Case Study #4: Mr. JM

1. 2010 Guidelines Case Study #4:Mr. JM

2. Case Presentation • 64-year-old retired firefighter • Retired nine years ago; now doing contract carpentry • Presents for physical examination, complaining his back has been “worse than usual” the past three weeks • On no medications • Prior smoker (45 pack/year history) • Quit smoking one year ago

3. Physical Examination • Height: 180 cm (5'11") • Patient recalls being 185.5 cm (6'1") • Weight: 80 kg (up 5 kg from one year ago) • Body mass index (BMI): 24.7 kg/m2 • Changes in height and weight can be signs of vertebral fractures • Other indicators of vertebral fracture in physical examination: Rib-pelvis distance and occiput-wall distance

4. Risk Factor Assessment • Family history: none significant • No history of systemic glucocorticoids or androgen-deprivation therapy • No history of secondary causes of osteoporosis • Historical height loss • No previous trauma • Alcohol use: approximately two drinks per week Click here for a discussion of factors known to increase fracture risk in men.

5. Why is Osteoporosis Underappreciated in Men? • Men have higher peak bone mass • Slower rate of bone loss • Shorter life expectancy • Greater periosteal bone formation (greater cross-sectional bone diameter and a biomechanical advantage since larger bones have less fracture risk) Khan AA, et al. CMAJ 2007;176(3):345-348.

6. Question • What tests would you consider ordering?

7. Mr. JM: Diagnostic Testing • Screening for osteoporosis with dual energy X-ray absorptiometry (DXA) is indicated, based on 2010 guideline criteria • T-score -1.9 at femoral neck • Lateral thoraco-lumbar spine X-ray is ordered to rule out vertebral compression deformities • The radiologist makes note of two vertebrae being wedge shaped and just meeting the criteria for vertebral compression fracture

8. Question • Given the presence of vertebral fractures, is further risk assessment necessary before initiating pharmacologic therapy?

9. Considerations for Therapy • The guidelines do recommend that diagnosis and treatment decisions should be based on a validated 10-year risk-assessment tool (i.e., CAROC or FRAX) • FRAX predicts 12% risk (moderate)1 • However, the presence of multiple vertebral fractures in this case place Mr. JM at high risk • In fact, 10-year assessment tools underestimate risk in patients with vertebral fractures 1. Leslie WD, Lix LM, et al. Osteoporos Int 2010. In press.

10. Question • How would you proceed with therapy for Mr. JM?

11. Treatment Considerations • Bloodwork to rule out secondary causes of osteoporosis • Assume vitamin D level is low and start supplementation (with calcium) • According to the 2010 OC guidelines • Pharmacotherapy is indicated for a high-risk patient (see integrated management model) • Testosterone therapy is not recommended

12. Mr. JM: Conclusions • Mr. JM is high risk because of his vertebral fractures • In this case, 10-year assessment tools underestimate risk • Patients at high risk benefit from pharmacologic therapy • Recommended agents for first-line use in men are alendronate, risedronate, or zoledronic acid

13. Back-up Material Additional slides that can be accessed from hyperlinks on case slides Case 4 – Mr. JM

14. Importance of Weight • In men > 50 years and postmenopausal women, the following are associated with low bone mineral density (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

15. 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

16. Additional Tests for Clinical Identification of Vertebral Fracture 1. Olszynski WP, et al. BMC Musculoskeletal Disorders 2002; 3:22. 2. Green AD, et al. JAMA 2004; 292(23):2890-2900. 3. Siminoski K, et al. J Bone Miner Res 2001; 16(Suppl):S274.

17. Height loss 4 cm 3 cm 8 cm 12 cm 8 cm 3 FBs 2 FBs Rib-Pelvis and Occiput-to-Wall Distances Return to case

18. Risk Factors with Good Evidence for Low BMD in men • Advancing age • Between 50 and 80 years, men have1.5% – 2.5% decline in hip BMD per year • BMD at lumbral-sacral spine increases with age (falsely elevated due to osteophyte formation) • Smoking • Current smokers have greater risk of low BMD at the hip compared to former smokers. • Highest risk subgroups • Men > 20 pack years • Current smokers with low body weight (< 75 kgs) Papaioannou A, et al. Osteoporosis Int 2009;20:507-518.

19. Risk Factors with Good Evidence for Low BMD in Men • Low weight/weight loss • BMD at the hip increases roughly 3% – 7% for every 10 kg weight gain • Low baseline weight/BMI predicts subsequent bone loss at the hip • Physical functional limitations • Men who can rise from a chair without using arms have 2% – 4% higher hip BMD than those who cannot • Prevalent fracture after 50 years of age Return to case Papaioannou A, et al. Osteoporosis Int 2009;20:507-518.

20. Indications for BMD Testing • All women and men age > 65 • Postmenopausal women, and men aged 50 – 64 with clinical risk factors for 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. Return to case

21. Plain RadiographicExaminations of the Spine

22. Other RadiographicExaminations of the Spine Return to case

23. 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.

24. 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].

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

26. 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

27. 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.

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

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

30. Recommended Biochemical Tests for Patients Being Assessed for Osteoporosis • Calcium, corrected for albumin • Complete blood count • Creatinine • Alkaline phosphatase • Thyroid stimulating hormone (TSH) • Serum protein electrophoresis for patients with vertebral fractures • 25-hydroxy vitamin D (25-OH-D)* * Should be measured after three to four months of adequate supplementation and should not be repeated if an optimal level ≥ 75 nmol/L is achieved.

31. Tests for Potential Secondary Causes Return to case

32. Recommended Vitamin D Supplementation Hanley DA, et al. CMAJ 2010; 182:E610-E618.

33. 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.

34. 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 Hanley DA, et al. CMAJ 2010; 182:E610-E618.

35. Recommended Calcium Intake • From diet and supplementscombined: 1200 mg daily • Several different types of calcium supplements 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

36. Agents Recommended First-line for Fracture Prevention in Men • Alendronate • Risedronate • Zoledronic acid Return to case

37. Integrated Approach to Management ofPatients Who Are at Risk for Fracture Encourage basic bone health for all individuals over age 50, including regular active weight-bearing exercise, calcium (diet and supplementation) 1200 mg daily, vitamin D 800-2000 IU (20-50µg) daily and fall-prevention strategies Age < 50 yr Age 50-64 yr Age > 65 yr • Fragility fractures • Use of high-risk medications • Hypogonadism • Malabsorption syndromes • Chronic inflammatory conditions • Primary hyperparathyroidism • Other disorders strongly associated with rapid bone loss or fractures • Fragility fracture after age 40 • Prolonged use of glucocorticoids or other high-risk medications • Parental hip fracture • Vertebral fracture or osteopenia identified on radiography • High alcohol intake or current smoking • Low body weight (< 60 kg) or major weight loss (> 10% of body weight at age 25) • Other disorders strongly associated with osteoporosis • All men and women Initial BMD Testing

38. Integrated Approach, Continued Initial BMD Testing Assessment of fracture risk Low risk (10-year fracture risk < 10%) Moderate risk (10-year fracture risk 10%-20%) High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Unlikely to benefit from pharmacotherapy Reassess in 5 yr Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures Always consider patient preference Factors warranting consideration of pharmacologic therapy… Good evidence of benefit from pharmacotherapy

39. Integrated Approach, Continued Initial BMD Testing Assessment of fracture risk Low risk (10-year fracture risk < 10%) Moderate risk (10-year fracture risk 10%-20%) High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Unlikely to benefit from pharmacotherapy Reassess in 5 yr Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures Always consider patient preference Factors warranting consideration of pharmacologic therapy… Good evidence of benefit from pharmacotherapy

40. Integrated Approach, Continued Initial BMD Testing Assessment of fracture risk Low risk (10-year fracture risk < 10%) Moderate risk (10-year fracture risk 10%-20%) High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Unlikely to benefit from pharmacotherapy Reassess in 5 yr Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures Always consider patient preference Factors warranting consideration of pharmacologic therapy… Good evidence of benefit from pharmacotherapy

41. Moderate risk (10-year fracture risk 10%-20%) Integrated Approach, Continued Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures • Factors warranting consideration of pharmacologic therapy: • Additional vertebral fracture(s) (by vertebral fracture assessment or lateral spine radiograph) • Previous wrist fracture in individuals aged > 65 or those withT-score < -2.5 • Lumbar spine T-score much lower than femoral neck T-score • Rapid bone loss • Men undergoing androgen-deprivation therapy for prostate cancer • Women undergoing aromatase inhibitor therapy for breast cancer • Long-term or repeated use of systemic glucocorticoids (oral or parenteral) not meeting conventional criteria for recent prolonged use • Recurrent falls (> 2 in the past 12 mo) • Other disorders strongly associated with osteoporosis, rapid bone loss or fractures Good evidence of benefit from pharmaco-therapy Repeat BMD in 1-3 yr and reassess risk

42. Moderate risk (10-year fracture risk 10%-20%) Integrated Approach, Continued Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures • Factors warranting consideration of pharmacotherapy: • Additional vertebral fracture(s) (by vertebral fracture assessment or lateral spine radiograph) • Previous wrist fracture in individuals aged > 65 or those with T-score < -2.5 • Lumbar spine T-score much lower than femoral neck T- score • Rapid bone loss • Men on ADT for prostate cancer • Women on AI for breast cancer • Long-term or repeated use of systemic glucocorticoids (oral or parenteral) not meeting conventional criteria for recent prolonged use • Recurrent falls (> 2 in the past 12 mo) • Other disorders strongly associated with osteoporosis, rapid bone loss or fractures Good evidence of benefit from pharmaco-therapy Repeat BMD in 1-3 yr and reassess risk Return to case

43. Testosterone in Men: Summary Statement and Recommendation Return to case