Case Study #1 Mrs. DT

1. 2010 Guidelines Case Study #1Mrs. DT

2. Case Presentation • Age 59: nine years post-menopause with treated osteoporosis • Has always enjoyed excellent health with no past medical or surgical history • Comes in for her periodic health exam—concerned about calcium and cardiovascular risk

3. Physical Examination • Height = 154 cm (60.5 in.) • Weight = 55.5 kg (122 lbs.) • No significant changes in height, weight, posture, or gait from previous visits • Changes in height and weight can be signs of vertebral fractures

4. Medications • Risedronate 35 mg weekly for past six years • Calcium 600 mg + vitamin D 400 IU (single-tablet supplement)

5. History of Osteoporosis:T-scores and Treatment Decisions

6. Current Risk Factor Assessment • Non-smoker, no regular alcohol consumption • No previous history of fracture • No parental history of hip fracture • No history of systemic glucocorticoid use • No comorbidities • Diet rich in calcium (1200 mg daily from foods) • High caffeine intake

7. Question • Were the diagnosis and treatment initiation in line with today's guideline recommendations?

8. Reflections on theDecision-making Process • Previous diagnosis and treatment decisions were largely based on bone density T-scores • 2010 osteoporosis guidelines advocate making decisions based on an assessment of overall 10-year fracture risk • Tools endorsed: CAROC and FRAX • Current recommendations for: • Calcium: 1200 mg from diet and supplement combined • Vitamin D: 800 – 2000 IU daily for age over 50

9. Should This Patient Have Been Receiving Treatment? FRAX 10-year Risk Assessment

10. FRAX Calculation of Original Risk(Age 53 – Six Years Ago)

11. Mrs. DT: Reflection on Diagnosis • Six years ago, the diagnosis and therapy were appropriate, given the low BMD at the femoral neck (-2.4) and two minor risk factors (weight < 57kg, high caffeine intake) • With today's tools (e.g., CAROC, FRAX), however, Mrs. DT would have been low risk • Treatment would not have been recommended under the current system

12. Question • Would you consider using a risk-assessment tool to check Mrs. DT's current level of risk on treatment?

13. 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 • One could use these tools to assess what the risk might be for a woman like Mrs. DT who had never been treated

14. FRAX Calculation of Risk for a Woman Like Mrs. DT, but Who Had Never Been Treated

15. Question • What would you do in this case? • Would you continue or discontinue treatment with risedronate? • Discuss the rationale for your decision

16. Mrs. DT: Conclusions • Diagnosis and treatment decisions should now be based on 10-year assessment of risk using a validated tool • Patients at low risk (10-year risk < 10%) should not be receiving treatment • Her current risk level is not known: • 10-year absolute risk tools were developed to assess patients who are treatment naive • Mrs. DT currently gets adequate calcium from her diet (~1200 mg daily) • Calcium supplementation should be stopped • Vitamin D supplementation should continue

17. Back-up Material Additional slides that can be accessed from hyperlinks on case slides Case 1 – Mrs. DT

18. Potential Risks of Calcium Supplementation • High-dose calcium supplementation has been associated with • Renalcalculi in older women • Cardiovascular events in older women • Prostate cancer in older men 1. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181. 2. Bolland MJ, et al. BMJ 2008; 336(7638):262-266. 3. Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123. Return to case

19. Importance of Weight • In men > 50 years and in postmenopausal women, the following are associated with low BMD and fractures • Low body weight (< 60 kg) • Major weight loss (> 10% of weight at age 25) 1. Papaioannou A, et al. Osteoporos Int 2009; 20(5):703-715. 2. Waugh EJ, et al. Osteoporos Int 2009; 20:1-21. 3. Cummings SR,et al. N Engl J Med 1995; 332(12):767-773. 4. Papaioannou A, et al. Osteoporos Int 2005; 16(5):568-578. 5. Kanis J, et al. Osteoporos Int 1999; 9:45-54. 6. Morin S, et al. Osteoporos Int 2009; 20(3):363-70. Return to case

20. Importance of Height Loss • Increased risk of vertebral fracture: • Historical height loss (> 6 cm)1,2 • Measured height loss (> 2 cm)3-5 • Significant height loss should be investigated by a lateral thoracic and lumbar spineX-ray 1. Siminoski K, et al. Osteoporos Int 2006; 17(2):290-296. 2. Briot K, et al. CMAJ 2010; 182(6):558-562. 3. Moayyeri A, et al. J Bone Miner Res 2008; 23:425-432. 4. Siminoski K, et al. Osteoporos Int 2005; 16(4):403-410. 5. Kaptoge S, et al. J Bone Miner Res 2004; 19:1982-1993. Return to case

21. First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* Return to case * For postmenopausal women,  indicates first line therapies and Grade A recommendation. For men requiring treatment,alendronate, risedronate, and zoledronic acid can be used as first line therapies for prevention of fractures [Grade D]. + In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle. ** Hormone therapy (estrogen) can be used as first line therapy in women with menopausal symptoms.

22. 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 • Other fractures attributable to osteoporosis are not reflected; total osteoporotic fracture burden is underestimated • * Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus • Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188.

23. 10-year Risk Assessment for Women (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

24. 10-year Risk Assessment for Women (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

25. 10-year Risk Assessment for Men (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

26. 10-year Risk Assessment for Men (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

27. Risk Assessment with CAROC: Important Additional Risk Factors • Factors that increase CAROC basal risk by one category (i.e., from low to moderate or moderate to high) • Fragility fracture after age 40*1,2 • Recent prolonged systemic glucocorticoid 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. Return to case

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

29. FRAX Tool: Online Calculator • www.shef.ac.uk/FRAX.

30. FRAX Clinical Risk Factors • Parental hip fracture • Prior fracture • Glucocorticoid use • Current smoking • High alcohol intake • Rheumatoid arthritis Return to case

31. Recommended Vitamin D Supplementation Hanley DA, et al. CMAJ 2010; Jul 26. [epub before print].

32. Vitamin D: Optimal Levels • To most consistently improve clinical outcomes such as fracture risk, an optimal serum level of 25-hydroxy vitamin D is probably > 75 nmol/L • For most Canadians, supplementation is needed to achieve this level Hanley DA, et al. CMAJ 2010; 182:E610-E618.

33. When to Measure Serum 25-OH-D • In situations where deficiency is suspected or where levels would affect response to therapy • Individuals with impaired intestinal absorption • Patients with osteoporosis requiring pharmacotherapy • Should be checked no sooner than three months after commencing standard-dose supplementation in osteoporosis • Monitoring of routine supplement use and routine screening of otherwise healthy individuals are not necessary Return to case Hanley DA, et al. CMAJ 2010; 182:E610-E618.

34. Recommended Calcium Intake • From diet and supplementscombined: 1200 mg daily • Several different types of calciumsupplements are available • Evidence shows a benefit ofcalcium on reduction of fracturerisk1 • Concerns about serious adverse effects with high-dose supplementation2-4 1. Tang BM, et al. Lancet 2007; 370(9588):657-666. 2. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181. 3. Bolland MJ, et al. BMJ 2008; 336(7638):262-266. 4 Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123. Return to case