1. Bone Mineral Density Testing in Clinical Practice
Screen & Intervene
Critical Challenges in Osteoporosis and Women’s Health

2. Outline Background Diagnosis of osteoporosis BMD and fracture risk
Indications for BMD testing
Interpretation of BMD tests
Combining BMD and clinical risk factors
Selecting patients for treatment
Serial BMD testing
Peripheral bone density testing

3. Osteoporosis is a Silent Disease
No symptoms
No findings on physical exam
No laboratory abnormalities
Increase in fracture risk
Fractures have serious consequences
Treatment can reduce fracture risk
Challenge: To identify and treat patients at risk for fracture before the first fracture occurs

4. Consequences of Fractures
Increased risk of future fractures
Chronic pain
Surgery
Loss of height
Impaired pulmonary function
Abdominal symptoms
Medical expenses / lost income
Hospitalization
Surgery
Rehab hospital
Nursing home
Loss of self-esteem
Depression
Loss of independence
Disability
Death

5. Relative Risk of Death Following Clinical Fractures
Fracture Intervention Trial (FIT): postmenopausal women aged years followed for an average of 3.8 years
Any Symptomatic
Nonspine
Other
Forearm
Spine
Hip
0.3
1.0
2.0
5.0
16.0
10.0
6.7
8.6
Osteoporotic 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.” 1
1. Cauley JA et al., Osteoporos Int 2000;11:556-61
Age-Adjusted Relative Risk (95% CI)
Cauley JA et al. Osteoporos Int. 2000;11:

6. Diagnosis of Osteoporosis
Densitometric Diagnosis
Dual-energy X-ray absorptiometry (DXA)
World Health Organization (WHO) criteria
Clinical Diagnosis
Fragility 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 BMD
SD of Young-Adult BMD in g/cm2
Example:
T-score =
0.7 g/cm g/cm2
0.1 g/cm2 =

9. WHO Classification of BMD
T-score
Normal
-1.0 or greater
Low Bone Mass (Osteopenia)
Between -1.0 and -2.5
Osteoporosis
-2.5 and below
Severe Osteoporosis
-2.5 and below with history of fragility fracture
WHO 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.

11. L1-L4 T-score = -2.6

12. Left Femoral Neck T-score = -2.6

13. Use Clinical Judgment
T-score greater than -2.5 does not eliminate the possibility of osteoporosis
Clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture
T-score -2.5 or less does not always mean that osteoporosis is present
Primary 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 derived
WHO criteria based on BMD measured by DXA
Correlation with fracture risk
Low radiation
Excellent precision

15. Clinical Uses of DXA Diagnose osteoporosis Predict fracture risk
Monitor changes in BMD

16. Indications for BMD Testing
Official Position
Indications for BMD Testing
Screening
Women aged 65 and older.
Men aged 70 and older.
Risk Factors
Postmenopausal 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.
Treatment
Anyone 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 Services
Estrogen-deficient women at clinical risk for osteoporosis
Individuals with vertebral abnormalities
Individuals receiving long-term glucocorticoid therapy
Individuals with primary hyperparathyroidism
Individuals being monitored to assess the response to or efficacy of an FDA-approved osteoporosis drug therapy
Vertebral abnormalities = x-ray evidence of VF, osteopenia, or osteoporosis
Federal Register, Volume 63, Number 121, June 24, 1998.

18. Diagnosis in Postmenopausal Women and in Men Age 50 and Older
Official Position
Diagnosis in Postmenopausal Women and in Men Age 50 and Older
Osteoporosis 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 Position
Diagnosis in Premenopausal Women and Men Younger than Age 50
Z-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 Risk
for Fracture
Exponential Relationship
Bone 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 (%)
Age 80 70 60 50
Probability 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-score
Relative Risk (a) (2.6)2.5
10-Year Probability (b) 50
-2.5
17.6
1.9% 80
19.4%
Relative Risk = (RR per SD)T-score or Z-score Difference
10-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 Fracture
Site of Prior Fracture
Wrist
Vertebra
Hip
3.3
1.7
1.9
1.4
4.4
2.3 NA
2.5
Klotzbuecher CM et al. J Bone Miner Res. 2000;15:

24. BMD and Clinical Risk Factors Predict Hip Fractures
Age ≥ 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
(per 1000 woman-years)
Rate of Hip Fracture
No. of Risk Factors
Calcaneal Bone Density
SOF in 9516 white women over age 65 with no previous hip fracture
Cummings SR et al. N Engl J Med. 1995;332:

25. NOF Treatment Guidelines
Initiate therapy to reduce fracture risk in women with
T-Score less than -2.0, regardless of risk factors†
T-score between -1.5 and -2.0, if at least one risk factor is present
Previous 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 older
54% 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 65
82% 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 Project
Goal: To develop a standardized methodology for expressing fracture risk and intervention thresholds for men and women worldwide
Method: 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 risk
T-score alone does not provide a complete assessment of fracture risk
Combination 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 obtainable
Amenable to intended treatment
Intuitive
Adapted from Kanis JA et al. Osteoporos Int. 2005;16:

30. Clinical Risk Factors Femoral neck T-score + Age
Previous low trauma fracture
Current cigarette smoking
Rheumatoid arthritis
High alcohol intake (> 2 units/day)
Parental history of hip fracture
Prior or current glucocorticoid use
Adapted 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 agents
Based on statistical modeling using many medical, social, and economic assumptions

32. Decision to Treat Fracture probability Cost-effectiveness Efficacy
Safety
Expected adherence to therapy
Non-skeletal risks and benefits
Patient beliefs and preferences

33. Why do serial BMD testing?
To monitor response to therapy by finding an increase or stability of bone density, and
To evaluate for non-response by finding loss of bone density- suggesting the need for re-evaluation of treatment and evaluation for secondary causes of osteoporosis
J 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 status
Consider 1 year after initiation or change of therapy
Longer intervals once therapeutic effect is established
Shorter intervals when rapid bone loss is expected
typically 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 BMD
Never Compare T-scores

36. BMD Values from Different Manufacturers are Not Comparable
Different dual energy methods
Different calibration
Different detectors
Different edge detection software
Different regions of interest

37. Vertebral Fracture Assessment (VFA)
Recognition of vertebral fracture may
Change diagnostic classification
Change estimate of fracture risk
Change treatment decisions
Normal
Vertebral Fx

38. Peripheral Measuring Devices

39. Peripheral Bone Density Measurement
Good prediction of fracture risk
Good tool for skeletal health education
Cannot be used with the WHO criteria for diagnosis of osteoporosis
Not useful for monitoring bone density changes
J Clin Densitom. 2002;5(Suppl):S1-S45.

40. Summary
BMD testing can diagnose osteoporosis, predict fracture risk, and monitor changes in BMD over time
Combination of BMD and clinical risk factors is as better predictor of fracture risk than BMD or clinical risk factors alone
Patients at high risk for fracture are most likely to benefit from therapy