1. NICE, FRAX & NOGG VTS meeting Jonathan Day 7 th April 2010

5. Osteoporotic fractures - one of most common causes of disability - a major source of medical expenditure - a systemic disease – any fracture results in approx 2x increased risk of another fracture

6. FRACTURE is the only important outcome of Osteoporosis Osteoporosis not the only cause of low trauma fractures Fragility fracture – Osteoporosis/BMD Other skeletal factors Falls, force of impact

7. Age For same BMD on DXA scan, risk of hip fracture 5x greater for 80yr old than 50yr old NB overlap with risk of falls

8. Family History of Hip Fracture Risk increases by 4x for women with parental history at younger age Parental age of hip fracture 80yrs+, heritability nearly 0%

9. Non Vertebral fractures usually associated with Falls Risk of fracture increases with age independent of BMD Fragility fractures can occur with normal BMD 2 or more vertebral fractures increase risk of fracture x12 for given BMD

10. Epidemiology of Fracture Fracture often first sign = importance of secondary prevention Predictive of further # (not wrist in men) even ribs (EPOS) Especially in first year after incident # (shared factors with falls?) Risk is exponential with increasing #

12. Oct 2008 NICE technological appraisal guidance TA 160: Alendronate, Etidronate, Risedronate & Strontium Ranelate for the primary prevention of osteoporotic fragility fractures in postmenpausal women TA 161: Alendronate, Etidronate, Risedronate, Raloxifene, Strontium Ranelate and Teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenpausal women

13. Hip and Spine DXA The ‘gold standard’ T score >-1.0SD = Normal -1.0 to –2.49SD = Osteopenia -2.5SD or below = Osteoporosis -2.5SD or below + fracture = Severe Osteoporosis Strict criteria = Hip BMD diagnosis has best predictive value (Hip BMD best predictor of hip # risk RR2.6)

16. Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D Vert fracture Non-vert fracture Hip fracture Alendronate A A A Etidronate A B nae Ibandronate A A# nae Risedronate A A A Zoledronate A A A Calcitonin A B B Calcitriol A B nae Raloxifene A nae nae Strontium ranelate A A A# Teriparatide A A nae Recom human PTH (1-84) A nae nae HRT A A A nae: not adequately evaluated # in subsets of patients only (post-hoc analysis) PTH: parathyroid hormone HRT: hormone replacement therapy

17. TA 160: Does not apply to women with a fracture, who have normal BMD or Osteopenia, on long term systemic corticosteroids Assumes woman adequate intake of Ca & Vit D Diagnosis assumed in women 75+ if clinician considers DXA scan clinically inappropriate or unfeasible Otherwise, Osteoporosis DXA T-score -2.5 SD or lower

18. Independent Clinical Risk Factors for Fracture (ICRFs) - parental hip fracture - alcohol 4 or more units per day - Rheumatoid Arthritis Indicators of low Bone Mineral Density - low BMI < 22 - medical conditions such as Ank Spondylitis, Crohns - prolonged immobility - untreated premature menopause (also fracture & steroids – not covered)

19. Alendronate 70years or older with Osteoporosis with 1 or more ICRF or 1 indicator of low BMD (75+: if have 2 ICRFs or 2 indicators of low BMD, DXA may not be required) 65-69 years with Osteoporosis with 1 ICRF 64 years or less with Osteoporosis with 1 ICRF or 1 indicator of low BMD

20. Risedronate or Etidronate where woman cannot comply with, or intolerant of, or contraindication for Alendronate

21. T-scores (SD) at (or below) which risedronate or etidronate is recommended when alendronate cannot be taken Age (years) Number of independent clinical risk factors for fracture 012 65–69–a–a −3.5−3.0 70–74−3.5−3.0−2.5 75 or older−3.0 −2.5 a Treatment with risedronate or etidronate is not recommended.

22. Strontium Ranelate - cannot comply, intolerant or contraindicted T-scores (SD) at (or below) which strontium ranelate is recommended when alendronate and either risedronate or etidronate cannot be taken Age (years) Number of independent clinical risk factors for fracture 012 65–69– a −4.5−4.0 70–74−4.5−4.0−3.5 75 or older−4.0 −3.0 a Treatment with strontium ranelate is not recommended.

23. Raloxifene - not recommended Example: 73 year old woman, parental hip fracture, T- score -2.7SD

25. TA 161: Does not apply to women who have normal BMD or Osteopenia, on long term systemic corticosteroids Assumes woman adequate intake of Ca & Vit D Diagnosis assumed in women 75+ if clinician considers DXA scan clinically inappropriate or unfeasible Otherwise, Osteoporosis DXA T-score -2.5 SD or lower

26. Independent Clinical Risk Factors for Fracture (ICRFs) - parental hip fracture - alcohol 4 or more units per day - Rheumatoid Arthritis

27. Alendronate Postmenopausal woman with Osteoporosis with fragility fracture (75+: DXA may not be required)

28. Risedronate or Etidronate where woman cannot comply with, or intolerant of, or contraindication for Alendronate T-scores (SD) at (or below) which risedronate or etidronate is recommended when alendronate cannot be taken Number of independent clinical risk factors for fracture Age (years)012 50–54– a −3.0−2.5 55–59−3.0 −2.5 60–64−3.0 −2.5 65–69−3.0−2.5 70 or older−2.5 a Treatment with risedronate or etidronate is not recommended

29. Strontium Ranelate or Raloxifene - cannot comply, intolerant or contraindicated T-scores (SD) at (or below) which strontium ranelate or raloxifene is recommended when alendronate and either risedronate or etidronate cannot be taken Number of independent clinical risk factors for fracture Age (years)012 50–54– a −3.5 55–59−4.0−3.5 60–64−4.0−3.5 65–69−4.0−3.5−3.0 70–74−3.0 −2.5 75 or older−3.0−2.5 a Treatment with raloxifene or strontium ranelate is not recommended

30. Teriparatide - cannot comply, intolerant or contraindicated - or unsatisfactory response to other drugs (fragility fracture & drop in BMD inspite of full adherence to Rx for 1 year) 65 years or older T-score of –4.0 SD or below T-score of –3.5 SD or below plus more than two fractures 55–64 years T-score of –4 SD or below plus more than two fractures.

31. Example: 73 year old woman, wrist fracture, parental hip fracture, T-score -2.7SD 63 year old woman, wrist fracture, parental hip fracture, T-score -2.7SD

32. Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D Vert fracture Non-vert fracture Hip fracture Alendronate A A A Etidronate A B nae Ibandronate A A# nae Risedronate A A A Zoledronate A A A Calcitonin A B B Calcitriol A B nae Raloxifene A nae nae Strontium ranelate A A A# Teriparatide A A nae Recom human PTH (1-84) A nae nae HRT A A A nae: not adequately evaluated # in subsets of patients only (post-hoc analysis) PTH: parathyroid hormone HRT: hormone replacement therapy

33. Risk of fracture Relative Absolute – e.g. 10 year risk of fracture BMD best single factor Clinical factors – poor sensitivity & specificity Some factors consistent Low BMI, Parental History of hip #, Fragility #, Current smoking, 3+ units alcohol, RhA, Current or previous steroids

34. FRAX & NOGG (see website)

35. 3 categories Low risk of fracture High risk of fracture Intermediate risk of fracture (Johansson et al Osteo Int 2009)

36. Investigations DXA FBC, ESR, U&E, LFTs, Ca, Phosphate, PTH, TFTs, Myeloma screen (men +/- male hormone profile)

37. Summary NICE TA 160 & 161 - recommend Alendronate as first-line - women intolerant of Alendronate may be left with no other treatment or have to wait until BMD deteriorates further - not easy to use and has inconsistencies - FRAX & NOGG easier to use and more consistent