1. ANA Testing Carrie Marshall 1/18/08

2. Treatment of Osteoporosis Azami Ahad. MD Rheumatologist Assistant professor of Ardabil University of Medical Sciences 1392/7/28 2

3. Preventing Osteoporosis Pay attention to your modifiable risk factors – mainly what you put in your mouth! Pay attention to your modifiable risk factors – mainly what you put in your mouth! Anyone not taking in adequate dietary Calcium and Vitamin D should get supplements Anyone not taking in adequate dietary Calcium and Vitamin D should get supplements –Dairy –Fortified juice or soy milk Adequate calcium intake Adequate calcium intake Lowers risk of kidney stone 3

4. Calcium Recommended Intake http://ods.od.nih.gov/factsheets/calcium.asp Age 0-6 months 210 mg 7-12 months 270 mg 1-3 years 500 mg 4-8 years 800 mg 9-13 years 1,300 mg 14-18 years 1,200 -1500 mg 19-50 years 1,000 mg 50+ years 1,200 -1500 mg 4

5. Calcium Absorption Absorption 6-20% Food improves absorption by 20-25% Heaney, RP et al. Am J Clin Nutr. 1989; 49(2): 372-6 Low stomach acid reduces absorption (Long term use of PPI correlated to low BMD) Only a small amount can be absorbed at one time, so more frequent intake is better 5

6. Calcium supplements Preparation % Elemental Calcium Solubility Calcium carbonate 40%Insoluble (take with food) Calcium citrate 24%Soluble Calcium lactate 13%Soluble Calcium gluconate 9%Soluble 6

7. Vitamin D & Calcium Supplements 7

8. Vitamin D 8

9. Positive Effects of Vit D Increases Calcium absorption Increases Calcium absorption Strengthens Bones Strengthens Bones Reduces Falls Reduces Falls - Increases muscle function, decreases muscle pain, and reduces body sway. Bischoff-Ferrari 2004 JAMA 291;16:1999-2006 Glerup H, et al. 2000 J Int Med 247:260-8 Glerup H, et al. 2000 J Int Med 247:260-8 Reduces Fractures Reduces Fractures –As effective as Alendronate in cardiac transplant patients –Alendronate 10 mg vs. Calcitriol 0.5 mcg daily Shane E, et al. N Engl J Med. Feb 19 2004;350(8):767-776 9

10. Vitamin D Requirements increase with age Requirements increase with age –600 IU <70 yo –800 IU >70 yo IOM report 11/30/2010 http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium- and-Vitamin-D.aspx http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium- and-Vitamin-D.aspx In Osteoporosis give 1,000 IU daily In Osteoporosis give 1,000 IU daily http://www.nof.org/prevention/vitaminD.htm 10

11. Exercise Back strengthening exercise lead to fewer vertebral fractures over 10 years Back strengthening exercise lead to fewer vertebral fractures over 10 years –1.6% in exercising group –4.3% in control group Sinaki M, et al. Bone 2002;30:836-841 Increased spine BMD over 9 months 3.5% vs. 1.5% Increased spine BMD over 9 months 3.5% vs. 1.5% Villareal DT, et al. JAGS 2003;51(7):985-90 Kemmler W, et al. Arch Int Med 2004;164(10):1084-91 11

12. Summary Break Osteoporosis is a growing epidemic Osteoporosis is a growing epidemic Prevention through lifestyle modification is important Prevention through lifestyle modification is important Calcium and vitamin D are key Calcium and vitamin D are key Exercise Exercise 12

13. Causes of Secondary Osteoporosis Tobacco Tobacco Alcohol Alcohol Vitamin deficiencies Vitamin deficiencies –Vit D, B12, Vit K Medications Medications –Anticonvulsants –Steroids >5mg/d for >6 months Diseases Diseases –Rheumatoid or other inflammatory arthritis –Multiple myeloma, lymphoma –Hyperthyroidism –Hyperparathyroidism 13

14. Treatments- Medications Anabolic Agents Anabolic Agents –Parathyroid hormone –Sodium flouride –Strontium ranelate –Growth hormone –Insulin-like growth factor-1 –Statins –RANK-L, Denosumab Antiresorptives Antiresorptives –Estrogens –Selective estrogen receptor modulators –Bisphosphonates –Calcitonin Others: Calcium, Vitamin D 14

16. Bisphosphonates Binds to bone Binds to bone Inhibits osteoclast activity Inhibits osteoclast activity Supports osteoblast bone formation Supports osteoblast bone formation First line treatment for osteoporosis First line treatment for osteoporosis 16

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18. Bisphophonates Block Bone Resorption Inhibits osteoclasts. Binds to bone 18

19. Bisphosphonates Alendronate (Fosamax) generic Alendronate (Fosamax) generic Risedronate (Actonel) better GI profile Risedronate (Actonel) better GI profile Ibandronate (Boniva) no hip protection Ibandronate (Boniva) no hip protection Zoledronic Acid (Reclast) once a year Zoledronic Acid (Reclast) once a year 19

20. Unusual Complications of Bisphosphonates Osteonecrosis of jaw- Osteonecrosis of jaw- –Rare 1/100,000 patient years –94% in cancer patients receiving zoledronic acid or pamidronate Woo S-B, et al. 2006 Ann Int Med 144(10):753-61 Unusual Fx in some patients with nl BMD Unusual Fx in some patients with nl BMD Neviaser AS, et al. 2008 Journal of Orthopaedic Trauma 22(5): 346-350 Lenart et al. 2008 NJEM 358 (12): 1304 20

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22. Estrogen ERT increases BMD and reduced bone markers more than SERM ERT increases BMD and reduced bone markers more than SERM Prestwood, KM et al. J Clin Enodocrinol Metab. 2000; 85(6): 2197-2202 Prestwood, KM et al. J Clin Enodocrinol Metab. 2000; 85(6): 2197-2202 WHI raised concerns about CV risks WHI raised concerns about CV risks E2 still approved for hot flashes E2 still approved for hot flashes Low-dose ERT at menopause will delay bone thinning ( but not recommended as first- line therapy) Low-dose ERT at menopause will delay bone thinning ( but not recommended as first- line therapy) 22

23. Selective Estrogen Receptor Blocker (SERM) Raloxifene (Evista) preferentially binds to the alpha estrogen receptor Raloxifene (Evista) preferentially binds to the alpha estrogen receptor – fewer estrogen+ breast cancers – fewer vertebral fractures – more venous thromboembolism – more fatal stroke – No difference in coronary deaths No difference in: hip fractures No difference in: hip fractures RUTH trial: Barrett-Connor, et al. 2006 NEJM 355(2);125-37 23

24. Calcitonin Calcitonin is effective for osteoporosis fracture pain. Effect takes about 2 weeks. Calcitonin is effective for osteoporosis fracture pain. Effect takes about 2 weeks. Silverman, SL. Osteoporos Int. Nov 2002;13(11):858-867. No significant effect in the hip No significant effect in the hip Antalgic Antalgic Cost:168000 RL Cost:168000 RL –Miacalcin ® $112 –Fortical ® $54 24

25. 25 Parathyroid Hormone (PTH)

26. Forteo (Teriparatide) -20$/d Forteo (Teriparatide) -20$/d Daily 20 mcg/d or 0.08ml SQ injection Daily 20 mcg/d or 0.08ml SQ injection PTH draws Ca out of cortical bone PTH draws Ca out of cortical bone –Hip 50% cortical bone –Spine 10% cortical bone Intermittent antiresorptive effect Intermittent antiresorptive effect Preferential anabolic activity Preferential anabolic activity Weak evidence for hip Fx Weak evidence for hip Fx ACP Practice Guideline. Ann Int Med 2008;149:404-415 26

27. Parathyroid Hormone (PTH) Forteo (Teriparatide) Forteo (Teriparatide) Approved for use of <2 years Approved for use of <2 years Neer, RM et al. NEJM 2001;344(19):1434-41 Do not use in combination with bisphosphoonate- Black et. al. N Engl J Med 2003;349(13):1207-15 Do not use in combination with bisphosphoonate- Black et. al. N Engl J Med 2003;349(13):1207-15 Increases BMD 6% Increases BMD 6% Not very effective for preventing fractures Not very effective for preventing fractures Risk of osteosarcoma in animal trials Risk of osteosarcoma in animal trials 27

28. Strontium ranelate 2 g bid 2 g bid Antiresorptive & anabolic actions Antiresorptive & anabolic actions 28

29. Denosumab - new kid on the block (Brand name Prolia) Denosumab (formerly AMG-162) Denosumab (formerly AMG-162) –Monoclonal antibody –Inhibits bone resorption by blocking KB-ligand (RANKL) Bekker et al. 2004 J Bone Miner Res 19:1059-66 –Injected sq twice yearly –Expensive $1650 per year, 10.000.000RL –? Effect on immune system 29

30. Summary of Medications Bisphosphonates- First line therapy Bisphosphonates- First line therapy –Boniva no hip benefit –Must have GFR > 30 Calcitonin only for spine, good for pain Calcitonin only for spine, good for pain Estrogen good for osteoporosis Estrogen good for osteoporosis SERM need long term data, only spine SERM need long term data, only spine PTH <2 yrs, not in combination PTH <2 yrs, not in combination Denosumab monoclonal antibody, 2x/yr Denosumab monoclonal antibody, 2x/yr 30

31. Balloon Kyphoplasty Stabilizes the Fracture and Corrects Spinal Deformity caused by one or more VCFs Stabilizes the Fracture and Corrects Spinal Deformity caused by one or more VCFs Indicated for vertebral compression fracture if pain not controlled with meds 31

32. Conclusion Osteoporosis is a growing epidemic Osteoporosis is a growing epidemic Save yourselves! Preach prevention! Save yourselves! Preach prevention! Test all women over 65, and others at risk for osteoporosis (DEXA) Test all women over 65, and others at risk for osteoporosis (DEXA) Treat all elderly, and patients at risk, with Calcium and Vitamin D Treat all elderly, and patients at risk, with Calcium and Vitamin D Don’t be afraid of bisphosphonates Don’t be afraid of bisphosphonates 32