1. Osteoporosis Case Studies March 2012 Ronald C. Hamdy, MD, FRCP, FACP Professor of Medicine Director, Osteoporosis Center Professor/Chair, Geriatric Medicine East Tennessee State University Editor-in-Chief, Journal of Clinical Densitometry Osteoporosis Case Studies March 2012 Ronald C. Hamdy, MD, FRCP, FACP Professor of Medicine Director, Osteoporosis Center Professor/Chair, Geriatric Medicine East Tennessee State University Editor-in-Chief, Journal of Clinical Densitometry

3. Mrs. MB, 51 years old WW, Concerned about Osteoporosis   Asymptomatic   Natural menopause 2 years ago   Exercises regularly – strenuous routine   Good dietary calcium and vitamin D intake   Family history: negative for osteoporosis   No prescribed medications   OsCal 500 mg + Vitamin D twice daily   Multivitamins once a day   Weight 121 pounds; height 64”

4. Mrs. MB, 51 years old WW, Concerned about Osteoporosis   Asymptomatic   Natural menopause 2 years ago   Exercises regularly – strenuous routine   Good dietary calcium and vitamin D intake   Family history: negative for osteoporosis   No prescribed medications   OsCal 500 mg + Vitamin D twice daily   Multivitamins once a day   Weight 121 pounds; height 64”

5. AreaBMDT-score L1 9.91.419 + 2.4 L211.41.445 + 2.9 L313.91.483 + 2.4 L414.11.494 + 1.7 L1-448.81.463 + 2.6 Mrs. MB, 51 years old WW, Concerned about Osteoporosis

6. AreaBMDT-score L1 9.91.419 + 2.4 L211.41.445 + 2.9 L313.91.483 + 2.4 L414.11.494 + 1.7 L1-448.81.463 + 2.6 RIGHT HIPBMDT-score Femoral Neck1.081 + 0.8 Trochanter0.773 - 0.2 Total Hip1.047 + 0.4 LEFT HIP Femoral Neck1.016 + 0.3 Trochanter0.818 + 0.3 Total Hip1.047 + 0.4 RIGHT HIPBMDT-score Femoral Neck1.081 + 0.8 Trochanter0.773 - 0.2 Total Hip1.047 + 0.4 LEFT HIP Femoral Neck1.016 + 0.3 Trochanter0.818 + 0.3 Total Hip1.047 + 0.4 Lunar, Prodigy Mrs. MB, 51 years old WW, Concerned about Osteoporosis

7.  Diagnosis: Normal bone density (WHO criteria) Mrs. MB, 51 years old WW, Concerned about Osteoporosis

8.  Diagnosis: Normal bone density (WHO criteria)  Management recommendations: Maintain Bone Mass – Healthy lifestyle Repeat DXA scan 2 years Mrs. MB, 51 years old WW, Concerned about Osteoporosis

9. Baseline2-yearsBMD change RegionBMDT-score BMD T-score % Abs LSC RIGHT Fem Neck1.081+ 0.8 0.985 + 0.0- 8.9 0.096 0.034 Trochanter0.773- 0.2 0.732 - 0.5- 5.3 0.0410.053 Total Hip1.047+ 0.4 0.969 - 0.3- 7.4 0.0780.050 LEFT Fem Neck1.016+ 0.3 0.945 - 0.3- 7.0 0.0710.031 Trochanter0.818+ 0.3 0.750 + 0.1- 8.3 0.0680.042 1.047+ 0.4 0.966 - 0.3 0.081 Total Hip1.047+ 0.4 0.966 - 0.3- 7.7 0.0810.022 L1-L4 1.463 + 2.6 1.394 + 1.8- 5.0 0.0690.028 Mrs. MB, 53 years old WW, Second visit Concerned about Osteoporosis

10. Baseline2-years BMD change RegionBMDT-score BMD T-score % Abs LSC RIGHT Fem Neck1.081+ 0.8 0.985 + 0.0- 8.9 0.096 0.034 Trochanter0.773- 0.2 0.732 - 0.5- 5.3 0.0410.053 Total Hip1.047+ 0.4 0.969 - 0.3- 7.4 0.0780.050 LEFT Fem Neck1.016+ 0.3 0.945 - 0.3- 7.0 0.0710.031 Trochanter0.818+ 0.3 0.750 + 0.1- 8.3 0.0680.042 1.047+ 0.4 0.966 - 0.3 0.081 Total Hip1.047+ 0.4 0.966 - 0.3- 7.7 0.0810.022 L1-L4 1.463 + 2.6 1.394 + 1.8- 5.0 0.0690.028 Laboratory investigations: Blood Chemistry profile, Vit. D, PTH: Within normal limits. Laboratory investigations: Blood Chemistry profile, Vit. D, PTH: Within normal limits. Mrs. MB, 53 years old WW, Second visit Concerned about Osteoporosis

11. Normal BMD Mrs. MB, 53 years old WW, Second visit Concerned about Osteoporosis

12. Normal BMD Normal BMD Mrs. MB, 53 years old WW, Second visit Concerned about Osteoporosis Bone loss sustained: Expected Post-menopausal loss Management recommendation: Maintain Bone mass Repeat DXA scan 1 year

13. Mrs. MB, 54 years old WW, Third visit VERY concerned about Osteoporosis

14. VERY

15. Mrs. MB, 54 years old WW, Third visit VERY concerned about Osteoporosis Base2-yrs % 1-yr BMD change 04-05 RegionBMDBMD Diff.BMDT-score % Abs LSC RIGHT Fem Neck1.0810.985 - 8.9 0.977- 0.1 - 0.80.0080.034 Trochanter0.7730.732 - 5.3 0.713- 0.5 - 0.30.0190.053 Total Hip1.0470.969 - 7.4 0.958- 0.3 - 0.80.0110.050 LEFT Fem Neck1.0160.945 - 7.0 0.938- 0.3 - 0.70.0070.031 Trochanter0.8180.750 - 8.3 0.739- 0.1 - 1.50.0110.042 1.0470.966 0.948- 0.3 - 1.80.018 Total Hip1.0470.966 - 7.7 0.948- 0.3 - 1.80.0180.022 L1-L4 1.4631.394 - 5.0 1.374+ 1.7 - 1.40.0200.028

16. Bone Mass Active Growth Slow Loss Rapid Loss Continuing Loss Age in Years 501020406070809030 MENOPAUSE Peak Bone Mass 1- 5% annually Age-associated Changes in Bone Mass 1- 2% annually

17.  Low back pain, gradually worsening  Episode of very severe pain, incapacitating, 3 weeks ago  Positive family history; Sister 85 yrs, died after hip fracture  Daily calcium intake: about 1500 mg  CBC, CMP, TSH; within normal limits  Meds: NSAID, calcium supplements  Weight 130 pounds, height 64”  X-ray evidence of vertebral compression fracture Mrs. MRW, 76 years WW

18.  Low back pain, gradually worsening  Episode of very severe pain, incapacitating, 3 weeks ago  Positive family history; Sister 85 yrs, died after hip fracture  Daily calcium intake: about 1500 mg  CBC, CMP, TSH; within normal limits  Meds: NSAID, calcium supplements  Weight 130 pounds, height 64”  X-ray evidence of vertebral compression fracture Mrs. MRW, 76 years WW

19.  Low back pain, gradually worsening  Episode of very severe pain, incapacitating, 3 weeks ago  Positive family history; Sister 85 yrs, died after hip fracture  Daily calcium intake: about 1500 mg  CBC, CMP, TSH; within normal limits  Meds: NSAID, calcium supplements  Weight 130 pounds, height 64”  X-ray evidence of vertebral compression fracture Mrs. MRW, 76 years WW

20. AreaBMDT-score L112.650.849- 0.69 L211.801.012- 0.15 L315.550.920- 1.49 L411.611.123+ 0.06 L1-451.610.969- 0.71

21. Mrs. MRW, 76 years WW AreaBMDT-score L112.650.849- 0.69 L211.801.012- 0.15 L315.550.920- 1.49 L411.611.123+ 0.06 L1-451.610.969- 0.71 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 Vertebral compression fractures

22. Mrs. MRW, 76 years WW AreaBMDT-score L112.650.849- 0.69 L211.801.012- 0.15 L315.550.920- 1.49 L411.611.123+ 0.06 L1-451.610.969- 0.71 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 Vertebral compression fractures Diagnosis: Osteoporosis 10-years % # probability: Hip #33 Other # 50 Diagnosis: Osteoporosis 10-years % # probability: Hip #33 Other # 50

23. Mrs. MRW, 76 years WW AreaBMDT-score L112.650.849- 0.69 L211.801.012- 0.15 L315.550.920- 1.49 L411.611.123+ 0.06 L1-451.610.969- 0.71 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 Goal: Reduce Fracture Risk especially hip Vertebral compression fractures Diagnosis: Osteoporosis

24. Mrs. MRW, 76 years WW RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 Vertebral compression fractures Goal: Reduce Fracture Risk especially hip  Bisphosphonates: Alendronate, Fosamax, generics Risedronate, Actonel, Atelvia Ibandronate, Boniva Zoledronate, Reclast  Raloxifene, Evista  Calcitonin, Miacalcin  Teriparatide, Forteo  Denosumab, Prolia  Bisphosphonates: Alendronate, Fosamax, generics Risedronate, Actonel, Atelvia Ibandronate, Boniva Zoledronate, Reclast  Raloxifene, Evista  Calcitonin, Miacalcin  Teriparatide, Forteo  Denosumab, Prolia

25. Risk for hip fractures relative to placebo for participants who are at high risk for fracture, by agent MacLean, C. et. al. Ann Intern Med 2008;148:197-213

26. FDA Approved Medication –Hip Fractures StudyNumbers Duration years risk reduction AlendronateFIT2,0273Yes RisedronateHIP5,4453Yes IbandronateBONE2,9463No ZoledronateHORIZON7,7363Yes RaloxifeneMORE7,7053No CalcitoninPROOF1,2555No DenosumabFREEDOM7,7363Yes Teriparatide1,6371.5* * Study aborted 18 months

27. Mrs. MRW, 76 years WW RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 Vertebral compression fractures  Bisphosphonates: Alendronate, Fosamax, generics Risedronate, Actonel, Atelvia Ibandronate, Boniva Zoledronate, Reclast  Raloxifene, Evista  Calcitonin, Miacalcin  Teriparatide, Forteo  Denosumab, Prolia  Bisphosphonates: Alendronate, Fosamax, generics Risedronate, Actonel, Atelvia Ibandronate, Boniva Zoledronate, Reclast  Raloxifene, Evista  Calcitonin, Miacalcin  Teriparatide, Forteo  Denosumab, Prolia Goal: Reduce Fracture Risk especially hip Diagnosis: Osteoporosis

28. Mrs. MRW, 76 years WW RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 RIGHT HIPBMDT-score Femoral Neck0.557- 2.6 Trochanter0.535- 1.7 Total Hip0.736- 1.7 LEFT HIP Femoral Neck0.554- 2.7 Trochanter0.516- 1.8 Total Hip0.724- 1.8 Vertebral compression fractures Goal: Reduce Fracture Risk especially hip  Bisphosphonates: Alendronate, Fosamax, generics Risedronate, Actonel, Atelvia Ibandronate, Boniva Zoledronate, Reclast  Raloxifene, Evista  Calcitonin, Miacalcin  Teriparatide, Forteo  Denosumab, Prolia  Bisphosphonates: Alendronate, Fosamax, generics Risedronate, Actonel, Atelvia Ibandronate, Boniva Zoledronate, Reclast  Raloxifene, Evista  Calcitonin, Miacalcin  Teriparatide, Forteo  Denosumab, Prolia Diagnosis: Osteoporosis

29. Mrs. MRW, 76 years WW CONCERNED ABOUT: OSTEONECROSIS OF THE JAW ATYPICAL FEMORAL SHAFT FRACTURES

30. Mrs. MRW, 76 years WW CONCERNED ABOUT: OSTEONECROSIS OF THE JAW ATYPICAL FEMORAL SHAFT FRACTURES Probability: 1:10,000 to 1:100,000 Probability: 1:10,000 to 1:100,000

31. Probability #: Hip#33 % 1:3 Other # 50 % 1:2 Probability #: Hip#33 % 1:3 Other # 50 % 1:2 Mrs. MRW, 76 years WW CONCERNED ABOUT: OSTEONECROSIS OF THE JAW (ONJ) ATYPICAL FEMORAL SHAFT FRACTURES (AFSF) Probability: 1:10,000 to 1:100,000 Probability: 1:10,000 to 1:100,000

32. Atypical femoral shaft fractures Prodromal symptoms/signs  Clinical: Pain, localised tenderness  Imaging: X-rays, technetium scan, MRI, CT-scans, MRI  Laboratory: Bone turnover markers: N-TX, C-TX

33. Cumulative Hazard of Hip Fractures Months 54%* Kannus P, et al. N Engl J Med 2000; 343:1506-1513 Prevention of Hip fracture with Hip Protectors *P=0.008 1801 elderly men and women in long stay or supported home care

34.  Bisphosphonates: alendronate, risedronate, ibandronate zoledronate  Raloxifene  Calcitonin  Teriparatide  Denosumab  Bisphosphonates: alendronate, risedronate, ibandronate zoledronate  Raloxifene  Calcitonin  Teriparatide  Denosumab ? Kyphoplasty ?? Vertebroplasty ? Kyphoplasty ?? Vertebroplasty Mrs. MRW, 76 years WW

35.  Bisphosphonates: alendronate, risedronate, ibandronate zoledronate  Raloxifene  Calcitonin  Teriparatide  Denosumab  Bisphosphonates: alendronate, risedronate, ibandronate zoledronate  Raloxifene  Calcitonin  Teriparatide  Denosumab ? Kyphoplasty ?? Vertebroplasty ? Kyphoplasty ?? Vertebroplasty Mrs. MRW, 76 years WW Calcium/vitamin D

36. DAILY CALCIUM INTAKE Elemental Calcium (mg)  Postmenopausal:1,500  Premenopausal:1,000  Pregnant/nursing:1,200 - 1,500  Men < 65 years:1,000  Men > 65 years:1,500

49. Mrs. IB, WW, 56 years   Asymptomatic   Surgical menopause when 41 years   Exercises regularly   Good dietary calcium and vitamin D intake   Family history: positive for osteoporosis   No prescribed medications   CitraCal 500 mg + Vitamin D twice daily   Multivitamins once a day   Weight 175 pounds; height 64” – No height loss

50. Mrs. IB, WW, 56 years   Asymptomatic   Surgical menopause when 41 years   Exercises regularly   Good dietary calcium and vitamin D intake   Family history: positive for osteoporosis   No prescribed medications   CitraCal 500 mg + Vitamin D twice daily   Multivitamins once a day   Weight 175 pounds; height 64” – No height loss

51. Mrs. IB, WW, 56 years AreaBMDT-score L111.10.910- 1.8 L211.30.914 - 1.8 L311.5 0.922 - 2.3 L412.30.927- 2.6 L1-446.20.925- 2.1 RIGHT HIPBMDT-score Femoral Neck0.887 - 1.2 Trochanter0.713 - 0.9 Total Hip0.925 - 0.9 LEFT HIP Femoral Neck0.910 - 1.1 Trochanter0.755 - 0.7 Total Hip0.961 - 0.8 RIGHT HIPBMDT-score Femoral Neck0.887 - 1.2 Trochanter0.713 - 0.9 Total Hip0.925 - 0.9 LEFT HIP Femoral Neck0.910 - 1.1 Trochanter0.755 - 0.7 Total Hip0.961 - 0.8 Diagnosis: Osteopenia

52. WHO – Fracture Risk Assessment Tool – FRAX – AgeAge WeightWeight HeightHeight

53. AgeAge WeightWeight HeightHeight Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day WHO – Fracture Risk Assessment Tool – FRAX –

54. AgeAge WeightWeight HeightHeight Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Femoral neck T-score or Z-score Femoral neck T-score or Z-score WHO – Fracture Risk Assessment Tool – FRAX –

55. AgeAge WeightWeight HeightHeight Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Femoral neck T-score or Z-score Femoral neck T-score or Z-score 10-year probability of fracture (%)  Hip  Others 10-year probability of fracture (%)  Hip  Others WHO – Fracture Risk Assessment Tool – FRAX –

56. AgeAge WeightWeight HeightHeight Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Previous fracture Parent fractured hip Current smoking Glucocorticoids Rheumatoid arthritis Secondary osteoporosis Alcohol > 3/day Femoral neck T-score or Z-score Femoral neck T-score or Z-score 10-year probability of fracture (%)  Hip  Others 10-year probability of fracture (%)  Hip  Others NOF Guidelines Hip > 3% Others > 20% NOF Guidelines Hip > 3% Others > 20% WHO – Fracture Risk Assessment Tool – FRAX –

57. Diagnosis: Osteopenia (WHO criteria)Diagnosis: Osteopenia (WHO criteria) 10-year % fracture probability10-year % fracture probability Hip 1Hip 1 Others26Others26 Mrs. IB, WW, 56 years NOF Guidelines Hip > 3% Others > 20% NOF Guidelines Hip > 3% Others > 20%

58.  Alendronate (Fosamax)  Risedronate (Actonel)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  ? ? HRT ? ? What is the goal of treatment ? Mrs. IB, WW, 56 years

59.  Alendronate (Fosamax)  Risedronate (Actonel)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  ? ? HRT ? ? What is the goal of treatment ? Fracture Risk Reduction Mrs. IB, WW, 56 years

60.  Alendronate (Fosamax)  Risedronate (Actonel)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  ? ? HRT ? ? What is the goal of treatment ? Fracture Risk Reduction Mrs. IB, WW, 56 years 10-year probability Hip #1 Other # 26 10-year probability Hip #1 Other # 26

61.  Alendronate (Fosamax)  Risedronate (Actonel)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  ? ? HRT ? ? What is the goal of treatment ? Fracture Risk Reduction Mrs. IB, WW, 56 years 10-year probability Hip #1 Other # 26 10-year probability Hip #1 Other # 26

62. FDA Approved Medication – Vertebral Fractures StudyNumbers Duration years risk reduction AlendronateFIT2,0273Yes RisedronateVERT 2,458 1,116 3Yes IbandronateBONE2,9463Yes ZoledronateHORIZON7,7363Yes RaloxifeneMORE7,7053Yes CalcitoninPROOF1,2555Yes DenosumabFREEDOM7,7363Yes Teriparatide1,6371.5Yes Hormonal Replacement Therapy - WHI

63.  Alendronate (Fosamax)  Risedronate (Actonel, Atelvia)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  ? ? Hormonal Replacement Therapy ? ? Mrs. IB, WW, 56 years Calcium Vitamin D Calcium Vitamin D

64.  Diagnosed with osteoporosis about 9 years ago Based on fragility fracture T10: moderate wedge  Secondary causes excluded.  Started risedronate (Actonel) 35 mg weekly, then converted to 150 mg once a month  No adverse effects, taking it as directed, own routine  Good compliance  Good daily calcium/vitamin D intake Mrs. PRP, WW, 82 years

65. Scan Date AgeBMDT-scores% BMD Change BaselinePrevious 2001730.700- 2.0 2003750.721- 1.8+ 3.0 2004760.724-1.8+ 1.8+ 1.3 2006780.757- 1.5+ 6.1+ 4.3 2007790.747 -1.6+ 6.3- 0.2 2010820.771- 1.4+ 9.2+ 2.9 Mrs. PRP, WW, 82 years Right Total Hip

66. Scan Date AgeBMDT-scores% BMD Change BaselinePrevious 2001730.700- 2.0 2003750.721- 1.8+ 3.0 2004760.724-1.8+ 1.8+ 1.3 2006780.757- 1.5+ 6.1+ 4.3 2007790.747 -1.6+ 6.3- 0.2 2010820.771- 1.4+ 9.2+ 2.9 Should risedronate (Actonel) be continued ? Mrs. PRP, WW, 82 years Right Total Hip

67. Atypical femoral shaft # Delayed # healing Bisphosphonate therapy Oversuppressed bone turnover Fracture Risk Reduction Osteo-necrosis Jaw

68. Bisphosphonate therapy & Bone Turnover Suppress, but not Over-suppress !

69. COLLAGEN CROSS LINKS CTx NTxN-TELOPEPTIDE REGION HELICAL REGIONC-TELOPEPTIDE REGION Pyr Dpd

70. C-Telopeptide or C-Tx  C-Telopeptide or  C-Tx 1000 pg/mL 100 pg/mL 200 pg/mL

71. Mrs. PRP, WW, 82 years Right Total Hip Scan Date AgeBMDT-scores% BMD Change BaselinePrevious 2001730.700- 2.0 2003750.721- 1.8+ 3.0 2004760.724-1.8+ 1.8+ 1.3 2006780.757- 1.5+ 6.1+ 4.5 2007790.747 -1.6+ 6.4- 0.3 2010820.771- 1.4+ 9.2+ 3.0 Continue risedronate (Actonel) C-Tx 320 pg/mL

72. Mrs. RV, 60 years, WW, Second visit 2008 2010 % Change RIGHT HIPBMDT-score BMDT-score BMD Fem Neck0.676- 1.6 0.655 - 1.7 - 3.3 Total Hip0.750- 1.6 0.688 - 2.1 - 8.3 LEFT HIP Fem Neck0.609- 2.2 0.597 - 2.3 - 2.0 Total Hip0.735- 1.7 0.646 - 2.4 - 12.2 L1-L4Cannot be interpreted: scoliosis and artifacts 2008 2010 % Change RIGHT HIPBMDT-score BMDT-score BMD Fem Neck0.676- 1.6 0.655 - 1.7 - 3.3 Total Hip0.750- 1.6 0.688 - 2.1 - 8.3 LEFT HIP Fem Neck0.609- 2.2 0.597 - 2.3 - 2.0 Total Hip0.735- 1.7 0.646 - 2.4 - 12.2 L1-L4Cannot be interpreted: scoliosis and artifacts Prescribed alendronate in 2008

73. Mrs. RV, 60 years, WW, Second visit Did not refill her second prescription of Alendronate 2008 2010 % Change RIGHT HIPBMDT-score BMDT-score BMD Fem Neck0.676- 1.6 0.655 - 1.7 - 3.3 Total Hip0.750- 1.6 0.688 - 2.1 - 8.3 LEFT HIP Fem Neck0.609- 2.2 0.597 - 2.3 - 2.0 Total Hip0.735- 1.7 0.646 - 2.4 - 12.2 L1-L4Cannot be interpreted: scoliosis and artifacts 2008 2010 % Change RIGHT HIPBMDT-score BMDT-score BMD Fem Neck0.676- 1.6 0.655 - 1.7 - 3.3 Total Hip0.750- 1.6 0.688 - 2.1 - 8.3 LEFT HIP Fem Neck0.609- 2.2 0.597 - 2.3 - 2.0 Total Hip0.735- 1.7 0.646 - 2.4 - 12.2 L1-L4Cannot be interpreted: scoliosis and artifacts

74. Mrs. WF, 68 yrs, Wt: 140 lbs Ht: 62 in   Known to have osteoporosis   CBC, Blood Chem. Profile, TSH: within normal limits.   Prescribed a bisphosphonate.

75. Mrs. WF, 68 yrs, Wt: 140 lbs Ht: 62 in DXA Scan Baseline 2 yrs later % Change LSC Results BMD T-score BMD T-score BMD Right Total Hip 0.721 -2.5 0.689 - 2.9 - 4.5 2.2 Left Total Hip 0.688 -2.7 0.657 - 2.9 - 5.1 2.8 Lumbar Vertebrae Multiple vertebral compression fractures DXA Scan Baseline 2 yrs later % Change LSC Results BMD T-score BMD T-score BMD Right Total Hip 0.721 -2.5 0.689 - 2.9 - 4.5 2.2 Left Total Hip 0.688 -2.7 0.657 - 2.9 - 5.1 2.8 Lumbar Vertebrae Multiple vertebral compression fractures Complete blood picture Blood chemistry profileNormal Thyroid stimulating hormone Complete blood picture Blood chemistry profileNormal Thyroid stimulating hormone Bisphosphonates, good compliance

76. Mrs. WF, 68 yrs, Wt: 140 lbs Ht: 62 in DXA Scan Baseline 2 yrs later % Change LSC Results BMD T-score BMD T-score BMD Right Total Hip 0.721 -2.5 0.689 - 2.9 - 4.5 2.2 Left Total Hip 0.688 -2.7 0.657 - 2.9 - 5.1 2.8 Lumbar Vertebrae Multiple vertebral compression fractures DXA Scan Baseline 2 yrs later % Change LSC Results BMD T-score BMD T-score BMD Right Total Hip 0.721 -2.5 0.689 - 2.9 - 4.5 2.2 Left Total Hip 0.688 -2.7 0.657 - 2.9 - 5.1 2.8 Lumbar Vertebrae Multiple vertebral compression fractures Complete blood picture Blood chemistry profileNormal Thyroid stimulating hormone Complete blood picture Blood chemistry profileNormal Thyroid stimulating hormone Bisphosphonates, good compliance 25(OH) Vitamin D 12 ng/mL

77. Non-response to oral bisphosphonates ComplianceCompliance Inadequate Calcium/vitamin DInadequate Calcium/vitamin D Secondary osteoporosisSecondary osteoporosis

78. Osteoporosis Diagnosis: Fragility fractures DXA - WHO Guidelines:  < -2.5 Osteoporosis  < - 1.0 to – 2.5: Osteopenia  > - 1.0: Normal

79. Osteoporosis Diagnosis: Fragility fractures DXA - WHO Guidelines:  < -2.5 Osteoporosis  < - 1.0 to – 2.5: Osteopenia  > - 1.0: Normal Management strategy: WHO FRAX 10 year # probability % NOF guidelines: Hip # > 3.0 Other # >20 Management strategy: WHO FRAX 10 year # probability % NOF guidelines: Hip # > 3.0 Other # >20

80. Osteoporosis Diagnosis: Fragility fractures DXA - WHO Guidelines:  < -2.5 Osteoporosis  Osteopenia  > - 1.0: Normal Medications:  Alendronate (Fosamax, generics)  Risedronate (Actonel, Atelvia)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  HRT ?? Medications:  Alendronate (Fosamax, generics)  Risedronate (Actonel, Atelvia)  Ibandronate (Boniva)  Zoledronate (Reclast)  Raloxifene (Evista)  Calcitonin (Miacalcin)  Teriparatide (Forteo)  Denosumab (Prolia)  HRT ?? Management strategy: WHO FRAX 10 year # probability % NOF guidelines: Hip # > 3.0 Other # >20 Management strategy: WHO FRAX 10 year # probability % NOF guidelines: Hip # > 3.0 Other # >20

81. FDA Approved Medication for Osteoporosis # Risk Reduction  Calcium  Vitamin D  Diet  Exercise  No smoking  Calcium  Vitamin D  Diet  Exercise  No smokingVertebraeHipsAlendronateYesYes RisedronateYesYes IbandronateYesNo ZoledronateYesYes RaloxifeneYesNo CalcitoninYesNo TeriparatideYes DenosumabYesYes WHO – FRAX NOF – Guidelines Hip > 3% Others > 20% WHO – FRAX NOF – Guidelines Hip > 3% Others > 20%

82. Management Of Osteoporosis Management Of Osteoporosis Medications Lifestyle changes Calcium & Vitamin D Fall Prevention Diseases Medications causing bone loss Reduce impact of falls Early diagnosis Prevention

83. Osteoporosis It is never too early or too late to prevent or treat osteoporosis !