1. 2010 Guidelines Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print]. 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis ( AACE/CMAJ 2010 ) Dr.Waleed Albaker.MD,FRCP,FACP,Consultant of Diabetes and Endocrinology

2. 2010 Guidelines 77 years old lady with back pain Clinical Approach to Osteoporosis 77 years old lady with back pain Clinical Approach to Osteoporosis.

3. 2010 Guidelines Risk Factors for Fracture 1-5 Fragility fracture after the age of 40 Family history of hip fracture Premature menopause Glucocorticoid use (> 7.5 mg/d) > 3 months in the prior year Lifestyle factors: smoking, excessive alcohol, and physical inactivity Weight loss since age 25 > 1 0% Poor nutrition, calcium intake, vitamin D status Recurrent falls Return to main presentation 1. Papaioannou A, et al. Osteoporos Int 2009; 20:507-518. 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. van Staa TP, et al. J Bone Miner Res 2000; 15(6):993-1000.

4. 2010 Guidelines AssessmentRecommended Elements of Clinical Assessment Physical examination Measure weight (weight loss of >10% since age 25 is significant)weight Measure height annually (prospective loss > 2cm)height (historical height loss > 6 cm) Measure rib to pelvis distance < 2 fingers' breadthrib to pelvis distance Measure occiput-to-wall distance (for kyphosis) > 5cmocciput-to-wall distance Assess fall risk by using Get-Up-and-Go Test (ability to get out of chair without using arms, walk several steps and return) Diagnosis of vertebral fractures Recommendations for Clinical Assessment

5. 2010 Guidelines 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) Return to main presentation 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.

6. 2010 Guidelines 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 spine X-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.

7. 2010 Guidelines Appropriate Measurement of Height Use a wall-mounted stadiometer Instructions for subjects: –Shoes off –Heels, buttocks, and back against the upright board –Face directly forward, head stable Record height after exhalation Siminoski K, et al. Osteoporos Int 2005; 16(4):403-410. Return to main presentation

8. 2010 Guidelines Additional Tests for Clinical Identification of Vertebral Fracture TestRationaleMethodInterpretation Rib-pelvis distance 1 To identify lumbar fractures Measure the distance between the costal margin and the pelvic rim on the mid-axillary line < 2 fingerbreadths is associated with vertebral fractures Occiput-to- wall distance 2,3 To help identify thoracic spine fractures Stand straight with heels and back against the wall > 5 cm raises suspicion 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.

9. 2010 Guidelines Rib-Pelvis and Occiput-to-Wall Distances 4 cm 3 FBs 8 cm 12 cm 2 FBs Height loss 3 cm 8 cm Return to main presentation

10. 2010 Guidelines Plain Radiographic Examinations of the Spine TypeUse(s) Plain radiographs, complete To investigate symptoms such as back pain, or after trauma Plain radiographs, limited Specifically to look for osteoporotic fracturing Plain radiographs, incidental Incidental views of the spine on radiographs undertaken for other purposes (e.g., lateral chest films)

11. 2010 Guidelines % of Confirmed Vertebral Fractures Mentioned in ER Radiology Reports* Majumdar SR, et al. Arch Intern Med 2009; 165(8):905-909. Return to main presentation *n = 500 patients undergoing chest radiograph for any indication ER = emergency room

12. 2010 Guidelines Tests for Potential Secondary Causes In patients with Condition / Disease Test Persistently elevated serum calcium Hyperparathyroidism Parathyroid hormone (PTH) Multiple or atypical vertebral fractures Multiple myeloma Protein electrophoresis Immunoelectrophoresis Symptoms/signs of malabsorption or non response to vitamin D therapy Celiac disease Antibodies associated with gluten enteropathy Signs and symptoms of androgen deficiency (in men) Hypogonadism Testosterone (bioavailable or total) Serum prolactin History of kidney stonesHypercalciuria24-hour urine for calcium Return to main presentation

13. 2010 Guidelines Falls Risk Assessment History of falls in the last year is one of the most significant risk factors for predicting future fall 1-6 Dementia and poor physical function have also been found to be associated with falls and fractures in older adults 2,4,5 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. Age 80 Age 60

14. 2010 Guidelines

15. 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 factors for fracture: –Fragility fracture after age 40 –Prolonged glucocorticoid use † –Other high-risk medication use* –Parental hip fracture –Vertebral fracture or osteopenia identified on X-ray –Current smoking –High alcohol intake –Low body weight ( 10% of weight at age 25) –Rheumatoid arthritis –Other disorders strongly associated with osteoporosisOther 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.

16. 2010 Guidelines Indications for BMD Testing for Individuals Under Age 50 Years Fragility fracture Prolonged use of glucocorticoids* Use of other high-risk medications † Hypogonadism or premature menopause 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.

17. 2010 Guidelines BMD Reporting Categories AgeCategoryCriteria* < 50 years Below expected range for ageZ-score < -2.0 Within expected range for ageZ-score > -2.0 > 50 years Severe (established) osteoporosis T-score < -2.5 with fragility fracture OsteoporosisT-score < -2.5 Low bone massT-score -1.0 to -2.5 NormalT-score > -1.0 Click here for a list of considerations about BMD reporting.

18. 2010 Guidelines Absolute 10-year Fracture-Risk Tools Tools validated in several countries (choice based on personal preference and convenience) FRAX : Fracture Risk Assessment Tool developed by the World Health Organization WHO There are large differences in fracture rates from country to country 3-5fracture rates from country to country –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.

19. 2010 Guidelines 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 Canada 1 There is an online FRAX calculator with detailed instructions at: www.shef.ac.uk/FRAX 1. Leslie WD, et al. Osteoporos Int; In press. * composite of hip, vertebra, forearm, and humerus

20. 2010 Guidelines FRAX Tool: On-line Calculator www.shef.ac.uk/FRAX.

21. 2010 Guidelines FRAX Clinical Risk Factors Parental hip fracture Prior fracture Glucocorticoid use Current smoking High alcohol intake Rheumatoid arthritis

22. 2010 Guidelines Absolute Fracture Risk Tools Calculate risk for treatment-naïve patients only Cannot be used to monitor response to therapy Using 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

23. 2010 Guidelines Impact of Prior Vertebral Fracture on 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 system.

24. 2010 Guidelines Considerations for BMD Reporting ( Cont'd ) Osteoporosis cannot be diagnosed by BMD alone below age 50 BMD reporting is based upon lowest value for lumbar spine (minimum two vertebral levels), total hip, and femoral neck –If either the lumbar spine or hip is invalid, then the forearm should be scanned and the distal one-third region reported Fracture risk assessment under the FRAX / CAROC system is based upon the femoral neck T-score only Return to main presentation

25. 2010 Guidelines Variations in Estimated FRAX 10-Year Fracture Probabilities According to Country Version 3.1 FRAX website (www.sheffield.ac.uk/FRAX). Which country ? Return to main presentation

26. 2010 Guidelines Integrated Approach to Management of Patients Who Are at Risk for Fracture Age < 50 yrAge 50-64 yrAge > 65 yr 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 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 ( 10% of body weight at age 25) Other disorders strongly associated with osteoporosis 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 All men and women Initial BMD Testing

27. 2010 Guidelines Assessment of fracture risk Moderate risk (10-year fracture risk 10%-20%) Low risk (10-year fracture risk < 10%) Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Good evidence of benefit from pharmacotherapy Always consider patient preference Unlikely to benefit from pharmacotherapy Reassess in 5 yr Factors warranting consideration of pharmacologic therapy… Integrated Approach, Continued Initial BMD Testing

28. 2010 Guidelines Integrated Approach, Continued Assessment of fracture risk Moderate risk (10-year fracture risk 10%-20%) Low risk (10-year fracture risk < 10%) Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Good evidence of benefit from pharmacotherapy Always consider patient preference Unlikely to benefit from pharmacotherapy Reassess in 5 yr Factors warranting consideration of pharmacologic therapy… Initial BMD Testing

29. 2010 Guidelines Integrated Approach, Continued Assessment of fracture risk Moderate risk (10-year fracture risk 10%-20%) Low risk (10-year fracture risk < 10%) Lateral thoracolumbar radiography (T4-L4) or vertebral fracture assessment may aid in decision-making by identifying vertebral fractures High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Good evidence of benefit from pharmacotherapy Always consider patient preference Unlikely to benefit from pharmacotherapy Reassess in 5 yr Factors warranting consideration of pharmacologic therapy… Initial BMD Testing

30. 2010 Guidelines Moderate risk (10-year fracture risk 10%-20%) 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 Integrated Approach, Continued

31. 2010 Guidelines Calculating Absolute 10-year Fracture Risk: FRAX Tool Sarah is at moderate risk of fractures using the FRAX model.

32. 2010 Guidelines Modalities Used to Prevent Fracture Lifestyle modifications –Vitamin D –Calcium –Exercise –Falls prevention Pharmacologic therapy –Bisphosphonates –Other anti-resorptives Calcitonin Denosumab Hormone therapy Raloxifene –Parathyroid hormone –Combination therapy

33. 2010 Guidelines Recommended Vitamin D Supplementation Group Recommended Vitamin D Intake (D3) Adults <50 without osteoporosis or conditions affecting vitamin D absorption 400 – 1000 IU daily (10 mcg to 25 mcg daily) Adults > 50 or high risk for adverse outcomes from vitamin D insufficiency (e.g., recurrent fractures or osteoporosis and comorbid conditions that affect vitamin D absorption) 800 – 2000 IU daily (20 mcg to 50 mcg daily) Hanley DA, et al. CMAJ 2010; 182:E610-E618.

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

35. 2010 Guidelines Recommended Calcium Intake From diet and supplements combined: 1200 mg daily –Several different types of calcium supplements are availableSeveral different types of calcium supplements are available Evidence shows a benefit of calcium on reduction of fracture risk 1reduction of fracture risk 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.

36. 2010 Guidelines Summary Statements for Calcium & Vitamin D StatementStrength Vitamin D3 with calcium supplementation increases bone density in postmenopausal women and men over age 50 and reduces the risk of fractures Level 1 Vitamin D3 at daily doses of 800 IU (20 mcg) with calcium (1000 mg) reduces the risk of hip and non-vertebral fractures in elderly populations in institutions Level 1 The evidence in community-dwelling individuals is less strongLevel 2 There is evidence that daily 800 IU (20 mcg) vitamin D3 reduces fall risk, particularly in trials that adequately ascertained falls Level 2 A daily intake of 1000 IU vitamin D3 (25 mcg)—a commonly available safe dose—will raise serum 25-OH-D level on average by 15 – 25 nmol/L Level 2 Click here for a summary of the grading system for levels of evidence.

37. 2010 Guidelines Vitamin D Supplementation (D3) and Reduced Non-vertebral Fracture Risk Bischoff-Ferrari HA, et al. JAMA 2005; 293(18):2257-2264.

38. 2010 Guidelines Fracture Risk Reduction with Vitamin D and Calcium Boonen S, et al. J Clin Endocrinol Metab 2005; 293(18):2257-2264.

39. 2010 Guidelines Vitamin D: Reduction of Falls in the Elderly Bischoff-Ferrari HA, et al. BMJ 2009; 339:b3692. Return to main presentation

40. 2010 Guidelines Association of Calcium Intake with Hip Fracture Risk Tang BM, et al. Lancet 2007; 370(9588):657-666. Return to main presentation

41. 2010 Guidelines

42. Medications Indicated for Osteoporosis Bisphosphonates— oral and IV oralIV Calcitonin Denosumab (RANK ligand inhibitor)Denosumab Hormone therapy Raloxifene (SERM)Raloxifene Teriparatide (PTH analogue)Teriparatide

43. 2010 Guidelines First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* Type of Fracture Antiresorptive therapy Bone formation therapy Bisphosphonates DenosumabRaloxifene Hormone therapy (Estrogen)** Teriparatide Alendronate Risedronate Zoledronic acid Vertebral Hip - - Non- vertebral + - * 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.

44. 2010 Guidelines Reduction in Mortality with Anti-osteoporotic Medication Zoledronic acid has demonstrated a 28% relative reduction in mortality after hip fracture 128% relative reduction in mortality –Absolute risk reduction: 3.7% Meta-analysis has shown a 10% relative reduction in mortality with anti-osteoporosis therapies in older individuals at high risk of fracture 210% relative reduction in mortality –Absolute risk reduction: 0.4% 1. Lyles KW, et al. N Engl J Med 2007; 357(18):1799-809. 2. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181.

45. 2010 Guidelines Zoledronic Acid Hip Fracture Trial: Reduction in Mortality Lyles KW, et al. N Engl J Med 2007; 357(18):1799-809. Return to main presentation

46. 2010 Guidelines

47. Oral Bisphosphonates: Summary Drug (Brand name)Dosing Schedules Alendronate (Fosamax ®, Fosavance ® ) 10 mg daily 70 mg weekly Risedronate (Actonel ® ) 5 mg daily 35 mg weekly 150 mg monthly Etidronate (Didrocal ® ) Cyclical therapy of daily 200 mg for 14 days followed by calcium supplements for 10 weeks See notes page for information on patient instructions, precautions and adverse events Return to main presentation

48. 2010 Guidelines IV Bisphosphonate: Summary Drug (Brand name)Dosing Schedule Zoledronic Acid (Aclasta ® )5 mg intravenously once yearly See notes page for information on patient instructions, precautions and adverse events Return to main presentation

49. 2010 Guidelines Other Medications: Summary Drug (Brand name)Dosing Schedule Calcitonin (Miacalcin ® )200 IU intranasally daily Calcium (many formulations)Many dosing schedules Denosumab (Prolia ® )60 mg subcutaneous injection every six months Hormone therapy (many formulations) Many dosing schedules Raloxifene (Evista ® )60 mg daily Teriparatide (Forteo ® )20 μg subcutaneously daily See notes page for information on patient instructions, precautions and adverse events Return to main presentation

50. 2010 Guidelines Meta-analysis of Anti-osteoporosis Medication: Reduction in Mortality AnalysisStudies included RR (95% CI) p value Primary Eight studies of four agents (risedronate, strontium ranelate, zoledronic acid, and denosumab) 0.89 (0.80 – 0.99) 0.036 Secondary Ten studies of five agents (as above, plus two studies of alendronate in which the dose changed during the studies) 0.90 (0.81 – 1.0) 0.044 Return to main presentation Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181.

51. 2010 Guidelines Evidence with Pharmacotherapies for Patients using Long-term Glucocorticoids Both alendronate 1,2 and risedronate 3,4 reduce risk of vertebral fracture Etidronate is protective against bone loss at the spine but does not prevent fractures 5,6 Zoledronic acid improves lumbar spine BMD more effectively than risedronate 7 –Study not powered to detect differences in fracture reduction Teriparatide reduces radiographic vertebral fractures compared to alendronate 8 Calcitonin prevents bone loss at the spine but not at the hip compared to placebo; no effect on fracture risk 1,9 5. MacLean C, et al. Ann Intern Med 2008; 148(3):197-213. 6. Qaseem A, et al. Ann Intern Med 2008; 149(6):404-415. 7. Reid DM, et al. Lancet 2009; 373(9671):1253-1263. 8. Saag KG, et al. N Engl J Med 2007; 357:2028-2039. 9. Cranney A, et al. Cochrane Database Syst Rev 2000; (2):CD001983. 1. Adachi JD, et al. Arthritis Rheum 2001; 44(1):202-211. 2. Saag KG, et al. N Engl J Med 1998; 339(5):292-299. 3. Wallach S, et al. Calcif Tissue Int 2000; 67(4):277-285. 4. Reid DM, et al. J Bone Miner Res 2000; 15(6):1006-1013. Return to main presentation

52. 2010 Guidelines

55. Evidence for Zoledronic Acid in Women with Breast Cancer Receiving AIs Reduces aromatase inhibitors (AI)-associated BMD loss Prevents bone loss in postmenopausal women with osteoporosis or low bone mass starting letrozole 1 When used upfront, prevents AI-associated BMD loss with early breast cancer more effectively than delaying therapy until BMD loss or fracture occurs 2 When added to adjuvant endocrine therapy improves disease-free survival in premenopausal patients with estrogen-responsive early breast cancer 3 1. Hines SL, et al. Breast 2010; 19(2):92-96. 2. Brufsky AM, et al. Clinical Breast Cancer 2009; 9(2):77-85. 3. Gnant M, et al. N Engl J Med 2009; 360(7):679-691.

56. 2010 Guidelines Evidence for Risedronate in Women with Breast Cancer Receiving AIs Reduces AI-associated bone loss Associated with a significant increase in lumbar spine and total hip BMD Van Poznak C, et al. J Clin Oncol 2010; 28(6):967-975. Return to main presentation

57. 2010 Guidelines Evidence for Treatment in Men Receiving Androgen- deprivation Therapy for Prostate Cancer Insufficient fracture data in studies with bisphosphonates and selective estrogen receptor modulators (SERMs) Denosumab showed a decreased cumulative incidence of new vertebral fractures at 36 months (absolute risk reduction, 2.4%) 1 Return to main presentation 1. Smith MR, et al. N Engl J Med 2009; 361(8):745-755.

58. 2010 Guidelines Bisphosphonates and Osteonecrosis of the Jaw Definition: The presence of exposed bone in the maxillofacial region that did not heal within eight weeks after identification by a health care provider 1 Incidence –Oral bisphosphonates: Between 1 in 10,000 and < 1 in 100,000 patient-treatment years –IV bisphosphonates: two cases reported in RCTs in postmenopausal osteoporosis (one in placebo group) 2 Information on incidence of Osteonecrosis of the Jaw (ONJ) is rapidly evolving: the true incidence may be higher 1 1. Khosla S, et al. J Bone Miner Res 2009; 22(10):1479-1491. 2. Grbic JT, et al. J Am Dent Assoc 2008; 139:32-40.

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60. Bisphosphonates and Atypical Fracture Case series reported increased incidence of subtrochanteric fractures with long-term use of bisphosphonates 1 –15 women treated with alendronate –Causation not proven Recent case-control study reported no increase in the incidence in subtrochanteric fractures among patients taking bisphosphonates versus controls 2 Increased incidence of subtrochanteric fractures has not been reported with the use of other bisphosphonates 1. Lenart BA, et al. N Engl J Med 2008; 358:1304-1306. 2. Abrahamsen B, et al. J Bone Miner Res 2009; 24:1095-1102. Return to main presentation

61. 2010 Guidelines

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63. 2010 Guidelines

64. Interpretation of Serial BMD Measurements Measurement error must be considered when interpreting serial BMD assessments –Each centre should determine its precision error in order to estimate the least significant change (LSC) 1 Continued BMD loss exceeding the LSC may reflect: –Poor adherence to therapy –Failure to respond to therapy –Previously unrecognized secondary causes of osteoporosis Most anti-osteoporosis therapies do not cause large BMD increases 2 –Stable BMD is consistent with successful treatment 1. Baim S, et al. J Clin Densitom 2005; 8(4):371-378. 2. Chen P, et al. J Bone Miner Res 2009; 24(3):495-502.

65. 2010 Guidelines Recommendations for Frequency of BMD Testing Usually repeated every 1 – 3 years, with a decrease in testing once therapy is shown to be effective In those at low risk without additional risk factors for rapid BMD loss, a longer testing interval (5 – 10 years) may be sufficient Return to main presentation

66. 2010 Guidelines Importance of Adherence in Treatment Success The expectation is that treated patients will experience anti-fracture benefits similar to those reported in clinical trials Suboptimal adherence reduces or eliminates anti-fracture benefits 1-3 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.

67. 2010 Guidelines

68. Types and Rates of Non-adherence in Osteoporosis Therapy Types of non-adherence: 1-3 –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.

69. 2010 Guidelines