Presentation is loading. Please wait.

Presentation is loading. Please wait.

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.

Similar presentations


Presentation on theme: "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."— Presentation transcript:

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 in Canada

2 2010 Guidelines Strategies for Fracture Prevention 2010 Guidelines Section Five

3 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

4 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.

5 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/L –For most Canadians, supplementation is needed to achieve this level Hanley DA, et al. CMAJ 2010; 182:E610-E618.

6 2010 Guidelines 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 an adequate supplementation dose Monitoring of routine supplement use and routine screening of otherwise healthy individuals are not necessary Hanley DA, et al. CMAJ 2010; 182:E610-E618. Click here for more information on vitamin D.

7 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 Concerns about serious adverse effects with high-dose supplementation 2-4serious adverse effects 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.

8 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.

9 2010 Guidelines Summary Statement for Other Nonpharmacologic Therapies StatementStrength Weight bearing, balance and strengthening exercises can improve outcomes in individuals with osteoporosiscan improve outcomes in individuals with osteoporosis Level 2 Exercise-focused interventions improve balance and reduce falls in community-dwelling older peoplereduce falls Level 2 Hip protectorsHip protectors may reduce the risk of hip fractures in long- term care residents; however adherence with their use may pose a challenge for the older adult Level 2

10 2010 Guidelines Medications Indicated for Osteoporosis in Canada Bisphosphonates— oral and IV oralIV Calcitonin Denosumab (RANK ligand inhibitor)Denosumab Hormone therapy Raloxifene (SERM)Raloxifene Teriparatide (PTH analogue)Teriparatide

11 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.

12 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.

13 2010 Guidelines Summary Statements for Pharmacotherapy StatementStrength Alendronate prevents vertebral, non-vertebral, hip, and wrist fractures in post-menopausal women Level 1 Cyclical etidronate prevents vertebral fractures, but has not demonstrated risk reductions for other non-vertebral fracture types Level 1 Risedronate prevents vertebral, non-vertebral, and hip fractures in post-menopausal women Level 1

14 2010 Guidelines Summary Statements for Pharmacotherapy ( Cont'd ) StatementStrength Zoledronic acid prevents vertebral, non-vertebral, hip fractures in men and women Level 1 Hormone therapy prevents vertebral, non-vertebral, and hip fractures, but is recommended for women with moderate to severe vasomotor symptoms Level 1 Raloxifene and calcitonin reduce vertebral fractures, but have not demonstrated risk reductions for non-vertebral fractures Level 1

15 2010 Guidelines Summary Statements for Pharmacotherapy ( Cont'd ) StatementStrength Teriparatide reduces vertebral and non-vertebral fracturesLevel 1 Denosumab reduces vertebral, non-vertebral, and hip fractures Level 1

16 2010 Guidelines Recommendations for High-risk Individuals RecommendationGrade For menopausal women requiring osteoporosis treatment, alendronate, denosumab, risedronate, and zoledronic acid can be used as first-line therapies for prevention of hip, non-vertebral, and vertebral fractures A For menopausal women requiring osteoporosis treatment, teriparatide can be used as a first-line therapy for prevention of non-vertebral and vertebral fractures A For menopausal women requiring osteoporosis treatment, raloxifene can be used as a first-line therapy for prevention of vertebral fractures A Click here for a summary of the system for grades of recommendations.

17 2010 Guidelines Recommendations for High-risk Individuals ( Cont'd ) RecommendationGrade For menopausal women requiring osteoporosis treatment and who require treatment for vasomotor symptoms, hormone therapy can be used as a first-line therapy for prevention of hip, non-vertebral, and vertebral fractures A Clinicians should avoid prescribing more than one anti-resorptive agent concurrently for fracture reduction A For menopausal women intolerant of first-line therapies, calcitonin or etidronate can be considered for prevention of vertebral fractures B For men requiring osteoporosis treatment, alendronate, risedronate, and zoledronic acid can be used as first-line therapies for prevention of fractures D

18 2010 Guidelines Recommendation for Duration of Therapy RecommendationGrade Individuals at high risk for fracture should continue osteoporosis therapy without a drug holiday D Evidence supporting recommendations for duration of treatment is limited Data for the above recommendation come from the FLEX study (long-term alendronate treatment) 1 and the risedronate discontinuation study 2 FLEX study risedronate discontinuation study 1. Black DM, et al. JAMA 2006; 296(24):2927-2938. 2. Watts NB, et al. Osteoporos Int 2008; 19(3):365-372.

19 2010 Guidelines Summary Statements ≥≥for Special Groups StatementStrength Osteoporosis therapies including alendronate, risedronate, and teriparatide reduce the risk of vertebral fractures and maintain BMD in those prescribed glucocorticoids for 3 months or longerthose prescribed glucocorticoids for 3 months or longer Level 1 Etidronate, zoledronic acid, and calcitonin maintain BMD in those prescribed glucocorticoids for 3 months or longer those prescribed glucocorticoids for 3 months or longer Level 2 Bisphosphonates and denosumab maintain BMD in women prescribed aromatase inhibitors and men prescribed androgen- deprivation therapywomen prescribed aromatase inhibitorsmen prescribed androgen- deprivation therapy Level 1

20 2010 Guidelines Summary Statements on Treatment Initiation StatementStrength Multiple fractures confer greater risk than a single fractureLevel 1 Prior fractures of the hip and vertebra carry greater risk than other fracture sites Level 1 Pharmacologic intervention, when based on prior fragility fractures affecting the vertebra or hip, has shown fracture benefit in clinical trials Level 1

21 2010 Guidelines Summary Statements on Treatment Initiation ( Cont'd ) StatementStrength In patients who initiated glucocorticoids, fractures can occur quickly (within three to six months) with prednisone doses as low as 2.5 – 7.5 mg daily with a rapid decline in fracture risk toward baseline after cessation Level 1 Rapid BMD loss in untreated individuals may be an independent risk for fracture Level 2

22 2010 Guidelines Recommendations on Treatment Initiation RecommendationGrade In individuals over age 50, fragility fracture of the hip or vertebra, or more than one fragility fracture event, constitutes a high risk for future fracture and such individuals should be offered pharmacologic therapy A For those at moderate risk (10% – 20% probability for major osteoporotic fracture over 10 years), lateral radiographs or Vertebral Fracture Assessment (VFA) of the thoracolumbar spine is recommended for further risk stratification and in clinical decision-making regarding pharmacologic interventions A

23 2010 Guidelines Recommendations on Treatment Initiation ( Cont'd ) RecommendationGrade Pharmacologic therapy should be offered to patients at high absolute risk (> 20% probability for major osteoporotic fracture over 10 years) D For those at moderate fracture risk, patient preference and additional clinical risk factors that are not already incorporated in the risk assessment system should be used to guide pharmacologic management decisions additional clinical risk factors D

24 2010 Guidelines Testosterone in Men: Summary Statement and Recommendation StatementStrength Testosterone maintains BMD in hypogonadal men but has not been shown to reduce the risk of fractures Level 2 RecommendationGrade Testosterone is not recommended for the treatment of osteoporosis in men B

25 2010 Guidelines Recommendation for Adverse Events RecommendationGrade Potential benefits and risks of the prescribed agent should be discussed with each patient prior to initiating therapy to support informed decision-making D Click here for more information on adverse events.

26 2010 Guidelines Considerations for Monitoring Rationale for monitoring: To identify individuals with continued BMD loss, despite appropriate osteoporosis treatment Aspects of monitoring –Serial BMD measurementsSerial BMD measurements –Assessment of adherenceAssessment of adherence –Bone turnover markers (BTMs)?Bone turnover markers (BTMs)?

27 2010 Guidelines When to Refer to Specialist Care: General Fracture on first-line therapy with optimal adherence Significant loss on follow-up BMD on first-line therapy with optimal adherence Intolerance of first- and second-line agents

28 2010 Guidelines When to Refer to Specialist Care: Special Populations Referrals to physicians with an interest or expertise in osteoporosis –Secondary causes of osteoporosis outside the comfort zone of the individual primary care physician –Patients with extremely low BMD Referrals to other specialists –Complex individuals with multiple comorbidities, such as those with frequent falling, Alzheimer’s disease, stroke, and Parkinson’s disease

29 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

30 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

31 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

32 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

33 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 pharmacologic therapy: 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 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 Integrated Approach, Continued

34 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

35 2010 Guidelines Section Five – Section Five – Fracture Risk Assessment Back-up Material Additional slides that can be accessed from hyperlinks on core slides

36 2010 Guidelines Classification of Vitamin D Status by Serum Level of 25-OH-D Serum 25-OH-D, nmol/L* † Category Level of evidence < 25Vitamin D deficiency3 25 – 75Vitamin D insufficiency ‡ 2 > 75Desirable vitamin D status3 > 250Potential adverse effects2 Hanley DA, et al. CMAJ 2010; 182:E610-E618. * Assumes that serum 25-OH-D is measured by a clinical laboratory participating in an external quality assurance program. † 2.5 nmol/L = 1 ng/mL. ‡ ”Insufficiency” is a milder form of deficiency and should preferably be termed “suboptimal vitamin D status.”

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 Calcium Supplements Supplement typeNotes Calcium carbonateCan be refined from limestone, natural elements of the earth, or may come from shell sources, usually oyster Shell sources are often described on the label as a "natural" source Calcium carbonate from oyster shells is not "refined" and can contain variable amounts of lead Chelated calciumRefers to a special way in which calcium is chemically combined with another substance Calcium citrate, calcium lactate, calcium gluconate are examples of chelated preparation Powdered bone (bonemeal) Not recommended, as it may contain contaminants DolomiteA mineral found in rock Return to main presentation www.osteoporosis.cawww.osteoporosis.ca; Accesssed September 2010.

41 2010 Guidelines Association of Calcium Intake with Hip Fracture Risk Tang BM, et al. Lancet 2007; 370(9588):657-666. Return to main presentation

42 2010 Guidelines Potential Risks of Calcium Supplementation High-dose calcium supplementation has been associated with –Renal calculi 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 main presentation

43 2010 Guidelines Benefits of Exercise: Fractures and Bone Health Programs > 1 year including aerobic exercises and strength training have demonstrated positive effects on BMD and thoracic kyphosis but have limited evidence for fracture reduction 1 Moderate to vigorous exercise has demonstrated an ability to reduce hip fracture risk 2 1. De Kam D, et al. Osteoporos Int 2009; 20(12):2111-25. 2. Moayyeri A. Ann Epidemiol 2008; 18:827-835. Return to main presentation

44 2010 Guidelines Nonpharmacologic Interventions Associated with Reduction in Falls Exercise-focused interventions for community-dwelling older people 1 Tai chi, gait, and balance training 1-3 Home safety assessment (only effective in those at high risk for falls) 1 Cataract removal 3 Return to main presentation 1. Gillespie LD, et al. Cochrane Database Syst Rev 2009; CD007146. 2. Cameron ID, et al. Cochrane Database Syst Rev 2010; 1(CD005465). 3. McClure RJ, et al. Cochrane Database Syst Rev 2008; 1(CD004441).

45 2010 Guidelines Benefit of Hip Protectors in Long-term Care A modest reduction in hip fractures in elderly long-term care residents 1,2 Cost effective for fracture reduction in long- term care 3 Compliance poses a challenge 1 Not effective for older adults residing in the community 1,4 1. Sawka AM, et al. J Clin Epidemiol 2007; 60(4):336-344. 2. Oliver D, et al. BMJ 2006; 334:82-87. 3. Canadian Agency for Drugs and Technologies in Health. Health Technology Inquiry Service (HTIS). Rapid Review. 4. Parker MJ, et al. BMJ 2006; 332(7541):571-574. Return to main presentation

46 2010 Guidelines 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

47 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

48 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

49 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

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 Clinical Vertebral Fractures in Patients Continuing or Stopping Alendronate Therapy: FLEX Study Black DM, et al. JAMA 2006; 296(24):2927-2938. Return to main presentation

52 2010 Guidelines New Vertebral Fractures in Those Stopping or Continuing Risedronate Therapy Watts NB, et al. Osteoporos Int 2008; 19(3):365-372. Return to main presentation Continued risedronate Stopped risedronate

53 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

54 2010 Guidelines 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.

55 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

56 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.

57 2010 Guidelines Factors that Warrant Consideration for Pharmacological Therapy in Moderate Risk Patients Additional vertebral fracture(s) (> 25% height loss with end-plate disruption) identified on VFA or lateral spine X-ray Previous wrist fracture in individuals > 65 or those with T-score < -2.5 Lumbar spine T-score much lower than femoral neck T-score Rapid bone loss Men on androgen deprivation therapy for prostate cancer Women on aromatase inhibitor therapy for breast cancer Long-term or repeated systemic glucocorticoid use (oral or parenteral) that does not meet the conventional criteria for recent prolonged systemic glucocorticoid use (i.e., > 3 months cumulative during the preceding year at a prednisone equivalent dose > 7.5 mg daily) Recurrent falls defined as falling 2 or more times in the past 12 months Other disorders strongly associated with osteoporosis, rapid bone loss or fractures

58 2010 Guidelines Disorders Associated with Osteoporosis and Increased Fracture Risk Primary hyperparathyroidism Type I diabetes Osteogenesis imperfecta Untreated long-standing hyperthyroidism, hypogonadism, or premature menopause (< 45 years) Cushing’s disease Chronic malnutrition or malabsorption Chronic liver disease Chronic obstructive pulmonary disease Chronic inflammatory conditions (e.g., rheumatoid arthritis, inflammatory bowel disease ) Return to main presentation

59 2010 Guidelines 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 acidalendronaterisedronate zoledronic acid –CalcitoninCalcitonin –DenosumabDenosumab –RaloxifeneRaloxifene –TeriparatideTeriparatide

60 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.

61 2010 Guidelines 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

62 2010 Guidelines 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.

63 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

64 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.

65 2010 Guidelines Poor Adherence Leaves Patients at Higher Risk of Fracture Siris E, et al. Mayo Clin Proc 2006; 81:1013-22. 50% adherence leaves patients at approximately the same fracture risk as no therapy 0.12 0.11 0.10 0.09 0.08 0.07 0.000.100.200.300.400.500.600.700.800.901.00 Probability of fracture MPR

66 2010 Guidelines 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.

67 2010 Guidelines Approaches for Optimizing Adherence Reminders Patient information Counselling Simplification of the dosing regimen Self-monitoring Return to main presentation

68 2010 Guidelines Desirability of Serial BTMs Have the potential to provide earlier evidence of treatment effects (within first three to six months) Further clinical trial validation is required Measurement variability between individuals may limit clinical utility Return to main presentation

69 2010 Guidelines Criteria Used to Assign Levels of Evidence: Studies of Diagnosis LevelCriteria 1 iIndependent interpretation of test results iiIndependent interpretation of the diagnostic standard iiiSelection of people suspected, but not known to have the disorder ivReproducible description of the test and diagnostic standard vAt least 50 people with and 50 people without the disorder 2Meets four of the Level 1 criteria 3Meets two of the Level 1 criteria 4Meets one or two of the Level 1 criteria

70 2010 Guidelines Criteria Used to Assign Levels of Evidence: Studies of Treatment and Intervention LevelCriteria 1+Systematic overview of meta-analysis of RCTs 1One RCT with adequate power 2+Systematic overview or meta-analysis of Level 2 RCTs 2RCT that does not meet Level 1 criteria 3Non-RCT or cohort study 4 Before/after study, cohort study with non-contemporaneous controls, case-control study 5Case series without controls 6Case report or case series of < 10 patients RCT = randomized, controlled study

71 2010 Guidelines Criteria Used to Assign Levels of Evidence: Studies of Prognosis LevelCriteria 1 i Inception cohort of patients with the condition of interest, but free of the outcome of interest iiReproducible inclusion and exclusion criteria iiiFollow-up of at least 80% of participants ivStatistical adjustment for confounders vReproducible description of the outcome measures 2Meets criterion i and three of the other four Level 1 criteria 3Meets criterion i and two of the other four Level 1 criteria 4Meets criterion i and one of the other four Level 1 criteria Return to main presentation

72 2010 Guidelines Criteria Used to Assign Grades of Recommendation LevelCriteria ANeed supportive level 1 or 1+ evidence plus consensus* BNeed supportive level 2 or 2+ evidence plus consensus* CNeed supportive level 3 evidence plus consensus DAny lower level of evidence supported by consensus * As appropriate level of evidence was necessary, but not sufficient to assign a grade in recommendation; consensus was required in addition. Return to main presentation


Download ppt "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."

Similar presentations


Ads by Google