Presentation on theme: "Bone Mineral Density Testing in Clinical Practice"— Presentation transcript:
1 Bone Mineral Density Testing in Clinical Practice Screen & InterveneCritical Challenges in Osteoporosis and Women’s Health
2 Outline Background Diagnosis of osteoporosis BMD and fracture risk Indications for BMD testingInterpretation of BMD testsCombining BMD and clinical risk factorsSelecting patients for treatmentSerial BMD testingPeripheral bone density testing
3 Osteoporosis is a Silent Disease No symptomsNo findings on physical examNo laboratory abnormalitiesIncrease in fracture riskFractures have serious consequencesTreatment can reduce fracture riskChallenge: To identify and treat patients at risk for fracture before the first fracture occurs
4 Consequences of Fractures Increased risk of future fracturesChronic painSurgeryLoss of heightImpaired pulmonary functionAbdominal symptomsMedical expenses / lost incomeHospitalizationSurgeryRehab hospitalNursing homeLoss of self-esteemDepressionLoss of independenceDisabilityDeath
5 Relative Risk of Death Following Clinical Fractures Fracture Intervention Trial (FIT): postmenopausal women aged years followed for an average of 3.8 yearsAny SymptomaticNonspineOtherForearmSpineHip0.31.02.05.016.010.06.78.6Osteoporotic fracture is also associated with significant mortality in postmenopausal women.These data summarize results from 6459 postmenopausal women followed for an average of 3.8 years in the Fracture Intervention Trial (FIT).There was an approximate 2-fold increase in risk of death following any clinical fracture, primarily due to a 6-fold increase in mortality following hip fracture and an 8-fold increase in mortality following vertebral fracture.In contrast, there was no increase in risk of mortality associated with forearm fracture or fractures at sites other than the spine, wrist, or hip.These data suggest that clinical fractures, particularly vertebral fractures, are associated with an increased risk of mortality in postmenopausal women.Interestingly, the mortality following vertebral fracture is comparable to or greater than that associated with hip fractures. “The observed excess mortality among women who experience a clinical vertebral fracture widens the public health impact of these fractures.” 11. Cauley JA et al., Osteoporos Int 2000;11:556-61Age-Adjusted Relative Risk (95% CI)Cauley JA et al. Osteoporos Int. 2000;11:
6 Diagnosis of Osteoporosis Densitometric DiagnosisDual-energy X-ray absorptiometry (DXA)World Health Organization (WHO) criteriaClinical DiagnosisFragility fracture
7 What DXA measures: bone mineral content (BMC) in grams & area in cm2 “Areal” BMD is calculated in g/cm2 (aBMD = BMC/Area)“T-score” is calculated using the patient’s BMD and a reference database
8 Calculation of T-score Patient’s BMD – Young-Adult Mean BMDSD of Young-Adult BMD in g/cm2Example:T-score =0.7 g/cm g/cm20.1 g/cm2=
9 WHO Classification of BMD T-scoreNormal-1.0 or greaterLow Bone Mass (Osteopenia)Between -1.0 and -2.5Osteoporosis-2.5 and belowSevere Osteoporosis-2.5 and below with history of fragility fractureWHO Study Group 1994.
10 Why is a T-score of -2.5 or less used to diagnose osteoporosis? “Such a cutoff value identifies approximately 30% of postmenopausal women as having osteoporosis using measurements made at the spine, hip or forearm. This is approximately equivalent to the lifetime risk of fracture at these sites.”Kanis JA et al. J Bone Miner Res. 1994;9:1137.
13 Use Clinical JudgmentT-score greater than -2.5 does not eliminate the possibility of osteoporosisClinical diagnosis of osteoporosis may be made in the presence of a fragility fractureT-score -2.5 or less does not always mean that osteoporosis is presentPrimary disease may be something else (e.g., osteomalacia, multiple myeloma)
14 DXA is the “Gold Standard” Widely used in epidemiological studies from which prevalence data is derivedWHO criteria based on BMD measured by DXACorrelation with fracture riskLow radiationExcellent precision
15 Clinical Uses of DXA Diagnose osteoporosis Predict fracture risk Monitor changes in BMD
16 Indications for BMD Testing Official PositionIndications for BMD TestingScreeningWomen aged 65 and older.Men aged 70 and older.Risk FactorsPostmenopausal women under age 65 with risk factors.Adults with a fragility fracture.Adults with a disease or condition associated with low bone mass or bone loss.Adults taking medications associated with low bone mass or bone loss.TreatmentAnyone being considered for pharmacologic therapy.Anyone being treated, to monitor treatment effect.Anyone not receiving therapy in whom evidence of bone loss would lead to treatment.Women discontinuing estrogen should be considered for bone density testing according to the indications listed above.
17 Bone Mass Measurement Act, 7/1/98 Five Categories of Medicare Covered ServicesEstrogen-deficient women at clinical risk for osteoporosisIndividuals with vertebral abnormalitiesIndividuals receiving long-term glucocorticoid therapyIndividuals with primary hyperparathyroidismIndividuals being monitored to assess the response to or efficacy of an FDA-approved osteoporosis drug therapyVertebral abnormalities = x-ray evidence of VF, osteopenia, or osteoporosisFederal Register, Volume 63, Number 121, June 24, 1998.
18 Diagnosis in Postmenopausal Women and in Men Age 50 and Older Official PositionDiagnosis in Postmenopausal Women and in Men Age 50 and OlderOsteoporosis may be diagnosed in postmenopausal women and in men age 50 and older if the T-score of the lumbar spine, total hip or femoral neck is -2.5 or less:*In certain circumstances the 33% radius (also called 1/3 radius) may be utilized.*Note: Other hip regions of interest, including Ward’s area and the greater trochanter, should not be used for diagnosis. Application of recommendation may vary according to local requirements.
19 Diagnosis in Premenopausal Women and Men Younger than Age 50 Official PositionDiagnosis in Premenopausal Women and Men Younger than Age 50Z-scores, not T-scores are preferred. This is particularly important in children.A Z-score of -2.0 or lower is defined as “below the expected range for age” and a Z-score above -2.0 is “within the expected range for age.”
20 Bone Density and Fracture Risk Relative Riskfor FractureExponential RelationshipBone Density (T-score)Adapted from Faulkner KG. J Bone Miner Res. 2000;15:
21 Age is an Independent Risk Factor for Fracture Ten Year Fracture Probability (%)Age80706050Probability of first fracture of hip, distal forearm, proximal humerus, and symptomatic vertebral fracture in women of Malmö, Sweden.Adapted from Kanis JA et al. Osteoporosis Int. 2001;12:
22 Predicting Hip Fractures: Relative Risk vs. Fracture Probability Age*Hip T-scoreRelative Risk (a) (2.6)2.510-Year Probability (b)50-2.517.61.9%8019.4%Relative Risk = (RR per SD)T-score or Z-score Difference10-Year Probability from Swedish National Bureau of Statistics*Postmenopausal Woman(a) Marshall D et al. BMJ. 1996;32: (b) Kanis JA et al. Osteoporos Int. 2001;12:
23 Prior Fracture Increases Relative Risk of Subsequent Fractures Site of Subsequent FractureSite of Prior FractureWristVertebraHip22.214.171.124.44.42.3NA2.5Klotzbuecher CM et al. J Bone Miner Res. 2000;15:
24 BMD and Clinical Risk Factors Predict Hip Fractures Age ≥ 80Family Hx Hip FxAny Fx Except Hip Since Age 50Fair, Poor or Very Poor HealthHx HyperthyroidismAnticonvulsant TherapyCurrent Benzodiazepine RxCurrent Weight < Age 25 WeightCaffeine > 2 Cups Coffee per DayOn Feet ≤ 4 hours per DayNo Walking for ExerciseCan’t Rise From Chair Without Using ArmsLowest Quartile Depth PerceptionLowest Quartile Contrast SensitivityHeart Rate > 80(per 1000 woman-years)Rate of Hip FractureNo. of Risk FactorsCalcaneal Bone DensitySOF in 9516 white women over age 65 with no previous hip fractureCummings SR et al. N Engl J Med. 1995;332:
25 NOF Treatment Guidelines Initiate therapy to reduce fracture risk in women withT-Score less than -2.0, regardless of risk factors†T-score between -1.5 and -2.0, if at least one risk factor is presentPrevious vertebral or hip fracture†Major risk factors = fracture as an adult, first degree relative with fragility fracture, weight less than 127 lbs., current smoking, glucocorticoid therapy more than 3 mo.Physician’s Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation
26 Most Fractures Occur in Patients with T-score Greater Than -2.5 Study of Osteoporotic Fractures (SOF)8,065 postmenopausal women age 65 or older54% of women with hip fracture had baseline T-scores greater than -2.5 (total hip)National Osteoporosis Risk Assessment (NORA)149,524 postmenopausal women with mean age of 6582% of 2,259 women with fragility fractures had baseline T-scores greater than -2.5 (peripheral)Wainwright SA et al. J Clin Endocrinol Metab. 2005;90: Siris ES et al. Arch Intern Med. 2004;164:
27 WHO ProjectGoal: To develop a standardized methodology for expressing fracture risk and intervention thresholds for men and women worldwideMethod: Study correlations of BMD and clinical risk factors with fracture outcomes in large prospective observational studies, and apply cost utility analysis to set intervention thresholds
28 Fracture Risk Reporting Since the goal of osteoporosis therapy is fracture prevention, patient selection is best based on fracture riskT-score alone does not provide a complete assessment of fracture riskCombination of clinical risk factors with BMD may provide a better way of identifying patients for treatment
29 Selection of Clinical Risk Factors Independent of BMD (if BMD is known)Validated in multiple populations (sex, ethnicity, country)Easily obtainableAmenable to intended treatmentIntuitiveAdapted from Kanis JA et al. Osteoporos Int. 2005;16:
30 Clinical Risk Factors Femoral neck T-score + Age Previous low trauma fractureCurrent cigarette smokingRheumatoid arthritisHigh alcohol intake (> 2 units/day)Parental history of hip fracturePrior or current glucocorticoid useAdapted from Kanis JA et al. Osteoporos Int. 2005;16:
31 Intervention Threshold A fracture probability above which it is cost-effective to treat with pharmacological agentsBased on statistical modeling using many medical, social, and economic assumptions
32 Decision to Treat Fracture probability Cost-effectiveness Efficacy SafetyExpected adherence to therapyNon-skeletal risks and benefitsPatient beliefs and preferences
33 Why do serial BMD testing? To monitor response to therapy by finding an increase or stability of bone density, andTo evaluate for non-response by finding loss of bone density- suggesting the need for re-evaluation of treatment and evaluation for secondary causes of osteoporosisJ Clin Densitom. 2002;5(Suppl):S1-S45.
34 When should repeat BMD testing be done? When expected change in BMD equals or exceeds the “Least Significant Change” (LSC)Intervals between BMD testing should be determined according to each patient’s clinical statusConsider 1 year after initiation or change of therapyLonger intervals once therapeutic effect is establishedShorter intervals when rapid bone loss is expectedtypically 1year after initiation or change of therapy is appropriate, with longer intervals once therapeutic effect is established. In conditions associated with rapid bone loss, such as glucocorticoid therapy, more often is appropriate.J Clin Densitom. 2002;5(Suppl):S1-S45.
35 Never Compare T-scores Always Compare BMDNever Compare T-scores
36 BMD Values from Different Manufacturers are Not Comparable Different dual energy methodsDifferent calibrationDifferent detectorsDifferent edge detection softwareDifferent regions of interest
37 Vertebral Fracture Assessment (VFA) Recognition of vertebral fracture mayChange diagnostic classificationChange estimate of fracture riskChange treatment decisionsNormalVertebral Fx
39 Peripheral Bone Density Measurement Good prediction of fracture riskGood tool for skeletal health educationCannot be used with the WHO criteria for diagnosis of osteoporosisNot useful for monitoring bone density changesJ Clin Densitom. 2002;5(Suppl):S1-S45.
40 SummaryBMD testing can diagnose osteoporosis, predict fracture risk, and monitor changes in BMD over timeCombination of BMD and clinical risk factors is as better predictor of fracture risk than BMD or clinical risk factors alonePatients at high risk for fracture are most likely to benefit from therapy