International Osteoporosis Foundation & European Society of Musculoskeletal Radiology

1. International Osteoporosis Foundation&European Society of Musculoskeletal Radiology VERTEBRAL FRACTURE INITIATIVESlide Kit Part 1: Osteoporosis and Related Fractures: An Under-diagnosed and Under-treated Public Health Issue

2. Why is the Vertebral Fracture Initiative needed? • Most vertebral fractures are a complication of osteoporosis and increase the likelihood of subsequent fractures • Currently mild and moderate vertebral fractures are often not being recognised and reported, leading to under-diagnosis and under-treatment • Radiographic diagnosis is considered the best way to identify and confirm the presence of vertebral fractures in clinical practice • All vertebral fractures identified should be reported as FRACTURED to avoid ambiguity caused by other terminology • Early radiographic diagnosis followed by appropriate therapy will help prevent subsequent fractures

3. What is the Vertebral Fracture Initiative? • An educational initiative to improve recognition and reporting of vertebral fractures: Pilot phase in five European countries Teaching Faculty • Initiative Leaders:Harry K. Genant & Pierre D. Delmas • France: Jean-Denis Larédo & Pierre D. Delmas • Germany: Helmut Minne & Michael Jergas / Dieter Felsenberg • Italy: Silvano Adami & Giuseppe Guglielmi • Spain: Jorge Cannata & Francisco Aparisi • UK: David Reid & Judith Adams A clinician and radiologist team taking the lead in each country

4. What does the Vertebral Fracture Initiative include? 1. Presentations at radiology conferences 2. Articles in radiology & related publications 3. A resource document and a slide kit including: Part 1. Osteoporosis and Related Fractures: An Under-diagnosed and Under-Treated Public Health Issue Part 2. Recognition and Reporting of Vertebral Fractures 4. Summary handout 5. Interactive teaching programme on CD-ROM Teaching tools available from: www.osteofound.org

5. Definition of Osteoporosis A disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. World Health Organization (WHO) , 1994 Normal bone Osteoporosis

6. OSTEOPOROSIS:THE SIZE OF THE PROBLEM

7. Osteoporosis is a Prevalent Disease • Affects 200 million women worldwide1 - 1/3 of women aged 60 to 70 - 2/3 of women aged 80 or older • Approximately 20-25% of women over the age of 50 have one or more vertebral fractures2 - United States: 25%3 - Australia: 20%4 - Western Europe: 19%5 - Scandinavia: 26%5 - Denmark: 21%6 1. International Osteoporosis Foundation 4. Jones G et al., Osteoporos Int 1996, 6:233 2. Melton LJ 3rd et al., Spine 1997, 22:2S 5. O'Neill et al., J Bone Miner Res 1996, 11:1010 3. Ettinger B et al., J Bone Miner Res 1992,7:449 6. Jensen GF et al., Clin Orthop 1982,166:75

8. 40 30 20 10 Vertebrae Annual incidence per 1000 women Hip Wrist 50 60 70 80 Age (Years) Incidence Rates for Vertebral, Wrist & Hip Fractures in Women after Age 50 Wasnich RD, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th edition, 1999

9. 2000 *annual incidence all ages † annual estimate women 29+ ‡annual estimate women 30+ §1996 new cases, all ages 1 500 000* 1500 250 000hip 250 000forearm Annual incidence x 1000 1000 250 000 other sites 513 000† 500 750 000 vertebral 228 000‡ 184 300§ 0 Osteoporotic Fractures Heart Attack Stroke Breast Cancer Osteoporotic Fractures in Women: Comparison with Other Diseases Riggs BL, Melton LJ. Bone 1995 Heart and Stroke Facts, 1996, American Heart Association Cancer Facts & Figures, 1996, American Cancer Society

10. 3250 1990 2050 800 600 Estimated number hip fractures (x1000) 400 200 0 North America Europe Latin America Asia Projected Burden of Osteoporotic Hip Fractures Worldwide Total no. hip fractures1990 = 1.66 million2050 = 6.26 million Adapted from Cooper C., Melton LJ, Osteoporos Int 1992, 2:285

11. OSTEOPOROSIS: MORTALITY & MORBIDITY

12. Hip Fracture vs. Stroke Mortality:Death Rates per 100,000 in Older Women Hip Fracture Stroke Sweden 177 154 Denmark 154 180 Germany 131 190 Hip fracture data: age 80; Kanis JA, J Bone Miner Res 2002, 17:1237 Stroke data: ages 65-74; Sans et al., Eur Heart J 1997, 18:1231

13. Relative Risk of Death Following Clinical FracturesFracture Intervention Trial (FIT)* *6459 postmenopausal women ages 55-81 years followed for an average of 3.8 years Any Symptomatic Non-spine 6.7 Hip 8.6 Spine Forearm Other 0 1 2 5 10 16 Age-Adjusted Relative Risk (95% CI) Cauley JA et al., Osteoporos Int 2000, 11:556

14. Dubbo Population Vertebral/Major Fractures Proximal Femur Fractures 1.0 1.0 0.8 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0 0 Cumulative Survival Probability Center JR et al., Lancet 1999, 353:878 WOMEN MEN Survival probability Survival probability 60 65 70 75 80 85 60 65 70 75 80 85 Age Age

15. Mortality Rates by Number of Prevalent Vertebral Fractures Kado DM et al., Arch Intern Med 1999,159:1215 45 40 35 30 25 Mortality (per 1000 person-years) 20 15 10 5 0 5+ 0 1 2 3 4 Number of Vertebral Fractures P for trend < 0.001

16. Clinical Consequences • Kyphosis • Loss of height • Bulging abdomen • Acute and chronic pain • Breathing difficulties, reflux and other GI symptoms • Depression REDUCED QUALITY OF LIFE

17. Vertebral Fractures Substantially Increase the Risk of New Fragility Fractures • Women with vertebral fractures have a5-fold increased riskof a newvertebral fractureand a2-fold increased risk of hip fracture Black et al., J Bone Miner Res 1999 Melton et al, Osteoporos Int 1999 • One woman in fivewill suffer from another vertebral fracturewithin a year Lindsay et al., JAMA, 2001

18. Effect of Prior Vertebral Fracture on Risk of Subsequent Vertebral Fracture First Year of Study 2725 postmenopausal women randomised to placebo 15 RR=7.3 (4.4, 12.3) RR=5.1 (3.1, 8.4) 10 Incidence of New Vertebral Fracture (%) RR=2.6 (1.4, 4.9) 5 0 1 2 0 1 No. of Vertebral Fractures at Baseline Adapted from Lindsay R et al., JAMA 2001, 285:320

19. All Types of Vertebral Fractures are Associated With Morbidity Nevitt MC et al., Arch Intern Med.2000, 160:77 93.2 100 Limited Activity 76.2 Bed Rest 75 Due to back pain 52.7 Patients (%) 50 36.8 26.9 25 3.9 0 No Incident Fracture Radiographic Fracture Clinical Fracture

20. Vertebral Fractures in Summary • Arethe most commonosteoporotic fractures • Are associated withexcess mortality • Are associated withsignificant morbidity,even if they do not come to clinical attention • Increase the risk of subsequent vertebral fracture(s)by 5 fold and ofother fragility fractures(including hip) by 2 fold

21. COST OF OSTEOPOROSIS

22. Some Costs of Osteoporosis in Europe • In Europe the total direct costs of osteoporotic fractures are over €31 billion and are expected to increase to more that €76 billion in 2050. Kanis JA & Johnell O. - Osteoporos Int 2005 (in press) • In France osteoporotic hip fractures are estimated to cost about €1 billion every year* • In Spain the total direct hospital cost of osteoporotic fractures in 1995 was approximately €222 million* • In England & Wales the total direct hospital cost of osteoporotic fractures in 1999 was approximately €847 million* *Osteoporosis in the European Community: A Call to Action. IOF Nov, 2001

23. Osteoporosis Results in More Disability & Direct Hospital Cost Than Many Other Diseases • 8% of vertebral fractures are hospitalised and 2% require long-term nursing care Ross et al., Am Journal of Medicine 1997, 103(2A):30S – 42S • Annual cost of acute hospitalisation in Switzerland in 1992: 600 million Swiss francs (US$350 million) Lippuner et al., Osteoporosis Int 1997, 7:414-25 – Number of bed days (men & women) • 891,000 for COPD • 701,000 for osteoporosis • 533,000 for stroke • 328,000 for myocardial infarction • 201,000 for breast cancer Osteoporosis # 1 when looking at women only

24. UNDER-DIAGNOSIS OF VERTEBRAL FRACTURES:WHAT IS THE SIZE OF THE PROBLEM?

25. A Retrospective Study Suggests that Vertebral Fractures are Under-Diagnosed Gehlbach et al.,Osteoporos Int 2000, 11:577 132 140 934 hospitalised women with a lateral chest x-ray 120 100 80 65 Patients (n) 60 40 25 23 20 0 Fracture identified by study radiologists Fracture noted in radiology report Fracture noted in medical record Received osteoporosis treatment

26. A Large Prospective Study Demonstrates Under-Diagnosis of Vertebral Fractures is a Worldwide Problem • Vertebral fractures were markedly under-diagnosed in radiology reports in a multicenter, multinational study population of osteoporotic women (n=2451) in which 789 (32%) women had 1 vertebral fracture at baseline. • Adjudicated discrepancies (n=350) between local and central readings due to undetected vertebral fracture (68%) or equivocal terminology in the local radiology report (32%) yielded a false-negative rate of 34%. • Under-diagnosis of vertebral fractures was observed in all geographic regions (false-negative rates: North America 45.2%, Latin America 46.5%, Europe/South Africa/Australia 29.5%). The false-positive rate was 5% globally. • Under-diagnosis of vertebral fracture is a worldwide problem attributable in part to a lack of radiographic detection or use of ambiguous terminology in the radiology report, or both. Delmas et al., J Bone Miner Res 2005, in press.

27. Awareness & Treatment of Vertebral Fractures in Europe is Low Despite… • Knowndisabilityassociated with all fractures • Excess mortality associated with vertebral and hip fractures • €31 billion total direct hospitalcostsin Europe • A validatedradiographic diagnosistechnique • Effective and safe treatments • Evidence based guidelinesfor diagnosis and management

28. Effective therapies are widely available and can reduce vertebral, hip and other fractures by 30% to 65%.

29. Antifracture Efficacy of Antiosteoporotic Agents Incident vertebral fractures - Relative risk RR ± 95% CI Updated from Delmas, Lancet 2002 RLX 60 (MORE)* RLX 60 (MORE)** ALN 5/10 (FIT1)* ALN 5/10 (FIT2)** RIS 5 (VERT - NA)* RIS 5 (VERT - MN)* CT 200 (PROOF)* Teriparatide 20µg Strontium ranelate (SOTI)* Strontium ranelate (SOTI + TROPOS)** 0.4 0.6 0.8 1.0 0.2 * with prev vert fracture(s) ** without prev vert fractures

30. RECOGNITION & REPORTING OF VERTEBRAL FRACTURES

31. Normal (Grade 0) Wedge fracture Biconcave fracture Crush fracture Mild fracture (Grade 1, ~20-25%) Moderate fracture (Grade 2, ~25-40%) Severe fracture (Grade 3, ~40%) Vertebral FracturesSemi-quantitative reading / visual scoring Genant et al., J Bone Miner Res 1993, 8:137

32. SQ Mild FX SQ Severe FX 3 1 1 3

33. Single Energy Fan-beam DXA Imaging a Potential Alternative to Conventional Radiographs • Singleenergy imaging • Fast (10 sec) scanning / breath hold • Simple visual evaluation • Low dose (1/100 of radiographs) • Available at point of care

34. Lateral Vertebral Assessment: …Point-of-Care tools

35. Combining BMD & Vertebral Fracture Assessment: A New Approach to Improve the Diagnosis Rate of Vertebral Fractures • Improve risk assessment • Identify many (~30%) of “missed” fractures • Improve targeting of therapy • May improve patient understanding, acceptance and compliance

36. Conclusions • Most vertebral fractures are a complication of osteoporosis and increase the likelihood of subsequent fractures • Currently mild and moderate vertebral fractures are often not being recognised and reported, leading to under-diagnosis and under-treatment • Radiographic diagnosis is considered the best way to identify and confirm the presence of vertebral fractures in clinical practice • All vertebral fractures identified should be reported as FRACTURED to avoid ambiguity caused by other terminology • Early radiographic diagnosis followed by appropriate therapy will help prevent subsequent fractures – Effective therapies are widely available and can reduce vertebral, hip and other fragility fractures by 30% to 65%.

37. Action is needed by Radiologists to ensure: • Recognition of vertebral fractures using radiography imaging techniques • Reporting as FRACTURED to avoid ambiguity • These actions will help patients receive effective treatment and prevent subsequent fractures This is the goal of the IOF / ESSR Vertebral Fracture Initiative