Bone Mineral Density Testing Bone Mineral Density Testing in Clinical Practicein Clinical Practice

Screen & InterveneScreen & InterveneCritical Challenges in Osteoporosis and Women’s HealthCritical Challenges in Osteoporosis and Women’s Health

OutlineOutline

► BackgroundBackground► Diagnosis of osteoporosisDiagnosis of osteoporosis► BMD and fracture riskBMD and fracture risk► Indications for BMD testingIndications for BMD testing► Interpretation of BMD testsInterpretation of BMD tests► Combining BMD and clinical risk factorsCombining BMD and clinical risk factors► Selecting patients for treatmentSelecting patients for treatment► Serial BMD testingSerial BMD testing► Peripheral bone density testingPeripheral bone density testing

Osteoporosis is a Silent DiseaseOsteoporosis is a Silent Disease

► No symptomsNo symptoms► No findings on physical examNo findings on physical exam► No laboratory abnormalitiesNo laboratory abnormalities► Increase in fracture riskIncrease in fracture risk

– Fractures have serious consequencesFractures have serious consequences– Treatment can reduce fracture riskTreatment can reduce fracture risk

Challenge: To identify and treat patients at risk for fracture before the first fracture occurs

Consequences of FracturesConsequences of Fractures

► Increased risk of future Increased risk of future fracturesfractures

► Chronic painChronic pain

► SurgerySurgery

► Loss of heightLoss of height

► Impaired pulmonary Impaired pulmonary functionfunction

► Abdominal symptomsAbdominal symptoms

► Medical expenses / lost Medical expenses / lost incomeincome

► HospitalizationHospitalization

► SurgerySurgery

► Rehab hospitalRehab hospital

► Nursing homeNursing home

► Loss of self-esteemLoss of self-esteem

► DepressionDepression

► Loss of independenceLoss of independence

► DisabilityDisability

► DeathDeath

Relative Risk of Death Relative Risk of Death Following Clinical FracturesFollowing Clinical Fractures

Age-Adjusted Relative Risk (95% CI)

Any Symptomatic

Nonspine

Other

Forearm

Spine

Hip

0.3 1.0 2.0 5.0 16.010.0

6.7

8.6

Fracture Intervention Trial (FIT): 6459 postmenopausal women aged 55-81 years followed for an average of 3.8 years

Cauley JA et al. Osteoporos Int. 2000;11:556-561.

Diagnosis of OsteoporosisDiagnosis of Osteoporosis

► Densitometric DiagnosisDensitometric Diagnosis– Dual-energy X-ray absorptiometry (DXA)Dual-energy X-ray absorptiometry (DXA)– World Health Organization (WHO) criteriaWorld Health Organization (WHO) criteria

► Clinical DiagnosisClinical Diagnosis– Fragility fractureFragility fracture

WHO Classification of BMDWHO Classification of BMD

ClassificationClassification T-scoreT-score

NormalNormal -1.0 or greater-1.0 or greater

Low Bone Mass Low Bone Mass (Osteopenia)(Osteopenia) Between -1.0 and -2.5Between -1.0 and -2.5

OsteoporosisOsteoporosis -2.5 and below-2.5 and below

Severe OsteoporosisSevere Osteoporosis-2.5 and below with -2.5 and below with history of fragility history of fragility fracturefracture

WHO Study Group 1994.

L1-L4 T-score = -2.6L1-L4 T-score = -2.6

Left Femoral Neck T-score = -2.6Left Femoral Neck T-score = -2.6

Use Clinical JudgmentUse Clinical Judgment

► T-score greater than -2.5 does not T-score greater than -2.5 does not eliminate the possibility of osteoporosiseliminate the possibility of osteoporosis– Clinical diagnosis of osteoporosis may be Clinical diagnosis of osteoporosis may be

made in the presence of a fragility fracturemade in the presence of a fragility fracture

► T-score -2.5 or less does not always T-score -2.5 or less does not always mean that osteoporosis is presentmean that osteoporosis is present– Primary disease may be something else Primary disease may be something else

(e.g., osteomalacia, multiple myeloma)(e.g., osteomalacia, multiple myeloma)

DXA is the “Gold Standard”DXA is the “Gold Standard”

► Widely used in epidemiological studies Widely used in epidemiological studies from which prevalence data is derivedfrom which prevalence data is derived

► WHO criteria based on BMD measured WHO criteria based on BMD measured by DXAby DXA

► Correlation with fracture riskCorrelation with fracture risk► Low radiationLow radiation► Excellent precisionExcellent precision

Clinical Uses of DXA Clinical Uses of DXA

► Diagnose osteoporosisDiagnose osteoporosis

► Predict fracture riskPredict fracture risk

► Monitor changes in BMDMonitor changes in BMD

Indications for BMD TestingIndications for BMD Testing

► ScreeningScreening– Women aged 65 and older.Women aged 65 and older.– Men aged 70 and older.Men aged 70 and older.

► Risk FactorsRisk Factors– Postmenopausal women under age 65 with risk factors.Postmenopausal women under age 65 with risk factors.– Adults with a fragility fracture.Adults with a fragility fracture.– Adults with a disease or condition associated with low bone mass or bone Adults with a disease or condition associated with low bone mass or bone

loss.loss.– Adults taking medications associated with low bone mass or bone loss.Adults taking medications associated with low bone mass or bone loss.

► TreatmentTreatment– Anyone being considered for pharmacologic therapy. Anyone being considered for pharmacologic therapy. – Anyone being treated, to monitor treatment effect.Anyone being treated, to monitor treatment effect.– Anyone not receiving therapy in whom evidence of bone loss would lead to Anyone not receiving therapy in whom evidence of bone loss would lead to

treatment.treatment.

Women discontinuing estrogen should be considered for Women discontinuing estrogen should be considered for bone density testing according to the indications listed above. bone density testing according to the indications listed above.

Official Position

Bone Mass Measurement Act, Bone Mass Measurement Act, 7/1/987/1/98

► Estrogen-deficient women at clinical risk for Estrogen-deficient women at clinical risk for osteoporosisosteoporosis

► Individuals with vertebral abnormalitiesIndividuals with vertebral abnormalities► Individuals receiving long-term glucocorticoid Individuals receiving long-term glucocorticoid

therapytherapy► Individuals with primary hyperparathyroidismIndividuals with primary hyperparathyroidism► Individuals being monitored to assess the Individuals being monitored to assess the

response to or efficacy of an FDA-approved response to or efficacy of an FDA-approved osteoporosis drug therapyosteoporosis drug therapy

Federal Register, Volume 63, Number 121, June 24, 1998.

Five Categories of Medicare Covered Services

Diagnosis in Postmenopausal Women Diagnosis in Postmenopausal Women and in Men Age 50 and Olderand in Men Age 50 and Older

► Osteoporosis may be diagnosed in Osteoporosis may be diagnosed in postmenopausal women and in men age postmenopausal women and in men age 50 and older if the T-score of the lumbar 50 and older if the T-score of the lumbar spine, total hip or femoral neck is -2.5 or spine, total hip or femoral neck is -2.5 or less:*less:*– In certain circumstances the 33% radius In certain circumstances the 33% radius

(also called 1/3 radius) may be utilized.(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.

Official Position

Diagnosis in Premenopausal Women Diagnosis in Premenopausal Women and Men Younger than Age 50and Men Younger than Age 50

► Z-scores, not T-scores are preferred. Z-scores, not T-scores are preferred. This is particularly important in children.This is particularly important in children.

► A Z-score of -2.0 or lower is defined as A Z-score of -2.0 or lower is defined as “below the expected range for age” and “below the expected range for age” and a Z-score above -2.0 is “within the a Z-score above -2.0 is “within the expected range for age.”expected range for age.”

Official Position

Bone Density and Fracture RiskBone Density and Fracture Risk

0

5

10

15

20

25

30

35

1.0 0.0 -1.0 -2.0 -3.0 -4.0 -5.0

Bone Density (T-score)

Relative Risk

for Fracture

Adapted from Faulkner KG. J Bone Miner Res. 2000;15:183-187.

Age is an Independent Risk Factor Age is an Independent Risk Factor for Fracturefor Fracture

Adapted from Kanis JA et al. Osteoporosis Int. 2001;12:989-995.

0

10

20

30

40

50

1.0 0.5 0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0

Femoral Neck T-score

Ten Year Fracture

Probability (%)

Age

8070

60

50

Probability of first fracture of hip, distal forearm, proximal humerus, and symptomatic vertebral fracture in women of Malmö, Sweden.

Predicting Hip Fractures: Predicting Hip Fractures: Relative Risk vs. Fracture ProbabilityRelative Risk vs. Fracture Probability

(a) Marshall D et al. BMJ. 1996;32:1254-1259.(b) Kanis JA et al. Osteoporos Int. 2001;12:417-427.

Age*Age* Hip T-scoreHip T-score Relative Risk (a) Relative Risk (a) (2.6)(2.6)2.52.5

10-Year 10-Year Probability (b)Probability (b)

5050 -2.5-2.5 17.617.6 1.9%1.9%

8080 -2.5-2.5 17.617.6 19.4%19.4%

Relative Risk = (RR per SD)T-score or Z-score Difference

10-Year Probability from Swedish National Bureau of Statistics

*Postmenopausal Woman

Prior Fracture Increases Relative Prior Fracture Increases Relative Risk of Subsequent FracturesRisk of Subsequent Fractures

Klotzbuecher CM et al. J Bone Miner Res. 2000;15:721-739.

Site of Subsequent FractureSite of Subsequent Fracture

Site of Prior FractureSite of Prior Fracture WristWrist VertebraVertebra HipHip

WristWrist 3.33.3 1.71.7 1.91.9

VertebraVertebra 1.41.4 4.44.4 2.32.3

HipHip NANA 2.52.5 2.32.3

BMD and Clinical Risk Factors BMD and Clinical Risk Factors Predict Hip FracturesPredict Hip Fractures

Risk FactorsAge ≥ 80

Family Hx Hip Fx

Any Fx Except Hip Since Age 50

Fair, Poor or Very Poor Health

Hx Hyperthyroidism

Anticonvulsant Therapy

Current Benzodiazepine Rx

Current Weight < Age 25 Weight

Caffeine > 2 Cups Coffee per Day

On Feet ≤ 4 hours per Day

No Walking for Exercise

Can’t Rise From Chair Without Using Arms

Lowest Quartile Depth Perception

Lowest Quartile Contrast Sensitivity

Heart Rate > 80

Cummings SR et al. N Engl J Med. 1995;332:767-773.

27.3

14.7

9.4

4.0 5.61.9

2.6 1.1 1.10

5

10

15

20

25

30

Lowest Third Middle Third Highest Third

0-2

3-4

>4

Calcaneal Bone DensityNo. o

f Risk

Facto

rs

Rat

e of

Hip

Fra

ctur

e

(per

100

0 w

oman

-yea

rs)

SOF in 9516 white women over age 65 with no previous hip fracture

NOF Treatment GuidelinesNOF Treatment Guidelines

Initiate therapy to reduce fracture risk in Initiate therapy to reduce fracture risk in women withwomen with– T-Score less than -2.0, regardless of risk T-Score less than -2.0, regardless of risk

factorsfactors††

– T-score between -1.5 and -2.0, if at least one T-score between -1.5 and -2.0, if at least one risk factor is presentrisk factor is present

– Previous vertebral or hip fracturePrevious vertebral or hip fracture

Physician’s Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation. 2003.

†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.

Most Fractures Occur in Patients Most Fractures Occur in Patients with T-score Greater Than -2.5with T-score Greater Than -2.5

► Study of Osteoporotic Fractures (SOF)Study of Osteoporotic Fractures (SOF)– 8,065 postmenopausal women age 65 or older8,065 postmenopausal women age 65 or older– 54% of women with hip fracture had baseline 54% of women with hip fracture had baseline

T-scores greater than -2.5 (total hip)T-scores greater than -2.5 (total hip)► National Osteoporosis Risk Assessment National Osteoporosis Risk Assessment

(NORA)(NORA)– 149,524 postmenopausal women with mean 149,524 postmenopausal women with mean

age of 65age of 65– 82% of 2,259 women with fragility fractures 82% of 2,259 women with fragility fractures

had baseline T-scores greater than -2.5 had baseline T-scores greater than -2.5 (peripheral)(peripheral)

Wainwright SA et al. J Clin Endocrinol Metab. 2005;90:2787-2793. Siris ES et al. Arch Intern Med. 2004;164:1108-1112.

WHO ProjectWHO Project

► Goal: To develop a standardized Goal: To develop a standardized methodology for expressing fracture risk methodology for expressing fracture risk and intervention thresholds for men and and intervention thresholds for men and women worldwidewomen worldwide

► Method: Study correlations of BMD and Method: Study correlations of BMD and clinical risk factors with fracture outcomes clinical risk factors with fracture outcomes in large prospective observational studies, in large prospective observational studies, and apply cost utility analysis to set and apply cost utility analysis to set intervention thresholdsintervention thresholds

Fracture Risk ReportingFracture Risk Reporting

► Since the goal of osteoporosis therapy is Since the goal of osteoporosis therapy is fracture prevention, patient selection is fracture prevention, patient selection is best based on fracture riskbest based on fracture risk

► T-score alone does not provide a T-score alone does not provide a complete assessment of fracture riskcomplete assessment of fracture risk

► Combination of clinical risk factors with Combination of clinical risk factors with BMD may provide a better way of BMD may provide a better way of identifying patients for treatmentidentifying patients for treatment

Selection of Clinical Risk FactorsSelection of Clinical Risk Factors

► Independent of BMD (if BMD is known)Independent of BMD (if BMD is known)

► Validated in multiple populations Validated in multiple populations (sex, ethnicity, country) (sex, ethnicity, country)

► Easily obtainableEasily obtainable

► Amenable to intended treatmentAmenable to intended treatment

► IntuitiveIntuitive

Adapted from Kanis JA et al. Osteoporos Int. 2005;16:581-589.

Clinical Risk FactorsClinical Risk Factors

Femoral neck T-scoreFemoral neck T-score + +► AgeAge► Previous low trauma fracturePrevious low trauma fracture► Current cigarette smokingCurrent cigarette smoking► Rheumatoid arthritisRheumatoid arthritis► High alcohol intake (> 2 units/day)High alcohol intake (> 2 units/day)► Parental history of hip fractureParental history of hip fracture► Prior or current glucocorticoid usePrior or current glucocorticoid use

Adapted from Kanis JA et al. Osteoporos Int. 2005;16:581-589.

Intervention ThresholdIntervention Threshold

► A fracture probability above which it is A fracture probability above which it is cost-effective to treat with cost-effective to treat with pharmacological agentspharmacological agents

► Based on statistical modeling using Based on statistical modeling using many medical, social, and economic many medical, social, and economic assumptions assumptions

Decision to TreatDecision to Treat

► Fracture probabilityFracture probability► Cost-effectivenessCost-effectiveness► EfficacyEfficacy► SafetySafety► Expected adherence to therapyExpected adherence to therapy► Non-skeletal risks and benefitsNon-skeletal risks and benefits► Patient beliefs and preferencesPatient beliefs and preferences

Why do serial BMD testing? Why do serial BMD testing?

► To monitor response to therapy by To monitor response to therapy by finding an increase or stability of bone finding an increase or stability of bone density, anddensity, and

► To evaluate for non-response by finding To evaluate for non-response by finding loss of bone density- suggesting the loss of bone density- suggesting the need for re-evaluation of treatment and need for re-evaluation of treatment and evaluation for secondary causes of evaluation for secondary causes of osteoporosisosteoporosis

J Clin Densitom. 2002;5(Suppl):S1-S45.

When should repeat When should repeat BMD testing be done? BMD testing be done?

► When expected change in BMD equals or When expected change in BMD equals or exceeds the “Least Significant Change” (LSC)exceeds the “Least Significant Change” (LSC)

► Intervals between BMD testing should be Intervals between BMD testing should be determined according to each patient’s clinical determined according to each patient’s clinical statusstatus– Consider 1 year after initiation or change of therapyConsider 1 year after initiation or change of therapy– Longer intervals once therapeutic effect is establishedLonger intervals once therapeutic effect is established– Shorter intervals when rapid bone loss is expectedShorter intervals when rapid bone loss is expected

J Clin Densitom. 2002;5(Suppl):S1-S45.

Always Compare BMDAlways Compare BMD

Never Compare T-scoresNever Compare T-scores

BMD Values from Different BMD Values from Different Manufacturers are Not ComparableManufacturers are Not Comparable

► Different dual energy methodsDifferent dual energy methods

► Different calibrationDifferent calibration

► Different detectorsDifferent detectors

► Different edge detection softwareDifferent edge detection software

► Different regions of interestDifferent regions of interest

Vertebral Fracture Assessment (VFA)Vertebral Fracture Assessment (VFA)

Recognition of vertebral Recognition of vertebral fracture mayfracture may

1.1. Change diagnostic Change diagnostic classificationclassification

2.2. Change estimate of Change estimate of fracture riskfracture risk

3.3. Change treatment Change treatment decisionsdecisions

Normal Vertebral Fx

Peripheral Measuring DevicesPeripheral Measuring Devices

Peripheral Bone Density Peripheral Bone Density MeasurementMeasurement

► Good prediction of fracture risk Good prediction of fracture risk

► Good tool for skeletal health educationGood tool for skeletal health education

► Cannot be used with the WHO criteria for Cannot be used with the WHO criteria for diagnosis of osteoporosisdiagnosis of osteoporosis

► Not useful for monitoring bone density Not useful for monitoring bone density changeschanges

J Clin Densitom. 2002;5(Suppl):S1-S45.

SummarySummary

► BMD testing can diagnose osteoporosis, BMD testing can diagnose osteoporosis, predict fracture risk, and monitor predict fracture risk, and monitor changes in BMD over timechanges in BMD over time

► Combination of BMD and clinical risk Combination of BMD and clinical risk factors is as better predictor of fracture factors is as better predictor of fracture risk than BMD or clinical risk factors risk than BMD or clinical risk factors alonealone

► Patients at high risk for fracture are most Patients at high risk for fracture are most likely to benefit from therapylikely to benefit from therapy