2010 Guidelines Case Study #4: Mr. JM 2010 Guidelines

Case Presentation 64-year-old retired firefighter –Retired nine years ago; now doing contract carpentry Presents for physical examination, complaining his back has been “worse than usual” the past three weeks On no medications Prior smoker (45 pack/year history) –Quit smoking one year ago

2010 Guidelines Physical Examination Height: 180 cm (5'11") –Patient recalls being cm (6'1") Weight: 80 kg (up 5 kg from one year ago) Body mass index (BMI): 24.7 kg/m 2 –Changes in height and weight can be signs of vertebral fracturesheightweight –Other indicators of vertebral fracture in physical examination: Rib-pelvis distance and occiput-wall distanceOther indicators of vertebral fracture in physical examination

2010 Guidelines Risk Factor Assessment Family history: none significant No history of systemic glucocorticoids or androgen-deprivation therapy No history of secondary causes of osteoporosis Historical height loss No previous trauma Alcohol use: approximately two drinks per week Click here for a discussion of factors known to increase fracture risk in men.

2010 Guidelines Why is Osteoporosis Underappreciated in Men? Men have higher peak bone mass Slower rate of bone loss Shorter life expectancy Greater periosteal bone formation (greater cross-sectional bone diameter and a biomechanical advantage since larger bones have less fracture risk) Khan AA, et al. CMAJ 2007;176(3):

2010 Guidelines Question What tests would you consider ordering?

2010 Guidelines Mr. JM: Diagnostic Testing Screening for osteoporosis with dual energy X-ray absorptiometry ( DXA) is indicated, based on 2010 guideline criteria2010 guideline criteria –T-score -1.9 at femoral neck Lateral thoraco-lumbar spine X-ray is ordered to rule out vertebral compression deformitiesspine X-ray –The radiologist makes note of two vertebrae being wedge shaped and just meeting the criteria for vertebral compression fracture

2010 Guidelines Question Given the presence of vertebral fractures, is further risk assessment necessary before initiating pharmacologic therapy?

2010 Guidelines Considerations for Therapy The guidelines do recommend that diagnosis and treatment decisions should be based on a validated 10-year risk-assessment tool (i.e., CAROC or FRAX) CAROCFRAX –FRAX predicts 12% risk (moderate) 1 However, the presence of multiple vertebral fractures in this case place Mr. JM at high risk –In fact, 10-year assessment tools underestimate risk in patients with vertebral fractures 1. Leslie WD, Lix LM, et al. Osteoporos Int In press.

2010 Guidelines Question How would you proceed with therapy for Mr. JM?

2010 Guidelines Treatment Considerations Bloodwork to rule out secondary causes of osteoporosis secondary causes of osteoporosis Assume vitamin D level is low and start supplementation (with calcium)vitamin D level According to the 2010 OC guidelines –Pharmacotherapy is indicated for a high-risk patient (see integrated management model)Pharmacotherapysee integrated management model –Testosterone therapy is not recommendedTestosterone therapy

2010 Guidelines Mr. JM: Conclusions Mr. JM is high risk because of his vertebral fractures In this case, 10-year assessment tools underestimate risk Patients at high risk benefit from pharmacologic therapy –Recommended agents for first-line use in men are alendronate, risedronate, or zoledronic acid

2010 Guidelines Case 4 – Case 4 – Mr. JM Back-up Material Additional slides that can be accessed from hyperlinks on case slides

2010 Guidelines Importance of Weight In men > 50 years and postmenopausal women, the following are associated with low bone mineral density (BMD) and fractures –Low body weight (< 60 kg) –Major weight loss (> 10% of weight at age 25) 1. Papaioannou A, et al. Osteoporos Int 2009; 20(5): Waugh EJ, et al. Osteoporos Int 2009; 20: Cummings SR,et al. N Engl J Med 1995; 332(12): Papaioannou A, et al. Osteoporos Int 2005; 16(5): Kanis J, et al. Osteoporos Int 1999; 9: Morin S, et al. Osteoporos Int 2009; 20(3): Return to case

2010 Guidelines Importance of Height Loss Increased risk of vertebral fracture –Historical height loss (> 6 cm) 1,2 –Measured height loss (> 2 cm) 3-5 Significant height loss should be investigated by a lateral thoracic and lumbar spine X-ray 1. Siminoski K, et al. Osteoporos Int 2006; 17(2): Briot K, et al. CMAJ 2010; 182(6): Moayyeri A, et al. J Bone Miner Res 2008; 23: Siminoski K, et al. Osteoporos Int 2005; 16(4): Kaptoge S, et al. J Bone Miner Res 2004; 19: Return to case

2010 Guidelines Additional Tests for Clinical Identification of Vertebral Fracture TestRationaleMethodInterpretation Rib-pelvis distance 1 To identify lumbar fractures Measure the distance between the costal margin and the pelvic rim on the mid- axillary line < 2 fingerbreadths is associated with vertebral fractures Occiput-to-wall distance 2,3 To help identify thoracic spine fractures Stand straight with heels and back against the wall > 5 cm raises suspicion of vertebral fracture 1. Olszynski WP, et al. BMC Musculoskeletal Disorders 2002; 3: Green AD, et al. JAMA 2004; 292(23): Siminoski K, et al. J Bone Miner Res 2001; 16(Suppl):S274.

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

2010 Guidelines Risk Factors with Good Evidence for Low BMD in men Advancing age –Between 50 and 80 years, men have1.5% – 2.5% decline in hip BMD per year –BMD at lumbral-sacral spine increases with age (falsely elevated due to osteophyte formation) Smoking –Current smokers have greater risk of low BMD at the hip compared to former smokers. –Highest risk subgroups Men > 20 pack years Current smokers with low body weight (< 75 kgs) Papaioannou A, et al. Osteoporosis Int 2009;20:

2010 Guidelines Risk Factors with Good Evidence for Low BMD in Men Low weight/weight loss –BMD at the hip increases roughly 3% – 7% for every 10 kg weight gain –Low baseline weight/BMI predicts subsequent bone loss at the hip Physical functional limitations –Men who can rise from a chair without using arms have 2% – 4% higher hip BMD than those who cannot Prevalent fracture after 50 years of age Papaioannou A, et al. Osteoporosis Int 2009;20: Return to case

2010 Guidelines 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 ( 10% of weight at age 25) –Rheumatoid arthritis –Other disorders strongly associated with osteoporosis Return to case † 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.

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

2010 Guidelines Other Radiographic Examinations of the Spine TypeUse(s) Vertebral fracture assessment (VFA), T4 to L4 Incidental to DXA – provides lower-resolution images of the spine, not subject to projection distortion Computed tomography (CT) of the spine To clarify subtle or uncertain findings on radiographs Magnetic resonance imaging (MRI) of the spine To examine soft tissues or clarify the acuteness of spinal fracturing Radionuclide bone scanning To look for disease activity or distribution May also be helpful in diagnosing such conditions as metastatic disease and acuteness of injury Return to case

2010 Guidelines 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: 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 Siminoski K, et al. Can Assoc Radiol J 2005; 56(3): * Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus

2010 Guidelines 10-year Risk Assessment for Men (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print]. Click here for CAROC risk assessment in table format.

2010 Guidelines 10-year Risk Assessment for Men (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print]. AgeLow RiskModerate RiskHigh Risk 50above to -3.9below above to -3.9below above to -3.7below above to -3.7below above to -3.7below above to -3.8below above to -3.8below above to -3.8below -3.8

2010 Guidelines 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 1. Siminoski K, et al. Can Assoc Radiol J 2005; 56(3): Kanis JA, et al. J Bone Miner Res 2004; 19(6): Return to case * 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

2010 Guidelines Risk Assessment Using FRAX Uses age, sex, BMD, and clinical risk factors to calculate 10-year fracture risk* –BMD must be femoral neck –FRAX also computes 10-year probability of hip fracture alone This system has been validated for use in Canada 1 There is an online FRAX calculator with detailed instructions at: 1. Leslie WD, et al. Osteoporos Int; In press. * composite of hip, vertebra, forearm, and humerus

2010 Guidelines FRAX Tool: On-line Calculator

2010 Guidelines FRAX Clinical Risk Factors Parental hip fracture Prior fracture Glucocorticoid use Current smoking High alcohol intake Rheumatoid arthritis Return to case

2010 Guidelines Recommended Biochemical Tests for Patients Being Assessed for Osteoporosis Calcium, corrected for albumin Complete blood count Creatinine Alkaline phosphatase Thyroid stimulating hormone (TSH) Serum protein electrophoresis for patients with vertebral fractures 25-hydroxy vitamin D (25-OH-D)* * Should be measured after three to four months of adequate supplementation and should not be repeated if an optimal level ≥ 75 nmol/L is achieved.

2010 Guidelines Tests for Potential Secondary Causes In patients with Condition / Disease Test Persistently elevated serum calcium HyperparathyroidismPTH Multiple or atypical vertebral fractures Multiple myeloma Protein electrophoresis Immunoelectrophoresis Symptoms/signs of malabsorption or non response to vitamin D therapy Celiac disease Antibodies associated with gluten enteropathy Signs and symptoms of androgen deficiency (in men) Hypogonadism Testosterone (bioavailable or total) Serum prolactin History of kidney stonesHypercalciuria 24-hour urine for calcium Return to case

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.

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.

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 standard-dose supplementation in osteoporosis Monitoring of routine supplement use and routine screening of otherwise healthy individuals are not necessary Hanley DA, et al. CMAJ 2010; 182:E610-E618.

2010 Guidelines 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 risk 1 Concerns about serious adverse effects with high- dose supplementation Tang BM, et al. Lancet 2007; 370(9588): Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3): Bolland MJ, et al. BMJ 2008; 336(7638): Reid IR, et al. Osteoporos Int 2008; 19(8): Return to case

2010 Guidelines Agents Recommended First-line for Fracture Prevention in Men Alendronate Risedronate Zoledronic acid Return to case

2010 Guidelines Integrated Approach to Management of Patients Who Are at Risk for Fracture Age < 50 yrAge 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 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

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

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

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

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

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 Return to case

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 Return to case