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Introduction to Osteoporosis Clinic Staff of the UHN OP Program Divisions of Internal Medicine, Endocrinology, Rheumatology and Geriatrics University Health Network Objectives What is osteoporosis? Why does it matter? How is osteoporosis/fracture risk assessed? How is it treated? Based on current guidelines Things to think about in the clinical setting… 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada 2010 Canadian Clinical Practice Guidelines: Target Population Focus is on Fracture Risk Identification and Prevention Women and men > 50 years of age Prior fracture Papaioannou A, et al. CMAJ 2010; in press. Osteoporosis - Definition Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength = bone density + bone quality. NIH consensus statement [online]. 2000;17:1-36. Bone Density Quantitative Best surrogate Measurable Precise Reproducible Predictive of # risk Fragility Fracture: Definition A fracture occurring spontaneously or following minor trauma such as a fall from standing height or less1,2 Excluding craniofacial, hand, ankle and foot fractures 1. Kanis JA, et al. Osteoporos Int 2001; 12(5):417-427. 2. Bessette L, et al. Osteoporos Int 2008; 19:79-86. Incidence Rates for Fractures Annual incidence (per 1000 women) 40 30 Vertebrae Wrist Hip 20 10 50 60 70 80 Age (years) Adapted from Riggs BL, et al. N Engl J Med 1986 Pathogenesis of osteoporotic fractures Neuromuscular function Environmental hazards Time spent at risk Type of fall Protective responses Energy absorption Risk of fall Force of impact Risk of fracture Bone mineral density Geometry of bone Quality of bone Strength of bone Falls resulting in Colle’s fracture Falls resulting in hip fracture Consequences of Fracture Increased risk of Hospitalization1 Institutionalization2 Death3-5 fracture6-8 Decreased quality of life9-12 Economic burden on healthcare system2 Subsequent 1. Papaioannou A, et al. Osteoporos Int 2001; 12(10):870-874. 2. Wiktorowicz ME, et al. Osteoporos Int 2001; 12(4):271-278. 3. Ioannidis G, et al. CMAJ 2009; 181(5):265-271. 4. Papaioannou A, et al. J SOGC 2000; 22(8):591-597. 5. Tosteson AN, et al. Osteoporos Int 2007; 18(11):1463-1472. 6. Papaioannou A, et al. J SOGC 2000; 22(8):591-597. 7. Colon-Emeric C, et al. Osteoporos Int 2003; 14:879-893. 8. Lindsay R, et al. JAMA 2001; 285:320-323. 9. Sawka AM, et al. Osteoporos Int 2005; 16:1836-1840. 10. Cranney A, et al. J Rheumatol 2005; 32(12):2393-2399. 11. Pasco JA, et al. Osteoporos Int 2005; 16(12):2046-2052. 12. Papaioannou A, et al. Osteoporos Int 2009; 20(5):703-715. Relevant Hx Genetics Lifestyle Diet, exercise, habits Disease Drugs Recommendations for Clinical Assessment History Identify risk factors for low BMD, future fractures and falls: Prior fragility fractures Parental hip fracture Glucocorticoid use Current smoking High alcohol intake (≥3 units per day) Rheumatoid arthritis Inquire about falls in the previous 12 months Inquire about gait and balance Relevant Physical Exam Vision Gait Quad Strength Balance Tandem gait Rhomberg Timed get up and go Height Kyphosis Rib to Iliac Crest Distance Occiput to Wall Percussion Tenderness General Physical Exam to rule out other disease Recommendations for Clinical Assessment Measure weight (weight loss of >10% since age 25 is significant) Measure height annually (prospective loss > 2cm) (historical height loss > 6 cm) Physical Measure rib to pelvis distance Examination (≤ 2 fingers' breadth) Measure occiput-to-wall distance (> 5cm) Screening for Vertebral Fractures Assess fall risk by using Get-Up-and-Go Test (ability to get out of chair without using arms, walk several steps and return) Recommended biochemical tests for patients being investigated for osteoporosis Baseline: Serum calcium, CBC Creatinine ALP corrected for albumin TSH SPEP (for patients with vertebral fractures) 25-OH vitamin D (should be measured after months of adequate supplementation) 3-4 Other testing may include 24 hour urine collection for PTH UPEP Celiac antibody screening Gonadal function Spine XR calcium DEXA ≥ age 65 ≥ age 50 if significant OP risk factors Prior Fragility fractures Disease Drugs Indications for measuring bone mineral density Older Adults (age ≥ 50 years) Clinical risk factors for fracture (menopausal women, men age 50-64yr): • Current smoking • High alcohol intake • Low body weight (< 60 kg) or major weight loss (>10% of weight at age 25) Younger Adults (age < 50 years) Indications for measuring bone mineral density Older Adults (age ≥ 50 years) Younger Adults (age < 50 years) Age ≥ 65 yr (both men and women) Fragility fracture + Prolonged use of glucocorticoids Menopausal women, men age 50Use of high-risk medication* 64yr – clinical risk factors for Hypogonadism or premature fracture menopause (age < 45yr) • Fragility fracture after age 40 yr Malabsorption syndrome • Prolonged use of glucocorticoids+ Primary hyperparathyroidism • Use of high-risk medication * Other disorders strongly associated • Parental hip fracture with rapid bone loss and /or • Vertebral fracture or osteopenia fracture on X-ray • • +At Rheumatoid arthritis Other disorders strongly associated with osteoporosis least three months cumulative therapy in the previous year at a prednisone equivalent dose ≥7.5 mg daily; *E.g. aromatase inhibitors or androgen deprivation therapy. DEXA World Health Organization (WHO) definitions for postmenopausal women (or older men) = T score ≥ -1.0 Osteopenia = -1.0 > T score > -2.5 Osteoporosis = T score ≤ -2.5 Normal But… Osteopenia is more common Most women who suffer fragility fractures have osteopenia – in one large cohort 82% of participants with fragility fractures had BMD > 2.5 More accurate to look at 10 year fracture risk Siris ES et al. Arch int Med 2004;164:1108-12. 2010 CAROC tool: Assessment of Basal 10-year Fracture Risk 2010 CAROC tool: Assessment of Basal 10-year Fracture Risk Ten Year Fracture Risk Gender Age Bone Density Value Previous Fragility Fracture Prednisone Move up 1 category FRAX Tool: www.shef.ac.uk/FRAX. Treatment Thresholds Risk of any fracture > 20 % Risk of hip fracture > 3 % Significant risk Pharmaco-economically advantageous to treat Initial BMD testing Assessment of fracture risk Low risk Moderate risk (10-year fracture risk 10%-20%) (10-year fracture risk < 10%) 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 Factors warranting consideration of pharmacologic therapy… High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Always consider patient preference Good evidence of benefit from pharmacotherapy Initial BMD testing Assessment of fracture risk Low risk (10-year fracture risk < 10%) Unlikely to benefit from pharmacotherapy Reassess in 5 yr 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… High risk (10-year fracture risk > 20% or prior fragility fracture of hip or spine or > 1 fragility fracture) Always consider patient preference Good evidence of benefit from pharmacotherapy 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 Repeat BMD in 1-3 yr and reassess risk 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 and those with Tscore ≤ -2.5 • Lumbar spine T-score << 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 pharmacotherapy VFA JB6/23/04;WW5/11/04 IVA/VFA On the left we see a normal lateral VFA (vertebral fracture assessment) showing no VCD as high as we can see (T6). On the right, we see a lateral VFA with a wedge deformity of T12 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: Repeat BMD in 1-3 yr and reassess risk • Additional vertebral fracture(s) (by vertebral fracture assessment or lateral spine radiograph) • Previous wrist fracture in individuals aged > 65 and those with T- score ≤ -2.5 • Lumbar spine T-score << 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 pharmacotherapy What are the therapeutic options? Exercise and prevention of falls Calcium and vitamin D Pharmacological therapy Calcium and D Vitamin D Higher daily vitamin D supplementation (D3)3 400 – 1000 IU for individuals < 50 years 800 – 2000 IU for individuals ≥ 50 years Calcium Lower daily calcium intake (from all sources) 1200 mg per day Diet preferred 1. Brown JP, Josse RG. CMAJ 2002; 167(10 Suppl):S1-34. 2. Papaioannou A, et al. CMAJ 2010; in press. 3. Hanley DA, et al. CMAJ 2010; 182: E610-E618. Pharmacological therapy First Line Therapies with Evidence for Fracture Prevention in Postmenopausal Women* Type of Fracture Bone Formation Therapy Antiresorptive Therapy Bisphosphonates Denosumab Raloxifene Estrogen** (Hormone therapy) Teriparatide Alendronate Risedronate Zoledronic Acid Vertebral Hip ---- --- NonVertebral+ ---- + In clinical trials, non-vertebral fractures are a composite endpoint including hip, femur, pelvis, tibia, humerus, radius, and clavicle. * 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]. ** Estrogen or hormone therapy can be used as first line therapy in women with menopausal symptoms. Considerations with osteoporosis medications: MSK pain Atypical femur fractures (~1/1000 pt yrs after 5-10 yrs of use) Osteonecrosis of the Jaw (~1/100,000) Esophageal Cancer Atrial fibrillation Duration of therapy X-ray, CT, Bone Scan AFFs Key points Importance of fragility fractures Management guided by absolute fracture risk Individualized treatment and therapy Questions?