2010 Guidelines Case Study #1 Mrs. DT 2010 Guidelines Case Presentation • Age 59: nine years post-menopause with treated osteoporosis • Has always enjoyed excellent health with no past medical or surgical history • Comes in for her periodic health exam— concerned about calcium and cardiovascular risk 2010 Guidelines Physical Examination • Height = 154 cm (60.5 in.) • Weight = 55.5 kg (122 lbs.) • No significant changes in height, weight, posture, or gait from previous visits – Changes in height and weight can be signs of vertebral fractures 2010 Guidelines Medications • Risedronate 35 mg weekly for past six years • Calcium 600 mg + vitamin D 400 IU (single-tablet supplement) 2010 Guidelines History of Osteoporosis: T-scores and Treatment Decisions Age BMD T-scores Action taken 53 Spine: -1.8 Femoral neck: -2.4 Ruled out secondary causes of osteoporosis Initiated risedronate 35 mg weekly Educated on importance of dietary calcium Initiated calcium 1500 mg daily Initiated vitamin D 400 IU daily 2010 Guidelines Current Risk Factor Assessment • • • • • • • Non-smoker, no regular alcohol consumption No previous history of fracture No parental history of hip fracture No history of systemic glucocorticoid use No comorbidities Diet rich in calcium (1200 mg daily from foods) High caffeine intake 2010 Guidelines Question • Were the diagnosis and treatment initiation in line with today's guideline recommendations? 2010 Guidelines Reflections on the Decision-making Process • Previous diagnosis and treatment decisions were largely based on bone density T-scores • 2010 osteoporosis guidelines advocate making decisions based on an assessment of overall 10-year fracture risk • Tools endorsed: CAROC and FRAX • Current recommendations for: – Calcium: 1200 mg from diet and supplement combined – Vitamin D: 800 – 2000 IU daily for age over 50 2010 Guidelines Should This Patient Have Been Receiving Treatment? FRAX 10-year Risk Assessment Age BMD 53 FRAX-calculated 10-year risk Spine: -1.8 6.0% for major osteoporotic fracture Femoral neck: -2.4 2010 Guidelines FRAX Calculation of Original Risk (Age 53 – Six Years Ago) 2010 Guidelines Mrs. DT: Reflection on Diagnosis • Six years ago, the diagnosis and therapy were appropriate, given the low BMD at the femoral neck (-2.4) and two minor risk factors (weight < 57kg, high caffeine intake) • With today's tools (e.g., CAROC, FRAX), however, Mrs. DT would have been low risk – Treatment would not have been recommended under the current system 2010 Guidelines Question • Would you consider using a risk-assessment tool to check Mrs. DT's current level of risk on treatment? 2010 Guidelines Absolute Fracture Risk Tools • Calculate risk for treatment-naïve patients only • Cannot be used to monitor response to therapy • Using CAROC or FRAX in a patient on therapy only reflects the theoretical risk of a hypothetical patient who is treatment naïve and does not reflect the risk reduction associated with therapy • One could use these tools to assess what the risk might be for a woman like Mrs. DT who had never been treated 2010 Guidelines FRAX Calculation of Risk for a Woman Like Mrs. DT, but Who Had Never Been Treated 2010 Guidelines Question • What would you do in this case? • Would you continue or discontinue treatment with risedronate? – Discuss the rationale for your decision 2010 Guidelines Mrs. DT: Conclusions • Diagnosis and treatment decisions should now be based on 10-year assessment of risk using a validated tool – Patients at low risk (10-year risk < 10%) should not be receiving treatment • Her current risk level is not known: – 10-year absolute risk tools were developed to assess patients who are treatment naive • Mrs. DT currently gets adequate calcium from her diet (~1200 mg daily) – Calcium supplementation should be stopped – Vitamin D supplementation should continue 2010 Guidelines Back-up Material Additional slides that can be accessed from hyperlinks on case slides Case 1 – Mrs. DT 2010 Guidelines Potential Risks of Calcium Supplementation • High-dose calcium supplementation has been associated with – Renal calculi in older women – Cardiovascular events in older women – Prostate cancer in older men Return to case 1. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181. 2. Bolland MJ, et al. BMJ 2008; 336(7638):262-266. 3. Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123. 2010 Guidelines Importance of Weight • In men > 50 years and in 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) Return to case 1. Papaioannou A, et al. Osteoporos Int 2009; 20(5):703-715. 2. Waugh EJ, et al. Osteoporos Int 2009; 20:1-21. 3. Cummings SR,et al. N Engl J Med 1995; 332(12):767-773. 4. Papaioannou A, et al. Osteoporos Int 2005; 16(5):568-578. 5. Kanis J, et al. Osteoporos Int 1999; 9:45-54. 6. Morin S, et al. Osteoporos Int 2009; 20(3):363-70. 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 Return to case 1. Siminoski K, et al. Osteoporos Int 2006; 17(2):290-296. 2. Briot K, et al. CMAJ 2010; 182(6):558-562. 3. Moayyeri A, et al. J Bone Miner Res 2008; 23:425-432. 4. Siminoski K, et al. Osteoporos Int 2005; 16(4):403-410. 5. Kaptoge S, et al. J Bone Miner Res 2004; 19:1982-1993. 2010 Guidelines First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* Bone formation therapy Antiresorptive therapy Type of Fracture Bisphosphonates Raloxifene Hormone therapy (Estrogen)** Teriparatide Alendronate Risedronate Zoledronic acid Denosumab Vertebral Hip - - Nonvertebral+ - Return to case * 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 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 * 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):178-188. 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) Age Low Risk Moderate Risk High Risk 50 above -2.5 -2.5 to -3.8 below -3.8 55 above -2.5 -2.5 to -3.8 below -3.8 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]. 2010 Guidelines 10-year Risk Assessment for Men (CAROC Basal Risk) Papaioannou A, et al. CMAJ 2010 Oct 12. [Epub ahead of print]. 2010 Guidelines 10-year Risk Assessment for Men (CAROC Basal Risk) Age Low Risk Moderate Risk High Risk 50 above -2.5 -2.5 to -3.9 below -3.9 55 above -2.5 -2.5 to -3.9 below -3.9 60 above -2.5 -2.5 to -3.7 below -3.7 65 above -2.4 -2.4 to -3.7 below -3.7 70 above -2.3 -2.3 to -3.7 below -3.7 75 above -2.3 -2.3 to -3.8 below -3.8 80 above -2.1 -2.1 to -3.8 below -3.8 85 above -2.0 -2.0 to -3.8 below -3.8 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 * 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 Return to case 1. Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188. 2. Kanis JA, et al. J Bone Miner Res 2004; 19(6):893-899. 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 Canada1 • There is an online FRAX calculator with detailed instructions at: www.shef.ac.uk/FRAX * composite of hip, vertebra, forearm, and humerus 1. Leslie WD, et al. Osteoporos Int; In press. 2010 Guidelines FRAX Tool: Online Calculator www.shef.ac.uk/FRAX. 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 Vitamin D Supplementation Recommended Vitamin D Intake (D3) Group 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; Jul 26. [epub before print]. 2010 Guidelines Vitamin D: Optimal Levels • To most consistently improve clinical outcomes such as fracture risk, an optimal serum level of 25hydroxy 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 Return to case 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 risk1 • Concerns about serious adverse effects with high-dose supplementation2-4 Return to case 1. Tang BM, et al. Lancet 2007; 370(9588):657-666. 2. Bolland MJ, et al. J Clin Endocrinol Metab 2010; 95(3):1174-1181. 3. Bolland MJ, et al. BMJ 2008; 336(7638):262-266. 4 Reid IR, et al. Osteoporos Int 2008; 19(8):1119-1123.