FF ก กก F ก กF F ก ก ก ก ก ก F F ก ก F ˁ F F ก ก ก ก F F ก F F (18) F ก F ก ˈ F F กF ก ˂ ก ก ก F ˈ F ก F ก F F ก F F ˆ F ก ˈ ก F ก ก กF ʾ กF 2-3 F F F ก F ˆ ก ก ก ก F F ก F ก ก ก psychotropic ก F sedative ˆ F F ˈ F 1. F ก ˈ F F ก ก ˆ F ก กF F ก 8-10% F F ˆ ˈ 20) ก ก ก ก ก ˆ (21) F ก ก F F กF ก F กก F Fก 4 F 12% F F ˆ ก 2. ˆ F F F ˁ ˆ ก F F F ก ก ก F ก F ก F F F Fก ˆ F F ก F ˆ ก ก F กก F ˆ F F ก F กF 69-78% F ˆ กก F Fก 4 F multivariate analysis F 3 ˆ F ก F ก ก ก F F F ˆ F ก กF F ก กF ˈ 100% Fก กF ˂ ก F ก ˆ F (19, ˆ − − − − − − − ก กF (22,23) (24) ก ก ก F ก ˆ F ก F (cognitive impairment) (25) ก F (26) (27) F F F ก (25) (27) F ก F ˈ F ˆ F
30 − กF − ก ˆ F /ก (28) (18) กF ก F − F ˂ ก ก (29) F F − − ก ก ก F F F F ก F F ก F F F / ʾ ก F F ˈ F F (30) F (22) ก F ก ˂ ก F ก (frail elderly) F ก F ก F F F ก ก F ก ก ˂ ก ก ก F ก F ก ˈ F 1. F 3 = ก 3 2. F ˁ กF กF F ก F Fก กF กF F (31) falls risk assessment tool F ก ก( , 11-20 = ก , 21-33 = ก F ˁ ก ก กF ก กก F F ก 3.1) ก) F F F F ก F ˈ F (0-10 ก ก ก F กF F F F ก (32) F F F กF FF F Berg balance scale, 180 degree (33) (34) turn, functional reach ก F F F F ก ก ก F timed up & go test (TUGT)(35) F F ˁ ก ก กF ˈ 3 ก ก F (36) F F ก F F ก F ก F F ก F ก 10 3. ก F F ก Fก F กก F Fก 4 (37) F ก กF ก กF F ก ก F ก F 9 F FF F (38) ก F psychotropic F กF F F ก กF FF ก F ˆ ก ก F F F (39) ก ก F F F ˈ ก F benzodiazepine ก กF 44% (40) ˈ ก กF F F F ˁ 4. ก กก ก ก ˆ F กF F ก ก F ก กก ก ˈ ก F ก F F F F ก ˂ ก ก ก F (41) ก ʿกก (balance training) ก กก ก กF (strengthening exercise) ก กก ʽ F (42,43) (cardiovascular fitness training) ก กก ก ก ก F F กF Fก F ˂ ก ก กF ก F ก กก ก F F ก F ก F ก ก ˈ F F ˁ ก ก ( ก 3.2) 5. กF ˆ F F ˆ F F ก ก กF ก F F F ก ก ˈ F ก F ˈ F ˆ F ก กก F F F
31 F counter) F F กF F F F F F 6. ก F F F F กF ก F ก F F F ก ˈ F 7. F ก ก F ˆ F ก ก ก ก F ก 8. F ก ก ก ˂ ก ก F กF F ก ก กก F F F ก F FFF ก ก กF ก F ก F ก F ( F ก F 2.5 . .) F F ก F ˂ ก ก ก F F F F F ก F F ก ก ก F F ก ก F FกF FF F F ก F F F F F กF F F ก F ก ˈ ก F ʾ ก F กF F ก ˆ ก F Fก F Fก ก ก ก ก Fก ก F กF ˆ กก F กF F กF F ˁ / F F ก F F FF ˈ F F ˁ F ˁ F ก ก F (firm heel F กF 1 . . F F F F ˁ ก F F ก ก F ก กF F ก ก F ˁ (44) FF ˆ F F F F F กก กF ก
32 ก 3.1 Falls Risk Assessment tool ก 0 F F 1 ก ก ก 2 8-14 ก 3 กก F 14 F ก F 0-19 ʾ F กF ʾกF ก F F ก ก F ก F F F , F ก 60-70 ʾ กF 3 กF F ก F F 1 F กก F 70 ʾ กF กF F F ก F F F ก F F , ก ก ก , 20-59 ʾ กF 6 กF F ก F F 2 F ก ,ก ก F F, ก ก F ก ก , ก F F ก F , ก F ก ก ˆ ก ก F ก ก F / ˆ ก ก ก F F ก F F F F , , ก F psychoactive β-blocker, ˆ , F F ก กF 1 F ˆ ˆ F 0-10= 11-20= F >1 ˆ ก , ˆ (stress incontinence) ก 21-33= ˆ (urge incontinence), ˆ ก ก Fall prevention: Best Practice Guidelines, Quality improvement and Enhancement Program, version 3, 2003
33 ก 3.2 ก F ˈ − − − − − ก กก ก F กFก F กก F กก F ก F ก ก ก ก ก ก ก ก ก 2 F (weight bearing exercises) F กF ก ก ก F กF กก กF F F กก ก ก F F 3-5 ก F ก กก ก F F (45-49) ก ก F 1-3% ก กก F F F F ˁ F ก F กก ก ก ก ก F F Rotator cuff Pectoralis major Biceps Triceps Wrist flexors wrist extensors Hip extensors Hip flexors Quadriceps Hamstrings Back extensors Abdominal muscles − − − − − − − − − − − ก ก กก ก กก F ก กF ก ˈ กก ก 9% F ก F 20 - 60 F ˂ ก ก F F ก ก ก ก กF F F ก 9% ก ก ก ก F ก F ก Fก F ก กก ก ก F F ก ก ก ก ก กก ก F ก ก 40 F F ก ก กก F 12% ก ก ก กก F ก ก ก ก ก กก F ก F ก กก ก F กก ก 7%
34 ก ˂ ก ก ก F F ʾ 30% F F F 2 กก F 9 F กF 6 ก ก F F 70% ก exercises) F F ก ก ก ก ก ก ก F 65 ʾ ก กF F F กก ก ˈ ก ก F ก ก ก F ก ก F ก ก ก ก ก ก กก F 50% ก ก ก F ˈ กF 6 F ˆ กก ก ก ก F ก กก ก ก ก ก กก ก ก ก ก ก F ก2-3 ʾ F F F F ก (vibratory F ก ก F 1. Bush TL, Wells HB, James MK, et al. Effects of hormone therapy on bone mineral density: 2. 3. 4. 5. 6. 7. 8. results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA. 1996;276:1389-96. Hulley S, Grady 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(7):605-13. Lufkin EG, Wahner HW, O'Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992;117(1):1-9. Recker RR, Davies KM, Dowd RM, Heaney RP. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women: a randomized, controlled trial. Ann Intern Med. 1999;130:897-904. Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980; 303:1195-8. Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, et al.; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev. 2002;23(4):529-39. Writing Group for the Women s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002;288:321-33. The North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006.
35 9. The North American Menopause Society. Estrogen and progestogen use in peri- and 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007. Tremollieres FA, Pouilles JM, Ribot C. Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women. Osteoporosis Int 2001;12;385-901. NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. JAMA 1994;272(24):1942-8. Uenishi K, Ishida H, Kamei A et al. Calcium requirement estimated by balance study in elderly Japanese people. Osteoporos Int 2001;12(10):858-63. Soontrapa Sp, Soontrapa Sk, Chailurkit L. The prevalence and the Calcidiol Levels of Vitamin D Deficiency in the Elderly Thai Women in municipality of Khon Kaen Province, Thailand. Srinagarind Med J 2002;17(4):219-26. Soontrapa Sp, Soontrapa Sk, Pongchaiyakul C, Somboonporn C, Somboonporn W O. Vitamin D deficiency and the risk of osteoporosis in elderly women. Srinagarind Med J 2002;17(3):154-63. Soontrapa S, Soontrapa S, Bunyaratavej N. Serum concentration of undercarboxylated osteocalcin and the risk of osteoporosis in Thai elderly women. J Med Assoc Thai 2005; 88(Suppl 5):S29-32. Rubenstein LZ, Josephson KR, Robbins AS. Falls in the nursing home. Ann Intern Med 1994;121:442-51. Krueger PD, Brazil K, Lohfeld LH. Risk factors for falls and injuries in a long-term care facility in Ontario. Can J Public Health 2001;92:117-20. Lachman ME, Howland J, Tennstedt S, Jette A, Assmann S, Peterson EW. Fear of falling and activity restriction: the survey of activities and fear of falling in the elderly (SAFE). J Gerontol B Psychol Sci Soc Sci 1998;53:43-50. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319:1701-7. Nevitt MC, Cummings SR, Kidd S, Black D. Risk factors for recurrent non-syncopal falls: a prospective study. JAMA 1989;261:2663-8. Robbins AS, Rubenstein LZ, Josephson KR, Schulman BL, Osterweil D, Fine G. Predictors of falls among elderly people. Results of two population-based studies. Arch Intern Med 1989;149:1628-33. Kiely DK, Kiel DP, Burrows AB, Lipsitz LA. Identifying nursing home residents at risk for falling. J Am Geriatr Soc 1998;46:551-5. Gluck T, Wientjes HJ, Rai GS. An evaluation of risk factors for in-patient falls in acute and rehabilitation elderly care wards. Gerontology 1996;42:104-7. Vellas B, Baumgartner RN, Wayne SJ, Conceicao J, Lafont C, Albarede JL, et al. Relationship between malnutrition and falls in the elderly. Nutrition 1992;8:105-8.
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37 42. Gardner MM, Robertson MC, Campbell AJ. Exercise in preventing falls and fall related 43. 44. 45. 46. 47. 48. 49. injuries in older people: a review of randomized controlled trials. Br J Sports Med 2000;34:7-17. Schoenfelder DP. A fall prevention program for elderly individuals. Exercise in long-term care settings. J Gerontol Nurs 2000;26:43-51. Lord SR, Dayhew J. Visual risk factors for falls in older people. J Am Geriatr Soc 2001;49:508-15. Virvidakis K, Georgiou E, Korkotsidis A, Ntalles K, Proukakis C. Bone mineral content of junior elite competitive weightlifers. Int J Sports Med 1990;11: 244-6. Hartard M, Haber P, Ilieva D, Preisinger E, Seidl, Huber J. Systematic strength training as a model of therapeutic intervention: a controlled trial in postmenopausal women with osteopenia. Am J Phys Med Rehab 1996; 75:21 8. Kerr D, Morton A, Dick I, Prince R. Exercise effects on bone mass in post menopausal women are site specific and load dependent. J Bone Miner Res 1996; 11:218 25. Chow R, Harrison J E, Notarius C. Effect of two randomized exercise programs on bone mass of healthy post menopausal women. Br Med J 1987; 295:1441 4. Heinonen A, Oja P, Sievanen H, Pasanen M, Vuori I. Effect of two training regimens on bone mineral density in healthy perimenopausal women: a randomized controlled trial. J Bone Miner Res 1998; 13: 483 90
38 Treatment of osteoporosis IV-1 Goal of osteoporosis treatment 1.1 ก ˂ ก ก ˂ ก ก ก F F F F ก ก Fก กF ก ก ก ก ก ก ˂ ก F Fก ก ก ก F ก ก ก F ก 3 1. 2. ( ก ก F ก. ก . ก . ก F F interventions F ˁ F ก ก ˈ ก F ก ก F F F / F ก F ก ก ก F ก ˈ ก ก F ก F ก ก ก ก ก ก Fก ก ก ก ก ก ก กก ก ก F ˁ ก 3. Fก ก ก Fก 1.3 ก ก ก ก interventions กF F ˈ ก ก ( ก Fก F II-4) F / ก ก ก ก ก ก ก F F F F ก ก ก ก ก ก ก ( ก) F F F ก F 1.2 ก กF F F ˈ F ก ก ก ก F F F ก ก ก ˂ ก ก ก F ก ก ก ก ก ก ก ก ก interventions ก F II-4) ˈ ก ก Fก ˂ ก ก ก ก ก ˈ F F ˂ ก ก F Fก ก ก ก F ก International Osteoporosis Foundation ก ก ก interventions F ก F anti-fracture efficacy Fก F F National Osteoporosis Foundation ก Fก Fก F F case finding strategy Fก F F ก ก 2 Fก ˈ F 1. International Osteoporosis Foundation F F F clinical risk factors (CRFs)(2) ʾ . . 2007 Fก ก F F F F ˈ (1) ˈ ˆ
39 ก ก ก ก 10 ʾ II-2 2. National Osteoporosis Foundation FRAX tool ก ก ก ก ก 10 ʾ ก ก ก F Fก ก Fก ก F ˁ F ก a. F F F 50 ก b. F F F 50 DXA ก ก ก ก 1.4 ก Fก ก F F F F F ก neck BMD ก ʾ . . 2008(4) F Fก ก F ก ≥ 3% ก F F F ʾ ก ʾ ก F ก F guideline F F F ˈ ก ≥ 20% ก Fก F FRAX ก ก ก ก ก ก ก ก F ก ก F F T-score ≤ -2.5 SD F ก Fก > 50 ʾ F F F F F F ก F F ก F F ก (Primary indication) F 1. 2. ก ก F FRAX(3) ก F F Fก ก F F F ก ก ก ก ก ก F F ก ก F axial DXA lumbar spine BMD total hip BMD F F T-score ≤ -2.5 femoral (Secondary indication) F ก ก ก ก ก ก ก F ก ก F axial DXA F F ก Fก ก (T-score < -1.0 F >-2.5 lumbar spine BMD femoral neck BMD total hip BMD) ก F ก ก ก F ˆ F F F F F F 1 F 1. ก ก ก F F F ก ก F 40 ʾ F ก F Fก ก ก ก ก F ก ก F ก (wrist fracture) ก ก ก ก (pelvic fracture) ก ก F ก (distal femur or proximal tibial fracture) ก ก F (proximal humeral fracture) ก ก F F (ankle fracture) 2. F glucocorticoid F prednisolone 7.5 ก. ก F 3 3. ˈ Fก secondary osteoporosis F type-1 DM, thyrotoxicosis, rheumatoid arthritis, SNSA(seronegative spondyloarthropathy) US-Asian Japan F F BMD F F 10 4. F FRAXTM year probability of hip fracture ≥ 3% 10 year probability of other major osteoporotic fractures ≥ 20% 5. clinical risk factors(CRFs) F F2 F ก. ˈ F ≥ 65 ʾ F ≥ 70 ʾ . ก < 19 กก./ .
40 . . . . F กF ก ก ก ก ก ก 45 ʾ ˈ ˈ ก ก Fก ก ก F ก ก ก F F ก axial DXA F F F F F − CRFs F − ก F ก ก F F ( ก ก axial DXA) ก F F ˆ ก ก กก ˈ ก F F F F F ก ก F ก ก axial DXA F F F F ˁ F Fก ก ก F F 1. ก ก ก ก ก ก 2. ก ก ก F ก F F F 65 ʾ F F 70 ʾ F ก ก ก F F ก F ก ก ก ก F − TM US-Asian F ก ก ก ก ก กก F FRAX − Japan F F BMD F10 year probability of hip fracture ≥ 3% 10 year probability of other major osteoporotic fractures ≥ 20% F IV-2 Pharmacological treatment of osteoporosis ก ก F ก ก ก ก ก ก ก ก F ก ก (potential adverse events) F ˁ F ก ˂ ก ก ก ก ก ก ก ก กก ก F (clinical trial) F ก F F ก F ˁ ˈ ก F ก ก ก ˂ ก (efficacy) F ก F F ก (tailor therapy) F Fก ก ก ก F ˈ anti-fracture efficacy(5) Anti-fracture efficacy ก ก F F ˈ clinical trial phase-III F F F F ก ก ก ก ก F ก placebo (relative risk reduction) F ก ก F bisphosphonates BMD ก bisphosphonate ก F dose F BMD F F ก F ˈ (control) F F anti-fracture efficacy F placebo F ก ก ก ก F bridging study F ก F dose ก
41 2.1 ก ก ก (Inhibitors of bone resorption) Bisphosphonates 1. Bisphosphonates ˈ ก F ก ก ก ก ก F ˆ F ก F bisphosphonates F ก ˈ ก F F ก F (5) simple bisphosphonates กF nitrogen-containing bisphosphonates 2. F ก F nitrogen-containing bisphosphonates action ก osteoclastic bone resorption F กF กก F ˆ ก F bisphosphonates F ก F ก ก F Fก ก ก Alendronate (10 ก.) Risedronate F8 F ก (5 ก.) ( ก ) Alendronate Once Weekly (70 ก.) Risedronate Once Weekly (35 ก.) ( F ) Ibandronate Once Monthly (150 ก.) ( ) ก Alendronate plus ˈ Alendronate 70 ก. ก Cholecalciferol 2800 iu F F F ก ก2 F ˈ F F F Ibandronate injection (3 ก.) (IV infusion F F ก ) Zoledronate injection (5 ก.) (IV infusion F F ʾ ) / 1. ก ก 2. ก ก F ก ก F ก ก F กF F 30-40% ก F Fก F ก (6,7) F F ก ก ก Fก F ก ก ก ก ก F ˈ F ก ก F F F ก F 3. ก ก F 55 ʾ F 60 ʾ 4. F invasive breast cancer(8) FF ก ก F F ก ก F F F ก F กF ก (premature menopause) F ก ˂ ก ก ก ก F F ก ˈ Fก F ˈ F ก ก cardiovascular diseases, stroke F ก F F ก F ˂ ก ก Selective estrogen receptor modulators (SERMs) 1. SERMs ˈ F F steroid ก estrogen receptor ก F (agonist) ก F (antagonist) ก F ก raloxifene ˈ SERM ˆ ก ก F F ก ก ก F 2. ก ก ก F raloxifene ˂ ก ก ก ก F F ก ก ก ก F 30 50% F ก ก F ก ก
42 (9) F ก ก ก ก F F F F กF F cardiovascular diseases raloxifene 3. Raloxifene F 60% F F Nasal spray calcitonin 1. Calcitonin ˈ F F C-cells receptor F osteoclast Fก ก (12) 2. กก ก F salmon calcitonin F ก ก ก ก ก F ก กF ก (RR = 0.64) F ก F ก ก F vertebral fracture hip fracture F 3. Salmon calcitonin F ก (13) กก ก ก F NSAIDs 2.2 ก 1. 2. 3. 4. F ก F ก ก ก ก กF ก กก ก Fก ก stroke(10,11) F F กก ก F ก F F invasive ก calcitonin ก ก F ก 100, 200, 400 IU ก F 36% ก F F calcitonin 200 IU F ก F ก F 100 IU 400 IU F calcitonin F ก nonFก F ก ก ก ก F ก F F (Stimulators of bone formation) Recombinant human parathyroid hormone 1-34 (Teriparatide, TPTD) ก ก prospective, randomized, double-blind, multinational, placebo-controlled F ก ก ก F F 1,637 (14) TPTD ก F ก ก ก ก ก F F 3 ʾ F ก F ก F TPTD 20 ก. (n = 541) ก F F TPTD 40 ก. (n=552) ก F F placebo (n=544) F TPTD 20 ก. F ก ก ก ก ก F 65% F ก ก non-vertebral fracture F 53% ก ก ก meta-analysis(15) F ก ก F ˁ ก ก ก ก ก F F TPTD 20 ก. 40 ก. F ˁ ก F กก F กF ก ก ก F bisphosphonates hormone therapy ก carcinogenicity study Fischer 344 F TPTD 24 20 F F F ก F 20 ก Fก F (70-80% F ) F F ก ก osteosarcoma ก dose (16) dependent F ก F F ก osteosarcoma F TPTD 25 (14) ก ก ก TPTD F F 20 ก. ก F F ˈ กF ก F F F F กF F F F ก ก กF 2 ʾ ก TPTD ˈ ˈ F F F potential side effects กก F ก F ก ก ก F F ก F
43 F F F 1. 2. 3. 4. ก F teriparatide ก ก ก ก F ก ก ก ก F ก ก ก ก ก F F ˁ F F 65 ʾ F F F F F F F BMD T-score axial DXA ก ก F ( F ก) F(lumbar spine BMD) ก ก ก(femoral neck or total hip BMD) ≤ -2.5 SD F ก ก ก ก ก ก ก ก F2 F BMD T-score axial DXA ก ก F ( F ก) F(lumbar spine BMD) ก ก ก(femoral neck or total hip BMD) ≤ -2.5 SD F ก ก ก ก ก ก ก ก ก BMD T-score axial DXA ก ก F ( F ก) F(lumbar spine BMD) ก ก ก(femoral neck or total hip BMD) ≤ -3.5 SD F ก ก ก ก ก ก ก ก 1 F ก FFก ก ก F bisphosphonate F F (inadequate(17) response) ก F F • vertebral fracture ก F1 F กก F vertebral fracture F ก ก ก ก ก กก F F F ก ก กก F 2 ʾ F • Lumbar spine BMD ʾ ≥ 3% ก (total hip femoral neck BMD) F ʾ ≥ 5% ( Fก ก F least significant change-LSC)(17,18) ก ก กก F 2 ʾ F F 4 F ก ก ก 2.3 กF F F ˁ F bisphosphonate F ก F F F (patient with good compliance and persistence) F teriparatide F F F F IV-4-7.5 F ก (mixed action agents) Vitamin D and vitamin D analogue 1. F ก Fก ก ก ก ก Fก F F ก F F F F กF 800 IU (19) F ก calcium F กF 1,000 ก. 2. ก F FF ก ก F ก ก hip fracture nonvertebral fracture F ก F (< 20%) F F vertebral fracture F (19) 3. F F ก F ˁ F F ก ก F F ก ก ก ˈ F F F Menatetrenone 1. ก F F ˁ high vitamin K intake ก ก ก ก ก ก F ก F F low (20,21) (22) vitamin K intake F low vitamin K intake BMD ก F 2. Menaquinone-4 menatetrenone ก ก ก ก ก F 50% F (23,24) Fก non-vertebral fracture F
44 3. F spine F (25-27) menatetrenone 45 maintain BMD BMD undercarboxylated osteocalcin F F 1,500 ก. ก. F ก Lumbar (25-28) Strontium ranelate 1. ก ก strontium ranelate (SR) ก F ก ก ก ก ก ˈ 3 ʾ F ก ก ก ก ก F F (29) 40-50% 2. ก ก ก F non-vertebral fractures F 16% F F hip fractures 36% ก F F strontium ranelate (30) ก ก 3. ก ก ˈ integrated analysis(31) F strontium ranelate ก ก ก ก F F กF (>80 ʾ) F 32% nonvertebral fracture F ก F 31% ก ก ก ก ก F F กF ˈ (32) F osteopenia 30-50% ก F ก ก ก ก F ก F ก ก F ( F ˈ F F กF F F FF ก F III-3) F / ก F F ˁ ˈ กF F ก F F ˁ F F ก ก F F IV-3 Alternative therapy and non-pharmacological treatment 3.1 Hip protector ก ก F F ก F nursing home ˆ fracture F F hip protector ก compliance ก F ก ก hip (33-35) IV-4 Potential adverse events, prerequisites and contraindications in using anti-osteoporotic agents 4.1 F F F F F F (36,37) ก − ก Fก ก ก F ก F F ก F ก ก F ก − ก F ก ก ก F ก F ) F ก ˈ ก ก (38) (36,37,39) ( F ก
45 F F F ˆ F F active form (40,41) − ก ก ก F F ก F ก F ก ( F ก ก − (42,43) F − F (43) F ก − ก − ก F ก ˈ F − F ก F F (43,45) F F F กก F F ก กF (43,44) F ก F F F F ก F กF ก ก F (46) กF F กF F F (cognitive (48-51) (dementia) F ก F ก ก F กF ก ก ก F ˁ F ก ˈ F F F mammogram ก Bisphosphonates − F ) F F ˁ − F / ก F กก F ก F ก ก − F F F F ก F calcitriol F F กF F F ก F function) F F (47) F ก ก ก F F กF F F ʾ F F F F alendronate, risedronate ibandronate ˈ ibandronate zoledronate F F ก F F non-ulcer dyspepsia ก (52) F ก ก atrial fibrillation ก F F ˁ F F ก ก F F ก ก F F ˈ F ECG กF ก F bisphosphonate กก F ก F ก ก Fก ก F F F − ก ก ก ก ก ก ก ก (osteonecrosis of the jaws) F ก F ก ก ก F bisphosphonate F ก ก ก F ก ก F ก ก ก ก F ก (53) F F กF ˈ F F F ก ก ก ก ก F 10 F ก F ก ก ก F ˈ F ˆ กF ก F − ก ก ก ก ก ก (atypical fracture) ก ก F F bisphosphonate ˈ ( >5 ʾ) ก ˈ low-energy trauma fracture ˈ transverse configuration subtrochanteric shaft of
46 femur (54,55) F F F ก ก F ก F ก ก F F กF ก ˂ F กF ˈ กF − ก F (post-dose reaction) F F (56,57) bisphosphonate ก F ก F ก F กF F F ˈ F F ก ก F ก ก F ก F F F ก 2-3 − ก F bisphosphonates F ˈ oral form F ก F ก ก ก. F F F F F F ก ก F F ก 1 F ก ก . ก F F ก F ก F ( F ก ก F F ก ) F ก ก ก F ก ก Fก ก ก F . F กก ก F F ก ก F F ˈ 1 F ก ก bisphosphonates ก ก F F F Fก ก F (esophagitis) ก F bisphosphonates F ˈ IV infusion F F F − F ก infusion F F F F ก F 15 ก F ก F ˁ F ˆ ก ก F ≥ 30 mL/min ( ˈ creatinine clearance ก F) F ก infusion F ˈ F F F F F Raloxifene − ก ʾ ก F F ก F ½ F ½ F ก F F F F GFR ก F (venous thromboembolism) F F F F ก (59) hot flushes ก ˈ (58,59) F กF ก Strontium F F F F F ˈ − F ก ก F − (61) thromboembolism) F Teriparatide F − ก ก ก − 5 ʾ ก F F F F F F ก F F F (60) F (venous F ก ก F ˆ (62) F ก F F ก (29,30,61) F ก F 2 ก F F ˁ ˈ F กF F(63,64) F F F
47 (16,65) ก F teriparatide ˈ กก F 20 F ก ก osteosarcoma F ก ˈ ก F 20 F F F ก Fก F (70-80% F ) F F F F ก ก osteosarcoma ก F teriparatide F 2 ก − F (66,67) ก F ก Fก ก F F F F F ˁ ก ˈ กF F ก ก (67) osteosarcoma กF ก ก ก 2 ก F F teriparatide ก ก F 500,000 F ก กF ก F ก ก osteosarcoma F (66) > 60 ʾ ʾ 1 F 250,000 F F F F F กก F ( F กก F ) F F ก ก ก ก (68) F F F − (prerequisite) ก F teriparatide ก. F F F F teriparatide ก 2 ʾ . F F F ˁ F ก ก osteosarcoma F ˈ Paget s disease F F ก ก ก F alkaline phosphatase F F ก epiphysis F ʽ . F F F F ˁ ˈ 5 ʾ . ก ˈ F F F ก F teriparatide ˈ F ก กF F F serum creatinine, serum calcium intact PTH F ก − ก F ก Calcitonin − ก F Menatetrenone F − F ก F (23,70) F F ก ก F F (12,69) F ก F F F warfarin ก F warfarin IV-5 Monitoring treatment and duration of treatment 5.1 ก ก (effectiveness) ก ก ก ก ก ก ก ก F ก 1. ก ก F ˁ F F ก ก ก ก ก ก F 2 F (adverse events) F F ˈ F F (drug response) ก ก ˂ ก ก F ก ˆ F ก F ก ก F ก F ˈ ก F F
48 ( Fก ก F ˁ F ก ก F 1.1. ก ) ก ก ก F F ˆ ก ก ก F ก F F F F กF F FF F2 axial DXA กก F BMD F F F F ก กF F F F ก 2 F F F กF 1 ʾ axial DXA F ˈ F กF F ก ก F ก กก BMD F axial DXA ก กก F F F Lumbar spine BMD F ʾ ≥ 3% (17,18) total hip BMD femoral neck BMD ʾ ≥ 5% Fก ก กF 1 ʾ F F ก BMD ก F ˁ F F (probable inadequate response) Fก BMD F ก ก F ก F F F F F ก F ก ก ก กก F ก ก F ก ก BMD กก F ก F ก F ก F F ˁ F F (inadequate response) 1.2. ก F bone turnover markers กก F ˈ ก ก ก F bone resorption marker F F ˈ ก F ก F ก ก F bone formation marker F F F ก 2 กF F ˈ F F F F F กF 3 ก F bone turnover markers (BTMs) F กก F 30-40% F ก ก กก BTMs variation กก F ก F กF ก F NPO F ˁ 12 . . กF F F F (7.00-9.00 .) F ˈ F ก ก 2. ก ก F ก F ก F ˁ F F ก F F (compliance) ก F (persistence) ˆ F F ก ก F ก ก F ก F F F ก ก ก ก F F ˁ F F ก F กF Fก F ก F F F F F F F ก F F F 80% ʾ (medication possession ratio: MPR ≥ 80%) 5.2 BMD ก F F ก F ก ก F ก F ก กF Fก ˆ F F ˆ F ˆ ก F ก F ˁ ก F ˈ clinical trial กก ก F F F ก ก ก ก ก F ˁ F กF F ก ˆ ก ˆ F FF ก ˈ F F F ก ก ก F ˁ ˈ F ก F F F ก clinical study F ก ก ก F anti-fracture efficacy F ก F ก 5 ʾ F( ก F) F F ˁ F F ก F (good compliance and persistence) F new fracture ก F F
49 ก BMD axial DXA ˆ ก F ˁ F ก F BMD F F F ˁ / F BTMs ก 1-2 ʾ 5 ʾ F F ก F ˁ F ก ก ก F ก F ˁ ก ก F กก ก ก (drug holiday) F ˁ ก F ก F F
50 4.1 Alendronate 10 mg (ALN) ก ก F Benefit and Indication for use ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) - F ก ก ก ก ก ก ก F F (Glucocorticoidinduced osteoporosis, GIO) - F ก ก ก ก F (Male idiopathic osteoporosis, MIO) ˂ ก ก ก ก F F ก F F ก ALN 10 mg Alendronate once weekly 70 mg (ALN-OW) Alendronate ˂ ก plus F F ALN 70 mg mg + Cholecalcifer ol 2800 IU (ALN-plus) ก ก ก F F ก ก ALN 10 ก ก ก F F ก ก(71-74) ก (vertebral fracture),ก ก ก (hip fracture) ก กF ก กก ก (nonvertebral fracture) - F ก - F - F ก ALN 10 mg(75) F - F ก ALN 10 mg - F F - ก F vitamin D3 2800 IU F F = 400 IU/d F กF ˆ hypovitaminosis D vitamin D deficiency(76)
51 Risedronate 5 mg (RIS) Risedronate once weekly 35 mg (RIS-OW) Ibandronate Once monthly 150 mg (IBN-OM) Benefit and Indication for use ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) - F ก ก ก ก ก ก ก F F (Glucocorticoid-induced osteoporosis, GIO) - F ก ก ก ก F (Male idiopathic osteoporosis, MIO) ˂ ก ก ก ก F F ก F F ก RIS 5 mg F - Fก ก ก ก (vertebral fracture),ก ก ก (hip fracture) ก กF ก ก ก ก (non-vertebral fracture) - F (77,78) - F - F ก RIS 5mg(79) F F ก ก(80,81) ก ก (vertebral fracture), ก กF ก ก (82) ก ก (non-vertebral fracture) - F Zoledronate ˂ ก ก ก ก F ก ก(56,57) infusion F F ก F ( US-FDA) ก ก (vertebral fracture), ก ก ก ก ก (hip fracture) ก ก every 1 year - F ก ก 5 mg (postmenopausal F ก กก ก (ZOL) osteoporosis, PMO) (non-vertebral fracture) - F ก ก ก ก ก ก - F F ก1 ʾ ก F F(Glucocorticoidinduced osteoporosis, GIO) * Ibandronate F ก F ก ก ก ก (vertebral fracture) ˈ ก ก RCTs F ก F ก ก ก ก F ก กก ก (non-vertebral fracture) ˈ ก กก synthesis data ก pooled analysis RCTs ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) -
52 Estrogen Benefit and Indication for use ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) Raloxifene (RLX) 60 mg Calcitonin nasal spray 200 IU/puff ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) Menatetrenone (MK-4) 15 mg ก ก ก F F ก F ( Japan FDA) - F ก ก ก ก F ก ก ก ก - F ( preparation F ก ก F ก ก(6,7,8) (vertebral fracture), ก (hip fracture) ก F F efficacy) F ก ก(9,83) (vertebral fracture) - F F ก ก(12) ก ก (vertebral fracture) - F ก กก ก (13) ( Fก 8 ก ก ก ก F) - F ก - ก - F ก F ก ก(23) (vertebral fracture) 3 (45 mg/d) (postmenopausal osteoporosis, PMO) ** ก F ก ก ก WHI F ก ก ก ก (vertebral fracture) ก ก F ก กก ก (non-vertebral fracture) ˈ ก F conjugate equine estrogen F F extend ก F preparation ก
53 Strontium ranelate 2 g/sachet Benefit and Indication for use ก ก ก F F ก F ( EMEA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) Teriparatide 20 µg/inject F ก 1,200 mg/d (Elemental Calcium) ก ก ก F F ก F ( US-FDA) - F ก ก ก ก F F ก ก(29,30) ก ก (vertebral fracture) ก กF ก ก ก ก (non-vertebral fracture) - F - F ก ก(14,15) ก ก (vertebral fracture), ก ก ก (hip fracture) ก กF ก กก ก (non-vertebral fracture) - F F - (postmenopausal osteoporosis, PMO) - F ก ก ก ก ก ก ก F F (Glucocorticoid-induced osteoporosis, GIO) - F ก ก ก ก F (Male idiopathic osteoporosis, MIO) F ˁ ก ก F F (84) F ˁ F ก F ก ก F F ˂ ก ก ก ก ก ก ก
54 Benefit and Indication for use F ˁ ก FF ก 400-800 ก F F IU / d F F F ก ก ก ก ก ก ก F F -Alphacalcidol (Glucocorticoid-induced (0.5-1 osteoporosis, GIO) (86,87) ก F FF ก ก ก ก ก F ) -Calcitriol ก F (88,89) (0.25-0.5 ก ( ≥ 65 ʾ) ก F ) ก F FF ก ก ก F F ก FF ก F F (85) ก ก ก F - ก ก hypercalcemia (88) hypercalcicuria F 1. Kanis JA, Seeman E, Johnell O, Rizzoli R, Delmas P. The perspective of the international osteoporosis foundation on the official positions of the international society for clinical densitometry. J Clin Densitom. 2005;8(2):145-7. 2. Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, et al. Assessment of fracture risk. Osteoporos Int. 2005;16(6):581-9. 3. FRAX-WHO fracture risk assessment tool, http://www.shef.ac.th/FRAX. 4. NOF Clinician s Guide to Prevention and Treatment of Osteoporosis 2008. 5. Russell G, Xia ZD, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, et al. Bisphosphonate: an update on mechanisms of action and how these related to clinical efficacy. Ann NY Acad Sci 2007;1117:209-57. 6. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of non-vertebral fractures: a meta-analysis of randomized trials. JAMA 2001;285:2891-7. 7. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women s Health Initiative randomized trial. JAMA 2003;290:1729-8.
55 8. Roussow JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women s Health Initiative randomized controlled trial. JAMA 2002;288:321-33. 9. Ettinger B, Black DM, 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 1999;282:637-45. 10. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN et al. Effect of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trail. JAMA 2006;295:2727-41. 11. Mosca L, Barrett-Connor E, Wenger NK, Collins P, Grady D, Kornitzer M et al. Design and methods of the Raloxifene Use for The Heart (RUTH) study. Am J Cardiol 2001;88:392-5. 12. Chesnut CH III, Silverman S, Andriano K, Genant H, Gimona A, Harris S, 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): 267-76. 13. Silverman SL, Azria M. The analgesic role of calcitonin following osteoporotic fracture. Osteoporosis Int 2002;13:858-67. 14. Neer RM, Arnaud CD, 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;344:1434-41. 15. Nevitt MC, Chen P, Dore RK, Reginster JY, Kiel DP, Zanchetta JR, et al. Reduced risk of back pain following teriparatide treatment: a meta-analysis. Osteoporosis Int 2006;17(2):273-80. 16. Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M. Bone neoplasms in F344 rats given teriparatide [rhPTH(1 34)] are dependent on duration of treatment and dose. Toxicol Pathol 2004;32(34):426 38. 17. Diez-Perez A, Gonzalez-Macias J. Inadequate responders to osteoporosis treatment: proposal for an operational definition. Osteoporosis Int 2008;19:1511 16. 18. Lewiecki EM, Watts NB. Assessing response to osteoporosis therapy. Osteoporosis Int 2008;19:1363 8. 19. Avenell A, Gillespie WJ, Gillespie LD, O Connell DL. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2005, 20(3). Art. No.: CD000227. DOI: 10.1002/14651858.CD000227.pub2. 20. Feskanich D, Weber P, Willett WC, Rocket H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 1999;69:74-9.
56 21. Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon D, Cupples LA, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 2000;71:1201-8. 22. Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, et al. Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr 2003;77:512-6. 23. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis. J Bone Miner Res 2000;15(3):515-21. 24. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the Prevention of Fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2006;166(12):1256-61 . 25. Purwosunu Y, Muharram , Rachman IA, Reksoprodjo S, Sekizawa A. Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res 2006;32(2):230-4. 26. Ushiroyama T, Ikeda A, Ueki M. Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas 2002;41:211 21. 27. Iwamoto J, Takeda T, Ichimura S. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci 2000;5:546 51. 28. Bunyaratavej N, Penkitti P, Kitimanon N, Boonsangsom P, Bonjongsat P, Yunoi S. Efficacy and safety of menaquinone-4 in postmenopausal Thai women. J Med Assoc Thai 2001;84(suppl2):S553-9. 29. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350(5):459-68. 30. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis; Treatment of Peripheral Osteoporosis (TROPOS) Study. J Clin Endocrinol Metab 2005;90(5):2816 22. 31. Seeman E. Strontium ranelate: vertebral and non-verttenral fractures risk reduction. Curr Opin Rheumatol 2006;18(suppl1):S17-20. 32. Seeman E, Devogelaer JP, Lorenc R, Spector T, Brixen K, Balogh A, et al. Strontium Ranelate Reduces the Risk of Vertebral Fractures in Patients With Osteopenia. J Bone Miner Res 2008;23:433 8. 33. Van Schoor NM, Smit JH, Twisk JW, Bouter LM, Lips P. Prevention of hip fractures by external hip protectors: a randomized controlled trial. JAMA 2003;289(15):1957-62. 34. Birks YF, Porthouse J, Addie C, Loughney K, Saxon L, Baverstock M, et al. for the Primary Care Hip Protector Trial Group. Randomized controlled trial of hip protectors among woman living in the community. Osteoporos Int 2004;15(9):701-6.
57 35. Sawka AM, Boulos P, Beattie K, Thabane L, Papaioannou A, Gafni A, et al. Do hip protectors decrease the risk of hip fracture in institutional and community-dwelling elderly? A systematic review and meta-analysis of randomized controlled trials. Osteoporos Int 2005;16(12):1461-74. 36. Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, et al. for RECORD Trial Group. Oral vitamin D3 and calcium for secondary prevention of lowtrauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomized placebo-controlled trial. Lancet 2005;365(9471):1621-8. 37. Prince RL, Devine A, Dhaliwal SS, Dick IM. Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women. Arch Intern Med 2006;166(8):869-75. 38. Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, et al. Vascular events in healthy older women receiving calcium supplementation: randomized controlled trial. BMJ 2008;336(7638):262-6. 39. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, et al. for Women's Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007;115(7):846-54. 40. Avenell A, Gillespie WJ, Gillespie LD, O'Connell DL. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev (Online) 2005(3):CD000227. 41. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess; 2007(158):1-235. 42. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. for WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 2003;289(24):3243-53. 43. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. for Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291(14):1701-12. 44. Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. for Women's Health Initiative Investigators. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004;292(13):1573-80. 45. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, et al. for Women's Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349(6): 523-34. 46. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, et al. for WHI Investigators. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. JAMA 2003;289(20):2673-84.
58 47. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297(13):1465-77. 48. Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, et al. for WHIMS Investigators. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289(20):2663-72. 49. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. for WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289(20):2651-62. 50. Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al. for Women's Health Initiative Memory Study. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004;291(24):2947-58. 51. Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, et al. for Women's Health Initiative Memory Study. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004;291(24):2959-68. 52. MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med 2008;148(3):197-213. 53. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, et al.; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22(10):1479-91. 54. Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG. Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma 2008;22(5):346-50. 55. Kweka EBK, Goh SK, Koh JSB, Ping MA, Howe TS. An emerging pattern of subtrochanteric stress fractures: A long-term complication of alendronate therapy? Injury 2008;39:224-31. 56. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. for the HORIZON Pivotal Fracture Trial. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. N Engl J Med 2007;356:1809-22. 57. Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, et al. for the HORIZON Recurrent Fracture Trial. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007;357(18):1799-809. 58. Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia A, et al. for the Multiple Outcomes of Raloxifene Evaluation Investigators. Safety and adverse effects associated
59 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. with raloxifene: multiple outcomes of raloxifene evaluation. Obstet Gynecol 2004;104(4):837-44. Davies GC, Huster WJ, Lu Y, Plouffe L Jr., Lakshmanan M. Adverse events reported by postmenopausal women in controlled trials with raloxifene. Obstet Gynecol 1999; 93(4): 558-65. Cranney A, Adachi JD. Benefit-risk assessment of raloxifene in postmenopausal osteoporosis. Drug Saf 2005;28(8):721-30. Reginster JY, Sarlet N, Lejeune E, Leonori L. Strontium ranelate: a new treatment for postmenopausal osteoporosis with a dual mode of action. Curr Osteoporos Rep 2005;3(1):30-4. Miller PD, Bilezikian JP, Diaz-Curiel M, Chen P, Marin F, Krege JH, et al. Occurrence of hypercalciuria in patients with osteoporosis treated with teriparatide. J Clin Endocrinol Metab 2007;92(9):3535-41. Neer RM, Arnaud CD, 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(19):1434-41. Miller PD. Monitoring osteoporosis therapies. Curr Osteoporos Rep 2007;5(1):38-43. Jolette J, Wilker CE, Smith SY, Doyle N, Hardisty JF, Metcalfe AJ, et al. Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats. Toxicol Pathol 2006; 34; 929-40. Harper KD, Krege JH, Marcus R, Mitlak BH. Letter to the Editor: Osteosarcoma and Teriparatide? J Bone Miner Res 2007;22(2):334. Subbiah V, Madsen VS, Raymond AK, Benjamin RS, Ludwig JA. Of mice and men: divergent risks of teriparatide-induced osteosarcoma. Osteoporos Int 2009 (on line first) DOI 10.1007/s00198-009-1004-0. Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005;26(5):688-703. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev 2002;23(4):570-8. Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 2007;18(7):963-72. Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. J Clin Endocrinol Metab 2000;85:4118-24.
60 72. Cranney A, Wells G, Willan A, Griffith L, Zytarak N, Robinson V, et al. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002;23:508-16. 73. Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. Osteoporosis Int 2005;16:468-74. 74. Well GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. (Review) Cochrane Database of Systematic Rev 2008;1:1-71. 75. Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Keil D, et al. Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis: Alendronate Once-weekly Study Group. Aging Clin Exp Res 2000;12:1-12. 76. Recker R, Lips P, Felsenberg D, Lippuner K, Benhamou L, Hawkins F, et al. Alendronate with and without cholecalciferol for osteoporosis: result of a 15 week randomized controlled trial. Curr Med Res Opin 2006;22:1745-55. 77. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al. Effects of risedronate treatment on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 1999;282:1344-52. 78. Cranney A, Tugwell P, Adachi J, Weaver B, Zytarak N, Papaioannou A, et al. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:51723. 79. Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD, Bolognese MA, et al. The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int 2002;71:103-11. 80. Chesnut-III C, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, et al. Effect of oral Ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res 2004;19:1241-49. 81. Reginster JY, Adami S, Lakatos P, Greenwald M, Stepan JJ, Silverman C, et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 2006;65:654-61. 82. Adachi R, et al. J Bone Miner Res 2007; 22(suppl 1):S210-S211(Abstract). 83. Cranney A, Tugwell P, Zytaruk N, Robinson V, Weaver B, Adachi J, et al. for the Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Metaanalyses of therapies for postmenopausal osteoporosis. IV. Meta-analysis of raloxifene for the prevention and treatment of postmenopausal osteoporosis. Endocr Rev. 2002;23(4): 524-8. 84. Sanders KM, Nowson CA, Kotowicz MA, Briffa K, Devine A, Reid IR. Calcium and bone health: position statement for the Australian and New Zealand Bone and Mineral Society,
61 85. 86. 87. 88. 89. Osteoporosis Australia and the Endocrine Society of Australia. Med J Aust 2009;190:316 20. Richy F, Schacht E, Bruyere O, Ethgen O, Gourlay M, Reginster JY. Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int 2005;76(3):176-86. Richy F, Ethgen O, Bruyere O, Reginster JY. Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 2004;15(4):301-10. de Nijs RN, Jacobs JW, Algra A, Lems WF, Bijlsma JW. Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D3 analogues: a review with metaanalysis of randomized controlled trials including organ transplantation studies. Osteoporos Int 2004;15(8):589-602. Avenell A, Gillespie WJ, Gillespie LD, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009;15(2):CD000227. Ringe JD, Schacht E. Potential of alfacalcidol for reducing increased risk of falls and fractures. Rheumatol Int 2009;29(10):1177-85.
62 Glucocorticoid-induced osteoporosis (GIO) V-1 Introduction and epidemiology 1.1 ก F F (glucocorticoids) ˈ Fก ก ก inflammatory immunosuppressive ก F ก ก F F (rheumatic disease) ˈ F F F ก ก F F F F ก F F ˈ Fก ก ก ก ˈ F ก ˈ F secondary osteoporosis ก ก F ก F F F ก ก ก ˈ 1.33 F non-vertebral fracture 1.61 F ก ก ก ก F ก ก ก ก ก F Fก (1,2) F ก ก F F antiFก ก 2.6 ก ก 1.2 กก ก 3% ก ก F 1 70 ( 3 ʾ(4) (3) ก F ก ก ก ก Fก กก F F ก 1.4%) กก F 50 ʾ ก F ˁ กก F 55 ʾ F F ก F F 3 F ก F ก กก F 6-12 ก F ก ก กก ก ก ก ก ก ก F F ก ก ก 5% ʾ ก 1-2% ก ก Fก ก F F F (daily dose) F ก F ก (5) F ก 1F F ก F F F ก ก trabecular ʾ F ก ก F (cumulative dose) (6,7) V-2 Pathophysiology and risk assessment 2.1 ก กก ก glucocorticoid-induced osteoporosis (GIO) F F F ก ˆ F ก F F F F ก ก (8-9) GIO ก ก ก ก ก ก F ˁ F F F ก ก Fก F F ก (10-11) F F F ก ก ก กF F F Fก ˂ ก ก F ก F ก F F ก ก ˈ F F ก F (8) F ก F Fก ก ก F F F F F ก F F ก ก ก (ankylosing spondylitis) ˆ ก F F กF ก F (12) ก กกF F
63 ก ก ก F F Fก ก ก ก ก Fก F ก ก ก (14) ก ก F ก secondary hyperparathyroidism ก ก F (15) (16) ก F ก ˆ ก F F ก ก (osteoblast) F ก ก (apoptosis) osteoblast F ก ก (osteoclast)(14,17) receptor activator NF-KB ligand (RANKL) osteoprotegerin (OPG)(18) ก ก (19) hypothalamic pituitary gonad axis ก F F testosterone(20) adrenal androgen(21) F ก F ก ก F ก F F ก ก ก ก (13) 2.2 ˆ ˆ ก ˆ ก ก ก ˆ F ก ก ก ก ก F F F ˆ F F กF ก (≥ 65 ʾ)(22) body mass index) F ˈ Fก ก (25) (chronic lung disease) F F ก ก กก F ก ก F ก F F ก ก ก ก ก F ก F T Score < -1.0 F F ก ก F F ก ʾ ก guideline ก F ˁ F ก F F ก ก กก F ก F ก F ก ก F F ก ก ก ก ก (23-24) (low ( F F ก F) (26) F (organ transplantation) F ก F กF F F F F F ˁ F F ก ก กF F ก F F ก 10% 1 standard deviation (SD) F 1 F F T-score < -1.0 ˈ F F ก ก V-3 Diagnosis ก ก ก score ≤ -2.5 SD ก ก ก กก F ก ก F F L-spine, femoral neck F F F F ก total hip ˈ ก ก F ก F F ก BMD T- V-4 Prevention and treatment 4.1 ก ก ก ก 1. ก 1.1. ˂ ก F ˂ ก ก ก F ก F F F 1.2. กก ก F 1.3. ก 1.4. ˂ ก ก ก F ก ก ก กก ก ก ก ก F F F F ˁ F ก กก F F F ก F ก F ก F F F ก F F ˈ
64 1.5. F F calcium 1.6. F F 2. ก F F F F 800 IU F F F ก F ก ก F3 F F 1,200 ก. F Fก ˆ F F ก elemental 7.5 ก. ก BMD T-score ก F -1.0 F F ก F F F ก 4.1( IV) (27-29) 2.1. ก F ˈ ก 2.1.1. Alendronate 2.1.2. Risedronate 2.1.3. Zoledronate 2.2. ก F ˈ ( F F F ก F ก F)(27,28) 2.2.1. F F alphacalcidol, calcitriol 2.2.2. F 2.2.2.1. Estrogen replacement therapy premature menopause 2.2.2.2. Testosterone replacement therapy F testosterone (30) ก ก ก ก ก 2.2.3. Teriparatide F F ก F ก ก F F bisphosphonates F F F ก F IV-2 2.2 (Teriparatide, TPTD) 2.3. SERMs, calcitonin, menatetrenone strontium ranelate evidence F ก Fก ก ก ก ก F F F ก F F V-5 Monitoring treatment 5.1 ก 1. ก ก ก ก F ก bisphosphonates F ก ก F 2. ก ก ก F ก F (31) กก F ก F F ก ก ก 6-12 F F 1 ʾ ก F ก ก ก ก F F ก F F ˁ ก F ก F ก F ก ก F ก กF F ก F กF
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010
Osteoporosis guideline2010

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Osteoporosis guideline2010

  • 1. Definition, epidemiology, burden and etiology of osteoporosis .....1 I-1 I-2 Definition and concept ............................................................................................................1 Epidemiology of osteoporosis and osteoporotic fractures ....................................................1 2.1 ก (Worldwide epidemiology) ...............................................................1 2.2 (Epidemiology in Asia and Thailand)........2 I-3 Burden and impact of osteoporosis and osteoporotic fractures ...........................................2 3.1 ก ก กก ก ก ก ก ก ก ก (Osteoporosis related mortality and morbidity) .................................................................................................3 3.2 ก ก ก ก ก ก F (Health economic aspect of osteoporotic fractures) ...................................................................................3 I-4 Pathogenesis and etiology .....................................................................................................4 4.1 ก (Pathogenesis) ...........................................................................................4 ก F ......................................................................................................................................5 Diagnosis and bone mass assessment in osteoporosis .................8 II-1 History, physical examination and differential diagnosis .......................................................8 1.1 ก ก ก ก (Classification of osteoporosis) .........................8 II-2 Risk factors for osteoporosis and osteoporotic fractures ......................................................9 2.1 ˆ ก ก ก ก ก ก ก ก (Risk factors of osteoporosis and osteoporotic fracture) ........................................................................9 2.2 ก ˆ ก ก ก ก ก ก ก ก F FRAXTM Fก ก (Risk assessment of osteoporotic fracture using WHO-FRAXTM) 9 II-3 Laboratory investigations and bone strength assessments ................................................11 3.1 ก F ก (Laboratory investigation) ................................................11 3.2 ก ก F ก ก (Bone strength assessment) ............................11 II-4 Diagnostic criteria for osteoporosis ......................................................................................12 4.1 ก F ก ก (Measurement of bone density) ..................................12 4.2 ก ก F ก ก (Biochemical markers of bone turnover) .......................................................................................................................13 4.3 ก ก (Screening) .......................................................................................14 ก 2.1 ...................................................................................................................................15 OSTA (Osteoporosis Self-Assessment Tool for Asians) ...................................................15 Khon Kaen Osteoporosis study score (KKOS) ..................................................................16 ก 2.2 ...................................................................................................................................18 ก ก ก ก ก ก F ก QUS ...........................................................................................................18 ก F ....................................................................................................................................19
  • 2. Prevention of osteoporosis and prevention of falls .......................21 III-1 Strategies to maximize peak bone mass ............................................................................21 III-2 Strategies to prevent bone loss ...........................................................................................21 ก F F (Hormone replacement therapy) .....................................................22 III-3 Nutritional aspect in osteoporosis ........................................................................................22 (Calcium) .............................................................................................................22 (Vitamin D) ............................................................................................................26 (Vitamin K) ...........................................................................................................27 III-4 Life style modification and prevention of fall .......................................................................28 4.1 ก ก Fก ˈ ก ก ............................................28 4.2 ก ˂ ก ก ก F F ˁ ก ก ................................................................29 ก 3.1 Falls Risk Assessment tool ............................................................................32 ก 3.2 ก กก ก ˂ ก ก ก ....................................................33 ก กก ก F ก ก ก ก ก ก ..........................................33 ก ˂ ก ก กF ก ก ก ก ก ......................................................................34 ก F ....................................................................................................................................34 Treatment of osteoporosis ................................................................38 IV-1 Goal of osteoporosis treatment ............................................................................................38 1.1 ก ˂ ก ก ก ก ก .........................................................38 1.2 F ก ก ก ก ......................................................................38 1.3 ก Fก ก ก ก F ก Fก F F International Osteoporosis Foundation National Osteoporosis Foundation 38 1.4 ก Fก ก ก ก F ก Fก F F ก ก F ....................................................................39 IV-2 Pharmacotherapy for osteoporosis ......................................................................................40 2.1 ก ก ก (Inhibitors of bone resorption) ..............................................41 2.2 ก F ก F ก ก F (Stimulators of bone formation) ....................................42 2.3 ก (mixed action agents) ............................................................43 IV-3 Alternative therapy and non-pharmacological treatment .....................................................44 3.1 Hip protector .................................................................................................................44 IV-4 Potential adverse events, prerequisites and contraindications in using anti-osteoporotic agents ..................................................................................................................................44 4.1 F F F F ก F ก ก ก ..........................44 IV-5 Monitoring treatment and duration of treatment ..................................................................47 5.1 ก ก ก ...............................................................................47 5.2 ก ก ........................................................................................................48 ก F ....................................................................................................................................54 Glucocorticoid-induced osteoporosis (GIO) ...................................62
  • 3. V-1 Introduction and epidemiology .............................................................................................62 1.1 ............................................................................................................................62 1.2 ...................................................................................................................62 V-2 Pathophysiology and risk assessment .................................................................................62 2.1 ก กก ก ...........................................................................................................62 2.2 ˆ .....................................................................................................................63 V-3 Diagnosis ..............................................................................................................................63 V-4 Prevention and treatment .....................................................................................................63 4.1 ก ˂ ก ก ก ก ก กก F ก F F ..........63 V-5 Monitoring treatment ............................................................................................................64 5.1 ก ก ก .................................................................................................64 ก F ....................................................................................................................................65 Osteoporosis in men ..........................................................................68 VI-1 Introduction and epidemiology .............................................................................................68 1.1 ก ..............................................................................................68 1.2 ...................................................................................................................68 1.3. ˆ .....................................................................................................................69 VI-2 Assessment and diagnosis ..................................................................................................69 2.1 ก ....................................................................................................................69 2.2 ก F ก ก ..............................................................................69 VI-3 Prevention .............................................................................................................................70 3.1 ก ˂ ก ก ก F ................................................................................70 VI-4 Treatment and follow-up ......................................................................................................71 4.1 ก ก ก ก F .......................................................................71 4.2 ก ก ก ..................................................................................................71 ก F ....................................................................................................................................72
  • 4. 1 Definition, epidemiology, burden and etiology of osteoporosis I-1 Definition and concept ʾ . . 2543 National Institute of Health F ก (1) F ˈ ก ก กF ก ก (bone strength) F ก ก ก กF ก ก ก F 2 F ก (bone density) ก ก (bone quality) ก ก F F F ก ก I-2 Epidemiology of osteoporosis and osteoporotic fractures 2.1 ก (Worldwide epidemiology) ʾ . . 2536 F กก (2) ก (WHO) F ก fractures) 1.3 F F ʾ 25% ˈ ก ก ก ก (hip fractures) ก ก F ก F 30% F Consensus Development Conference ก F F ก ก ก ก ก ก ก (osteoporotic 50% ˈ ก ก ก (vertebral fractures) ก 25% ˈ ก ก ก ก F ก ก F 50 ʾ ˈ ก ก กก ก National Health and Nutrition Survey (NHANES III) ก ʾ . . 2540 F ก F F ก 13-18% ˈ ก ก (osteoporosis) ก 27-50% F ก ก (osteopenia) ก ก ก ก F F ก F ก FF F กF F ก Fก กก F 80 ʾ F ˈ ก ก 70% (3) F ก ก ก F ก F (incidence) F กF F F F F F (adolescence) ก (middle life) ก F ก ก (working) ก (lifestyle) F กก F ก ก ก ก FF ˈ ก ก ก ก (high-energy trauma) F F 40-50 ʾ ก ก ก F ก ก ก ก F ก F ก ก ก F F ก ก ก ก F ก ก ก (4) ก ก ก F ก F ก ก ก F ˈ ก F (low-energy trauma) ก ก ก กก ก (osteoporotic fractures) ก (4) ก ก ก F ˁ ก ก ก ก ʾ 500,000 ก กก F 10 F FF F ก กก F 70 ʾ (4) ก ก ก F F F ก Fก ก ก ก ก ก F (Caucasian) F ʾ 737 F 100,000 F F F (5) ʾ 280 F 100,000 F ʽ F
  • 5. 2 2.2 (Epidemiology in Asia and Thailand) ก F F 76.3 ʾ F F ก 2541(7) . . 2544(8) ก FF F F F F 40 ʾ 11-13% ˈ ก ʾ . . 2551 (life expectancy) ก 69.5 ʾ F ก ก (prevalence) ก ก F F กก F F ก ก ʾ . . F F F ก Fก ก ก Fก ก F F ก ก Fก ก F 2.5 F F ก ก ก F (T-score ≤ -2.5) F 19-21% F ˈ ก ก ก ก F (lumbar spine osteoporosis) ก ก ก ก (femoral neck osteoporosis) (6) ʾ . . 2540-2541(9) ก F ก F 50 ʾ ʾ 162 F 100,000 851 F 100,000 ก ก 75 ʾ F ก F 50 ʾ ก F ก ก ก ก ʾ 269 ˈ ʾ 1,011 F 100,000 F กก F 75 ʾ กF ก ก ก F ก ก F ก ก Fก ก ก ก ก ก F Fก ก ก ก ก ก F F ก (Hong Kong Chinese) 179 F 100,000 ʾ . . 2508 ˈ ʾ 389 F 100,000 (10) กF F กก ˁ ( . . 2545) ก ก ก ก ʾ 92,400 5 ʾกF F ˈ ʾ 117,900 (11) ʾ . . 2050 ก 40 ก F ʾ F F ก ก ก ก ก ก กF 6 F 3 F ก F ก ก ก ก ก ˈ ʾ ก F 100,000 ก F ก ก F F F F ก ก ก ก F ก ʾ ʾ . . 2528 ก ก F ก ก F FF ก ก (10) F F I-3 Burden and impact of osteoporosis and osteoporotic fractures F ก 1. ก ก ก กF ก F 2. ก ก ก ก ˈ ก fractures ก ก ˈ ก ก ก ก ก FF ก F ก ก F ก ก ก F ก ก F ก F ˈ F ก ก กก ˈ กF F ก (burden) F ก F clinical consequence F ก F ˈ 2ก (low-energy trauma) F ก ก ก ก กก กF ก ก F ก F ˈ F ก F ก ก ก กก กF ก ก F ก ก ก ก ก ก ก (impact) ก กF ก ก osteoporotic ก ก ก ก ก
  • 6. 3 3.1 ก ก กก ก ก ก ก ก (Osteoporosis related mortality and morbidity) 1. ก ก ก 2. 3. 4. 5. 6. ก ก ก ก ก ก ก ก (osteoporotic vertebral fractures) ก ก กก ก ก F F ˈ F 40% F ก ก ก F F F F ˈ ก ก ก ก ก ก ก F ก F ก F ก F F F F ก ก ก ก ก ก ก (12) (13) ˁ (morbidity) ก (mortality) กก F F F ก ก ก F F ˁ ก (height loss) F (kyphosis) (scoliosis) F ก F F ก กก ก ก ก ก ก ก ก ก ก (functional disability) ก F F ก ก ก F ก F ก morbidity mortality ก F (12-14) ก ก ก ก F ก ก ก ก F (14) ก ก ก ก (hip fractures) ˈ ก ก ก ก ก ก ˆ ก ก ก ก ก ก ก F ก ก ก ก ก F ก ก F FF ก ก ก ก ก กก กก F ก ก ก ก F F F ก F ก F ˁ F F ก ก F F ก F F (15F ก ก ก ก ˁ ก ก ก ก 16) ก 20% 1 ʾ ก ก ก F F 30% ก ก (permanent disability) F F ก ก F F (nursing home) 40% F F F ก F F F F F 80% F ก F F F F กF ก ก ก ก ก ก ก ก ก กก ก F(17) F 2.1% F ก กก ก ก ก 3 ,6 1 ʾ F ก 9%, 12% 17% ก ก ก ก (18) ก ก ก ก F F F ˁ (22%) F F 23% F F wheel chair ก F ก ก F ˁ F F F ก F ก ก F F 11% F F 10% F F F 22% F F ก F 5% F F ก 3.2 ก ก ก ก ก ก F (Health economic aspect of osteoporotic fractures) 1. ก ก International Osteoporosis Foundation (IOF) F ก ก ก ก ก ก ก (osteoporotic fractures) FF ก ก ก ก ก ก ก ก ʾ 25 F (19) F FF (cost) F ก F
  • 7. 4 ก 2. F ก (20) ʾ 1.8 F F ก ก ʾ . . 1995(21) F ʾ 17 F F ก ˆ ก ก ก ก ก F F ˁ ก ก ก ก ก ก ก ก National Osteoporosis Foundation (NOF) FF ก ก ก ก ก ก ก ก F F F F F ก 120,000 F ʾ (22) F FF ก I-4 Pathogenesis and etiology 4.1 ก 1. ก (Pathogenesis) ก ก กก ก ก ก ก 2 ก F ก ก F F กF ˈ ก ก ก กก F ก F F กก ก ก ก กก F ก ก กก F ก ก ก F ก ก ก ก ก ก ก F F F กF ก ก (peak bone mass) ก ก (8) ก F F 30-34 ʾ ก ก F ก ก ก ก F ก ก F 40-45 ʾ ก ก ก ก กก F ก F ก ก F ก ก F F ก F F F ก ก ก (rate of bone loss) F ก FF ก ก ก ก F F F ก กก ก F F F ก ก ก ก กF ก ก ก ก ก ก F ก ก ก ก ก ก F F Fก Fก ก ก ก F 2. ˆ F ก ก F กF F ก ก ก F กF F ก F F ก ก (23-25) Fก ก ก ก กก ก ก ก (26,27) F F ก ก ก ก F F (28,29) (30) ก ก ก ก F F ก ก 3. ก ก ก F ก F F 10 ʾ ก ก F postmenopausal bone loss ก ก ก ʾ 3-5% ˈ กก F F F F ก ก(osteoclast) ก F ก F ก ก ก กก F ก F ก ก ก ก ก F (cancellous or trabecular bone) กก F ก ก (cortical bone) ก ก ก ก ก ก ก F ก ก กF F ก ก F ก F ก ก F F ก ก F (31) ก ก ก ก F ก F ก ก ก ก ก F F ก F 4. ก ก ก F ก กF F ʾ 1-2% F F F F 40-50 ʾ F F F ( F >70 ʾ) F ก ก ก กก F F ก ก
  • 8. 5 (osteoblast) ก ก ก F age-related bone loss 5. ก F ก ก ก ก ก ก F 65 ʾ F F ก ก ก ก ก ก ˈ exponential ก 6. ˆ Fก ก ก F กF ก F ก F F F F F F กก F ˈ ก ก F 7. ก ก ก ก ก ก ก ก กก ก F ˆ ก F ก ก F (factors reflexes F ก coordination ก F ก ก ก F F ก ก ก กก ก F ก ก ก ก ก ก ก ก ก ก ก F ก F 70-75 ʾ ก ก F F Fก F ก F F ˈ F ก ก ก F F (32) of fall) F กF ก postural fat padding ก ก F F ก F ก กก ˂ ก ก F ก F F 1. Osteoporosis prevention, diagnosis and therapy. NIH consensus statements 2000; 17: 1-36. 2. Consensus Development Conference: prophylaxis and treatment of osteoporosis. Am J Med 1991;90:107-10. 3. Johnell O. The socioeconomic burden of fracture: today and in the 21st century. Am J Med 1997;103(suppl 2A):S20-5. 4. Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL. How many women have osteoporosis? J Bone Miner Res 1992;7(9):1005-10. 5. Maggi S, Kelsey JL, Litvak J, Heyse SP. Incidence of hip fractures in elderly; a crossnational analysis. Osteoporosis Int 1991;1:232-41. 6. Mahidol Population Gazette. Institute of Population and Social Research, Mahidol University, 2008. 7. Taechakraichana N, Angkawanich P, Panyakhamlerd K, Limpaphayom K. Postmenopausal osteoporosis: what is the real magnitude of problem? J Med Assoc Thai 1998;81:397-401. 8. Limpaphayom K, Taechakraichana N, Jaisamrarn U, Bunyavejchevin S, Chaikittisilpa S, Poshyachinda M, et al. Prevalence of osteopenia and osteoporosis in Thai women. Menopause 2001;8:65-9. 9. Lau EM, Lee JK, Suriyawongpaisal P, Saw SM, Das De S, Khir A, et al. The incidence of hip fracture in four Asian Countries: the Asian Osteoporosis Study (AOS). Osteoporosis Int 2001;12:239-43.
  • 9. 6 10. Lau EM, The epidemiology of osteoporosis in Asia. In: Lau EM, Ho SC, Leung S, Woo J, (eds). Osteoporosis in Asia: crossing the frontiers. Singapore World Scientific, 1997:1-20. 11. Orimo H, Nakamura T, Fukunaga M. The Japanese guidelines for prevention and treatment of osteoporosis. (Translated abridged edition). Life Science Publishing, 2006:5. 12. Nevitt MC, Ettinger B, Black DM, et al. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 1998; 128:793-800. 13. Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR, for the Study of Osteoporotic Fractures Research Group. Vertebral fractures and mortality in older women; a prospective study. Arch Intern Med 1999;159:1215-20. 14. Pongchaiyakul C, Nguyen ND, Jones G, Center JR, Eisman JA, Nguyen TV. Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J Bone Miner Res 2005;20:1349-55. 15. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999;353:878-82. 16. Scaf-Klomp W, van Sonderen E, Sanderman R, Ormel J, Kempen GI. Recovery of physical function after limb injuries in independent older people living at home. Aging 2001;30:213-9. 17. Chariyalertsak S, Suriyawongpaisal P, Thakkinstain A. Mortality after hip fracture in Thailand. Int Orthop 2001;25:294-7. 18. Suriwongpaisal P, Chariyalertsak S, Wanvarie S. Quality of life and functional status of patients with hip fractures in Thailand. Southeast Asian J Trop Med Public Health 2003;34:427-32. 19. European Union Osteoporosis Consultation Panel. Osteoporosis in the European Community: Action plan, 2003. 20. Burge RT, Worley D, Johansen A, Bhattacharyya S, Bose U. The cost of osteoporotic fractures in the UK: projections for 2000-2020. J Med Econ 2001;4:51-62. 21. Ray NF, Chan JK, Thamler M, Melton LJ-III. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 1997;12:24-35. 22. Woratanarat P, Wajanavisit W, Lertbusayanukul C, Loahacharoensombat W, Ongphiphatanakul B. Cost analysis of osteoporotic hip fracture. J Med Assoc Thai 2005; 88(5):S96-104. 23. Krall EA, Dawson-Hughes B. Heritable and life style determinants of bone mineral density. J Bone Miner Res 1993;8(1):1-9. 24. Brown MA, Haughton MA, Grant SF, Gunnell AS, Henderson NK, Eisman JA. Genetic control of bone density and turnover: role of the collagen 1alpha1, estrogen receptor, and vitamin D receptor genes. J Bone Miner Res 2001;16(4):758-64. 25. Ralston SH. Genetics of osteoporosis. Rev Endocr Metab Disord 2001;2(1):13-21.
  • 10. 7 26. Taaffe DR, Robinson TL, Snow CM, Marcus R. High-impact exercise promotes bone gain in well-trained female athletes. J Bone Miner Res 1997;12(2):255-60. 27. Kemper HC, Twisk JW, van Mechelen W, Post GB, Roos JC, Lips P. A fifteen-year longitudinal study in young adults on the relation of physical activity and fitness with the development of the bone mass: The Amsterdam Growth And Health Longitudinal Study. Bone 2000;27(6):847-53. 28. Matkovic V, Fontana D, Tominac C, Goel P, Chesnut CH, 3rd. Factors that influence peak bone mass formation: a study of calcium balance and the inheritance of bone mass in adolescent females. Am J Clin Nutr 1990;52(5):878-88. 29. Johnston CC Jr, Miller JZ, Slemenda CW, Reister TK, Hui S, Christian JC, et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med 1992;327(2):82-7. 30. Välimäki MJ, Kärkkäinen M, Lamberg-Allardt C, Laitinen K, Alhava E, Heikkinen J, et al. Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. Cardiovascular Risk in Young Finns Study Group. BMJ 1994;309:230-5. 31. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996; 11(3):337-49. 32. Bouxsein ML, Myers ER, Hayes WC. Biomechanics of age-related fractures. In Marcus R, Feldmen D, Kelsey J. (eds). Osteoporosis. Academic Press 1996, San Diego, CA.
  • 11. 8 Diagnosis and bone mass assessment in osteoporosis II-1 History, physical examination and differential diagnosis 1.1 ก ก ก ก (Classification of osteoporosis) (1) ก ก 1. ก ก 2. ก ก ก F ก ก ก ก ˈ ˆ กก (Primary osteoporosis) F F ˈ (postmenopausal osteoporosis) ก ก F ˈ ก (age-related senile osteoporosis) ก F F F ก ก F F ก F F ก ก ก (Secondary osteoporosis) F ก ก ก F ˈ 2.1 1. − − − − ก F F F Cushing s syndrome hypogonadism F F ˈ F ก F F 2. 3. − ก F F − F ก (heparin, warfarin) − ก ก F กF phenytoin, phenobarbital − ก F ก ก ก − − − ก (malabsorption) F − F ก F 4. − − − multiple myeloma osteogenesis imperfecta ก 2.1
  • 12. 9 II-2 Risk factors for osteoporosis and osteoporotic fractures 2.1 ˆ ก ก ก ก ก ก ก ก (Risk factors of osteoporosis and osteoporotic fracture) ก ก ˆ ก ก F ก F F F F ก ก (bone densitometer) ก (risk assessment) ˈ F FF ก ก ก ก ก ก F ˈ ˆ ก ˆ 1. 2. 3. 4. Fก ก F ก ก ก F ก ก ก ก F F ก ก F ก Fก ก F (2) ก กF ก ก ก ก ก ˆ F F F (Non-modifiable risk factors) ( F 65 ʾ F ) F กF 5. 6. 7. F ก F ก F F ก F กF ก ˈ ก ก ˈ ก F 19 กก./ . F (estrogen deficiency) กF F F gonadotropin releasing hormone (GnRH) analogue F ก F F (Modifiable risk factors) F (inadequate calcium intake) ก (sedentary lifestyle) F F ˈ ก F ก ก (small body build) F ˈ ก ก ก ก ก ก ก ก (fragility fracture) ก ก ก ˆ 1. 2. 3. 4. 5. 6. 7. 45 ʾ (early menopause) F ก กก กก ก F ก ˈ 8. Fก 2.2 ก ก F (propensity to falls) F ก ˆ ก ก ก ก ก ก F ก (impaired vision) ก F FRAXTM Fก ก (Risk assessment of osteoporotic fracture using WHO-FRAXTM) WHO(3) F ก ก ˆ ก ก meta-analysis population-based cohorts ก ˆ ก ก ก ก
  • 13. 10 1. Independent F BMD 2. ก ก 3. adjusts 4. F 5. กก ก F ก , F ก F ˈ ˆ ก ก ก F F F F F F F( ก F F ˆ 9 ˆ F F F ก ก (bone mass density, BMD) F femoral neck BMD ˈ ก F F F (BMI) F ˆ F ˈ F BMD/BMI F F F กก ˈ ˆ F modifiable) F 2.2 F F F BMD F F F F body mass index กF F (yes/no) ก F 2.2 ˆ WHO F FRAXTM Age (yr) BMD(FN) / BMI (T-score or kg/M2) A prior fragility fracture (yes/no) Parental history of hip fracture (yes/no) Current tobacco smoking (yes/no) Ever long-term use of oral glucocorticoids (yes/no) Rheumatoid arthritis (yes/no) Other causes of secondary osteoporosis (yes/no) Daily alcohol consumption of three or more units daily (yes/no) BMD(FN) = femoral neck bone mass density, BMI = bone mass density WHO task force conference held in Brussels, Belgium in May 2004 F กก F ˈ ก ก ˈ F ˈ ก ก ก ก 10 ʾ (10-year probability of fracture) TM F ก FRAX F F F internet http://www.shef.ac.uk/FRAX(4) F TM 10-year probability ก F F website ก FRAX F ก ˁ US-Asian F F ˈ 2 10-year probability of hip fracture 10-year probability of other major osteoporotic fractures F F F ˁ F ก ก F (therapeutic threshold) F ก ˆ F F ˁ F fracture BMD F กF -2.5 Fก F 10-year probability of fracture ˈ ก F F ก F F F ˁ 10-year probability of hip fracture ≥ 3% 10-year probability of other major osteoporotic (5) fractures ≥ 20% ก F ก F ˆ ˆ F ก F F F ก ก F FRAXTM F F ก ก ก ก FRAX TM FRAX ก F F F กF US-Asian Japan F ก ก Asia F F
  • 14. 11 ก F ก ก ก ก F ก Fก ก F NOF 10-year probability of hip fracture ≥ 3% osteoporotic fractures ≥ 20% ก F ก F F ก ก F F F F 10-year probability of other major II-3 Laboratory investigation and bone strength assessments 3.1 ก F F 1. 2. 3. − − − − − 3.2 ก ก ก ก 1. 2. 3. 4. ก ก (Laboratory investigation) ก F ก ก ก ก ก ก ก ก ก ก F F ก Complete blood count (CBC) Serum calcium, phosphate, albumin liver transaminases Serum alkaline phosphatase Renal function (blood urea nitrogen and creatinine) Plain x-rays F ก ก F ก F F (lateral thoraco-lumbar spine) ก ก ก F F (antero-posterior hip) F F F ก ก ก กF ก ก (Bone strength assessment) ก F ก กก ก ˆ ก ก ก (bone mass) ก ก (bone quality) ˆ F F F ก F F F ก F ก กF ก ก Fก F ก ก ˈ ก ก F plain x-ray F F กก ก ก F ก x-ray F ก ก ก F F ก ก F กก F 30% ก F ก F Semi-quantitative method ก plain film x-ray F Singh s index ˈ F F ก F F ก intra-observer inter-observer variation ก F F F Bone mass measurements WHO ก F ˈ ก ก ก ก axial dual-energy x-ray absorptiometry (axial DXA) F Bone mass measurements F F quantitative ultrasonography (QUS) peripheral DXA (pDXA) F F ก F axial DXA ก ก ก F F ก F ก F F ก ก ก F axial DXA ก
  • 15. 12 II-4 Diagnostic criteria for osteoporosis 4.1 ก F ก F ก ก (Measurement of bone density) ก (Bone mass density, BMD) F F F Dual Energy X-ray Absorptiometry ก ก ก ก Fก 2.3 ก Fก F BMD กF F ก -2.5 F F ก ก ก ก ก ก 1.4 - 2.6 F ก 1 F F 2.3 ก ก ก ก ก ก (normal) ก ก F F BMD F F ก -1 F F ก ก (osteoporosis) ก ก (severe/established osteoporosis) F F Caucasian) ก F Fก ก ก ก F F F ก ก F กก F ก F Fก ก F กก F ก ก ก F F ก ก ก F (female reference) ก F F F F F (fragility fracture) F ก ก F (lumbar spine ก F axial DXA F ˈ F ก ก ก F axial DXA F F ก F ก DXA F F F ก ก ก F ก (Asian female reference) ก F ก ก ก F Fก F F F F (8) F F ก 2.3) F F ก F F ก BMD ก L-spine) ก ก ก (hip) F (peripheral DXA) ก F F ˁ F F ก F ก F (T-score ≥ -1) F ก ก ก F -1 F F -2.5 F F F ( -2.5 < T-score < -1) F ก ก กF F ก -2.5 ก F ก ก (T-score ≤ -2.5) F ก ก กF F ก -2.5 ก F ก ก (T-score ≤ -2.5) F ก ก ก ก ก (osteopenia) F F F F F ก ก(6,7) Fก ก FF F (male reference) ˈ Fก F ˈ F ˁ F F ก ก F ( (reference young adult mean) ก กF ก ก F( F F F
  • 16. 13 F F 1. 2. ก F F F 65 ʾ ก F 65 ʾ F 1 F − กF − 4. 5. 6. กF ˆ 45 ʾ (early menopause) F กF 1 ʾ ก F ก F ก F ˈ กF 3 ) ก ก F F ก (estrogen deficiency) กF F F ( F F F F F F 7.5 ก. F ˈ ก ก F ก F ก F 19 กก./ . ก ก ก ก กก F ก F (radiographic osteopenia and / or vertebral deformity by x-ray) ก ก ก ก F F F กF กก ก F OSTA score(10), KKOS score(11) nomogram กก F 0.3 F ( ก 2.2) ( OSTA; Osteoporosis Self Assessment Tool for Asians, KKOS; Khon Kaen Osteoporosis Study score) − − 3. F F − axial DXA(9) F 70 ʾ F ก F 70 ʾ BMD F Quantitative Ultrasound (QUS) QUS ก ก F QUS F QUS F F ก OSTA(10) ก F QUS F ก F (13) F ก ก 4.2 ก (sensitivity) KKOS(11) ก F ก ก F 16) ก F ก F F ก ก F F ก ก F ก ก 3 ก F ก ก F ก ˆ F F ก BMD ก F F ก 1 ʾ F ก F F ก ก (12) ก ก F ก (nomogram) F F ก ก ก ก ก F ก (Biochemical markers of bone turnover) ก F (specificity) ก ก ก ก ก ก ก F F F ก ก ก ก ก ก ก ก (17) F ก ก F ก F ก ก F(14F F F telopeptide (NTx) ก ก ก F กF urinary deoxypyridinoline (DPD), urinary Nserum C-telopeptide (CTx) F ก F ก ก F กF bone
  • 17. 14 specific alkaline phosphatase (BSAP), osteocalcin, C-terminal propeptide of type 1 procollagen (P1CP) N-terminal propeptide of type 1 procollagen (P1NP)(18) 4.3 ก ก ก ก F F ก BMD F F F( (Screening) ก ก F ก F F FF ก 2.1) F axial DXA F ˆ ก F F F ก F ก F KKOS(11) (10) OSTA ก ก ก ก
  • 18. 15 ก 2.1 OSTA (Osteoporosis Self-Assessment Tool for Asians) ก ก ก OSTA index F F F ˈ ʾ OSTA F ก 0.2 X ( ก F F ˈ ก ก F ก F -4 F -4 -1 F -1 ก ก- ) F F F
  • 19. 16 Khon Kaen Osteoporosis study score (KKOS)(13) Age (y) Score Weight (kg) Score < 45 45 - 49 50 - 54 55 - 59 60 - 64 65 - 69 70 - 74 75 - 79 80 - 84 85 89 > 90 + 7.5 + 6.0 + 4.5 + 3.0 + 1.5 0 - 1.5 - 3.0 - 4.5 - 6.0 - 7.5 < 30 30 - 34 35 - 39 40 - 44 45 - 49 50 - 54 55 - 59 60 - 64 65 - 69 70 - 74 75 - 79 80 - 84 85 - 89 > 90 - 14 - 12 - 10 -8 -6 -4 -2 0 +2 +4 +6 +8 + 10 + 12 ก KKOS F KKOS < -1 : KKOS > -1 : F ก ก ก ก ก ( ʾ) ก ก ก (ก ก ) กก ก ก F ก 52 ʾ, ก 48 ก ก KKOS = (+ 4.5) + (- 6) = - 1.5 ..=.. ก 20% ก ก F 80% F กF KKOS F กF ก ก ก ก 21-79% F กF ก F ก ก F กF
  • 21. 18 ก 2.2 ก ก ก ก ก ก F QUS(15) ก ก 1. 2. 3. 4. 5. ก F ก F ก F กก ก (point) กก ก ก (point) ก ก QUS ก (point) 3 ก (total points) ก F กก (total points) ก osteoporosis) 6. ก ก ก ก ก F 0.3 ก ก F BMD F ก ก (risk of ˈ กF ก ก F F 193 ( F F ก 0.5 ( 70 ʾ ก 50 ก ก ก F 4) ก ก ก 1-3 ก F กก F QUS T-score -3 SD 48, 67 193 78 ก Fก ก ก 5) : F ก ก 70 ʾ 50 ก 50 ก ก QUS T-score -3 SD 100
  • 22. 19 ก F 1. Greenspan SL, Luckey MM. Evaluation of postmenopausal osteoporosis. In : Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th ed. Lippincott Raven Press; New York, NY, USA, 2006, pp.268-72. 2. Riggs BL, Melton LJ. Evidence for two distinct syndromes of involutional osteoporosis. Am J Med 1983;75:899-901. 3. Kanis JA, Black D, Cooper C, et al. on behalf of the IOF and the NOF USA. A new approach to the development of assessment guidelines for osteoporosis. Osteoporosis Int 2002;13:527-36. 4. FRAX-WHO fracture risk assessment tool, http://www.shef.ac.th/FRAX 5. NOF(National Osteoporosis Foundation). Clinician Guide for Prevention and Treatment of Osteoporosis 2008. 6. Gallagher JC. The pathogenesis of osteoporosis. Bone Miner 1990;9(3):215-27. 7. National Osteoporosis Foundation. Osteoporosis: review of the evidence for prevention, diagnosis, and treatment and cost-effectiveness analysis. Osteoporosis Int 1998; 8 (Suppl 4):S1-80. 8. World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. No. 843 of Technical Reports Series. Geneva: 1994. 9. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994 ;9:1137-41. 10. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312(7041):1254-9. 11. WHO.1994. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Technical report series 843. Geneva: WHO 12. Koh LK, Sedrine WB, Torralba TP, Kung A, Fujiwara S, Chan SP, et al. A simple tool to identify asian women at increased risk of osteoporosis. Osteoporosis Int 2001;12:699-705. 13. Pongchaiyakul C, Nguyen ND, Pongchaiyakul C, Nguyen TV. Development and validation of a new clinical risk index for prediction of osteoporosis in Thai women. J Med Assoc Thai 2004;87:910-6. 14. Pongchaiyakul C, Panichkul S, Songpatanasilp T. Combined clinical risk indices with quantitative ultrasound calcaneus measurement for identifying osteoporosis in Thai postmenopausal women. J Med Assoc Thai 2007;90(10):2016-23. 15. Pongchaiyakul C, Panichkul S, Songpatanasilp T, Nguyen TV. A nomogram for predicting osteoporosis risk based on age, weight and quantitative ultrasound measurement. Osteoporos Int 2007;18(4):525-31. 16. Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A, et al. Biochemical Markers of Bone Metabolism and Prediction of Fracture in Elderly Women. J Bone Miner Res 2004;19(3):386-93.
  • 23. 20 17. Riis BJ, Hansen MA, Jensen AM, Overgaard K, Christiansen C. Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15 year follow-up study. Bone 1996;19(1):9-12. 18. Riggs B, Melton LJ, O Fallon WM. Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone 1996;18:197S-201S.
  • 24. 21 Prevention of osteoporosis and falls ก ˂ ก ก ก ก ˂ ก F F ก ก F ˈ ก ก ˆ ก F ก ˂ ก ก ก F ก F F (nonpharmacologic strategy) F F F กก F ก ˂ ก F ก F ˈ F F ˈ ก F F ก ก ก ˂ ก ก ก ก F F กก F 50 ʾ III-1 Strategies to maximize peak bone mass ก F Fก 1. ก F ก ก (peak bone mass) F F F ก (weight bearing exercises) ก ก F กก ก ก (resistive exercises) 2. ก 3. ก 4. ก 4.1. 4.2. 4.3. 4.4. 5. 6. 7. 8. Fก F ก F F ก ก ก F ก ก กก ก F F F F กF F ก F ก F กก ก F ก ˈ ˆ ˈ ˆ ก F ก (physical activities) F ก ก F ก ก ก F F 20-23 กก./ . III-2 Strategies to prevent bone loss กF ก F 1. 2. ก ก ก 2.1. 2.2. ก F ก F ก ก F ก F ก ก (rate of bone formation) F ก ก (rate of bone resorption) กF ก F F กF ก ก ก F F F (non-pharmacological management) ˈ F III-1 F (pharmacological management) ก F ก F F กF F ก ˈ ก ก F ก F กF F
  • 25. 22 ก F F (Hormone replacement therapy) 1. ก ก F (estrogen therapy, ET) F (hormone [replacement] therapy, H[R]T) ก ก F F ก F F ˈ F ก ก F F F ก F F F ˂ ก ก ก (1-6) ก F F F F ก F F F F ˂ ก ก 2. ก ก F Women Health Initiative (WHI) study(7) F ก F F ˈ conjugated equine estrogen (CEE) F ก medroxy progesterone acetate (MPA) ˈ 5 ʾ F ก F ก ก ก ก ก ก ก ก ก F 34% ก ก ก ก F 23% 3. ก WHI study F ก F F F F ก F Fก ก F ก F F WHI F ก F ก F F (CEE F ก MPA) F F ก F 10 ʾ ก ก F F ˈ ก F F ก ˈ 7.1 ʾ ก F ก ก F F กF F F F F F F ก F F ก ก ก CEE MPA F F F ก Fก F F / F ก F F ก Fก ก F F F ˈ (8, 9) 4. ก F F ˈ F ก F F ก ก ก ก F F F F F (9) ก F F F 5. ก F Fก ก ก ก ʾ 3% 6% F F ก F F F ก ก ก ก ก ก F (catch-up phenomenon) ก F ก ก ก Fก F F F F (10) ʾ F F F F F F F III-3 Nutritional aspect in osteoporosis Fก F ก F F F กF F ก ก F กF ก ก ก NIH ก F ˈ F (Calcium) 3.1 (11) F ก F
  • 26. 23 3.1 F a Health Consensus Panel ก F Infant Birth- 6 months 6 months- 1 year Children 1-5 years 6-10 years Adolescents/young adults 11-24 years Men 25-50 years Over 65 years Women 25-50 years Over 50 years (postmenopausal) − On estrogen − Not on estrogen Over 65 years Pregnant and nursing F กF National Institutes of Optimal calcium intake (mg/day) 400 600 800 800-1200 1200-1500 1000 1500 1000 1000 1500 1500 1200-1500 ก ก a NIH Consensus Development Panel on Optimal Calcium Intake: Optimal Calcium Intake. JAMA 272:1942-1948; 1994. ก F กF ʾ . . 2545 3.2 F
  • 27. 24 3.2 F F กF ก . . 2545 ก F F ก 0-5 6-11 1-3 ʾ 800 9-18 ʾ 1,000 19-50 ʾ 800 กก F 50 ʾ 1,000 F F F F∗ F ∗ ก ∗∗∗ ก 800 F F ˈ F F F F 1 กF 1 ก F (200 ก ก ก 2545:16-23 ก 230 ) ก . ˁ : F F 702 ก. F ก ˈ F F ก Fก ก F balance study(12) ก 842 ก. F F F F F ก . ก ก F ก. F F กก 788 800 ∗ F ∗∗ ก ) 210 270 500 4-8 ʾ ก ( F F F ก F F ก F F ก 20% 946 ˈ ก. ก ˈ F ˈ Fก ก F ก ก ˆ ก F F F ก F กก ˈ ก FF F ก 3.3 ก ˆ ก
  • 28. 25 3. 3 ( ก.) , กF , กF F กF ก ʽ ก F ก F ˈ F กF F กก , F F ก ก ˆก ก F ก . F 240 150 145 167 156 76 52 106 78 63 30 116 97 240 245 125 469 429 230 49 299 76 17 200 (1 ก F ) 150 (1 ก F ) 1 F F ( ) 1 2 F ( ) 1/2 F ( ) 10 ก 1 1 1 1 1 1 1 กF 10 10 1 10 ˆก 1 1 1 1 4 F F F F .
  • 29. 26 (Vitamin D) 1. 2. 3. 4. 5. ˈ F F F ก F ก ก F ก F ก ก ก F F ก parathyroid hormone ก F ก ก ก F F ก ก ก ก ก F Fก ก ก ก F ก ก ก ก F ก ก (bone formation and mineralization) F F ก กก F กก ก F F F (ultraviolet B, UVB) F F ก F กF ˈ F F F ก ก F Fก ก F F ergocalciferol ( ก ) cholecalciferol ( ก ) F ˈ F F F ก OH group ก OH F 25 ก ˈ 25-hydroxyvitamin D (25(OH)D calcidiol vitamin D2)ก ก ก OH F 1 ก ˈ 1,25-dihydroxyvitamin D (1,25(OH)2D calcitriol vitamin D3) ˈ (active form) ก ก ก F F ก F F กF − ก F 7-dehydrocholesterol ˈ F 3 F F F F − ก ก F F F F ( F F F ก F F F ) − ก Fก F 1,25(OH)2D − ก F F ก ก F F F F F F ก F secondary hyperparathyroidism ก ก ก ก ก ก (13,14) F F F กก ก F F ก 400-800 IU ˈ F ก ˂ ก ก
  • 30. 27 3.4 Food International Units (IU) per serving 1,360 360 345 200 250 98 Cod liver oil, 1 Tablespoon Salmon, cooked, 3 ounces Mackerel, cooked, 3 ounces Tuna fish, canned in oil, 3 ounces Sardines, canned in oil, drained, 1 ounces Milk, nonfat, reduced fat, and whole, vitamin D fortified, 1 cup Margarine, fortified, 1 Tablespoon 60 Pudding, prepared from mix and made with vitamin D 50 fortified milk, cup Ready-to-eat cereals fortified with 10% of the DV for vitamin 40 D, 1 cup servings (servings vary according to the brand) Egg, 1 whole (vitamin D is found in egg yolk) 20 Liver, beef, cooked, 3 ounces 15 Cheese, Swiss, 1 ounce 12 Percent DV* 340 90 90 50 70 25 15 10 10 6 4 4 * DV = daily value. DVs are reference numbers developed by the Food and Drug Administration (FDA) to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for vitamin D is 400 IU (10 µg) for adults. Most food labels do not list vitamin D content unless a food has been fortified with this nutrient. ก ก http://www.usda.gov/cnpp/pyramid2.htm. (Vitamin K) 1. 2. 3. 4. 5. -1 (phylloquinone) ˈ ก -2 (menaquinone) ˈ F F F F ก F phylloquinones phylloquinone ˈ F ก chloroplasts normal flora F F spore-forming Actinomyces spp. F menaquinones F ก F F F ก F F F menaquinone F Fก ˈ passive diffusion ก F F F ก F F ก ก (osteoblast) F collagen matrix osteocalcin ˈ non-collagen matrix osteocalcin F ก F F ˈ osteocalcin F ก ˈ undercarboxylated osteocalcin (ucOC) ก ucOC ก carboxylated F ˈ mature osteocalcin carboxylated osteocalcin (Gla protein) ก F F osteocalcin ก F ˈ F ก ก ก ก F ก ก
  • 31. 28 F ก ucOC ก F ˈ F Fก F F ก F ก F ก ก Fก ก ucOC Fก ก ก ก 6. ก ก ucOC 2.314 ng/mL ˈ (15) F F F ก ก ก ก 2.314 ng/mL) 39.1% F ucOC ก F 2.314 ultradistal radius distal 1/3 of radius 25(OH)D ucOC ก F (p<0.05) 7. F F6 ʾ ก ก ก F ก ก 80 µg F กF 2 ก. F ก ( ˈ กก.) 8. F กF ก ก ก ก ก F F ˈ ก ก F กF F ˈ ก F 3.5 ก ก กF F ก ( ng/mL กF F (mcg/100 g) 817 400 231 205 147 193 141 775 III-4 Life style modification and prevention of falls 4.1 ก ก ก − − − − − − − ก ก F ก F ก ก ก ˈ ก ก F F F ก ก F กก ก F ก ˈ ˆ ˈ ˆ ก (physical activities) F ก ก F ก ก ucOC > F ก ก (Thai RDI) . . 2538 ก 70-140 ก. ก F ก F ก F (Kale) ก (Spinach) ก (Endive) Broccoli ก (Cabbage) Soybean oil Rapeseed oil F (Regular natto) F F F F F F
  • 32. 29 4.2 ก F ˆ ˆ ก ก F F ˁ F ˂ ก ก ก ก F ˁ ก ก ก ก ก ก FF ก ก ก F F ก ก ก ก ก F F ก กก ก Fก ก F F F ʾ F กก F 65 (16) F กก F 80 ʾ ก F กF F ก F ก F 3 F ก ก F กF ก F กF ก (17) กก F 40% F ก F กก F 1 F ʾ F ก กF F ก กF ˈ F F F กก F 5 F F ˁ F F FF ก กก F ก กF F ก ก ก ก ก ก F F ก ก F ˁ F F ก ก ก ก F F ก F F (18) F ก F ก ˈ F F กF ก ˂ ก ก ก F ˈ F ก F ก F F ก F F ˆ F ก ˈ ก F ก ก กF ʾ กF 2-3 F F F ก F ˆ ก ก ก ก F F ก F ก ก ก psychotropic ก F sedative ˆ F F ˈ F 1. F ก ˈ F F ก ก ˆ F ก กF F ก 8-10% F F ˆ ˈ 20) ก ก ก ก ก ˆ (21) F ก ก F F กF ก F กก F Fก 4 F 12% F F ˆ ก 2. ˆ F F F ˁ ˆ ก F F F ก ก ก F ก F ก F F F Fก ˆ F F ก F ˆ ก ก F กก F ˆ F F ก F กF 69-78% F ˆ กก F Fก 4 F multivariate analysis F 3 ˆ F ก F ก ก ก F F F ˆ F ก กF F ก กF ˈ 100% Fก กF ˂ ก F ก ˆ F (19, ˆ − − − − − − − ก กF (22,23) (24) ก ก ก F ก ˆ F ก F (cognitive impairment) (25) ก F (26) (27) F F F ก (25) (27) F ก F ˈ F ˆ F
  • 33. 30 − กF − ก ˆ F /ก (28) (18) กF ก F − F ˂ ก ก (29) F F − − ก ก ก F F F F ก F F ก F F F / ʾ ก F F ˈ F F (30) F (22) ก F ก ˂ ก F ก (frail elderly) F ก F ก F F F ก ก F ก ก ˂ ก ก ก F ก F ก ˈ F 1. F 3 = ก 3 2. F ˁ กF กF F ก F Fก กF กF F (31) falls risk assessment tool F ก ก( , 11-20 = ก , 21-33 = ก F ˁ ก ก กF ก กก F F ก 3.1) ก) F F F F ก F ˈ F (0-10 ก ก ก F กF F F F ก (32) F F F กF FF F Berg balance scale, 180 degree (33) (34) turn, functional reach ก F F F F ก ก ก F timed up & go test (TUGT)(35) F F ˁ ก ก กF ˈ 3 ก ก F (36) F F ก F F ก F ก F F ก F ก 10 3. ก F F ก Fก F กก F Fก 4 (37) F ก กF ก กF F ก ก F ก F 9 F FF F (38) ก F psychotropic F กF F F ก กF FF ก F ˆ ก ก F F F (39) ก ก F F F ˈ ก F benzodiazepine ก กF 44% (40) ˈ ก กF F F F ˁ 4. ก กก ก ก ˆ F กF F ก ก F ก กก ก ˈ ก F ก F F F F ก ˂ ก ก ก F (41) ก ʿกก (balance training) ก กก ก กF (strengthening exercise) ก กก ʽ F (42,43) (cardiovascular fitness training) ก กก ก ก ก F F กF Fก F ˂ ก ก กF ก F ก กก ก F F ก F ก F ก ก ˈ F F ˁ ก ก ( ก 3.2) 5. กF ˆ F F ˆ F F ก ก กF ก F F F ก ก ˈ F ก F ˈ F ˆ F ก กก F F F
  • 34. 31 F counter) F F กF F F F F F 6. ก F F F F กF ก F ก F F F ก ˈ F 7. F ก ก F ˆ F ก ก ก ก F ก 8. F ก ก ก ˂ ก ก F กF F ก ก กก F F F ก F FFF ก ก กF ก F ก F ก F ( F ก F 2.5 . .) F F ก F ˂ ก ก ก F F F F F ก F F ก ก ก F F ก ก F FกF FF F F ก F F F F F กF F F ก F ก ˈ ก F ʾ ก F กF F ก ˆ ก F Fก F Fก ก ก ก ก Fก ก F กF ˆ กก F กF F กF F ˁ / F F ก F F FF ˈ F F ˁ F ˁ F ก ก F (firm heel F กF 1 . . F F F F ˁ ก F F ก ก F ก กF F ก ก F ˁ (44) FF ˆ F F F F F กก กF ก
  • 35. 32 ก 3.1 Falls Risk Assessment tool ก 0 F F 1 ก ก ก 2 8-14 ก 3 กก F 14 F ก F 0-19 ʾ F กF ʾกF ก F F ก ก F ก F F F , F ก 60-70 ʾ กF 3 กF F ก F F 1 F กก F 70 ʾ กF กF F F ก F F F ก F F , ก ก ก , 20-59 ʾ กF 6 กF F ก F F 2 F ก ,ก ก F F, ก ก F ก ก , ก F F ก F , ก F ก ก ˆ ก ก F ก ก F / ˆ ก ก ก F F ก F F F F , , ก F psychoactive β-blocker, ˆ , F F ก กF 1 F ˆ ˆ F 0-10= 11-20= F >1 ˆ ก , ˆ (stress incontinence) ก 21-33= ˆ (urge incontinence), ˆ ก ก Fall prevention: Best Practice Guidelines, Quality improvement and Enhancement Program, version 3, 2003
  • 36. 33 ก 3.2 ก F ˈ − − − − − ก กก ก F กFก F กก F กก F ก F ก ก ก ก ก ก ก ก ก 2 F (weight bearing exercises) F กF ก ก ก F กF กก กF F F กก ก ก F F 3-5 ก F ก กก ก F F (45-49) ก ก F 1-3% ก กก F F F F ˁ F ก F กก ก ก ก ก F F Rotator cuff Pectoralis major Biceps Triceps Wrist flexors wrist extensors Hip extensors Hip flexors Quadriceps Hamstrings Back extensors Abdominal muscles − − − − − − − − − − − ก ก กก ก กก F ก กF ก ˈ กก ก 9% F ก F 20 - 60 F ˂ ก ก F F ก ก ก ก กF F F ก 9% ก ก ก ก F ก F ก Fก F ก กก ก ก F F ก ก ก ก ก กก ก F ก ก 40 F F ก ก กก F 12% ก ก ก กก F ก ก ก ก ก กก F ก F ก กก ก F กก ก 7%
  • 37. 34 ก ˂ ก ก ก F F ʾ 30% F F F 2 กก F 9 F กF 6 ก ก F F 70% ก exercises) F F ก ก ก ก ก ก ก F 65 ʾ ก กF F F กก ก ˈ ก ก F ก ก ก F ก ก F ก ก ก ก ก ก กก F 50% ก ก ก F ˈ กF 6 F ˆ กก ก ก ก F ก กก ก ก ก ก กก ก ก ก ก ก F ก2-3 ʾ F F F F ก (vibratory F ก ก F 1. Bush TL, Wells HB, James MK, et al. Effects of hormone therapy on bone mineral density: 2. 3. 4. 5. 6. 7. 8. results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA. 1996;276:1389-96. Hulley S, Grady 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(7):605-13. Lufkin EG, Wahner HW, O'Fallon WM, Hodgson SF, Kotowicz MA, Lane AW, et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med. 1992;117(1):1-9. Recker RR, Davies KM, Dowd RM, Heaney RP. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women: a randomized, controlled trial. Ann Intern Med. 1999;130:897-904. Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980; 303:1195-8. Wells G, Tugwell P, Shea B, Guyatt G, Peterson J, Zytaruk N, et al.; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women. Endocr Rev. 2002;23(4):529-39. Writing Group for the Women s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA. 2002;288:321-33. The North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006.
  • 38. 35 9. The North American Menopause Society. Estrogen and progestogen use in peri- and 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause 2007. Tremollieres FA, Pouilles JM, Ribot C. Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women. Osteoporosis Int 2001;12;385-901. NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. JAMA 1994;272(24):1942-8. Uenishi K, Ishida H, Kamei A et al. Calcium requirement estimated by balance study in elderly Japanese people. Osteoporos Int 2001;12(10):858-63. Soontrapa Sp, Soontrapa Sk, Chailurkit L. The prevalence and the Calcidiol Levels of Vitamin D Deficiency in the Elderly Thai Women in municipality of Khon Kaen Province, Thailand. Srinagarind Med J 2002;17(4):219-26. Soontrapa Sp, Soontrapa Sk, Pongchaiyakul C, Somboonporn C, Somboonporn W O. Vitamin D deficiency and the risk of osteoporosis in elderly women. Srinagarind Med J 2002;17(3):154-63. Soontrapa S, Soontrapa S, Bunyaratavej N. Serum concentration of undercarboxylated osteocalcin and the risk of osteoporosis in Thai elderly women. J Med Assoc Thai 2005; 88(Suppl 5):S29-32. Rubenstein LZ, Josephson KR, Robbins AS. Falls in the nursing home. Ann Intern Med 1994;121:442-51. Krueger PD, Brazil K, Lohfeld LH. Risk factors for falls and injuries in a long-term care facility in Ontario. Can J Public Health 2001;92:117-20. Lachman ME, Howland J, Tennstedt S, Jette A, Assmann S, Peterson EW. Fear of falling and activity restriction: the survey of activities and fear of falling in the elderly (SAFE). J Gerontol B Psychol Sci Soc Sci 1998;53:43-50. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319:1701-7. Nevitt MC, Cummings SR, Kidd S, Black D. Risk factors for recurrent non-syncopal falls: a prospective study. JAMA 1989;261:2663-8. Robbins AS, Rubenstein LZ, Josephson KR, Schulman BL, Osterweil D, Fine G. Predictors of falls among elderly people. Results of two population-based studies. Arch Intern Med 1989;149:1628-33. Kiely DK, Kiel DP, Burrows AB, Lipsitz LA. Identifying nursing home residents at risk for falling. J Am Geriatr Soc 1998;46:551-5. Gluck T, Wientjes HJ, Rai GS. An evaluation of risk factors for in-patient falls in acute and rehabilitation elderly care wards. Gerontology 1996;42:104-7. Vellas B, Baumgartner RN, Wayne SJ, Conceicao J, Lafont C, Albarede JL, et al. Relationship between malnutrition and falls in the elderly. Nutrition 1992;8:105-8.
  • 39. 36 25. Salgado R, Lord SR, Packer J, Ehrlich F. Factors associated with falling in elderly hospital 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. patients. Gerontology 1994;40:325-31. Oliver D, Britton M, Seed P, Martin FC, Hopper AH. Development and evaluation of evidence based risk assessment tool (STRATIFY) to predict which elderly inpatients will fall: case-control and cohort studies. BMJ 1997;315:1049-53. Morse JM, Tylko SJ, Dixon HA. Characteristics of the fall-prone patient. Gerontologist 1987;27:516-22. Lipsitz LA, Nakajima I, Gagnon M, Hirayama T, Connelly CM, Izumo H, et al. Muscle strength and fall rates among residents of Japanese and American nursing homes: an International Cross-Cultural Study. J Am Geriatr Soc 1994;42:953-9. Mitchell A, Jones N. Striving to prevent falls in an acute care setting--action to enhance quality. J Clin Nurs 1996;5:213-20. Menz HB, Lord SR. Foot problems, functional impairment, and falls in older people. J Am Podiatr Med Assoc 1999;89:458-67. Joanna Briggs Institute: Evidence based practice information sheets for health professionals. Falls in hospital. Best Practice 1998;2:1-6. Berg K, Wood-Dauphinee S, Williams JI, Gayton D. Measuring balance in the elderly: preliminary development of an instrument. Physiother Can 1989;41:304 11. Simpson JM, Worsefield C, Reilly E, Nye N. A standard procedure for using TURN180 to test dynamic postural stability among elderly people. Physiotherapy 2002;88:342 51. Weiner DK, Duncan PW, Chandler J, Studenski SA. Functional reach: a marker of physical frailty. J Am Geriatr Soc 1992;40:203-7. Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991;39:142-8. Kuptniratsaikul V, Dejpratham P, Praditsuwan R. The timed Up & Go: the practical basic mobility skills assessment. Siriraj Hosp Gaz 2006;58:588-91. Koski K, Luukinen H, Laippala P, Kivela SL. Physiological factors and medications as predictors of injurious falls by elderly people: a prospective population-based study. Age Ageing 1996;25:29-38. Nygaard HA. Falls and psychotropic drug consumption in long-term care residents: is there an obvious association? Gerontology 1998;44:46-50. Ray WA, Thapa PB, Gideon P. Benzodiazepines and the risk of falls in nursing home residents. J Am Geriatr Soc 2000;48:682-5. Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med 1989;320:1055-9. Mulrow CD, Gerety MB, Kanten D, Cornell JE, DeNino LA, Chiodo L, et al. A randomized trial of physical rehabilitation for very frail nursing home residents. JAMA 1994;271:519-24.
  • 40. 37 42. Gardner MM, Robertson MC, Campbell AJ. Exercise in preventing falls and fall related 43. 44. 45. 46. 47. 48. 49. injuries in older people: a review of randomized controlled trials. Br J Sports Med 2000;34:7-17. Schoenfelder DP. A fall prevention program for elderly individuals. Exercise in long-term care settings. J Gerontol Nurs 2000;26:43-51. Lord SR, Dayhew J. Visual risk factors for falls in older people. J Am Geriatr Soc 2001;49:508-15. Virvidakis K, Georgiou E, Korkotsidis A, Ntalles K, Proukakis C. Bone mineral content of junior elite competitive weightlifers. Int J Sports Med 1990;11: 244-6. Hartard M, Haber P, Ilieva D, Preisinger E, Seidl, Huber J. Systematic strength training as a model of therapeutic intervention: a controlled trial in postmenopausal women with osteopenia. Am J Phys Med Rehab 1996; 75:21 8. Kerr D, Morton A, Dick I, Prince R. Exercise effects on bone mass in post menopausal women are site specific and load dependent. J Bone Miner Res 1996; 11:218 25. Chow R, Harrison J E, Notarius C. Effect of two randomized exercise programs on bone mass of healthy post menopausal women. Br Med J 1987; 295:1441 4. Heinonen A, Oja P, Sievanen H, Pasanen M, Vuori I. Effect of two training regimens on bone mineral density in healthy perimenopausal women: a randomized controlled trial. J Bone Miner Res 1998; 13: 483 90
  • 41. 38 Treatment of osteoporosis IV-1 Goal of osteoporosis treatment 1.1 ก ˂ ก ก ˂ ก ก ก F F F F ก ก Fก กF ก ก ก ก ก ก ˂ ก F Fก ก ก ก F ก ก ก F ก 3 1. 2. ( ก ก F ก. ก . ก . ก F F interventions F ˁ F ก ก ˈ ก F ก ก F F F / F ก F ก ก ก F ก ˈ ก ก F ก F ก ก ก ก ก ก Fก ก ก ก ก ก ก กก ก ก F ˁ ก 3. Fก ก ก Fก 1.3 ก ก ก ก interventions กF F ˈ ก ก ( ก Fก F II-4) F / ก ก ก ก ก ก ก F F F F ก ก ก ก ก ก ก ( ก) F F F ก F 1.2 ก กF F F ˈ F ก ก ก ก F F F ก ก ก ˂ ก ก ก F ก ก ก ก ก ก ก ก ก interventions ก F II-4) ˈ ก ก Fก ˂ ก ก ก ก ก ˈ F F ˂ ก ก F Fก ก ก ก F ก International Osteoporosis Foundation ก ก ก interventions F ก F anti-fracture efficacy Fก F F National Osteoporosis Foundation ก Fก Fก F F case finding strategy Fก F F ก ก 2 Fก ˈ F 1. International Osteoporosis Foundation F F F clinical risk factors (CRFs)(2) ʾ . . 2007 Fก ก F F F F ˈ (1) ˈ ˆ
  • 42. 39 ก ก ก ก 10 ʾ II-2 2. National Osteoporosis Foundation FRAX tool ก ก ก ก ก 10 ʾ ก ก ก F Fก ก Fก ก F ˁ F ก a. F F F 50 ก b. F F F 50 DXA ก ก ก ก 1.4 ก Fก ก F F F F F ก neck BMD ก ʾ . . 2008(4) F Fก ก F ก ≥ 3% ก F F F ʾ ก ʾ ก F ก F guideline F F F ˈ ก ≥ 20% ก Fก F FRAX ก ก ก ก ก ก ก ก F ก ก F F T-score ≤ -2.5 SD F ก Fก > 50 ʾ F F F F F F ก F F ก F F ก (Primary indication) F 1. 2. ก ก F FRAX(3) ก F F Fก ก F F F ก ก ก ก ก ก F F ก ก F axial DXA lumbar spine BMD total hip BMD F F T-score ≤ -2.5 femoral (Secondary indication) F ก ก ก ก ก ก ก F ก ก F axial DXA F F ก Fก ก (T-score < -1.0 F >-2.5 lumbar spine BMD femoral neck BMD total hip BMD) ก F ก ก ก F ˆ F F F F F F 1 F 1. ก ก ก F F F ก ก F 40 ʾ F ก F Fก ก ก ก ก F ก ก F ก (wrist fracture) ก ก ก ก (pelvic fracture) ก ก F ก (distal femur or proximal tibial fracture) ก ก F (proximal humeral fracture) ก ก F F (ankle fracture) 2. F glucocorticoid F prednisolone 7.5 ก. ก F 3 3. ˈ Fก secondary osteoporosis F type-1 DM, thyrotoxicosis, rheumatoid arthritis, SNSA(seronegative spondyloarthropathy) US-Asian Japan F F BMD F F 10 4. F FRAXTM year probability of hip fracture ≥ 3% 10 year probability of other major osteoporotic fractures ≥ 20% 5. clinical risk factors(CRFs) F F2 F ก. ˈ F ≥ 65 ʾ F ≥ 70 ʾ . ก < 19 กก./ .
  • 43. 40 . . . . F กF ก ก ก ก ก ก 45 ʾ ˈ ˈ ก ก Fก ก ก F ก ก ก F F ก axial DXA F F F F F − CRFs F − ก F ก ก F F ( ก ก axial DXA) ก F F ˆ ก ก กก ˈ ก F F F F F ก ก F ก ก axial DXA F F F F ˁ F Fก ก ก F F 1. ก ก ก ก ก ก 2. ก ก ก F ก F F F 65 ʾ F F 70 ʾ F ก ก ก F F ก F ก ก ก ก F − TM US-Asian F ก ก ก ก ก กก F FRAX − Japan F F BMD F10 year probability of hip fracture ≥ 3% 10 year probability of other major osteoporotic fractures ≥ 20% F IV-2 Pharmacological treatment of osteoporosis ก ก F ก ก ก ก ก ก ก ก F ก ก (potential adverse events) F ˁ F ก ˂ ก ก ก ก ก ก ก ก กก ก F (clinical trial) F ก F F ก F ˁ ˈ ก F ก ก ก ˂ ก (efficacy) F ก F F ก (tailor therapy) F Fก ก ก ก F ˈ anti-fracture efficacy(5) Anti-fracture efficacy ก ก F F ˈ clinical trial phase-III F F F F ก ก ก ก ก F ก placebo (relative risk reduction) F ก ก F bisphosphonates BMD ก bisphosphonate ก F dose F BMD F F ก F ˈ (control) F F anti-fracture efficacy F placebo F ก ก ก ก F bridging study F ก F dose ก
  • 44. 41 2.1 ก ก ก (Inhibitors of bone resorption) Bisphosphonates 1. Bisphosphonates ˈ ก F ก ก ก ก ก F ˆ F ก F bisphosphonates F ก ˈ ก F F ก F (5) simple bisphosphonates กF nitrogen-containing bisphosphonates 2. F ก F nitrogen-containing bisphosphonates action ก osteoclastic bone resorption F กF กก F ˆ ก F bisphosphonates F ก F ก ก F Fก ก ก Alendronate (10 ก.) Risedronate F8 F ก (5 ก.) ( ก ) Alendronate Once Weekly (70 ก.) Risedronate Once Weekly (35 ก.) ( F ) Ibandronate Once Monthly (150 ก.) ( ) ก Alendronate plus ˈ Alendronate 70 ก. ก Cholecalciferol 2800 iu F F F ก ก2 F ˈ F F F Ibandronate injection (3 ก.) (IV infusion F F ก ) Zoledronate injection (5 ก.) (IV infusion F F ʾ ) / 1. ก ก 2. ก ก F ก ก F ก ก F กF F 30-40% ก F Fก F ก (6,7) F F ก ก ก Fก F ก ก ก ก ก F ˈ F ก ก F F F ก F 3. ก ก F 55 ʾ F 60 ʾ 4. F invasive breast cancer(8) FF ก ก F F ก ก F F F ก F กF ก (premature menopause) F ก ˂ ก ก ก ก F F ก ˈ Fก F ˈ F ก ก cardiovascular diseases, stroke F ก F F ก F ˂ ก ก Selective estrogen receptor modulators (SERMs) 1. SERMs ˈ F F steroid ก estrogen receptor ก F (agonist) ก F (antagonist) ก F ก raloxifene ˈ SERM ˆ ก ก F F ก ก ก F 2. ก ก ก F raloxifene ˂ ก ก ก ก F F ก ก ก ก F 30 50% F ก ก F ก ก
  • 45. 42 (9) F ก ก ก ก F F F F กF F cardiovascular diseases raloxifene 3. Raloxifene F 60% F F Nasal spray calcitonin 1. Calcitonin ˈ F F C-cells receptor F osteoclast Fก ก (12) 2. กก ก F salmon calcitonin F ก ก ก ก ก F ก กF ก (RR = 0.64) F ก F ก ก F vertebral fracture hip fracture F 3. Salmon calcitonin F ก (13) กก ก ก F NSAIDs 2.2 ก 1. 2. 3. 4. F ก F ก ก ก ก กF ก กก ก Fก ก stroke(10,11) F F กก ก F ก F F invasive ก calcitonin ก ก F ก 100, 200, 400 IU ก F 36% ก F F calcitonin 200 IU F ก F ก F 100 IU 400 IU F calcitonin F ก nonFก F ก ก ก ก F ก F F (Stimulators of bone formation) Recombinant human parathyroid hormone 1-34 (Teriparatide, TPTD) ก ก prospective, randomized, double-blind, multinational, placebo-controlled F ก ก ก F F 1,637 (14) TPTD ก F ก ก ก ก ก F F 3 ʾ F ก F ก F TPTD 20 ก. (n = 541) ก F F TPTD 40 ก. (n=552) ก F F placebo (n=544) F TPTD 20 ก. F ก ก ก ก ก F 65% F ก ก non-vertebral fracture F 53% ก ก ก meta-analysis(15) F ก ก F ˁ ก ก ก ก ก F F TPTD 20 ก. 40 ก. F ˁ ก F กก F กF ก ก ก F bisphosphonates hormone therapy ก carcinogenicity study Fischer 344 F TPTD 24 20 F F F ก F 20 ก Fก F (70-80% F ) F F ก ก osteosarcoma ก dose (16) dependent F ก F F ก osteosarcoma F TPTD 25 (14) ก ก ก TPTD F F 20 ก. ก F F ˈ กF ก F F F F กF F F F ก ก กF 2 ʾ ก TPTD ˈ ˈ F F F potential side effects กก F ก F ก ก ก F F ก F
  • 46. 43 F F F 1. 2. 3. 4. ก F teriparatide ก ก ก ก F ก ก ก ก F ก ก ก ก ก F F ˁ F F 65 ʾ F F F F F F F BMD T-score axial DXA ก ก F ( F ก) F(lumbar spine BMD) ก ก ก(femoral neck or total hip BMD) ≤ -2.5 SD F ก ก ก ก ก ก ก ก F2 F BMD T-score axial DXA ก ก F ( F ก) F(lumbar spine BMD) ก ก ก(femoral neck or total hip BMD) ≤ -2.5 SD F ก ก ก ก ก ก ก ก ก BMD T-score axial DXA ก ก F ( F ก) F(lumbar spine BMD) ก ก ก(femoral neck or total hip BMD) ≤ -3.5 SD F ก ก ก ก ก ก ก ก 1 F ก FFก ก ก F bisphosphonate F F (inadequate(17) response) ก F F • vertebral fracture ก F1 F กก F vertebral fracture F ก ก ก ก ก กก F F F ก ก กก F 2 ʾ F • Lumbar spine BMD ʾ ≥ 3% ก (total hip femoral neck BMD) F ʾ ≥ 5% ( Fก ก F least significant change-LSC)(17,18) ก ก กก F 2 ʾ F F 4 F ก ก ก 2.3 กF F F ˁ F bisphosphonate F ก F F F (patient with good compliance and persistence) F teriparatide F F F F IV-4-7.5 F ก (mixed action agents) Vitamin D and vitamin D analogue 1. F ก Fก ก ก ก ก Fก F F ก F F F F กF 800 IU (19) F ก calcium F กF 1,000 ก. 2. ก F FF ก ก F ก ก hip fracture nonvertebral fracture F ก F (< 20%) F F vertebral fracture F (19) 3. F F ก F ˁ F F ก ก F F ก ก ก ˈ F F F Menatetrenone 1. ก F F ˁ high vitamin K intake ก ก ก ก ก ก F ก F F low (20,21) (22) vitamin K intake F low vitamin K intake BMD ก F 2. Menaquinone-4 menatetrenone ก ก ก ก ก F 50% F (23,24) Fก non-vertebral fracture F
  • 47. 44 3. F spine F (25-27) menatetrenone 45 maintain BMD BMD undercarboxylated osteocalcin F F 1,500 ก. ก. F ก Lumbar (25-28) Strontium ranelate 1. ก ก strontium ranelate (SR) ก F ก ก ก ก ก ˈ 3 ʾ F ก ก ก ก ก F F (29) 40-50% 2. ก ก ก F non-vertebral fractures F 16% F F hip fractures 36% ก F F strontium ranelate (30) ก ก 3. ก ก ˈ integrated analysis(31) F strontium ranelate ก ก ก ก F F กF (>80 ʾ) F 32% nonvertebral fracture F ก F 31% ก ก ก ก ก F F กF ˈ (32) F osteopenia 30-50% ก F ก ก ก ก F ก F ก ก F ( F ˈ F F กF F F FF ก F III-3) F / ก F F ˁ ˈ กF F ก F F ˁ F F ก ก F F IV-3 Alternative therapy and non-pharmacological treatment 3.1 Hip protector ก ก F F ก F nursing home ˆ fracture F F hip protector ก compliance ก F ก ก hip (33-35) IV-4 Potential adverse events, prerequisites and contraindications in using anti-osteoporotic agents 4.1 F F F F F F (36,37) ก − ก Fก ก ก F ก F F ก F ก ก F ก − ก F ก ก ก F ก F ) F ก ˈ ก ก (38) (36,37,39) ( F ก
  • 48. 45 F F F ˆ F F active form (40,41) − ก ก ก F F ก F ก F ก ( F ก ก − (42,43) F − F (43) F ก − ก − ก F ก ˈ F − F ก F F (43,45) F F F กก F F ก กF (43,44) F ก F F F F ก F กF ก ก F (46) กF F กF F F (cognitive (48-51) (dementia) F ก F ก ก F กF ก ก ก F ˁ F ก ˈ F F F mammogram ก Bisphosphonates − F ) F F ˁ − F / ก F กก F ก F ก ก − F F F F ก F calcitriol F F กF F F ก F function) F F (47) F ก ก ก F F กF F F ʾ F F F F alendronate, risedronate ibandronate ˈ ibandronate zoledronate F F ก F F non-ulcer dyspepsia ก (52) F ก ก atrial fibrillation ก F F ˁ F F ก ก F F ก ก F F ˈ F ECG กF ก F bisphosphonate กก F ก F ก ก Fก ก F F F − ก ก ก ก ก ก ก ก (osteonecrosis of the jaws) F ก F ก ก ก F bisphosphonate F ก ก ก F ก ก F ก ก ก ก F ก (53) F F กF ˈ F F F ก ก ก ก ก F 10 F ก F ก ก ก F ˈ F ˆ กF ก F − ก ก ก ก ก ก (atypical fracture) ก ก F F bisphosphonate ˈ ( >5 ʾ) ก ˈ low-energy trauma fracture ˈ transverse configuration subtrochanteric shaft of
  • 49. 46 femur (54,55) F F F ก ก F ก F ก ก F F กF ก ˂ F กF ˈ กF − ก F (post-dose reaction) F F (56,57) bisphosphonate ก F ก F ก F กF F F ˈ F F ก ก F ก ก F ก F F F ก 2-3 − ก F bisphosphonates F ˈ oral form F ก F ก ก ก. F F F F F F ก ก F F ก 1 F ก ก . ก F F ก F ก F ( F ก ก F F ก ) F ก ก ก F ก ก Fก ก ก F . F กก ก F F ก ก F F ˈ 1 F ก ก bisphosphonates ก ก F F F Fก ก F (esophagitis) ก F bisphosphonates F ˈ IV infusion F F F − F ก infusion F F F F ก F 15 ก F ก F ˁ F ˆ ก ก F ≥ 30 mL/min ( ˈ creatinine clearance ก F) F ก infusion F ˈ F F F F F Raloxifene − ก ʾ ก F F ก F ½ F ½ F ก F F F F GFR ก F (venous thromboembolism) F F F F ก (59) hot flushes ก ˈ (58,59) F กF ก Strontium F F F F F ˈ − F ก ก F − (61) thromboembolism) F Teriparatide F − ก ก ก − 5 ʾ ก F F F F F F ก F F F (60) F (venous F ก ก F ˆ (62) F ก F F ก (29,30,61) F ก F 2 ก F F ˁ ˈ F กF F(63,64) F F F
  • 50. 47 (16,65) ก F teriparatide ˈ กก F 20 F ก ก osteosarcoma F ก ˈ ก F 20 F F F ก Fก F (70-80% F ) F F F F ก ก osteosarcoma ก F teriparatide F 2 ก − F (66,67) ก F ก Fก ก F F F F F ˁ ก ˈ กF F ก ก (67) osteosarcoma กF ก ก ก 2 ก F F teriparatide ก ก F 500,000 F ก กF ก F ก ก osteosarcoma F (66) > 60 ʾ ʾ 1 F 250,000 F F F F F กก F ( F กก F ) F F ก ก ก ก (68) F F F − (prerequisite) ก F teriparatide ก. F F F F teriparatide ก 2 ʾ . F F F ˁ F ก ก osteosarcoma F ˈ Paget s disease F F ก ก ก F alkaline phosphatase F F ก epiphysis F ʽ . F F F F ˁ ˈ 5 ʾ . ก ˈ F F F ก F teriparatide ˈ F ก กF F F serum creatinine, serum calcium intact PTH F ก − ก F ก Calcitonin − ก F Menatetrenone F − F ก F (23,70) F F ก ก F F (12,69) F ก F F F warfarin ก F warfarin IV-5 Monitoring treatment and duration of treatment 5.1 ก ก (effectiveness) ก ก ก ก ก ก ก ก F ก 1. ก ก F ˁ F F ก ก ก ก ก ก F 2 F (adverse events) F F ˈ F F (drug response) ก ก ˂ ก ก F ก ˆ F ก F ก ก F ก F ˈ ก F F
  • 51. 48 ( Fก ก F ˁ F ก ก F 1.1. ก ) ก ก ก F F ˆ ก ก ก F ก F F F F กF F FF F2 axial DXA กก F BMD F F F F ก กF F F F ก 2 F F F กF 1 ʾ axial DXA F ˈ F กF F ก ก F ก กก BMD F axial DXA ก กก F F F Lumbar spine BMD F ʾ ≥ 3% (17,18) total hip BMD femoral neck BMD ʾ ≥ 5% Fก ก กF 1 ʾ F F ก BMD ก F ˁ F F (probable inadequate response) Fก BMD F ก ก F ก F F F F F ก F ก ก ก กก F ก ก F ก ก BMD กก F ก F ก F ก F F ˁ F F (inadequate response) 1.2. ก F bone turnover markers กก F ˈ ก ก ก F bone resorption marker F F ˈ ก F ก F ก ก F bone formation marker F F F ก 2 กF F ˈ F F F F F กF 3 ก F bone turnover markers (BTMs) F กก F 30-40% F ก ก กก BTMs variation กก F ก F กF ก F NPO F ˁ 12 . . กF F F F (7.00-9.00 .) F ˈ F ก ก 2. ก ก F ก F ก F ˁ F F ก F F (compliance) ก F (persistence) ˆ F F ก ก F ก ก F ก F F F ก ก ก ก F F ˁ F F ก F กF Fก F ก F F F F F F F ก F F F 80% ʾ (medication possession ratio: MPR ≥ 80%) 5.2 BMD ก F F ก F ก ก F ก F ก กF Fก ˆ F F ˆ F ˆ ก F ก F ˁ ก F ˈ clinical trial กก ก F F F ก ก ก ก ก F ˁ F กF F ก ˆ ก ˆ F FF ก ˈ F F F ก ก ก F ˁ ˈ F ก F F F ก clinical study F ก ก ก F anti-fracture efficacy F ก F ก 5 ʾ F( ก F) F F ˁ F F ก F (good compliance and persistence) F new fracture ก F F
  • 52. 49 ก BMD axial DXA ˆ ก F ˁ F ก F BMD F F F ˁ / F BTMs ก 1-2 ʾ 5 ʾ F F ก F ˁ F ก ก ก F ก F ˁ ก ก F กก ก ก (drug holiday) F ˁ ก F ก F F
  • 53. 50 4.1 Alendronate 10 mg (ALN) ก ก F Benefit and Indication for use ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) - F ก ก ก ก ก ก ก F F (Glucocorticoidinduced osteoporosis, GIO) - F ก ก ก ก F (Male idiopathic osteoporosis, MIO) ˂ ก ก ก ก F F ก F F ก ALN 10 mg Alendronate once weekly 70 mg (ALN-OW) Alendronate ˂ ก plus F F ALN 70 mg mg + Cholecalcifer ol 2800 IU (ALN-plus) ก ก ก F F ก ก ALN 10 ก ก ก F F ก ก(71-74) ก (vertebral fracture),ก ก ก (hip fracture) ก กF ก กก ก (nonvertebral fracture) - F ก - F - F ก ALN 10 mg(75) F - F ก ALN 10 mg - F F - ก F vitamin D3 2800 IU F F = 400 IU/d F กF ˆ hypovitaminosis D vitamin D deficiency(76)
  • 54. 51 Risedronate 5 mg (RIS) Risedronate once weekly 35 mg (RIS-OW) Ibandronate Once monthly 150 mg (IBN-OM) Benefit and Indication for use ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) - F ก ก ก ก ก ก ก F F (Glucocorticoid-induced osteoporosis, GIO) - F ก ก ก ก F (Male idiopathic osteoporosis, MIO) ˂ ก ก ก ก F F ก F F ก RIS 5 mg F - Fก ก ก ก (vertebral fracture),ก ก ก (hip fracture) ก กF ก ก ก ก (non-vertebral fracture) - F (77,78) - F - F ก RIS 5mg(79) F F ก ก(80,81) ก ก (vertebral fracture), ก กF ก ก (82) ก ก (non-vertebral fracture) - F Zoledronate ˂ ก ก ก ก F ก ก(56,57) infusion F F ก F ( US-FDA) ก ก (vertebral fracture), ก ก ก ก ก (hip fracture) ก ก every 1 year - F ก ก 5 mg (postmenopausal F ก กก ก (ZOL) osteoporosis, PMO) (non-vertebral fracture) - F ก ก ก ก ก ก - F F ก1 ʾ ก F F(Glucocorticoidinduced osteoporosis, GIO) * Ibandronate F ก F ก ก ก ก (vertebral fracture) ˈ ก ก RCTs F ก F ก ก ก ก F ก กก ก (non-vertebral fracture) ˈ ก กก synthesis data ก pooled analysis RCTs ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) -
  • 55. 52 Estrogen Benefit and Indication for use ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) Raloxifene (RLX) 60 mg Calcitonin nasal spray 200 IU/puff ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) ˂ ก ก ก ก F F ก F ( US-FDA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) Menatetrenone (MK-4) 15 mg ก ก ก F F ก F ( Japan FDA) - F ก ก ก ก F ก ก ก ก - F ( preparation F ก ก F ก ก(6,7,8) (vertebral fracture), ก (hip fracture) ก F F efficacy) F ก ก(9,83) (vertebral fracture) - F F ก ก(12) ก ก (vertebral fracture) - F ก กก ก (13) ( Fก 8 ก ก ก ก F) - F ก - ก - F ก F ก ก(23) (vertebral fracture) 3 (45 mg/d) (postmenopausal osteoporosis, PMO) ** ก F ก ก ก WHI F ก ก ก ก (vertebral fracture) ก ก F ก กก ก (non-vertebral fracture) ˈ ก F conjugate equine estrogen F F extend ก F preparation ก
  • 56. 53 Strontium ranelate 2 g/sachet Benefit and Indication for use ก ก ก F F ก F ( EMEA) - F ก ก ก ก (postmenopausal osteoporosis, PMO) Teriparatide 20 µg/inject F ก 1,200 mg/d (Elemental Calcium) ก ก ก F F ก F ( US-FDA) - F ก ก ก ก F F ก ก(29,30) ก ก (vertebral fracture) ก กF ก ก ก ก (non-vertebral fracture) - F - F ก ก(14,15) ก ก (vertebral fracture), ก ก ก (hip fracture) ก กF ก กก ก (non-vertebral fracture) - F F - (postmenopausal osteoporosis, PMO) - F ก ก ก ก ก ก ก F F (Glucocorticoid-induced osteoporosis, GIO) - F ก ก ก ก F (Male idiopathic osteoporosis, MIO) F ˁ ก ก F F (84) F ˁ F ก F ก ก F F ˂ ก ก ก ก ก ก ก
  • 57. 54 Benefit and Indication for use F ˁ ก FF ก 400-800 ก F F IU / d F F F ก ก ก ก ก ก ก F F -Alphacalcidol (Glucocorticoid-induced (0.5-1 osteoporosis, GIO) (86,87) ก F FF ก ก ก ก ก F ) -Calcitriol ก F (88,89) (0.25-0.5 ก ( ≥ 65 ʾ) ก F ) ก F FF ก ก ก F F ก FF ก F F (85) ก ก ก F - ก ก hypercalcemia (88) hypercalcicuria F 1. Kanis JA, Seeman E, Johnell O, Rizzoli R, Delmas P. The perspective of the international osteoporosis foundation on the official positions of the international society for clinical densitometry. J Clin Densitom. 2005;8(2):145-7. 2. Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, et al. Assessment of fracture risk. Osteoporos Int. 2005;16(6):581-9. 3. FRAX-WHO fracture risk assessment tool, http://www.shef.ac.th/FRAX. 4. NOF Clinician s Guide to Prevention and Treatment of Osteoporosis 2008. 5. Russell G, Xia ZD, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, et al. Bisphosphonate: an update on mechanisms of action and how these related to clinical efficacy. Ann NY Acad Sci 2007;1117:209-57. 6. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of non-vertebral fractures: a meta-analysis of randomized trials. JAMA 2001;285:2891-7. 7. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women s Health Initiative randomized trial. JAMA 2003;290:1729-8.
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  • 59. 56 21. Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon D, Cupples LA, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 2000;71:1201-8. 22. Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, et al. Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr 2003;77:512-6. 23. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis. J Bone Miner Res 2000;15(3):515-21. 24. Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the Prevention of Fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2006;166(12):1256-61 . 25. Purwosunu Y, Muharram , Rachman IA, Reksoprodjo S, Sekizawa A. Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia. J Obstet Gynaecol Res 2006;32(2):230-4. 26. Ushiroyama T, Ikeda A, Ueki M. Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women. Maturitas 2002;41:211 21. 27. Iwamoto J, Takeda T, Ichimura S. Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis. J Orthop Sci 2000;5:546 51. 28. Bunyaratavej N, Penkitti P, Kitimanon N, Boonsangsom P, Bonjongsat P, Yunoi S. Efficacy and safety of menaquinone-4 in postmenopausal Thai women. J Med Assoc Thai 2001;84(suppl2):S553-9. 29. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350(5):459-68. 30. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis; Treatment of Peripheral Osteoporosis (TROPOS) Study. J Clin Endocrinol Metab 2005;90(5):2816 22. 31. Seeman E. Strontium ranelate: vertebral and non-verttenral fractures risk reduction. Curr Opin Rheumatol 2006;18(suppl1):S17-20. 32. Seeman E, Devogelaer JP, Lorenc R, Spector T, Brixen K, Balogh A, et al. Strontium Ranelate Reduces the Risk of Vertebral Fractures in Patients With Osteopenia. J Bone Miner Res 2008;23:433 8. 33. Van Schoor NM, Smit JH, Twisk JW, Bouter LM, Lips P. Prevention of hip fractures by external hip protectors: a randomized controlled trial. JAMA 2003;289(15):1957-62. 34. Birks YF, Porthouse J, Addie C, Loughney K, Saxon L, Baverstock M, et al. for the Primary Care Hip Protector Trial Group. Randomized controlled trial of hip protectors among woman living in the community. Osteoporos Int 2004;15(9):701-6.
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  • 64. 61 85. 86. 87. 88. 89. Osteoporosis Australia and the Endocrine Society of Australia. Med J Aust 2009;190:316 20. Richy F, Schacht E, Bruyere O, Ethgen O, Gourlay M, Reginster JY. Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int 2005;76(3):176-86. Richy F, Ethgen O, Bruyere O, Reginster JY. Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 2004;15(4):301-10. de Nijs RN, Jacobs JW, Algra A, Lems WF, Bijlsma JW. Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D3 analogues: a review with metaanalysis of randomized controlled trials including organ transplantation studies. Osteoporos Int 2004;15(8):589-602. Avenell A, Gillespie WJ, Gillespie LD, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2009;15(2):CD000227. Ringe JD, Schacht E. Potential of alfacalcidol for reducing increased risk of falls and fractures. Rheumatol Int 2009;29(10):1177-85.
  • 65. 62 Glucocorticoid-induced osteoporosis (GIO) V-1 Introduction and epidemiology 1.1 ก F F (glucocorticoids) ˈ Fก ก ก inflammatory immunosuppressive ก F ก ก F F (rheumatic disease) ˈ F F F ก ก F F F F ก F F ˈ Fก ก ก ก ˈ F ก ˈ F secondary osteoporosis ก ก F ก F F F ก ก ก ˈ 1.33 F non-vertebral fracture 1.61 F ก ก ก ก F ก ก ก ก ก F Fก (1,2) F ก ก F F antiFก ก 2.6 ก ก 1.2 กก ก 3% ก ก F 1 70 ( 3 ʾ(4) (3) ก F ก ก ก ก Fก กก F F ก 1.4%) กก F 50 ʾ ก F ˁ กก F 55 ʾ F F ก F F 3 F ก F ก กก F 6-12 ก F ก ก กก ก ก ก ก ก ก F F ก ก ก 5% ʾ ก 1-2% ก ก Fก ก F F F (daily dose) F ก F ก (5) F ก 1F F ก F F F ก ก trabecular ʾ F ก ก F (cumulative dose) (6,7) V-2 Pathophysiology and risk assessment 2.1 ก กก ก glucocorticoid-induced osteoporosis (GIO) F F F ก ˆ F ก F F F F ก ก (8-9) GIO ก ก ก ก ก ก F ˁ F F F ก ก Fก F F ก (10-11) F F F ก ก ก กF F F Fก ˂ ก ก F ก F ก F F ก ก ˈ F F ก F (8) F ก F Fก ก ก F F F F F ก F F ก ก ก (ankylosing spondylitis) ˆ ก F F กF ก F (12) ก กกF F
  • 66. 63 ก ก ก F F Fก ก ก ก ก Fก F ก ก ก (14) ก ก F ก secondary hyperparathyroidism ก ก F (15) (16) ก F ก ˆ ก F F ก ก (osteoblast) F ก ก (apoptosis) osteoblast F ก ก (osteoclast)(14,17) receptor activator NF-KB ligand (RANKL) osteoprotegerin (OPG)(18) ก ก (19) hypothalamic pituitary gonad axis ก F F testosterone(20) adrenal androgen(21) F ก F ก ก F ก F F ก ก ก ก (13) 2.2 ˆ ˆ ก ˆ ก ก ก ˆ F ก ก ก ก ก F F F ˆ F F กF ก (≥ 65 ʾ)(22) body mass index) F ˈ Fก ก (25) (chronic lung disease) F F ก ก กก F ก ก F ก F F ก ก ก ก ก F ก F T Score < -1.0 F F ก ก F F ก ʾ ก guideline ก F ˁ F ก F F ก ก กก F ก F ก F ก ก F F ก ก ก ก ก (23-24) (low ( F F ก F) (26) F (organ transplantation) F ก F กF F F F F F ˁ F F ก ก กF F ก F F ก 10% 1 standard deviation (SD) F 1 F F T-score < -1.0 ˈ F F ก ก V-3 Diagnosis ก ก ก score ≤ -2.5 SD ก ก ก กก F ก ก F F L-spine, femoral neck F F F F ก total hip ˈ ก ก F ก F F ก BMD T- V-4 Prevention and treatment 4.1 ก ก ก ก 1. ก 1.1. ˂ ก F ˂ ก ก ก F ก F F F 1.2. กก ก F 1.3. ก 1.4. ˂ ก ก ก F ก ก ก กก ก ก ก ก F F F F ˁ F ก กก F F F ก F ก F ก F F F ก F F ˈ
  • 67. 64 1.5. F F calcium 1.6. F F 2. ก F F F F 800 IU F F F ก F ก ก F3 F F 1,200 ก. F Fก ˆ F F ก elemental 7.5 ก. ก BMD T-score ก F -1.0 F F ก F F F ก 4.1( IV) (27-29) 2.1. ก F ˈ ก 2.1.1. Alendronate 2.1.2. Risedronate 2.1.3. Zoledronate 2.2. ก F ˈ ( F F F ก F ก F)(27,28) 2.2.1. F F alphacalcidol, calcitriol 2.2.2. F 2.2.2.1. Estrogen replacement therapy premature menopause 2.2.2.2. Testosterone replacement therapy F testosterone (30) ก ก ก ก ก 2.2.3. Teriparatide F F ก F ก ก F F bisphosphonates F F F ก F IV-2 2.2 (Teriparatide, TPTD) 2.3. SERMs, calcitonin, menatetrenone strontium ranelate evidence F ก Fก ก ก ก ก F F F ก F F V-5 Monitoring treatment 5.1 ก 1. ก ก ก ก F ก bisphosphonates F ก ก F 2. ก ก ก F ก F (31) กก F ก F F ก ก ก 6-12 F F 1 ʾ ก F ก ก ก ก F F ก F F ˁ ก F ก F ก F ก ก F ก กF F ก F กF