PRACTICAL DENSITOMETRY



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PRACTICAL DENSITOMETRY The Challenge of Osteoporosis Osteoporosis is a silent disease that develops over decades Goal: identify patients with osteoporosis before fractures occur Means: measure bone density

Bone Densitometry In this workshop, we will discuss: Why bone density measurements are valuable Where and how to measure How to interpret results Who should be tested Bone Densitometry to Identify Patients at High Risk of Fractures Bone mineral density (BMD) Accounts for 60% to 80% of bone strength in untreated patients Is the best early predictor of fracture risk Correlates with fracture risk Better than cholesterol correlates with heart attack Similar to blood pressure for predicting stroke

Bone Density Predicts Fracture Risk Relative Risk of Hip Fracture 2 x -1 SD SD From Age-Matched Mean BMD Each SD (~ 10%) decrease in BMD is associated with an approximately 2-fold increase in fracture risk (RR = 1.5-2.6) Adapted from Cummings SR. Lancet. 1993;341:72-5. Where to Measure Bone Density DXA Hip Spine QCT Spine Hip Ultrasound Radius Tibia Heel Finger DXA or SXA Forearm Finger Heel Low bone density at any site indicates an increased risk of fractures Fracture risk at a specific site is best predicted by BMD at that site

Central DXA Bone Density Measurements Central DXA is the gold standard for diagnosis Hologic Measures the most important fracture sites (hip and spine) Norland Can be used to monitor response to therapy GE Lunar Central DXA Bone Density Measurements

DXA Measurements of Spine and Hip Spine Proximal femur Femoral neck Lumbar spine Trochanter Intertrochanter Ward s region Total hip To classify patient, use the lowest value of either the: Spine (L1-L4) Femoral neck Total hip DXA Measurements Bone mineral content (grams) Area of region measured (cm 2 ) Bone mineral density (calculated) BMC/area = BMD (g/cm 2 ) Region BMD T-score Z-score L1 0.589-3.1-1.3 L2 0.658-3.4-1.4 L3 0.695-3.5-1.4 L4 0.725-3.6-1.4 L1-L4 0.673-3.4-1.4

Densitometry Results: The T-score Region BMD T-score Z-score L1 0.589-3.1-1.3 L4 0.658-3.4-1.4 L3 0.695-3.5-1.4 L4 0.725-3.6-1.4 L1-L4 0.673-3.4-1.4 Compares the patient s actual BMD (g/cm 2 ) with mean BMD of young adults (age 25-30) of same gender Expressed as number of SD above or below mean BMD of normal young adults T-score = BMD of patient mean BMD of young normals SD of BMD in young normal population Interpretation of Bone Density Tests T-score: the key clinical result Comparison with young normal value Use to diagnose osteoporosis and in calculating fracture risk Z-score Comparison with age-matched values Use to determine if BMD is lower than expected for age Region BMD T-score Z-score L1 0.589-3.1-1.3 L2 0.658-3.4-1.4 L3 0.695-3.5-1.4 L4 0.725-3.6-1.4 L1-L4 0.673-3.4-1.4

BMD/Fracture Risk Is a Gradient Relative Risk of Hip Fracture SD From Age-Matched Mean BMD Relationship between BMD and fracture risk is continuous; there is no fracture threshold World Health Organization Criteria T-score* Classification 1 or above Normal Between 1 and 2.5 Low bone mass (osteopenia) 2.5 or lower Osteoporosis * T-score indicates the number of standard deviations below (-) or above (+) the average peak bone mass in young adults These criteria were developed for postmenopausal Caucasian women WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level. Summary Report. www.nof.org

WHO Criteria for Diagnosis Based on Central DXA Measurements The T-score cut-point of -2.5 for osteoporosis was chosen so that the proportion of women over age 50 who have osteoporosis by BMD is approximately the same percentage of women who will have fractures. BMD T-Score 2 1 0-1 -2-3 -4 Osteoporosis 20 30 40 50 60 70 80 90 Age Kanis JA. J Bone Miner Res. 1994;9:1137-41. Bone Density Measurements at Peripheral Sites QUS DXA pqct Advantages Portable Less expensive than central DXA Ultrasound does not involve radiation Limitations Less predictive for hip fracture than hip measurement Cannot be used for diagnosis with WHO criteria Cannot be used for monitoring (sites less likely to change) False negatives

NORA Study 200,160 ambulatory women age 50 and older Percent of subjects 2.5 SD or more below young adult mean 35 30 25 20 15 10 Missed 55% 66% 84% 90% 5 0 Estimated Spine+Hip* Finger DXA Forearm DXA Heel SXA Heel QUS *Estimated from NHANES III Siris E, et al. JAMA. 2001;286:2815-22. Using Bone Density in Clinical Practice Get central DXA if possible Limitations: Size and weight (> 300 lbs) Spine/hip degenerative disease, surgery, etc. If central DXA is not possible, measurement at any site is better than no measurement at all to assess fracture risk Include forearm measurement for conditions associated with preferential loss of cortical bone Primary hyperparathyroidism The International Society for Clinical Densitometry Position Statements. www.iscd.org.

US Preventive Services Task Force Evidence-Based Rationale and Recommendation In 2004, USPSTF made the following recommendations concerning bone density testing for osteoporosis by DXA: Good evidence that bone density measurements accurately predict fractures Good evidence that treating asymptomatic women with osteoporosis reduces their risk of fracture Women 65 and older (should) be screened routinely for osteoporosis US Preventive Services Task Force. Ann Intern Med. 2011;154:356-64.. Fracture Risk Rises After Age 65 4,000 Spine Fracture Hip Fracture 3,000 Incidence/1,000,000 Person-Years 2,000 1,000 0 40 60 80 Years 40 60 80 Years Cooper C, et al. J Bone Miner Res. 1992;7:221-7; Bone Health and Osteoporosis: A Report of the Surgeon General 2004. www.surgeongeneral.gov.

Hip Fractures Economic Impact Osteoporosis was one of the 10 most costly chronic conditions to Medicare in 2010.* The number of osteoporotic fractures annually currently exceeds the incidence of heart attack, stroke and breast cancer combined.** Fractures from osteoporosis and low bone mass cost $19 billion a year in the U.S. This is expected to rise to $25.3 billion per year by 2025 as the elderly population nearly doubles.*** * SOURCE: BLUME SW, CURTIS JR. OSTEOPOROS INT. 2011. 22(6):1835-4. ** SOURCE: BURGE R, ET AL. J BONE MINER RES. 2007. 22(3):465-75. ROGER VL, ET AL. CIRCULATION.2012. 125(1):E2-E220. DESANTIS C, ET AL. CA CANCER J CLIN. 2011. 61(6):409-18. *** SOURCE: BURGE R, ET AL. J BONE MINER RES. 2007. 22(3):465-75. Hip Fractures Mortality and Morbidity Hip Fractures substantially increase the risk of death and major morbidity in the elderly. One-year mortality estimates range from 17% [1] in otherwise healthy older women to 27% [2] in a population based study of older men and women. Few patients regain their former level of independence after hip fractures. 1. LeBlanc, E. et al: Hip fracture and increased short-term but not long-term mortality in healthy older women. Arch Intern Med. 2011 Nov 14;171(20):1831-7 2. Panula, J. et al: Mortality and cause of death in hip fracture patients aged 65 or older: a population-based study. BMC Musculoskelet Disord. 2011 May 20;12:105

Who Should Have a Bone Density Test? Screening All women age 65 and older 1,2 All men age 70 and older 1 Test younger postmenopausal women and men 50 to 69 1 Fracture after age 50 Risk factors for osteoporosis* Monitoring Treatment effect or untreated patient in whom evidence of bone loss would lead to treatment *Risk factors to consider include family history of osteoporosis, low body weight, smoking, premature menopause, other diseases and medications 1 NOF Clinician s Guide to Prevention and Treatment of Osteoporosis 2010. www.nof.org; 2 US Preventive Services Task Force. Ann Intern Med. 2011;154:356-64. Other Indications for DXA Signs of osteoporosis (eg, radiographic low bone mass ) Following patients not on treatment, to decide if/when treatment should be started Following patients on treatment, to monitor the response to treatment

Estrogen-deficient women at clinical risk of osteoporosis Individuals with vertebral abnormalities ( low bone mass or fracture) Individuals receiving chronic glucocorticoid therapy Individuals with primary hyperparathyroidism Individuals being monitored to assess the response to or efficacy of an FDA-approved osteoporosis drug therapy (every 2 years) ISCD reimbursement Web site: www.iscd.org Federal Register 1998;63:34320-81998. *Check with local Medicare provider/carrier to verify reimbursement WHO Diagnostic Criteria and NOF Treatment Guidelines WHO Diagnostic Criteria Therapy Decision Normal Bone Density No pharmacologic treatment T-score 1.0 2.5 Low Bone Mass (Osteopenia) Depends on the risk of fracture Osteoporosis Treat NOF Clinician s Guide to Prevention and Treatment of Osteoporosis 2010. www.nof.org.

Bone Densitometry: Summary Powerful tool for early identification of osteoporosis and prediction of fracture risk Screen women starting at age 65, men at age 70 Screen high-risk patients earlier Measurements by different technologies are not equivalent DXA of spine and hip preferred Can be used with WHO criteria to diagnose osteoporosis Spine and hip DXA assess risk of important fractures Spine and hip BMD change most with disease and therapy can be used to monitor How to View and Interpret Bone Density Studies

GE-Lunar Spine Report Example Hologic Spine Report Example

Viewing a Spine Scan Spine is centered in scan field Sacrum clearly identified All of L1-L5 visible with ribs present at T12 Spine is reasonably straight not angled (taking into account scoliosis/djd, etc) Correct vertebral bodies are selected Free of external artifacts Scoliosis and Degenerative Change Osteophytes usually occur at the level of intervertebral discs

Scoliosis and Degenerative Change (cont.) In the spine, individual vertebral T-scores should be within 1 SD, best and worst If not, look carefully at scan and suspect artifact ( best is usually wrong)

Artifact Buckshot Invalid Spine Study Region BMD (g/cm 2) T-score L1 1.226 0.8 L2 0.958 2.0 L3 0.928 2.3 L4 0.928 2.3 L1-L2 1.078 0.6 L1-L3 1.022 1.2 L2-L4 0.936 2.2 L1-L4 0.991 1.6

T-score (L1-L4): 1.7 T-score (L1-L2): 2.9 GE-Lunar Hip Report Example

Hologic Hip Report Example Viewing a Hip Scan Femoral shaft is straight Leg sufficiently rotated Little or none of the lesser trochanter visible Scan includes Ischium Greater trochanter Femoral neck box does not include the ischium Use lowest score from femoral neck and total hip (NOT other regions)

Hip Scans: Poor Positioning DXA Case Studies

Marie: Seeking Second Opinion for Treatment of Osteoporosis 50-year-old African American woman Bone density study ordered 2 months ago by her gynecologist; told of osteoporosis Started estrogen, a bisphosphonate, and calcitonin History Healthy, nonsmoker Two years post menopause No fractures; no height loss No family history of osteoporosis Weight 170 lbs; normal exam The Z-scale of the neck is 2.06 the Z-scale of L1-2 is 3.28 Impression: osteopenia of the hip; osteoporosis of the spine

Spine T-score: +3.3 Femoral neck T-score: +2.1 Case Study 1 Good positioning, correct ROIs Dx: osteoporosis Region BMD (g/cm 2 ) T-Score Z-Score L1 0.747 3.2 1.7 L2 0.793 3.4 1.9 L3 0.817 3.2 1.7 L4 0.714 4.1 2.5 L1-L2 0.771 3.2 1.6 L1-L3 0.788 3.2 1.7 L1-L4 0.767 3.2 1.9

Case Study 2 Region Good positioning, correct ROIs, no artifacts Dx: low bone density ( osteopenia ) BMD (g/cm 2 ) T-Score Z-Score L1 0.780 1.3 0.6 L2 0.832 1.8 1.0 L3 0.863 2.0 1.2 L4 0.899 2.0 1.1 L1-L4 0.850 1.8 1.0 Case Study 3 Wrong vertebral levels Degenerative change Region BMD (g/cm 2) T score L1 0.967 1.4 L2 1.114 0.7 L3 1.259 0.5 L4 1.305 0.9 L1-L2 1.046 0.9 L1-L3 1.125 0.4 L1-L4 1.176 0.0

Case Study 4 Probable degenerative changes at L3 and L4 Delete L3 and L4 Dx: osteoporosis Region BMD (g/cm 2) T-score L1 0.776 2.9 L2 0.817 3.2 L3 1.044 1.3 L4 1.070 1.1 L1-L2 0.798 2.9 L1-L3 0.891 2.3 L1-L4 0.946 2.0 Case Study 5 Region BMD (g/cm 2 ) T-Score L1 0.835 2.6 L2 1.286 4.2 L3 0.668 2.1 L4 0.917 0.7 Total 0.954 0.1 Hyperdense L2 and L4 Further investigation showed metastatic breast cancer

Case Study 6 Artifact over L4 Navel Stud Exclude L4 from the analysis T-Score L1-L3-2.5 Osteoporosis Case Study 7 Region BMD (g/cm 2 ) T-Score L1 0.989 1.2 L2 1.000 1.7 L3 0.992 1.7 L4 0.747 3.8 L1-L2 0.995 1.3 L1-L3 0.994 1.5 L1-L4 0.931 2.1 Laminectomy at L4-L5 Degenerative changes throughout spine; probably invalid study

Case Study 8 Hyperdense L2 (delete) Need x-ray Dx: osteoporosis Region BMD (g/cm 2 ) T-Score Z-Score L1 0.775 3.0 1.2 L2 0.979 1.8 0.1 L3 0.734 3.9 2.2 L4 0.776 3.5 1.8 L1-L2 0.868 2.3 0.6 L1-L3 0.816 2.9 1.2 L1-L4 0.805 3.1 1.4 L2-L3 0.836 3.0 1.3 L2-L4 0.814 3.2 1.5 L3-L4 0.756 3.7 2.0 Case Study 9 T-Score -2.3 T-Score -1.7 The marked increase in the lumbar spine is a significant change but is likely related to degenerative or vascular artifact. Calcified vessel

Unusual Spine Anatomy Unusual appearance of L1-L2 vertebral bodies Height of L1 reduced compression fracture? Analysis is confined to L3-L4 = T-Score -3.1 congenital block vertebra Case Study 10 Good study Normal bone density Region BMD (g/cm 2) T-score Neck 0.883 0.8 Ward s 0.720 1.3 Trochanter 0.798 0.1 Total 0.979 0.2

Case Study 11 Good hip study Dx: low bone mass Region BMD (g/cm 2) T-score Neck 0.658 1.7 Trochanter 0.744 0.4 Total 0.929 0.1 Case Study 11 Artifact (osteoma) This hip cannot be used for diagnosis

Non-Evaluable DXA Studies Severe scoliosis Hip dysplasia Spine Fusion Hardware Comparison of DXA Scans

Comparison of DXA Scans Acquired at Same Facility Scan 1 Scan 2 Comparison of DXA Scans Acquired at Same Facility, cont. Scan 1 Scan 2

THE CHALLENGE OF COMPARING DXA SCANS ACQUIRED AT DIFFERENT FACILITIES Results vary between facilities and instrument manufacturers. Densitometers are not cross calibrated between facilities. Quality of scans vary between facilities Scan images are not always available to determine quality Case Study 1 May 19,2011 HOLOGIC L1 0.699-3.4 L2 0.765-3.0 L3 0.934-1.5 L4 0.814-2.5 L1-L2 0.733-2.9 L1-L3 0.806-2.4 L2-L4 0.838-2.5 L1-L4 0.808-2.6 Diagnosis - Osteoporosis

Case Study 1, cont. 05/28/2013 Lunar Region BMD T-score L1 0.931-1.9 L2 1.108-1.1 L3 1.054-1.6 L4 1.128-0.9 L1-L2 1.025-1.5 L1-L3 1.035-1.5 L1-L4 1.064-1.3 L2-L4 1.099-1.2 L3-L4 1.095-1.2 Diagnosis Low Bone Density Case 1-Final Understanding the results: Was the increase in bone density genuine? L1-L4 T-Score -2.6 L1-L4 T-Score -1.3 L1-L4 T-score -2.0 Interpretation: The T-score value in the incorrect analysis suggests that there may have been some increase in bone density since the previous visit.

Case Study 2 Lunar 02/07/2011 L1-L4 T-score -1.8 Lunar 05/21/2012 Case Study 2, cont. T-Score -2.5 An 8.5% decrease in bone density in one year!

Case Study 2, cont. Tissue image of scan revealed unidentified internal artifact overlying the area of interest resulting in a questionable scan study. Contrast dye? Elastic waistband Interpretation: No change is noted in the hip region, it does appear that there has been a decrease in the lumbar spine value since her previous study. However, the technique of scan acquisition is somewhat different between the previous and current scans, so I am not confident that the apparent decrease is real or not. Diagnosis of Osteoporosis was based on femoral neck region t-score -2.5. Case Study 3 Lunar 03/17/2007 Lunar 06/19/2012 Total hip and femoral neck regions are consistent with osteoporosis. Not possible to make an accurate comparison to 2007 scan.

12/06/201 1 Case Study 4 A 43.7% reduction in bone density in 3 years! Bone edges not placed correctly at L1 Incorrect labeling of vertebrae Reporting only one vertebra Case Study 4, cont. 06/19/2012 L1-L2 T-score -2.5 Due to the incorrect acquisition and analysis of the 2011 scan, a comparison cannot be made.

Practical Densitometry: Summary Interpreting DXA studies Usefulness depends on the quality of the scan Important to look at the scan for positioning, correct regions of interest, and artifacts