Optimizing Osteoporosis Management Dr. Philip A. Baer Seacourses Asia CME December 2017
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2 Optimizing Osteoporosis Management Dr. Philip A. Baer Seacourses Asia CME December 2017
3 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.
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5 Learning Objectives Upon completion of this program participants will be able to: 1. Discuss the clinical impact of fractures and the current care gap in osteoporosis. 2. Evaluate a patient s individualized risk of osteoporotic fracture utilizing a practical risk assessment tool. 3. Treat osteoporosis based on the 2010 Osteoporosis Canada guideline. 4. Analyze controversies surrounding osteoporosis therapy.
6 Definition of Osteoporosis Normal Bone Osteoporotic Bone WHO Definition 1 Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. NIH Definition 2 Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength reflects the integration of 2 main features: bone density and bone quality. 1. Genant HK et al. Osteoporos Int 1999;10: NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. JAMA 2001;285:
7 Osteoporotic Fracture = Fragility Fracture He tried a little hip-hop. One hop and he broke a hip.
8 Fragility Fracture: Definition A fracture occurring spontaneously or following minor trauma such as a fall from standing height or less 1,2 Excluding craniofacial, hand, ankle and foot fractures 1. Kanis JA, et al. Osteoporos Int 2001; 12(5): Bessette L, et al. Osteoporos Int 2008; 19:79-86.
9 Osteoporosis: Fractures Primarily of Cortical Bone Humerus Tibia Femoral Neck Images courtesy of Dr Robert Josse
10 Osteoporosis: Fractures Primarily of Trabecular Bone Vertebral Vertebral Femur Inter-trochanteric Images courtesy of Dr Robert Josse
11 Burden of Osteoporosis
12 Annual incidence of common diseases Prevalence of Fractures in Canada Fractures from osteoporosis in Canadian women are more common than heart attack, stroke and breast cancer combined 1 200, , ,400 41,500 Other 80,000 40, ,900 Vertebral 32,700 Wrist 30,000 Hip * 10,300 Pelvis Osteoporotic fractures 1,2 49,220 29,874 22,700 Heart Stroke 3 Breast Attack 3 Cancer 4 * Canadian hip fractures from (1); Non-hip fracture data extrapolated from (2). Other represents non-osteoporotic fractures sites (humerus, clavicle, hands/fingers, patella, tibia, fibula) Leslie WD, et al. Osteoporos Int. 2010; 21: ; 2. Burge J, et al. J Bone Miner Res. 2007;22: ; 3. Canadian Institute for Health Information (2009) Health Indicators. ; 4. Canadian Cancer Society
13 Timeline: Consequences post fracture Lifetime risk of hip fracture in women >50 is 12.1% 5 Fracture Begets Future Fracture Deteriorated Quality of Life Long-term Care Admission Mortality 40% 40% 18% 23% In women with hip fracture: 40% had prior fracture 1 In women with hip fracture: 40% need assistance walking 2 In women with hip fracture: 18% enter LTC 3 In women with hip fracture: 23% die within 1 year 4 1. Hajcsar EE, et al. CMAJ 2000, 163: ; 2. Cooper C. Am J Med. 1997:103:12S-19S; 3. Jean et al. JBMR 2013; 28: Ioannidis G, et al. CMAJ 2009;181: Hopkins et al.osteo Intl 2012; 23:
14 Why is this Important to Family Physicians? Osteoporosis is managed primarily by Family Practitioners in Canada Based on Canadian prescriptions of osteoporosis therapies Source: IMSB, Compuscript (Aug 11)
15 Percentage of patients (%) Only 15% of Patients are Treated After an Osteoporotic Fracture A fracture is to osteoporosis what a heart attack is to cardiovascular disease 100% 80% 60% 40% How do we shift this paradigm? 80% 20% 15% 0% Osteoporosis Treatment Post Fracture 1 Beta Blockers Post Heart Attack 2 A history of fracture is the strongest predictor of new fractures, yet post-fracture treatment rates remain low 1. Bessette L, et al. Osteoporos Int. 2008;19: Austin PC, et al. CMAJ. 2008;179:
16 The osteoporosis care gap
17 Sending a letter to the primary care physician after a patient s fracture doubled rates of BMD testing and pharmacologic therapy versus usual care
18 Identifying Patients at High Risk for Fracture
19 Audience Question Is a BMD T-score of -2.5 alone sufficient to diagnose osteoporosis? A. Yes B. No Is a BMD T-score of -2.5 alone sufficient to treat osteoporosis? A. Yes B. No
20 BMD is not the Sole Predictor of Fracture Risk 60% of women with fractures have non-osteoporotic bone mineral density (T-score >-2.5) Adapted from Siris ES, et al. JAMA.
21 Fracture rate per 1000 person-years No of Fractures BMD vs. Osteoporotic Fracture Rates/Number 60 BMD distribution 450 Fracture Rate No of Fractures % of women with fragility fractures have non-osteoporotic bone mineral density (T-score >-2.5) > to to to to 3.0 < to to to 1.5 BMD T-scores 2.0 to to 3.5 Adapted from Siris ES, et al: JAMA 2001; 286:
22 OP: Contributors To Bone Strength Bone Quantity Bone Quality Bone Density Bone Turnover Bone Architecture Bone Mineral 22
23 Healthy Versus Osteoporotic Bone: MicroCT 52 year old Female 84 year old Female (with vertebral fracture) Borah et al, The Anatomical Record, 265: , 2001.
24 Bone Architecture: Key Factor in Bone Strength Euler Buckling Theory: A column will buckle at critical load as a function of: column material crosssectional geometry the length of the column 4 X stronger 16 X stronger Adding horizontal struts to a structure exponentially increases strength (increases buckling load) by decreasing the effective length of a column 24
25 2010 Canadian Osteoporosis Guidelines
26 Who Should Be Screened for Osteoporosis Women (and men) over the age of 50 Any individual with a history of fragility fracture A detailed history and physical exam can help identify individuals at high risk of fractures Papaioannou A, et al CMAJ *Fracture image courtesy of Dr Robert Josse
27 Major Risk Factors for Osteoporosis Age 65 years Vertebral compression fracture Fragility fracture after age 40 Family history of osteoporotic fracture (especially maternal hip fracture) Brown JP, Josse RG. CMAJ 2002;167(10 suppl):s1-s34.
28 Three Steps for Quick Screening in Office 1. ASK Since the last visit... "Have you broken any bones? "Have you fallen? "Have you had prolonged and unusual back pain? "Have you received oral or intravenous steroids (cortisone)?" 2. LOOK - Is there kyphosis? - Ability to perform the Get up and Go Test 3. MEASURE The patient s height Rib to pelvis distance Occiput-to-wall distance EMR reminder tools may help to prompt screening 4 1. Siminoski K et al. Osteoporos Int. 2006;17: Papaioannou A, et al CMAJ Timed Up-and-go test. Available at: 4. Loo TS et al. Arch Intern Med 171:
29 Screening for Osteoporosis: When to do a BMD 1 Aged 65 years Aged years Aged <50 years Everyone One or more risk factors for fracture: o Fragility fracture after age 40 o Parental hip fracture o Vertebral fracture or osteopenia identified on radiography o Medication with high risk of bone loss (i.e. steroids) o Smoking, alcohol ( 3/d) o Disorders associated with osteoporosis (i.e. RA) o Low weight or major weight loss 2 causes of osteoporosis (i.e. malabsorption) Prior fragility fracture Medication with high risk of bone loss Clinical Note: If you are ordering unrelated imaging (e.g. chest x-ray) for your patient, consider adding rule out vertebral fracture on the order Papaioannou A, et al CMAJ 2010;182: Steering Group Communications Feb 9 th 2012.
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31 Fracture Risk Assessment
32 68 year old woman Osteoporosis Case 1 BMD done because of age Femoral neck T-score 1.4 Prior vertebral compression fracture She asks what her fracture risk is over the next 10 years
33 There are Two Tools Available for Fracture Risk Assessment These tools incorporate other clinical risk factors for fracture in addition to BMD 1. OC Guidelines tool available at: 2. FRAX tool available at: 3. National Osteoporosis Foundation guidelines:
34 Femoral Neck T-score Calculating 10-Year Absolute Fracture Risk for Postmenopausal Women: CAROC Increases to the next risk category Prior fragility fracture after age 40 Prolonged corticosteroid therapy* 10-year absolute fracture risk in treatment naïve women combining femoral neck T-score and age Low Risk < 10% Moderate Risk 10% 20% Age (years) High Risk >20% Prior hip or vertebral fracture, or >1 nonvertebral fragility fracture Lumbar spine or total hip T-score -2.5: consider the individual to be at least at moderate risk Calibrated using Canadian fracture data and have been directly validated in Canadians 2 *At least three months cumulative use during the preceding year at a prednisone-equivalent dose 7.5 mg daily 1. Papaioannou A, et al. CMAJ. 2010;182: Leslie WD, et al. J Bone Miner Res. 2009;24:
35 68 year old woman Osteoporosis Case 1 BMD done because of age Femoral neck T-score 1.4 Prior vertebral compression fracture She asks what her fracture risk is over the next 10 years Answer: High
36 Pharmacological therapy should be offered to patients at high fracture risk 10-year fracture risk > 20% HIGH RISK OR Prior fragility fracture of hip or spine OR > 1 fragility fracture Papaioannou A, et al. CMAJ 2010;182:
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38 Treatment Guidelines: The Challenge of the Moderate Risk Patient Low risk (<10%) Lifestyle Modification High risk (>20%) Treat Moderate risk Lifestyle?Treat Papaioannou A, et al. CMAJ. 2010;182:
39 Top 5 Reasons to Consider Treatment in the Moderate Risk Patient: ❶ ❷ Fracture: vertebral (on lateral spine X-ray) or wrist fracture (in patient >65 or BMD -2.5) Lumbar spine T-score << femoral neck T-score ❸ ❹ ❺ Concurrent high risk disorder or medications, including: Hypogonadism or premature menopause (age <45 yr) Primary hyperparathyroidism Hyperthyroidism Rheumatoid arthritis Glucocorticoids (long-term or repeated use) Aromatase inhibitor therapy Falls ( 2 in the past year) Patient preference to be treated Steering Group Communications. Feb 9 th, Based on Osteoporosis Canada Guidelines: Papaioannou A, et al. CMAJ. 2010;182:
40 Medications known to cause/accelerate bone loss Proton Pump Inhibitors (PPI) Selective serotonin reuptake inhibitors (SSRIs) Aromatase inhibitors Hormonal/endocrine therapies - (GnRH agonists, LHRH analogs) Medications that increase fall risk and potential to fracture Benzodiazepines Neuroleptics Anticholinergics Anticonvulsants Antidepressants Antihypertensives Beta-blockers, nitrates, vasodilators * Note: not an exhaustive list
41 What biochemical tests should be ordered in the assessment of osteoporosis?
42 Secondary Causes of Osteoporosis
43 Assessment for Osteoporosis: Recommended Biochemical Tests Calcium, corrected for albumin CBC Creatinine Alkaline phosphatase Thyroid-stimulating hormone Serum protein electrophoresis (for patients with vertebral fractures) 25(OH)D* In clinical practice, these tests help rule out secondary causes of osteoporosis. *Should be measured after 3-4 months of adequate supplementation and should not be repeated if an optimal level (at least 75 nmol/l) is achieved. CBC = complete blood count; 25(OH)D = 25-hydroxyvitamin D Papaioannou A et al. CMAJ 2010; 182:
44 Osteoporosis treatment options NON-PHARMACOLOGIC PHARMACOLOGIC Non-Pharmacological Pharmacological Aerobic/walking-type exercise 3x/week Calcium: 1200 mg from diet and supplement Vitamin D: 800 IU/day or more Restrict alcohol consumption Avoid excess caffeine (> 4 cups of coffee/day) Bisphosphonates Hormone therapy (HRT) Estrogen agonist/antagonists (EAA/SERMs) Parathyroid hormone derivatives RANK Ligand Inhibitor Fall prevention 1. Brown JP et al. JOGC 2006;172:S95-S Brown JP et al. CMAJ 2002;167(10 suppl):s1-s34.
45 Osteoporosis Case 2 64 year old woman with femoral neck T score < -2.5 and prior wrist fracture She is on bisphosphonate therapy She asks what the optimal intake of calcium and vitamin D would be to maintain bone health and ensure efficacy of the bisphosphonate
46 OP: Controversies about Calcium BMJ 2010;341:c3691 and BMJ 2011;342:d2040
47 Proportion with verified MI (%) Vascular Events in Healthy Older Women Receiving Calcium Supplementation: Randomized Controlled Trial Participants received either 1 g of elemental calcium daily (as the citrate) or identical placebo 2 tablets (each with 200 mg elemental calcium) before breakfast and 3 tablets in the evening 6 5 women) Osteoporosis Canada recommendation: Placebo group (739 women) Calcium group ( mg calcium per day from all sources Time to first MI (months) MI = myocardial infarction Bollan MJ et al. BMJ 2008; 336:262-6.
48 IOF Calcium Calculator January 2015 IOF website App for Android and Apple mobile devices
49 Vitamin D Deficiency: 25(OH)D Continuum Deficiency Severe Moderate Mild Sufficiency* Serum 25(OH)D, ng/ml Serum 25(OH)D, nmol/l Severe vitamin D deficiency <12.5 nmol/ml; moderate vitamin D deficiency < nmol/ml; mild vitamin D deficiency nmol/l *Optimal serum 25-OHD level is unknown though threshold values of nmol/l have been proposed Adapted from Working Group of the Australian and New Zealand Bone and Mineral Society, Endocrine Society of Australia and Osteoporosis Australia Med J Aust 2005; 182:281-5.
50 Consequences of Vitamin D Insufficiency parathyroid hormone (PTH) calcium release (i.e. bone resorption) bone mineral density (BMD) Vitamin D insufficiency: 25(OH)D <75 nmol/l fractures muscle strength balance falls Dhesi JK et al. Age Aging 2002; 31:267-71; Simonelli C et al. j Bone Miner Res 2004; 19(Suppl 1):S433.
51 Proportion with 25-OH D levels above 75 nmol/l? 33-37%
52 What is the source of Vitamin D for supplements? Lanolin from sheep wool containing 7- dehydrocholesterol + UV light = Vitamin D3
53 Annualized adjusted* change in BMD, % Optimal Vitamin D Repletion Helped Maximize Response to Antiresorptive Therapy 2.5 ** Spine 1.70 Total hip 1.5 Neck IU daily for adults 0.22 < 50 yrs IU daily for adults > 50 yrs Postmenopausal Women with Osteoporosis or with a Prior Hip or Vertebral Fracture Treated for Months with Alendronate, Risedronate or Raloxifene Canadian Vitamin D Guidelines recommend: Vitamin D replete (n=1001) Vitamin D deficient (n=514) Note: replete is defined as 25(OH)D 20 ng/ml and deficient is defined as 25(OH)D <20 ng/ml *Adjusted for factors unrelated to vitamin D status (age, type of treatment, calcium intake and baseline BMD); **p=0.002 vs. vitamin D deficient; p<0.05 vs. vitamin D deficient Adami S et al. Osteoporos Int 2009; 20:
54 Criteria for ordering 25-OH Vitamin D test
55 Impact of Criteria on Vitamin D Tests Ordered: Alberta
56 Mechanism of Action of Available Osteoporosis Therapies Osteoclast Precursors Estrogen therapy Selective estrogen receptor modulators Hormones Multinucleated Osteoclast RANKL RANK Bisphosphonates Bind to bone; inhibit osteoclasts Teriparatide PTH analog Denosumab RANK Ligand inhibitor Osteoblast Osteoclast Adapted from: Boyle WJ et al. Nature 2003; 423:
57 Percentage of Patients With Fractures (%) Alendronate reduces Vertebral, Non-vertebral, and Hip Fractures Cochrane meta-analysis: Patient incidence of fracture and weighted relative risk for fractures after treatment with 10 mg alendronate RRR 45% n = 7156 RR 0.55 (95% CI, ) p<0.001 RRR 16% n = 9481 RR 0.84 (95% CI, ) p=0.003 RRR 39% n = 9807 Vertebral Fracture Non-vertebral Fracture Hip Fracture RR 0.61 (95% CI, ) p=0.02 Wells GA, et al. Cochrane Database Syst Rev. 2008, Issue 1, CD001155
58 Percentage of Patients With Fractures (%) Risedronate Reduces Vertebral, Non-vertebral, and Hip Fractures Cochrane meta-analysis: Patients incidence of fracture and weighted relative risk for fractures after treatment with 5 mg risedronate n = 3066 RRR 37% n = n = Vertebral Fracture Non-vertebral Fracture Hip Fracture RR 0.63 (95% CI, ) p< RRR 20% RR 0.80 (95% CI, ) p= RRR 26% RR 0.74 (95% CI, ) p=0.01 Wells GA, et al. Cochrane Database Syst Rev Jan 23;(1):CD004523
59 Cumulative Incidence (%) of New Clinical Fractures Over 3 Years Zoledronic Acid Reduces Vertebral, Non-vertebral, and Hip Fractures RCT: HORIZON 3 year Pivotal Fracture Trial in PMO RRR 70% RRR 25% 10.9% 10.7% n = (310/2853) n = (388/3875) Placebo 8.0% n = (292/3861) Zoledronic Acid 5 mg 5 3.3% n = (92/2822) RRR 41% 2.5% n = (88/3875) 1.4% n = (52/3861) 0 Vertebral Fracture* Non-vertebral Fracture** Hip Fracture** RR 0.30 (95% CI, ) p<0.001 RR 0.75 (95% CI, ) p<0.001 RR 0.59 (95% CI, ) p=0.002 Black DM, et al. N Engl J Med. 2007;356:1809 * Incidence rate ** 3-year cumulative event rates based on Kaplan-Meier estimates.
60 % of Patient with Fracture Hormone Therapy Reduces Vertebral, Non-vertebral, and Hip Fractures in Postmenopausal Women RCT: WHI study with postmenopausal women treated with hormone therapy for 5.2 years 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% Placebo HT RRR 35% 0.74% 0.48% n = (60/8102) n = (41/8506) Clinical Vertebral Fracture RRR 21% 8.70% n = (701/8102) 6.80% n = (579/8506) Non-vertebral Fracture 0.77% n = (62/8102) RRR 32% 0.52% n = (44/8506) Hip Fracture HR 0.66 (95% CI, ) HR 0.77 (95% CI, ) HR 0.66 (95% CI, ) CI = confidence interval, HR = hazard ratio, RRR = relative risk reduction HT = daily combined estrogen and progestin Rossouw JE, et al. JAMA. 2002;288:321
61 Percentage of Patients With Incident Vertebral Fracture (%) 1. Ettinger B, et al. JAMA. 1999;282: Seeman E, et al. Osteoporos Int. 2006;17:313 Raloxifene Reduces Vertebral Fractures RCT: MORE Study in postmenopausal women for 3 years Placebo Raloxifene 60 mg/day 21.2% n = (163/770) RRR 30% 14.7% n = (113/769) % n = (68/1522) RRR 50% 2.3% n = (35/1490) 0 No Pre-existing Vertebral Fractures Low-risk Population (95% CI, ) Pre-existing Vertebral Fractures High-risk Population (95% CI, ) Relative risk of non-vertebral, including hip, fractures was not significant (RR 0.9, 95% CI, ) 1 Meta-analysis of 7 Raloxifene clinical trials reported fracture reductions results consistent with results from the MORE study; overall odds ratio of
62 Percentage of Patients With 1 Fracture in 2 Years (%) Teriparatide Reduces Risk of Vertebral and Non-vertebral Fractures in Women With PMO RCT: Effect of daily PTH for 18 months on vertebral and non-vertebral fractures Placebo PTH 20 mcg 16% 14% 12% 14% n = (64/448) RRR 65% 10% 8% 6% 4% 5% n = (22/444) 5.5% n = (30/544) RRR 53% 2.6% n = (14/541) 2% 0% *Includes hip fracture Vertebral Fracture RR 0.35 (95% CI, ) p<0.001 vs placebo Non-vertebral Fracture* RR 0.47 (95% CI, ) p=0.02 vs placebo Neer RM, et al. N Engl J Med. 2001;344:1434
63 Fracture Incidence at Month 36 (%) Denosumab Reduces Vertebral, Non-vertebral, and Hip Fractures in Women With PMO 15% Placebo RCT: FREEDOM 3 year Pivotal Fracture Trial in PMO Denosumab RRR 20% 10% 7.2% n = (264/3691) RRR 68% 8.0% n = (84/3875) 6.5% n = (19/3861) RRR 40% 5% 2.3% n = (82/3702) 1.2% n = (388/3875) 0.7% n = (292/3861) 0% Vertebral Fracture* Non-vertebral Fracture Hip Fracture RR 0.32 (95% CI, ) p<0.001 vs placebo *Crude incidence Kaplan-Meier estimate of incidence RR 0.80 (95% CI, ) p=0.01 vs placebo RR 0.60 (95% CI, ) p=0.04 vs placebo Cummings SR, et al. N Eng J Med. 2009;361:756
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65 Osteoporosis Case 3 62 year old woman No history of fracture Lowest current BMD -3.1 Recommended to start bisphosphonate therapy She is worried about side effects from bisphosphonates
66 Trends in Bisphosphonate Google Searches
67 Trends in Bisphosphonate Use: USA
68 Drug Therapy and the Media: A Crisis in the Treatment of Osteoporosis An article appeared in the New York Times entitled Fearing Rare Side Effects, Millions Take Their Chances with Osteoporosis Sundeep Khosla, M.D and Elizabeth Shane MD. A Crisis in the Treatment of Osteoporosis Date Submitted June 15, 2016; Date Revision Submitted June 16, 2016; Date Final Disposition Set June 17, 2016 Journal of Bone and Mineral Research This article is protected by copyright. All rights reserved. DOI /jbmr.2888
69 Osteonecrosis of the Jaw (ONJ) ONJ is an oral cavity lesion characterized by 1 or more spots of bare alveolar or hard palate bone, in the absence of local malignancy or radiation therapy to the head or neck
70 Risk 1: 100,000 patients Risk 1:100,000 patients over 3 years
71 70 year old woman Osteoporosis Case 4 No history of fracture Taking weekly bisphosphonate for 5 years Lowest current BMD -2.4 She wants to discuss a drug holiday
72 Atypical (Subtrochanteric) Femur Fractures ASBMR Task Force Definition 1 : Major Features* Anywhere along the femur No trauma or minimal trauma Transverse or short oblique configuration Non-comminuted Complete fractures through both cortices (may be associated with a medial spike); incomplete fractures involve only the lateral cortex *All Major features required to define atypical femoral fracture. Image from: Lenart BA, et al. N Engl J Med. 2008;358: Shane E, Burr D, et al. Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Report of a Task Force of the American Society for Bone and Mineral Research. JBMR, 2010; On line Sept 7, DOI /jbmr Lenart BA, et al. N Engl J Med. 2008;358:1304
73 Bisphosphonate Risk Benefit Ratio
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75 Osteoporosis: Future Therapies Sclerostin inhibitors Romosozumab (concern re CV side effects raised in one RCT) Cathepsin K inhibitors Odanacatib (development halted late 2016) PTH analogues Abaloparatide (marketed 2017 in USA as TYMLOS)
76 ROMO: Phase 3 Fracture Trial (FRAME) Cosman et al NEJM 2016
77 Abaloparatide Daily SC Injection
78 Resources
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84 OP Treatment Decision Tools
85 Additional resources for osteoporosis in LTC» Educational resources and tool kits on medications, screening, falls prevention and more are available at:
86 PEARLs: Osteoporosis
87 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada Key points: Management of osteoporosis should be guided by an assessment of the patient s absolute risk of osteoporosis-related fractures Fragility fracture increases the risk of further fractures and should be considered in the assessment Lifestyle modifications and pharmacologic therapy should be individualized to enhance adherence to the treatment plan Papaioannou A et al. CMAJ 2010; 182:
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89 Fewer Fractures!
90 Barriers to Change: Osteoporosis Lack of coordination between fracture care at hospitals and osteoporosis care in the community Overreliance on BMD versus fracture risk assessment Lack of availability of bone turnover markers to follow therapeutic responses Patient fears of rare side effects of bisphosphonate therapy
91 Questions?? Wind up your presentation-he s losing bone mass.
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