2010 Guidelines Case Study #2: Mrs. BR 2010 Guidelines

Case Presentation 65-year-old woman Natural menopause at age year history of hypertension (currently treated and controlled) Presents for periodic health examination

2010 Guidelines Physical Examination Height: 160 cm (5'3")Height –1 cm less than self-reported historic peak height Weight: 63.5 kg (140 lbs.)Weight Body mass index (BMI): 24.8 kg/m 2 Blood Pressure: 136 / 84 mmHg Physical examination is unremarkable

2010 Guidelines Medications Perindopril 8 mg once daily (OD) Multivitamin (for adults over 50)

2010 Guidelines Screening and Risk Assessment Mrs. BR meets the 2010 guideline criteria for screening using dual energy X-ray absorptiometry (DXA)guideline criteria for screening –All women and men age > 65 Current recommendations are to use one of these validated tools to assess 10-year risk of osteoporotic fractures –CAROC developed by The Canadian Association of Radiologist and Osteoporosis CanadaCAROC –FRAX Fracture Risk Assessment Tool developed by The World Health OrganizationFRAX

2010 Guidelines Ms. BR: Risk Factor Assessment No hormone treatment No personal fracture history Positive family history: Hip fracture in her mother at age 75 (fell in own home; ended up in personal- care home) Non smoker No history of systemic steroid use No history of rheumatoid arthritis No potential secondary causes of osteoporosis Alcohol use: < 3 drinks/day

2010 Guidelines Question What is the impact of family history of hip fracture on risk assessment?

2010 Guidelines CAROC: Using Age, Sex, and BMD to Estimate 10-year Risk of Fracture Age: 65 BMD T-score: –Femoral neck: -2.3 –Spine: -2.2 Mrs. BR is at moderate risk of fractures using the CAROC model Age (years) Femoral neck T-score LOW RISK (<10%) MODERATE RISK HIGH RISK (> 20%)

2010 Guidelines Impact of Family History of Hip Fracture on CAROC Risk Assessment The CAROC risk-assessment tool does not include family history of hip fracture among its variables Family history is one of the potential additional factors that can be considered in decision- making if the patient is at moderate risk

2010 Guidelines Impact of Family History of Hip Fracture on FRAX Risk Assessment FRAX does include a family history of hip fracture as one of its variables The presence or absence of this risk factor dramatically changes the 10-year absolute-risk calculation (see next two slides)

2010 Guidelines FRAX Risk Calculation for Mrs. BR, with Family History of Hip Fracture

2010 Guidelines FRAX Risk Calculation for Mrs. BR, Hypothetical Situation Without Family History of Hip Fracture

2010 Guidelines Impact of Family History of Hip Fracture on FRAX Risk Assessment For a person like Mrs. BR, the family history of parental hip fracture increases her absolute 10-year risk of major osteoporotic fractures by 9.0% This has potential major implications for treatment In Mrs. BR's case, this factor moved her from the lower end to the higher end of the moderate-risk range using FRAX

2010 Guidelines Question What laboratory tests are recommended for patients with a diagnosis of osteoporosis?

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 Treatment Considerations for Moderate-risk Individuals The 2010 guidelines’ integrated management model recommends consideration of:integrated management model –Additional clinical risk factors to refine assessmentAdditional clinical risk factors –Lateral thoracolumbar X-ray (T4-L4) or vertebral fracture analysis (VFA) to aid in decision-making by identifying vertebral fracturesvertebral fracture analysis (VFA)

2010 Guidelines Vitamin D, Calcium and Other Nonpharmacologic Interventions The 2010 guidelines have new recommendations for vitamin D and calcium intakenew recommendations for vitamin D and calcium intake Optimal treatment strategies can also include other lifestyle interventions (e.g., physical activity, nutrition) other lifestyle interventions

2010 Guidelines Mrs. BR: To Treat or Not to Treat Decision whether or not to treat patients at moderate risk with pharmacologic therapy also involvespharmacologic therapy –Discussion of benefits (e.g., fracture risk reduction) and risks (e.g., adverse events) of treatment –Assessment of patient preferences and health priorities to come up with an "individualized intervention threshold"

2010 Guidelines Mrs. BR: Conclusions Diagnosis and treatment decisions should be based on 10-year assessment of risk using a validated tool –Mrs. BR is moderate risk using both the CAROC and FRAX tools Patients at moderate risk (10-year risk 10% – 20%) may benefit from pharmacologic therapy –Decision of whether to initiate treatment can be made after a discussion of benefits and risks with the patient Mrs. BR’s fear of hip fracture leads her to decide to initiate therapy

2010 Guidelines Case 2 – Case 2 – Mrs. BR Back-up Material Additional slides that can be accessed from hyperlinks on case slides

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 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) 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 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 Women (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

2010 Guidelines 10-year Risk Assessment for Women (CAROC Basal Risk) AgeLow RiskModerate RiskHigh Risk 50above to -3.8below above to -3.8below above to -3.7below above to -3.5below above to -3.2below above to -2.9below above to -2.6below above to -2.2below -2.2 Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print].

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: Online 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 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 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

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 case

2010 Guidelines VFA Recognition and Reporting VFA is a scanning and software option on bone densitometers A fracture detected by VFA or radiograph should be considered a prior fracture under the FRAX or CAROC system 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 Summary Statement for Other Nonpharmacologic Therapies StatementStrength Weight bearing, balance, and strengthening exercises can improve outcomes in individuals with osteoporosis Level 2 Exercise-focused interventions improve balance and reduce falls in community-dwelling older people Level 2 Hip 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 Return to case

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.

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 Return to case