2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada

1. 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

2. 2010 Guidelines Fracture Risk Assessment Section Four

3. Indications for BMD Testing in Older Adults (Age > 50 Years) • All women and men age > 65 • Postmenopausal women, and men aged 50 – 64 with clinical risk factorsfor fracture: • Fragility fracture after age 40 • Prolonged glucocorticoid use† • Other high-risk medication use* • Parental hip fracture • Vertebral fracture or osteopeniaidentified on X-ray • Current smoking • High alcohol intake • Low body weight (< 60 kg) or major weight loss (>10% of weight at age 25) • Rheumatoid arthritis • Other disorders strongly associated with osteoporosis †At least three months cumulative therapy in the previous year at a prednisone-equivalent dose ≥ 7.5 mg daily;* e.g. aromatase inhibitors, androgen deprivation therapy.

4. Indications for BMD Testing forIndividuals Under Age 50 Years • Fragility fracture • Prolonged use of glucocorticoids* • Use of other high-risk medications† • Hypogonadism or prematuremenopause • Malabsorption syndrome • Primary hyperparathyroidism • Other disorders strongly associated with rapid bone loss and/or fracture †At least three months cumulative therapy in the previous year at a prednisone-equivalent dose ≥ 7.5 mg daily;* e.g. aromatase inhibitors, androgen deprivation therapy.

5. BMD Reporting Categories Click here for a list of considerations about BMD reporting.

6. Absolute 10-year Fracture-Risk Tools • Tools validated in Canada (choice based on personal preference and convenience) • CAROC: Joint initiative of the Canadian Association of Radiologists and Osteoporosis Canada1 • FRAX: Fracture Risk Assessment Tool developed by the World Health Organization2 • There are large differences in fracture rates from country to country3-5 • Assessment tools need to be country specific 1. Leslie WD, Berger C, et al. Osteoporosi Int; In press.. 2. Leslie WD, Lix LM, et al. Osteoporosi Int; In press. 3. Kanis JA, et al. J Bone Miner Res 2002; 17(7):1237-1244. 4. Melton LJ, III. Endocrinol Metab Clin North Am 2003; 32(1):1-13. 5. Leslie WD, et al. J Bone Miner Res 2010; in press.

7. 10-year Risk Assessment: CAROC • Semiquantitative method for estimating 10-year absolute risk of a major osteoporotic fracture* in postmenopausal women and men over age 50 • Stratified into three zones (Low: < 10%, moderate, high: > 20%) • Basal risk category is obtained from age, sex, and T-score at the femoral neck • * Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus.  Other fractures attributable to osteoporosis are not reflected; total osteoporotic fracture burden is underestimated • Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.

8. 10-year Risk Assessment for Women (CAROC Basal Risk) Click here for CAROC risk assessment in table format. Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

9. 10-year Risk Assessment for Men (CAROC Basal Risk) Click here for CAROC risk assessment in table format. Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

10. Risk Assessment with CAROC:Important Additional Risk Factors • Factors that increase CAROCbasal risk by one category (i.e., from low to moderate ormoderate to high) • Fragility fracture after age 40*1,2 • Recent prolonged systemicglucocorticoid use**2 * Hip fracture, vertebral fracture, or multiple fracture events should be considered high risk ** >3 months use in the prior year at a prednisone-equivalent dose ≥ 7.5 mg daily • 1. Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188. • 2. Kanis JA, et al. J Bone Miner Res 2004; 19(6):893-899.

11. 0.0 -0.5 LOW RISK (<10%) -1.0 -1.5 Femoral neck T-score -2.0 MODERATE RISK -2.5 -3.0 HIGH RISK (> 20%) -3.5 -4.0 50 55 60 65 70 75 80 85 Age (years) Example of Adjusting Basal Risk:Based on Additional Risk Factors • 60-year-old woman • Femoral neckT-score = -2.8 • Based on age and T-score alone = moderate risk • History of fragilityfracture or prolonged systemic glucocorticoid use would shift her to high risk Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

12. Risk Assessment Using FRAX • Uses age, sex, BMD, and clinical risk factors tocalculate 10-year fracture risk* • BMD must be femoral neck • FRAX also computes 10-year probability of hip fracturealone • This system has been validated for use in Canada1 • There is an online FRAX calculator with detailedinstructions at: www.shef.ac.uk/FRAX • * composite of hip, vertebra, forearm, and humerus • 1. Leslie WD, et al. Osteoporos Int; In press.

13. FRAX Tool: On-line Calculator • www.shef.ac.uk/FRAX.

14. FRAX Clinical Risk Factors • Parental hip fracture • Prior fracture • Glucocorticoid use • Current smoking • High alcohol intake • Rheumatoid arthritis

15. Absolute Fracture Risk Tools • Calculate risk for treatment-naïve patients only • Cannot be used to monitor response to therapy • Using CAROC or FRAX in a patient on therapy only reflects the theoretical risk of a hypothetical patient who is treatment naïve and does not reflect the risk reduction associated with therapy

16. Laboratory assessment:Bone Turnover Markers (BTMs) • The value of bone turnover markers (BTMs) in estimating future risk of fracture in individual patients needs further research • As a result, BTMs have not yet been integrated in current fracture-risk assessment systems Brown JP, et al. Clin Biochem 2009; 42(10-11):929-42.

17. VFA Recognition and Reporting • VFA is a scanning and software option on bone densitometers • A fracture detected by vertebral fracture assessment (VFA) or radiograph should be considered a prior fracture under the FRAX or CAROC system

18. JB6/23/04;WW5/11/04 IVA/VFA VFA • On the left we see a normal lateral VFA (vertebral fracture assessment) showing no vertebral fracture as high as we can see (T6). • On the right, we see a lateral VFA with a wedge fracture of T12

19. Impact of Prior Vertebral Fractureon Risk Assessment • Unequivocal vertebral fractures unrelated to trauma are associated with a five-fold increased risk for recurrent vertebral fractures • A fracture detected from VFA or radiograph alone should be considered a prior fracture under the FRAX or CAROC system

20. Fracture Risk Assessment after Age 50: Summary Statements Click here for a summary of the grading system for levels of evidence.

21. Recommendations for Fracture Risk Assessment Click here for a summary of the grading system for levels of evidence.

22. Recommendations for Fracture Risk Assessment (Cont'd)

23. Back-up Material Additional slides that can be accessed fromhyperlinks on core slides Section Four – Fracture Risk Assessment

24. Disorders Associated with Osteoporosisand Increased Fracture Risk • Primary hyperparathyroidism • Type I diabetes • Osteogenesis imperfecta • Untreated long-standing hyperthyroidism, hypogonadism, orpremature menopause (< 45 years) • Cushing’s disease • Chronic malnutrition or malabsorption • Chronic liver disease • Chronic obstructive pulmonary disease (COPD) • Chronic inflammatory conditions (e.g., rheumatoid arthritis [RA],inflammatory bowel disease) Return to main presentation

25. Considerations for BMD Reporting • T-score is the number of standard deviations that BMD is above or below the mean normal peak BMD for young white women (NHANES III for hip measurements) • Z-score is the number of standard deviations that BMD is above or below the mean normal BMD for sex, age, and (if references are available) race/ethnicity

26. Considerations for BMD Reporting (Cont'd) • Osteoporosis cannot be diagnosed by BMD alonebelow age 50 • BMD reporting is based upon lowest value for lumbarspine (minimum two vertebral levels), total hip, andfemoral neck • If either the lumbar spine or hip is invalid, then the forearmshould be scanned and the distal one-third region reported • Fracture risk assessment under the FRAX / CAROCsystem is based upon the femoral neckT-score only Return to main presentation

27. Variations in Estimated FRAX 10-YearFracture Probabilities According to Country Canada Return to main presentation Version 3.1 FRAX website (www.sheffield.ac.uk/FRAX).

28. 4.0 3.5 Serum BAP 3.2 (1.4-7.4) Urinary CTX 3.0 2.5 2.1 (1.1-4.4) 1.8 (0.8-4.6) 2.0 Relative risk 1.3 (0.5-3.1) 1.5 1.2 (0.5-2.8) 0.7 (0.3-1.8) 1.0 0.5 0.0 Q1 Q2 Q3 Q4 Bone marker levels in quartiles Bone Turnover Markers and FractureRisk in Postmenopausal Women • Garnero P, et al. J Bone Miner Res 2000; 15(8):1526-1536.

29. Hip Fracture Risk: BMD and BTM Return to main presentation • Johnell O, et al. Osteoporos Int 2002; 13(7):523-526.

30. Criteria Used to Assign Levels ofEvidence: Studies of Diagnosis

31. Criteria Used to Assign Levels of Evidence:Studies of Treatment and Intervention RCT = randomized, controlled study

32. Criteria Used to Assign Levels ofEvidence: Studies of Prognosis Return to main presentation

33. Criteria Used to AssignGrades of Recommendation * As appropriate level of evidence was necessary, but not sufficient to assigna grade in recommendation; consensus was required in addition. Return to main presentation

34. 10-year Risk Assessment for Women (CAROC Basal Risk) Return to main presentation Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

35. 10-year Risk Assessment for Men (CAROC Basal Risk) Return to main presentation Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].