Case Study #5: Mrs. FB

1. 2010 Guidelines Case Study #5:Mrs. FB

2. Case Presentation • 82-year-old woman who recently fell at home • Slipped while in the bathroom • History of two previous falls • One coming down stairs four months ago; no serious injury • One on her driveway last year: right distal radial wrist fracture • Has a fear of falling

3. Past Medical History • Hypertension • Depression (after death of her husband seven years ago); no prior episodes • Insomnia • Gastroesophageal reflux (GERD) • Dependent pedal edema • Cholecystectomy

4. Medications • Hydrochlorothiazide 25 mg daily • Amlodipine 10 mg daily • Ramipril 10 mg daily • Sertraline 100 mg daily • Lorazepam 1 mg daily (at bedtime) • Calcium 500 mg daily • Multivitamin 1 daily

5. Social History • New to your practice (her previous family physician recently retired) • Lives alone in the community in a small two-storey house (her home of 40 years) • One supportive daughter (your patient) • Non-smoker (never smoked) • One alcoholic drink (“a small glass of wine with dinner”) most evenings • Relatively inactive physically (“no one to walk with”) • Husband died seven years ago • Retired bookkeeper

6. Functional History • Independent in all basic activities of daily living (e.g., dressing, transferring, bathing) • Daughter assists with weekly shopping; she is independent in all other instrumental daily activities (e.g., medication management, telephone, laundry and housekeeping) • Limited driving: “daytime/fair-weather” • No accidents • Receives no professional services at home

7. Family History • Mother became very stooped, but no history of fractures • Father had hypertension

8. Physical Examination • Height: 155 cm (61 inches) • “I used to be 5’ 4” • Weight: 54.5 kg (120 lbs) • Body mass index (BMI): 22.7 • Blood pressure: supine,125/80 mmHg; standing 105/70 mmHg • Rib-to-pelvis: one finger • Get-up-and-go test (timed): Can’t rise from chair without arm rests; Needs to steady herself before walking; 16 seconds for 3 m • One-foot stand: < 1 second on either foot • Mild kyphosis

9. Cognitive Assessment • Montreal Cognitive Assessment:1 27/30 • Not cognitively impaired • Geriatric Depression Scale (15-item):2 4/15 • Not depressed 1. Available online at: http://www.mocatest.org/ 2. Available online at: http://www.rgpc.ca/

10. Question • What impact does the fall history have on Mrs. FB's risk for osteoporosis and future fractures?

11. Falls Risk Assessment • The 2010 guidelines state that a history of falls over the past year should be elicited, and if positive, should prompt a falls risk assessment • History of falls in the last year is one of the most significant risk factors for predicting future fall1-6 • Dementia and poor physical function have also been found to be associated with falls and fractures in older adults2,4,5 1. Tinetti ME. N Engl J Med 2003; 348:42-49. 2. J Am Geriatr Soc 2001; 49:664-672. 3. Ganz DA, et al. JAMA 2007; 297:77-86. 4. Bensen R, et al. BMC Musculoskeletal Disorders 2005; 6:47. 5. Cawthon PM, et al. J Bone Miner Res 2008; 23:1037-1044. 6. Gates S,et al. BMJ 2008; 336(7636):130-133.

12. Periodic casefinding in primary care: Ask all patients about falls in past year No falls No intervention Recurrent falls Single fall Gait/balanceproblems No problem Check for gait/balanceproblem Patientpresentsto medicalfacility aftera fall Full evaluation* Assessment History Medications Vision Gait and balance Lower limb joints Neurological Cardiovascular Multifactorial intervention (as appropriate) Gait, balance & exercise programs Medication modifications Posteral hypotension treatment Environmental hazard modification Cardiovascular disorder treatment Assessment and Management of Falls From a joint guideline issued in 2001 by: American Geriatrics Society British Geriatrics Society American Academy of Orthopaedic Surgeons J Am Geriatr Soc 2001; 49(5):664-72.

13. Question • Given Mrs. FB's history, what further testing would you consider?

14. Radiologic Investigations • Physical examination is highly suggestive of vertebral fracture • Guidelines recommend spine X-ray • BMD testing is optional and only required for monitoring, as this patient needs treatment

15. Results of Radiologic Investigations • Lateral thoracolumbar spine plain film • Vertebral compression fractures of T10 and T12 (> 25% vertebral height loss with end-plate disruption); significant degenerative changes throughout • BMD • Femoral neck T score = -2.3 • Lumbar spine (L1-L4) T-score = -1.9

16. Question • Based on the history and results of investigations, what is Mrs. FB's risk level for future fracture?

17. Mrs. FB: Assessment ofRisk for Fracture • Based on the history alone, treatment can be initiated for Mrs. FB • Age • History of multiple fragilityfractures (wrist and spine) • Recurrent falls Click here to see the risk assessment calculations for Mrs. FB.

18. Laboratory Investigations • All laboratory investigations are normal • CBC • Calcium (corrected) • Creatinine • Alkaline phosphatase • TSH • Serum protein electrophoresis • No evidence for secondary osteoporosis

19. Question • What would you recommend for treatment to reduce Mrs. FB's risk of future fracture?

20. Considerations for Treatment • Physical activity can be beneficial in reduction of fracture risk • Optimal vitamin D and calcium intake should be ensured • Pharmacologic therapy should be initiated • Importance of adherence needs to be stressed

21. Question • Does Mrs. FB's other medical history raise any possible concerns with pharmacologic therapy for osteoporosis?

22. Mrs. FB: Considerations for Pharmacologic Therapy • Her history of GERD may be a concern— selecting an agent with lower incidence of GI side effects may be helpful • There may be a possible correlation with SSRI use and risk of fracture1 • Switching to another antidepressant or tapering off therapy may be considered • Polypharmacy: Try to reduce overall pill burden (e.g., one-pill combinations of antihypertensives if possible) 1. Ginzburg R, et al. Ann Pharmacother 2009; 43(1):98-103.

23. Mrs. FB: Conclusions • Integrating osteoporosis and falls risk assessment is critical in reducing the risk of fracture in the older adult • 10-year fracture-risk assessment may not be necessary in cases where clinical history suggests high risk • Pharmacologic therapy can be initiated without a 10-year risk assessment in such cases

24. Back-up Material Additional slides that can be accessed from hyperlinks on case slides Case 5 – Mrs. FB

25. Importance of Weight • In men > 50 years and 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

26. 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

27. 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.

28. 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

29. Plain RadiographicExaminations of the Spine

30. Other Radiographic Examinations of the Spine Return to case

31. 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

32. 10-year Risk Assessment for Women (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

33. 10-year Risk Assessment for Women (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

34. 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 Mrs. FB goes from moderate risk to high riskbecause of her history of fragility fractures * 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.

35. FRAX: Risk Calculation for Mrs. FB Mrs. FB is high risk using FRAX Return to case • www.shef.ac.uk/FRAX.

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

37. 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.

38. 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.

39. 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

40. Summary Statement for Other Nonpharmacologic Therapies Return to case

41. First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* * 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. Return to case

42. Importance of Adherencein Treatment Success • The expectation is that treated patients will experience antifracture benefits similar to those reported in clinical trials • Suboptimal adherence reduces or eliminates antifracture benefits1-3 1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):721-731. 2. McCombs JS, et al. Maturitas 2004; 48(3):271-287. 3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.

43. 0.12 0.11 0.10 Probability of fracture 0.09 50% adherence leaves patients at approximatelythe same fracture risk as no therapy 0.08 0.07 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 MPR Poor Adherence Leaves Patients At Higher Risk of Fracture Siris E, et al. Mayo Clin Proc 2006; 81:1013-22.

44. Types and Rates of Nonadherencein Osteoporosis Therapy • Types of non-adherence1-3 • Frequently missed doses • Failing to take the medication correctly to optimize absorption and action • Discontinuation of therapy • Reported one-year adherence rates: 25%–50%1,3 • Marginally better with less frequent dosing regimens 1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):721-731. 2. McCombs JS, et al. Maturitas 2004; 48(3):271-287. 3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.

45. Approaches for Optimizing Adherence • Reminders • Patient information • Counselling • Simplification of the dosing regimen • Self-monitoring Return to case

46. Adverse Events of Osteoporosis Therapies • Consult individual product monographs for adverse event information for approved therapies (click on drug names below to link to online resources) • Bisphosphonates: alendronate, risedronate, zoledronic acid • Calcitonin • Denosumab • Raloxifene • Teriparatide Return to case