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May 28 30, 2015, Montral, Qubec AN UNDERAPPRECIATED CAUSE OF MORBIDITY Sian E. Iles MD Associate Professor Dalhousie University Halifax Nova Scotia Gina Di Primio MD Professor McMaster University Hamilton, Ontario

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Disclosure Statement: No Conflict of Interest May 28 30, 2015, Montral, Qubec I do not have an affiliation, financial or otherwise, with a pharmaceutical company, medical device or communications organization. I have no conflicts of interest to disclose ( i.e. no industry funding received or other commercial relationships). I have no financial relationship or advisory role with pharmaceutical or device-making companies, or CME provider. I will not discuss or describe in my presentation at the meeting the investigational or unlabeled ("off-label") use of a medical device, product, or pharmaceutical that is classified by Health Canada as investigational for the intended use.

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Emphasis on clinical impact of fragility fractures CAROC: Joint initiative of the Canadian Association of Radiologists and Osteoporosis Canada www.osteoporosis.cawww.osteoporosis.ca www.car.cawww.car.ca

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AGE SEX BMD : Femoral neck T Score Clinical risk factors: fragility fracture and steroid use

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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 Siminoski K, et al. Can Assoc Radiol J 2005; 56(3):178-188. * Combined risk for fractures of the proximal femur, vertebra [clinical], forearm, and proximal humerus. Other fractures attributable to osteoporosis are not reflected; total osteoporotic fracture burden is underestimated

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Chemotherapy induced menopause Gonadotropin-releasing hormone (GnRH) suppression of gonadal function, Anti-estrogen and antiandrogen therapies Glucocorticoids (used predominantly in treatment of hematologic malignancies or as supportive agents in solid tumors) Inadequate calcium intake Vitamin D deficiency Inadequate exercise

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Vertebral fractures are the most common osteoporotic fractures. Existing vertebral fractures are a strong predictor of future vertebral and other fractures. Risk of sustaining subsequent fractures is grossly under-recognized

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2010 Guidelines Fracture is a Predictor of Future Fractures The risk of experiencing another fracture in the year following a hip fracture*: 5% 10% 1,2 The risk of experiencing another vertebral fracture in the year following a vertebral fracture : 20% 3 Prevalent vertebral fractures also predict hip fracture* 4,5 40% of Canadians who experience a fracture have a history of prior fracture 6 1. Papaioannou A, et al. JOGC 2000; 22(8):591-597. 2. Colon-Emeric C, et al. Osteoporos Int 2003; 14:879-893. 3. Lindsay R, et al. JAMA 2001; 285:320-323. 4. Ismail AA, et al. Osteoporos Int 2001; 12(2):85-90. 5. Melton LJ 3rd, et al. Osteoporos Int 1999; 10(3):214-21. 6. Hajcsar EE, et al. CMAJ 2000, 163:819-822. * in men and women in postmenopausal women

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2010 Guidelines Post-fracture Care Gap: Comparison with Heart Attack 1. Bessette L, et al. Osteoporos Int 2008; 19:79-86. 2. Austin PC, et al. CMAJ 2008; 179(9):901-908.

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In summary, all patients who begin cancer therapy that induces early menopause, reduces sex steroids or interferes with their action, or includes glucocorticoids should undergo assessment of bone loss risk and subsequent risk for osteoporosis and fracture. Risk for osteoporotic fractures can be considered a potential toxicity for a wide array of cancer therapies.

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Complications of bone metastases include pain, hypercalcemia, nerve compression, and pathologic fractures, and significant morbidity and mortality are associated with bone metastases.

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Clinically important differentiation for treatment and prognosis Multimodality assessment often necessary Important to remember possibility of osteoporosis complications Recommend appropriate investigation and treatment according to Osteoporosis Canada Guidelines Thoracolumbar Spine Anatomy and Pathology - Midlumbar Vertebra Pathological Fracture of a Midlumbar Vertebra Written by Wolfgang Rauschning, MD Wolfgang Rauschning, MD http://www.pathguy.com/lectures/bones.htm Benign fracture Pathologic fracture Renal cell Ca

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Patient is automatically at high risk for future fracture and treatment with a first line osteoporosis medication is indicated

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Known lung primary with bone mets Bone scan for back pain

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New fracture

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Typical appearance of benign fragility fracture on bone scan is horizontal end plate uptake Fracture may be very subtle on cross sectional or other imaging SPECT/CT superior if good quality CT

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64 yo male No obvious posterior bony protrusion but there does appear to be a paravertebral hematoma suggesting that the fracture is recent. Unfortunately the bone density is not accurately assessed by plain film and this study would suggest a reasonable bone density and therefore the concern for metastatic disease cannot be excluded. IMPRESSION: Grade 3 wedge compression of T12 would appear to be recent based on the paraspinal line suggesting a hematoma.

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Fracture at T 12 with retropulsion of fragments Clinically and radiologically assumed to be related to lymphoma

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Convex Posterior contour Epidural extension Complete marrow involvement of the vertebra

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Fracture T 12 Degenerative Change L4 L5 Uptake at T9 CT normal in area of bone scan

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No FDG uptake at T9

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New compression fractures KEY FEATURES Superior end plate Low signal band Background marrow not replaced (but may be edematous) Sequential @ T11 & T12

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Complete metabolic response T 12 also negative

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Abnormal signal posterior L2 Compression fracture T9 with abnormal signal Compression fracture L3

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No metabolic activity L2 or L3 End plate only at T9

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Pathologic and osteoporotic fractures may coexist Recognition of fragility fracture and recommendation of appropriate management may get lost in complicated cases Fragility fractures presenting as pain may mimic recurrent disease Multimodality imaging may be necessary to clarify findings When original tumour is FDG avid PET CT may be helpful

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Linear band like lines Usually Multiple # sequential Superior end plate NORMAL signal of marrow around the fx & other non collapsed vertebral bodies (VB) Partially preserved signal w/in affected VB Retro-pulsion of posterior bone fragment

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T1T2 FS Look for # elsewhere

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T1 Replacement Multiple focal lesions or Diffuse involvement of NON collapsed vertebral bodies (VB) Involvement of posterior arch & pedicle Convex posterior contour (scalloping) (beware superior end plate kyphosis) Muscle edema Sharp margins between normal & abnormal Involvement of inferior end plate (metaphyseal equivalent)

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FRACTURE LINES ARE NOT ALL BENIGN Non horizontal & Inferior end plate T1T2 GAD

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Osteoporosis & Cancer is common in the elderly They may co-exist or be sequelae of treatment Vertebral fractures are the most common fracture in osteoporosis Fracture complication is common & Implication on management is significant THEREFORE IMPORTANT to RECOGNIZE HOW to Differentiate Benign from Malignant dz What is available to make the diagnosis Recommend assessment and treatment of osteoporosis when fragility fractures detected according to guidelines from Osteoporosis Canada and CAR

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Osteoporosis is a complication of cancer treatment Patients with cancer have multiple risk factors for osteoporosis Vertebral fractures most common fracture in osteoporosis Important to differentiate osteoporotic compression fracture from pathologic fracture secondary to metastatic disease Recommend assessment and treatment of osteoporosis when fragility fractures detected according to guidelines from Osteoporosis Canada and CAR

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