1. Interpretation of Bone mineral density
Tuan Van Nguyen and Nguyen Dinh Nguyen
Garvan Institute of Medical Research
Sydney, Australia

2. Overview Definitions Bone strength and quality DXA and BMD
T-scores and interpretations
Clinical applications

3. Definition of Osteoporosis (WHO)
A systematic skeleton disease characterized by:
low bone mass
microarchitectural deterioration of bone tissue
consequent increase in bone fragility and susceptibility to fracture
Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis, Am J Med 1993;94: WHO Study Group 1994.

4. Definition of Osteoporosis (NIH)
Osteoporosis is defined as a skeletal disorder characterized by:
compromised bone strength predisposing a person to an increased risk of fracture.
bone strength primarily reflects the integration of bone density and bone quality.
(Source: NIH Consensus Development Panel on Osteoporosis JAMA 285:785-95; 2001)

5. Osteoporosis
Normal
Osteopenia
Osteoporosis

6. Normal bone
Osteoporosis

7. Gain and loss of Bone throughout the lifespan
Pubertal Growth Spurt
Menopause
BMD
Resorption
Formation
Age (Years)

8. BONE STRENGTH BONE MINERAL BONE QUALITY DENSITY Bone architechture
Gram of
mineral
per area
Bone
turnover
Bone
size &
geometry

9. Bone mass, Bone mineral density (BMD)
Bone mass = the amount of bone tissue as the total of protein and mineral or the amount of mineral in the whole skeleton or in a particular segment of bone. (unmeasurable)
BMD = the average concentration of mineral per unit area  assessed in 2 dimensions (measurable)

10. “Gold standard”
DXA is the “gold standard” machine for measurement of BMD
BMD is the “gold standard” to define osteoporosis
Only use BMD measurements at central skeletal sites (i.e. hip or vertebrae) to define osteoporosis, but BMD measured at hip is more reliable.

11. Femoral neck BMD

12. Lumbar spine BMD

13. Hip BMD: Results

14. Relationship between BMD and Age
Peak Bone Mass and SD
Relationship between BMD and Age
(VN 2006, unpublished data)

15. T-scores Patient’s BMD – Young-adult mean BMD
1 SD of Young-adult mean BMD
Example: peak bone mass (AU) = 1.00 ± 0.12
peak bone mass (VN) = 0.91 ± 0.11
T-score =
0.70 g/cm2 – 0.91 g/cm2
0.11 g/cm2 =
T-score =
0.70 g/cm g/cm2
0.12 g/cm2 =

16. Diagnostic Classification
T-scores
Normal
≥ - 1
Osteopenia
Between -1 and -2.5
Osteoporosis
≤ -2.5 or less
Severe Osteoporosis
≤ and fragility fracture
WHO Study Group, 1994

17. (Source: Kanis JA et al. J Bone Miner Res. 1994;9:1137)
Why -2.5?
“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.”
(Source: Kanis JA et al. J Bone Miner Res. 1994;9:1137)

18. Z-scores Patient’s BMD – Age-Matched Mean BMD
1 SD of Age-Matched Mean BMD in g/cm2
Low Z-score (less than -2.0) may suggest increased likelihood of secondary osteoporosis, however . . .
This is not validated in clinical trials
High index of suspicion for secondary causes of osteoporosis is suggested in all patients

19. Why T-scores And Not Z-scores?
T-scores related to bone strength
T-scores related to fracture risk
Using Z-scores would result in many “normal” patients having fragility fractures, and suggest that osteoporosis does not increase with age

20. T-score Discordance
Different skeletal sites have different peak bone mass at different times and lose bone at different rates
Different technologies
Different Region of Interests (ROIs)
Different reference databases have different means and SD (the hip is the only skeletal site with a standardized reference database used by all manufacturers – National Health and Nutrition Examination Survey III, NHANE III)

21. Rounding errors BMD values: 2 or 3 decimal points
T-scores, Z-scores: 1 decimal point ID
Sex
FNBMD (g/cm2)
T-scores*
Classification 1 F
0.704
-2.5
Osteoporosis 2
0.690 3
0.710
-2.4
Osteopenia 4
0.705
* Calculated based on young adult mean: / (g/cm2)

22. WHO definition
Derived from studies of White postmenopausal (PM) women and apply to them
Currently, no standard for:
non-white PM women
men

23. Prevalence of Osteoporosis
Using Vietnamese reference
Using Caucasian reference
(VN 2006, unpublished data)

24. BMD Values From Different Manufacturers Are Not Comparable
Different dual energy methods
Different calibration
Different detectors
Different edge detection software
Different regions of interest

25. Cut-off thresholds for diagnosis of Osteoporosis (Women)
Reference
Device
Women N
Mean SD
Osteopenia
Osteoporosis
(Looker, 1997)
Hologic
409
Hip
femoral neck
0.86
0.12
≤ 0.56
trochanter
0.71
0.099
≤ 0.46
intertrochanter
1.09
0.142
≤ 0.74
total femur
0.94
0.122
≤ 0.64
(Nguyen, 1998)
Lunar 37
Femoral neck
1.00
≤ 0.70
Lumbar spine
1.20
≤ 0.90
(Tenenhouse, 2000) 95
0.857
0.125
≤ 0.54
432
1.042
0.121

26. Cut-off thresholds for diagnosis of Osteoporosis (Men)
Reference
Men    N
Mean SD
Osteopenia
Osteoporosis
(Looker, 1997)
382
Hip
femoral neck
0.93
0.137
≤ 0.59
trochanter
0.78
0.118
≤ 0.49
intertrochanter
1.21
0.172
≤ 0.78
total femur
1.04
0.144
≤ 0.68
(Nguyen, 1998) 37
Femoral neck
0.12
≤ 0.74
Lumbar spine
1.2
≤ 0.90
(Tenenhouse, 2000)
101
0.91
0.125
≤ 0.60
366
1.058
0.127

27. Indications For Bone Density Testing
All women age 65 and older
All men age 70 and older
Adults with a fragility fracture
Adults with a disease or condition associated with low bone density
Adults taking medication associated with low bone density
Anyone being treated for low bone density to monitor treatment effect
Anyone not receiving therapy, in whom evidence of bone loss would lead to treatment
Women discontinuing treatment should be considered for bone density testing according to the indications listed above.

28. Indications For Bone Density Testing
All women age 65+ and men age 70+
Radiographic evidence of osteopenia or vertebral deformity or both
Adult with previous fragility fracture
Loss of height, thoracic kyphosis (after radiographic confirmation of vertebral deformities)
Presence of strong risk factors:
Anorexia nervosa
Malabsorption syndromes
Primary Hyperparathyroidism
Post-transplantation
Chronic renal failure
Hyperthyroidism
Prolonged immobilisation
Cushing’s syndrome
Oestrogen deficiency
Corticosteroid therapy
Premature menopause <45 y.
Maternal family history of hip fracture
Long-term secondary amenorrhoea >1y.
Low body mass index (<19 Kg/m2)
Primary hypogonadism
Other disorder associated with osteoporosis
(Source:Kanis JA, Lancet, 2002;359: )

29. Why Do Serial BMD Testing?
To monitor response to therapy by finding an increase or stability of bone density
To evaluate for non-response by finding loss of bone density - suggesting the need for reevaluation of treatment and evaluation for secondary causes of osteoporosis
To follow patients not being treated who are at risk of bone loss, in order to determine if treatment is needed

30. Screening for Osteoporosis: Bone Density Testing Guidelines
NOF1
AACE2
USPSTF3
BMD testing for:
All women ≥65 years
Younger postmenopausal women with one or more risk factors
Postmenopausal women who present with fractures
Pre- and postmenopausal women who have risk factors for fracture
All women ≥40 years who have sustained a fracture
Women beginning or receiving long-term glucocorticoid therapy
Screening for:
For women at increased risk for fractures, begin screening at age 60

31. Nomogram for predicting of osteoporosis in Women29 66 69
Points 10 20 30 40 50 60 70 80 90
100
Age (y) 35 45 55 65 75 85
Weight (kg) 95
QUS (T-scores) 4 3 2 1 -1 -2 -3 -4 -5
Total Points
120
160
200
240
280
Risk of Osteoporosis
0.01
0.1
0.3
0.6
0.8
0.95
0.99
A woman of 65 yrs old,
Weight = 45kg
QUS T-score = -2.5
What is the probability for her developing of osteoporosis?
164
The risk for this woman developing of osteoporosis is ~ 60%
Source: Pongchaiyakul C and Nguyen TV 2006, unpublished data

32. 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 one year after initiation or change of therapy
Longer intervals once therapeutic effect is established
Shorter intervals when rapid bone loss is expected

33. Peripheral BMD Testing Accurate & Precise
What it can do
Predict fracture risk
Tool for osteoporosis education
What it cannot do
Diagnose osteoporosis
Monitor therapy
A “normal” peripheral test does not necessarily mean that the patient does not have osteoporosis.
WHO criteria do not apply to peripheral BMD testing.

34. Perspective T-scores: arbitrary
 Move away from T-scores, use absolute value and absolute risk.

35. Lời Cảm tạ
Chúng tôi xin chân thành cám ơn Công ty Dược phẩm Bridge Healthcare, Australia là nhà tài trợ cho hội thảo.

36. Thank you!

38. Osteoporosis: Primary and Secondary
Bone loss that occurs with:
age
and sex steroid deficiency
Bone loss caused, at least in part by:
other diseases
and/or medications

39. Peak Bone Mass and SD
(VN 2006, unpublished data)