1. 2010 Guidelines
Case Study #3: Mrs. SP

2. Case Presentation
73-year-old woman presenting for a physical examination
History of low-trauma Colles' fracture (11 years ago)
BMD from three years ago
Spine -3.6; Hip -2.0
No prescription medications
Takes a multivitamin daily plus a calcium tablet
Looks and feels healthy and well

3. Physical Examination Weight: 55 kg (121 lbs.) Height: 157 cm (5’2”)
Body Mass Index (BMI): 22.3 kg/m2
Changes in height and weight can be signs of vertebral fractures
Other indicators of vertebral fracture in physical examination: Rib-pelvis distance and occiput-wall distance

4. Question
Should Mrs. SP be treated with pharmacologic therapy for osteoporosis?

5. Investigations
Mrs. SP should have her 10-year risk of fracture assessed
Prior DXA done, in accordance with Osteoporosis Canada guideline indications for use
CAROC and FRAX are the risk assessment tools validated for use in Canada
She has been taking multivitamin with vitamin D and calcium (800 IU and 500 mg)
Consider assessing serum 25-OH-D

6. Calculating Absolute 10-year Fracture Risk: FRAX Tool
Click here to see her CAROC assessment
Mrs. SP is at moderate risk of fractures using the FRAX model

7. Treatment Considerations
Counselling should be provided on benefits of vitamin D and calcium, as well as nonpharmacologic interventions (e.g., exercise)
The 2010 Osteoporosis Canada guidelines algorithm recommends assessment of additional risk factors among moderate-risk patients

8. Question
What additional risk factors may aid in decision-making for Mrs. SP?

9. Assessment of Other Risk Factors
Low spine T-score (-3.6):
Lumbar spine BMD is not considered in the initial risk assessment for either CAROC or FRAX, and fracture risk is slightly underestimated when the lumbar spine T-score is much lower than the hip T-score1
A lumbar spine T-score much lower than femoral neck T-score is one of the factors warranting consideration of pharmacologic therapy in those at moderate risk1
Lumbar spine BMD is not considered in the initial risk assessment for either CAROC or FRAX, and fracture risk is slightly underestimated when the lumbar spine T-score is much lower than the hip T-score. A lumbar spine T-score much lower than femoral neck T-score is one of the factors warranting consideration of pharmacologic therapy in those at moderate risk.
Reference
Leslie WD, Lix LM, Johansson H, et al. Spine–hip discordance and fracture risk assessment: a physician-friendly FRAX enhancement. Osteoporos Int In press.
1. Leslie WD, Lix LM, et al. Osteoporos Int In press.

10. Communicating the Benefits, Risks, and Harms of Therapy
There are several agents with level 1 evidence for fracture prevention in menopausal women
Counsel patients about these benefits as well as potential adverse events
Osteoporosis treatment is indefinite; counsel on importance of adherence

11. Question
How should you approach monitoring for a patient like Mrs. SP?

12. Considerations for Monitoring
Rationale for monitoring: To identify individuals with continued bone mineral density (BMD) loss, despite appropriate osteoporosis treatment
Aspects of monitoring
Serial BMD measurements
Assessment of adherence
Speaker notes
The major objective of follow-up testing is to identify individuals with continued bone mineral density (BMD) loss, despite appropriate osteoporosis treatment. Serial BMD measurement is an important aspect of follow-up, as is assessment of adherence. Assessment of bone turnover markers (BTMs) may also be an important element of monitoring, although further research is still required.

13. Mrs. SP: Follow-up (What if...?)
Mrs. SP presents to your office two years after being on therapy for follow-up of a vertebral compression fracture diagnosis made in the emergency room a short while ago
She assures you she is always adherent to therapy
Is this considered a treatment failure?
Consider referral to specialist

14. Mrs. SP: Conclusions
Diagnosis and treatment decisions should start with the 10-year assessment of risk using a validated tool
Mrs. SP is moderate risk using FRAX (10-year risk: 15%)
Additional clinical risk factors should be considered when making a treatment decisions
For monitoring, repeat BMD every one to three years, with a decrease in testing once therapy is shown to be effective

15. Additional slides that can be accessed from hyperlinks on case slides
Back-up Material
Additional slides that can be accessed from hyperlinks on case slides
Case C – Mrs. SP

16. 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)
Speaker notes
In postmenopausal women and men 50 years and older, low body weight (< 60 kg) and major weight loss (>10% of weight at age 25) are associated with low BMD and fractures.1-6
References
1. Papaioannou A, Kennedy CC, Ioannidis G, et al. The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study. Osteoporos Int 2009; 20(5):
2. Waugh EJ, Lam MA, Hawker GA, et al. Risk factors for low bone mass in healthy year old women: A systematic review of the literature. Osteoporos Int 2009; 20:1-21.
3. Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332(12):
4. Papaioannou A, Joseph L, Ioannidis G, et al. Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 2005; 16(5):
5. Kanis J, Johnell O, Gullberg B, et al. Risk factors for hip fracture in men from southern Europe: the MEDOS study. Mediterranean Osteoporosis Study. Osteoporos Int 1999; 9:45-54.
6. Morin S, Tsang JF, Leslie WD. Weight and body mass index predict bone mineral density and fractures in women aged 40 to 59 years. Osteoporos Int 2009; 20(3):
1. Papaioannou A, et al. Osteoporos Int 2009; 20(5):
2. Waugh EJ, et al. Osteoporos Int 2009; 20:1-21.
3. Cummings SR,et al. N Engl J Med 1995; 332(12):
4. Papaioannou A, et al. Osteoporos Int 2005; 16(5):
5. Kanis J, et al. Osteoporos Int 1999; 9:45-54.
6. Morin S, et al. Osteoporos Int 2009; 20(3):
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17. 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
Speaker notes
Historical height loss (difference between the tallest recalled height and current measured height)1,2 and measured height loss (from two or more office visits)3-5 are associated with the presence of vertebral fractures. Prospective loss of > 2 cm over three years should be investigated by a lateral thoracic and lumbar spine X-ray.
References
1. Siminoski K, Warshawski RS, Jen H, et al. The accuracy of historical height loss for the detection of vertebral fractures in postmenopausal women. Osteoporos Int 2006; 17(2):
2. Briot K, Legrand E, Pouchain D, et al. Accuracy of patient-reported height loss and risk factors for height loss among postmenopausal women. CMAJ 2010; 182(6):
3. Moayyeri A, Luben RN, Bingham SA, et al. Measured height loss predicts fractures in middle-aged and older men and women: the EPIC-Norfolk prospective population study. J Bone Miner Res 2008; 23:
4. Siminoski K, Adachi JG, Hanley DA, et al. Accuracy of height loss during prospective monitoring for detection of incident vertebral fractures. Osteoporos Int 2005; 16(4):
5. Kaptoge S, Armbrecht G, Felsenberg D, et al. When should the doctor order a spine x-ray? Identifying vertebral fractures for osteoporosis care: results from the European Prospective Osteoporosis Study (EPOS). J Bone Miner Res 2004; 19:
1. Siminoski K, et al. Osteoporos Int 2006; 17(2):
2. Briot K, et al. CMAJ 2010; 182(6):
3. Moayyeri A, et al. J Bone Miner Res 2008; 23:
4. Siminoski K, et al. Osteoporos Int 2005; 16(4):
5. Kaptoge S, et al. J Bone Miner Res 2004; 19:
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18. Additional Tests for Clinical Identification of Vertebral Fracture
Rationale
Method
Interpretation
Rib-pelvis distance1
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 distance2,3
To help identify thoracic spine fractures
Stand straight with heels and back against the wall
> 5 cm raises suspicion of vertebral fracture
Speaker notes
The rationale for measuring rib-pelvis distance is to identify lumbar fractures. This is done by assessment of the distance between the costal margin and the pelvic rim (measured on the mid-axillary line). A measurement of < 2 fingerbreadths is associated with vertebral fractures.1
The occiput-to-wall distance is a tool used to help identify thoracic spine fractures. The measurement is made as the individual stands straight with heels and back against the wall. Vertebral fractures should be suspected if distance between the wall and the occiput is > 5 cm.2,3
References
1. Olszynski WP, Ioannidis G, Sebaldt RJ, et al. The association between iliocostal distance and the number of vertebral and non-vertebral fractures in women and men registered in the Canadian Database For Osteoporosis and Osteopenia (CANDOO). BMC Musculoskeletal Disorders 2002; 3:22.
2. Green AD, Colon-Emeric C, Bastian L, et al. Does this woman have osteoporosis? JAMA 2004; 292(23):
3. Siminoski K, Warshawski R, Jen H, Lee K. Accuracy of physical exam for detection of thoracic vertebral fractures. J Bone Miner Res 2001; 16(Suppl):S274.
1. Olszynski WP, et al. BMC Musculoskeletal Disorders 2002; 3:22.
2. Green AD, et al. JAMA 2004; 292(23):
3. Siminoski K, et al. J Bone Miner Res 2001; 16(Suppl):S274.

19. Rib-Pelvis and Occiput-to-Wall Distances
4 cm
3 FBs
8 cm
12 cm
2 FBs
Height loss
3 cm
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20. 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)
Speaker notes
There is evidence that vitamin D supplementation is associated with increases in bone mineral density1-3 and reductions in fractures,4 particularly when combined with adequate calcium intake.5
 A recent review and guideline statement from Osteoporosis Canada6 recommends increased vitamin D supplementation for low-risk adults (without osteoporosis or conditions affecting vitamin D absorption) from 10 mcg (400 IU) daily to 10 – 25 mcg (400 – 1000 IU) daily. In those at high risk for adverse outcomes from vitamin D insufficiency (e.g., recurrent fractures or osteoporosis and comorbid conditions that affect vitamin D absorption), recommendations have been increased from 20 mcg (800 IU)/day to 20 – 50 mcg (800 – 2000 IU) daily; some of these patients need doses higher than 50 mcg (2000 IU) daily, and monitoring of the serum 25-OH-D response is appropriate. The optimal level of serum 25OH-D for musculoskeletal benefits is estimated to be at least 75 nmol/L.6
References
1. Dawson-Hughes B, Harris SS, Krall EA, et al. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med 1997; 337(10):
2. Grados F, Brazier M, Kamel S, et al. Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Joint Bone Spine 2003; 70(3):
3. Jackson RD, LaCroix AZ, Gass M, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354:
4. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293(18):
5. Tang BM, Eslick GD, Nowson et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007; 370(9588):
6. Hanley DA, Cranney A, Jones G, et al. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ 2010; 182:E610-E618.
Hanley DA, et al. CMAJ 2010; 182:E610-E618.

21. 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
Speaker notes
The optimal level of serum 25OH-D for musculoskeletal benefits is estimated to be at least 75 nmol/L.
Reference
Hanley DA, Cranney A, Jones G, et al. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ 2010; 182:E610-E618.
Hanley DA, et al. CMAJ 2010; 182:E610-E618.

22. 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
Speaker notes
Serum 25-OH-D should only be measured in situations where deficiency is suspected, or would affect response to therapy; e.g., individuals with impaired intestinal absorption, or in patients with osteoporosis requiring pharmacologic therapy. The half-life of 25-OH-D in the body is 15 – 20 days1 and the serum 25-OH-D response to standard-dose supplementation plateaus after three to four months.2 Therefore, serum 25-OH-D should be checked no sooner than three months after commencing standard-dose supplementation in patients who have osteoporosis. Monitoring of routine supplement use and routine testing of otherwise healthy individuals as a screening procedure are not necessary.3
References
1. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008; 88(2):582S-586S.
2. Heaney RP, Davies KM, Chen TC, et al. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003; 77(1):
3. Hanley DA, Cranney A, Jones G, et al. Vitamin D in adult health and disease: a review and guideline statement from Osteoporosis Canada. CMAJ 2010; 182:E610-E618.
Hanley DA, et al. CMAJ 2010; 182:E610-E618.

23. Recommended Calcium Intake
From diet and supplements combined: 1200 mg daily
Several different types of calcium supplements are available
Evidence shows a benefit of calcium on reduction of fracture risk1
Concerns about serious adverse effects with high-dose supplementation2-4
Speaker notes
Dietary calcium exerts a mild suppressive effect on bone turnover and this has a beneficial impact on BMD.1,2 In a meta-analysis it was concluded that calcium, with or without vitamin D, resulted in fewer fractures (both hip [shown] and vertebral).3
Health Canada defines adequate calcium intake (from diet and supplements) as 1200 mg daily with an upper tolerable level of 2500 mg per day for adults 50 and older. The upper tolerable levels were derived from historical concerns over the development of milk-alkali syndrome in individuals who consumed large doses of calcium. High doses of calcium supplements are difficult to achieve as individuals experience gastrointestinal symptoms such as constipation. There is also controversy regarding the potential adverse effects of high-dose calcium supplementation on renal calculi and cardiovascular events in older women and prostate cancer in older men.4-6
These symptoms may have contributed to compliance rates of 40% or less in the majority of randomized controlled trials on calcium supplementation.1,7 Therefore, we have revised our recommendation on total (diet plus supplements) daily calcium intake from 1500 mg to 1200 mg.
References
1. Reid IR, Bolland MJ, Grey A, Reid IR, Bolland MJ, Grey A. Effect of calcium supplementation on hip fractures. Osteoporos Int 2008; 19(8):
2. Moschonis G, Katsaroli I, Lyritis GP, et al. The effects of a 30-month dietary intervention on bone mineral density: The Post-menopausal Health Study. Br J Nutr 2010; 104(1):100-7.
3. Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007; 370(9588):
4. Bolland MJ, Grey AB, Gamble GD, et al. Effect of osteoporosis treatment on mortality: A meta-analysis. J Clin Endocrinol Metab 2010; 95(3):
5. Bolland MJ, Barber AP, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ 2008; 336(7638):
6. Reid IR, Bolland MJ, Grey A, et al. Effect of calcium supplementation on hip fractures. Osteoporos Int 2008; 19(8):
7. Prince RL, Devine A, Dhaliwal SS, et al. Effects if calcium supplementation on clinical fractures and bone structure: results of a 5-year double-blind placebo controlled trial in elderly women. Arch Intern Med 2006; 166:
1. Tang BM, et al. Lancet 2007; 370(9588):
2. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):
3. Bolland MJ, et al. BMJ 2008; 336(7638):
4 Reid IR, et al. Osteoporos Int 2008; 19(8):
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24. 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 osteopenia identified 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
Speaker notes
BMD assessment with dual energy X-ray absorptiometry (DXA) is well established for the diagnosis of osteoporosis and for fracture risk assessment in men and post-menopausal women.
The indications for DXA in older adults are shown here.
†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.
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25. 10-year Risk Assessment: CAROC
Semiquantitative method for estimating 10-year absolute risk of a major osteoporotic fracture* in postmenopausal women and men over age 50
Stratified into three zones (Low: < 10%, moderate, high: > 20%)
Basal risk category is obtained from age, sex, and T-score at the femoral neck
Other fractures attributable to osteoporosis are not reflected; total osteoporotic fracture burden is underestimated
Speaker notes
This risk-assessment model provides a semiquantitative (ordinal risk category) method for estimating 10-year absolute risk of a major osteoporotic fracture in postmenopausal women and men over age 50.1 An individual’s 10-year absolute fracture risk (combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus) is stratified into three 10-year absolute fracture risk zones designated low risk (< 10%), moderate risk (10% – 20%), and high risk (> 20%), similar to the absolute risk categories already used for cardiovascular risk assessment.2 Other fractures attributable to osteoporosis (e.g., pelvic fractures and undiagnosed vertebral fractures) are not reflected in the CAROC or FRAX predictions, which will therefore underestimate the total osteoporotic fracture burden.
References
1. Siminoski K, Leslie WD, Frame H, et al. Recommendations for bone mineral density reporting in Canada. Can Assoc Radiol J 2005; 56(3):
2. McPherson R, Frohlich J, Fodor G, et al. Canadian Cardiovascular Society position statement -- Recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol 2006; 22(11):
* Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus
Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):

26. 10-year Risk Assessment for Women (CAROC Basal Risk)
Speaker notes
An initial (basal) risk category is obtained from age, sex, and T-score at the femoral neck. The spine BMD is not considered in the initial risk assessment for either CAROC or FRAX. However when determining the risk category, a patient with a T-score of the spine or hip < -2.5 should not be considered low risk (i.e., should be classified having at least moderate risk).
Reference
Papaioannou A, Leslie WD, Morin S, et al Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada. CMAJ 2010 Oct 12. [Epub ahead of print].
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

27. 10-year Risk Assessment for Women (CAROC Basal Risk)
Age
Low Risk
Moderate Risk
High Risk 50
above -2.5
-2.5 to -3.8
below -3.8 55 60
above -2.3
-2.3 to -3.7
below -3.7 65
above -1.9
-1.9 to -3.5
below -3.5 70
above -1.7
-1.7 to -3.2
below -3.2 75
above -1.2
-1.2 to -2.9
below -2.9 80
above -0.5
-0.5 to -2.6
below -2.6 85
above +0.1
+0.1 to -2.2
below -2.2
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

28. 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
Speaker notes
Certain clinical factors increase fracture risk independently of BMD, the most important being: fragility fractures after age 40 (especially vertebral compression fractures1,2 and recent prolonged systemic glucocorticoid use (e.g., at least three months cumulative during the preceding year at a prednisone equivalent dose of at least 7.5 mg daily).2
References
1. Siminoski K, Leslie WD, Frame H, et al. Recommendations for bone mineral density reporting in Canada. Can Assoc Radiol J 2005; 56(3):
2. Kanis JA, Johansson H, Oden A, et al. A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 2004; 19(6):
* 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):
2. Kanis JA, et al. J Bone Miner Res 2004; 19(6):
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29. Risk Assessment Using FRAX
Uses age, sex, BMD, and clinical risk factors to calculate 10-year fracture risk*
BMD must be femoral neck
FRAX also computes 10-year probability of hip fracture alone
This system has been validated for use in Canada1
There is an online FRAX calculator with detailed instructions at:
Speaker notes
The WHO Collaborating Centre has identified clinical risk factors which, in addition to age and sex, contribute to fracture risk independently of BMD.1 The FRAX tool, released in 2008, computes 10-year probability of major osteoporotic fracture (composite of hip, vertebra forearm, and humerus) from sex, age, BMI, prior fracture, parental hip fracture, prolonged corticosteroid use, rheumatoid arthritis (or secondary causes of osteoporosis), current smoking, alcohol intake (three or more units daily) and femoral neck BMD.2 FRAX has been validated in Canada.3
Although FRAX also computes 10-year probability of hip fracture alone, the primary designation of risk for clinical decision-making should be the global assessment of major osteoporotic fracture probability. The online FRAX calculator and more details on how it is used is at: You can also type FRAX into a search engine (e.g., Google) and find this main FRAX site.
 References
1. Kanis JA, Johansson H, Oden A, et al. Assessment of fracture risk. Eur J Radiol 2009; 71(3):
2. Kanis JA, Oden A, Johnell O, et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 2007; 18(8):
3. Leslie WD, Lix LM, Langsetmo L, et al. Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment. Osteoporos Int; In press.
* composite of hip, vertebra, forearm, and humerus
1. Leslie WD, et al. Osteoporos Int; In press.

30. FRAX Tool: Online Calculator
Speaker notes
As fracture rates are known to vary by more than an order of magnitude worldwide,1 calibration for the FRAX tool is population/country specific. Using national fracture data, a FRAX model for Canada was recently constructed for the prediction of hip-fracture risk and major osteoporotic fracture risk with and without use of BMD. Performance of this system was independently assessed in CaMos (4778 women and 1919 men) and a clinical cohort from Manitoba (36,730 women and 2873 men).2 The Canadian FRAX tool generated fracture risk predictions that were generally consistent with observed fracture rates across a wide range of risk categories.2,3
Fracture discrimination using FRAX with BMD was better than FRAX without BMD or BMD alone, as has been seen in other cohorts.
In addition to the free on-line calculator, shown here, there is also an iphone app, which is available for a fee.
References
1. Kanis JA, Johnell O, De Laet C, et al. International variations in hip fracture probabilities: implications for risk assessment. J Bone Miner Res 2002; 17(7):
2. Leslie WD, Lix LM, Langsetmo L, et al. Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment. Osteoporos Int; In press.
3. Leslie WD, Lix LM, Johansson H, et al. Independent clinical validation of a Canadian FRAX® Tool: Fracture prediction and model calibration. J Bone Miner Res 2010; Apr 30. [Epub ahead of print].

31. FRAX Clinical Risk Factors
Parental hip fracture
Prior fracture
Glucocorticoid use
Current smoking
High alcohol intake
Rheumatoid arthritis
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32. 10-year Risk Assessment for Women (CAROC Basal Risk)
Age
Low Risk
Moderate Risk
High Risk 50
above -2.5
-2.5 to -3.8
below -3.8 55 60
above -2.3
-2.3 to -3.7
below -3.7 65
above -1.9
-1.9 to -3.5
below -3.5 70
above -1.7
-1.7 to -3.2
below -3.2 75
above -1.2
-1.2 to -2.9
below -2.9 80
above -0.5
-0.5 to -2.6
below -2.6 85
above +0.1
+0.1 to -2.2
below -2.2
Return to case
Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

33. Summary Statement for Other Nonpharmacologic Therapies
Strength
Exercises for individuals with osteoporosis should include weight bearing, balance, and strengthening exercises
Level 2
Exercise-focused interventions improve balance and reduce falls in community-dwelling older people
Hip protectors may reduce the risk of hip fractures in long-term care residents, however compliance with their use may pose a challenge for the older adult
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34. Integrated Approach to Management of Patients Who Are at Risk for Fracture
Encourage basic bone health for all individuals over age 50, including regular active weight-bearing exercise, calcium (diet and supplementation) 1200 mg daily, vitamin D IU (20-50µg) daily and fall-prevention strategies
Age < 50 yr
Age yr
Age > 65 yr
Fragility fractures
Use of high-risk medications
Hypogonadism
Malabsorption syndromes
Chronic inflammatory conditions
Primary hyperparathyroidism
Other disorders strongly associated with rapid bone loss or fractures
Fragility fracture after age 40
Prolonged use of glucocorticoids or other high-risk medications
Parental hip fracture
Vertebral fracture or osteopenia identified on radiography
High alcohol intake or current smoking
Low body weight (< 60 kg) or major weight loss (> 10% of body weight at age 25)
Other disorders strongly associated with osteoporosis
All men and women
Initial BMD Testing

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

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

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

38. Integrated Approach, Continued
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

39. Integrated Approach, Continued
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
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40. 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

41. 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)
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42. First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women*
Type of Fracture
Antiresorptive therapy
Bone formation therapy
Bisphosphonates
Denosumab
Raloxifene
Hormone therapy (Estrogen)**
Teriparatide
Alendronate
Risedronate
Zoledronic acid
Vertebral 
Hip -
Non- vertebral+
Speaker notes
The following agents have level 1 evidence to support their use for prevention of vertebral fracture: alendronate, denosumab, estrogen, raloxifene, risedronate, teriparatide and zoledronic acid. For hip fracture prevention, the following therapies have level 1 evidence: alendronate, denosumab, estrogen, risedronate, zoledronic acid. For non-vertebral fracture prevention, there is level 1 evidence for alendronate, denosumab, estrogen, teriparatide and zoledronic acid.
* 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.
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43. 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
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44. Recommendations for Duration of Therapy
Grade
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 study2
Speaker notes
There is very little evidence to support any recommendation regarding the questions of how long to treat, use of drug holidays, and the effectiveness of resuming treatment after discontinuation of therapy. No studies have compared the effects of various drug holiday regimens and holiday lengths; and no studies have examined the effectiveness of resuming therapy after a holiday. The possible benefits of a drug holiday include reduction of potential adverse events and costs.
In the FLEX (Fracture Intervention Trial Long-Term Extension) trial, after 5 years of treatment with alendronate, participants either continued on alendronate for five additional years, or were randomized to placebo for five years.1 At the end of the extension phase, the five-year clinical vertebral fracture rates were decreased by 55% in those who continued on alendronate (for a total of 10 years) compared to those randomized to placebo (i.e., five years alendronate and five years placebo). There were no differences in non-vertebral fractures or radiographic vertebral fractures.
In a randomized control trial with risedronate, participants who had been on treatment for three years (risedronate or placebo) discontinued their study medication and continued on calcium and vitamin D for an additional year.2 At the end of one year off treatment, BMD decreased in those who had been on risedronate previously, but remained higher than baseline in placebo treated subjects.
References
1. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006; 296(24):
2. Watts NB, Chines A, Olszynski WP, et al. Fracture risk remains one year after discontinuation of risedronate. Osteoporos Int 2008; 19(3):
1. Black DM, et al. JAMA 2006; 296(24):
2. Watts NB, et al. Osteoporos Int 2008; 19(3):
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45. 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 benefits1-3
Speaker notes
Once a decision to initiate osteoporosis drug therapy has been made, the expectation is that patients will experience anti-fracture benefits similar to those reported in clinical trials. Therapeutic benefit is reduced or eliminated if there is suboptimal adherence to the regimen.1-3
References
1. Silverman S. Adherence to medications for the treatment of osteoporosis. Rheum Dis Clin North Am 2006; 32(4):
2. McCombs JS, Thiebaud P, Laughlin-Miley C, et al. Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 2004; 48(3):
3. Gold DT, Silverman S. Review of adherence to medications for the treatment of osteoporosis. Curr Osteoporos Rep 2006; 4(1):21-27.
1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):
2. McCombs JS, et al. Maturitas 2004; 48(3):
3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.

46. Poor Adherence Leaves Patients At Higher Risk of Fracture
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
0.00
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
Probability of fracture
MPR
Siris E, et al. Mayo Clin Proc 2006; 81:

47. Types and Rates of Nonadherence in 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
Speaker notes
Types of non-adherence to anti-osteoporosis therapy include frequently missed doses, failing to take the medication correctly to optimize absorption and action, or discontinuation of therapy.1-3
Compliance rates at one year in the range 25% – 50% with oral anti-osteoporosis agents are commonly reported, and are only marginally better with less frequent dosing regimens.1,3
References
1. Silverman S. Adherence to medications for the treatment of osteoporosis. Rheum Dis Clin North Am 2006; 32(4):
2. McCombs JS, Thiebaud P, Laughlin-Miley C, et al. Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 2004; 48(3):
3. Gold DT, Silverman S. Review of adherence to medications for the treatment of osteoporosis. Curr Osteoporos Rep 2006; 4(1):21-27.
1. Silverman S. et al. Rheum Dis Clin North Am 2006; 32(4):
2. McCombs JS, et al. Maturitas 2004; 48(3):
3. Gold DT, et al. Curr Osteoporos Rep 2006; 4(1):21-27.

48. Approaches for Optimizing Adherence
Reminders
Patient information
Counselling
Simplification of the dosing regimen
Self-monitoring
Speaker notes
Several approaches can be considered to ensure that patients are adherent to therapy and to confirm treatment response. These include a combination of reminders, information, counselling, simplifying dosing regimen, and self-monitoring.
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49. 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 increases2
Stable BMD is consistent with successful treatment
Speaker notes
Measurement error must be considered when interpreting serial BMD assessments in order to determine whether the change is real and not simply random fluctuation or artifact. Each centre should determine its precision error in order to estimate the least significant change (LSC) (i.e., the change in BMD required to have 95% confidence that the change is real).1 Continued BMD loss exceeding the LSC may reflect poor adherence to therapy, failure to respond to therapy, or previously unrecognized secondary causes of osteoporosis (e.g., vitamin D insufficiency). However, most osteoporosis therapies do not cause large increases in BMD, and the anti-fracture effect of treatment is only partly explained by the relatively small changes in BMD.2 Stable BMD is consistent with successful treatment.
References
1. Baim S, Wilson CR, Lewiecki EM, et al. Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry. J Clin Densitom 2005; 8(4):
2. Chen P, Krege JH, Adachi JD, et al. Vertebral fracture status and the World Health Organization risk factors for predicting osteoporotic fracture risk. J Bone Miner Res 2009; 24(3):
1. Baim S, et al. J Clin Densitom 2005; 8(4):
2. Chen P, et al. J Bone Miner Res 2009; 24(3):

50. 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
Speaker notes
BMD scans are 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.
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51. 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
Speaker notes
Recognizing that there may be situations in which the management of osteoporosis can be complicated, primary care physicians should consider referral where specialized consultation and care is required.

52. 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
Speaker notes
Recognizing that there may be situations in which the management of osteoporosis can be complicated, primary care physicians should consider referral where specialized consultation and care is required.
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