Glucocorticoid-Induced Bone Disease (Clinical Practice) NEJM, July 7, 2011 Robert S. Weinstein, M.D. NEJM July 7 2011 Clinical Practice Glucocorticoid-Induced Bone Disease Arcansas Robert S. Weinstein, M.D. Arcansas Iroquois: 1 1998 Paula Underwood http://www.amazon.co.jp/%e4%b8%80%e4%b8%87%e5%b9%b4%e3%81%ae%e6%97%85 %E8%B7%AF%E2%80%95%E3%83%8D%E3%82%A4%E3%83%86%E3%82%A3%E3%83%B 4%E3%83%BB%E3%82%A2%E3%83%A1%E3%83%AA%E3%82%AB%E3%83%B3%E3%81 %AE%E5%8F%A3%E6%89%BF%E5%8F%B2-%E3%83%9D%E3%83%BC%E3%83%A9-%E3 %82%A2%E3%83%B3%E3%83%80%E3%83%BC%E3%82%A6%E3%83%83%E3%83%89/dp/ 4881356070 1 1998 3 1 16 1/14
16 9 Paula 869 7 9 TFC110503003 1 6 12 3 3 75 3 BMI24 18 64 PSL10 90 7 17 26 10 11 -hydroxysteroid dehydrogenase (11 -HSD) modulator ( prereceptor modulator) 11 -HSD1 11 -HSD2 isoenzymes cortisol prednisolone cortisone prednisone 2/14
11 -HSD1 activator 11 -HSD2 inactivator 11 -HSD1 prednisone prednisolone bone strength Medical ID Alert Jewerly Diabetes Asthma Epilepsy http://www.medids.com/ Medical ID Alert Jewerly BG,K,Cr,Ca,25-hydroxyvitaminD WHO FRAX FRAX 10 3.5 0.4 http://www.shef.ac.uk/frax/tool.jsp?lang=jp (WHO ) 3/14
MRI http://www.juntendo.ac.jp/hospital/clinic/seikei/kanja02_a.html Ca1200 / VD 800U-2000U/ Ca VD 600 / Ca 130 /g Ca600 4.6g Ca( Ca 26 / ) 23 Ca 6 / VD800U 20 g 0.25 0.5 1 3 g D3 0.025 g 1U 0.5 VD 1 bisphosphonate 2 teriparatide ( ) 3 denosumab PSL5mg 10mg 3 Denosumab humanized monoclonal antibody to the receptor activator of nuclear factor- B ligand (RANKL) FDA Amgen denosumab FDA alendronate ( ) risedronate ( ) zoledronic acid ( ) 1 1 1 PSL10 3 1 8 4/14
1 2 teriparatide alendronate vertebroplasty kyphoplasty NEJM Aug.6, 2009 A Randomized Trial of Vertebroplasty for Osteoporotic Spinal Fractures NEJM 35 NEJM 1. 2. 1 6 12 3 3. 3 75 4. 5. PSL2.5 7.5 6. PSL10 90 7 17 7. relative risk 26 8. BMI 24 9. 11 -HSD1 10. 11 -HSD1 11. 12. 13. 14. bone strength 15. 5/14
16. 17. 18. 19. 20. BG,K,Cr,Ca,25-hydroxyvitaminD 21. WHO FRAX 22. MRI 23. Ca1200 / VD 800U-2000U/ 24. 1 bisphosphonate (alendronate, risedronate, zoledronic acid) 25. 2 teriparatide ( ) 26. 3 denosumab 27. Alendronate,Risedronate relative risk 40 28. bisphosphonate 29. bisphosphonate 1 1 compliance 30. bisphosphonate 1 31. bisphosphonate 8 32. 33. 34. 35. Glucocorticoid-Induced Bone Disease (Clinical Practice) NEJM, July 7, 2011 Robert S. Weinstein, M.D. 55 3 albuterol ( fluticasone salmeterol fluticasone montelukast ( ) 10 / 15 / 45.5kg 157.5cm BMI18 wheezing scattered wheezing 6/14
The Clinical Problem 30 50 cancellous bone 1 6% 12 3 3 75 2.5 7.5 3.1 9.3 18 64 10 / 90 7 17 60 80 18 31 relative risk 26 BMI 24 RA Polymyalgia rheumatica Inflammatory bowel disease, 11 -HSD1 bone mass 10 11 -hydroxysteroid dehydrogenase (11 -HSD) 7/14
system modulator (prereceptor modulator) 11 -HSD1 11 -HSD2 isoenzymes cortisol predonisolone cortisone prednisone 11 -HSD1 activator 11 -HSD2 inactivator 11 -HSD1 osteoblast osteocyte bone strength bone strength osteoclast osteoblast PTH Strategies and Evidence withdrawal medication identification jewelry 8/14
K 25-hydroxyvitamin D X WHO Fracture Prevention Algorithm (FRAX) FRAX FRAX MRI 5 40 40 80 1200 / D 800U 2000U/ 1 bisphosphonate FDA alendronate ( ) risedronate ( ) zoledronic acid ( ) alendronate risedronate relative risk 40 prednisone 10 20 1 zoledronic acid ( ) risedronate 9/14
Alendronate ( ) osteocyte bisphosphonate bisphophonate glucocorticoid induced osteoporosis alendronate10 / 2 3.9 0.6 10 7 2.5 bisphosphonate primary end point 12 24 not powered bisphosphonate 1 1 compliance poor adherence Zoledronic acid ( ) 1 1 10 90 bisphosphonate Alendronate 0.7 alendronate 1 zoledronic acid 10 Zoledronic acid 5 15 alendronate70 / 90 bisphosphonate bisphosphonate bisphosphonate drug holiday 2 alendronate alendronate alendronate Bisphosphonate bisphosphonate 8 bisphosphonate 10/14
bisphosphonate 1 10 1 Bisphosphonate bisphosphonate Bisphosphonate 1 2 Bisphosphonate teriparatide (recombinant human parathyroid hormone 1-34 600 g) FDA Teriparatide Alendronate teriparatide alendronate 90 Teriparatide bone strength teriparatide Prednisone 5 / 15 / teriparatide 15 Insulin-like growth factor 1 teriparatide Teriparatide denosumab Amgen Denosumab humanized monoclonal antibody to the receptor activator of nuclear factor- B ligand (RANKL) FDA 6 denosumab+prednisone15mg MTX denosumab+mtx Denosumab bisphosphonate teriparatide (vertebropolasty kyphoplasty ) 11/14
dose-pack 7 10 1g prednisone 10mg 20 / Prednisone 5 7.5 a. American College of Rheumatology Prednisone 7.5 / 3 bisphosphonate teriparatide BMD FRAX algorithm 1200 1500 / VD800 1000U b. National Osteoporosis Foundation Prednisone 5 / 3 bisphosphonate teriparatide BMD modified FRAX Tscore -2.5 c. Royal College of Physicians of London 65 3 prednisone T-score -1.5 1 bisphosphonate 2 teriparatide VD 1g VD BMD d. Belgian Bone Club Prednisone 9.3 mg/ 3 bisphosphonate T-score -1.0-1.5 VD BMD 12/14
55 3 albuterol ( fluticasone salmeterol fluticasone montelukast ( ) 10 / 15 / 45.5kg 157.5cm BMI18 wheezing scattered wheezing prednisone 10 3 prednisone prednisone X D 55 BMI prednisone bisphosphonate (alendronate, risedronate, zoledronic acid) teriparatid FDA prednisone bisphosphonate zoledronic acid teriparatide teriparatide 1. 2. 1 6 12 3 3. 3 75 4. 5. PSL2.5 7.5 13/14
6. PSL10 90 7 17 7. relative risk 26 8. BMI 24 9. 11 -HSD1 10. 11 -HSD1 11. 12. 13. 14. bone strength 15. 16. 17. 18. 19. 20. BG,K,Cr,Ca,25-hydroxyvitaminD 21. WHO FRAX 22. MRI 23. Ca1200 / VD 800U-2000U/ 24. 1 bisphosphonate (alendronate, risedronate, zoledronic acid) 25. 2 teriparatide ( ) 26. 3 denosumab 27. Alendronate,Risedronate relative risk 40 28. bisphosphonate 29. bisphosphonate 1 1 compliance 30. 1 31. bisphosphonate 8 32. 33. 34. 35. 14/14