Transcript Slide 1

Interpretation of
Bone mineral density
Tuan Van Nguyen and Nguyen Dinh Nguyen
Garvan Institute of Medical Research
Sydney, Australia
Vietnam Osteoporosis Workshop, HCMC 2006
Overview
• Definitions
• Bone strength and quality
• DXA and BMD
• T-scores and interpretations
• Clinical applications
Vietnam Osteoporosis Workshop, HCMC 2006
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;94:646-650. WHO Study Group 1994.
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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)
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Osteoporosis
Normal
Osteopenia
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Osteoporosis
Normal bone
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Osteoporosis
Gain and loss of Bone throughout the
lifespan
Pubertal
Growth Spurt
Menopause
BMD
Resorption
Formation
5
15
25
35
45
55
Age (Years)
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65
75
85
BONE STRENGTH
BONE MINERAL
DENSITY
BONE QUALITY
Gram of
mineral
per area
Bone
architechture
Bone
turnover
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Bone
size &
geometry
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)
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“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.
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Femoral neck BMD
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Lumbar spine BMD
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Hip BMD: Results
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Relationship
between
BMD
and
Age
Peak Bone
Mass
and
SD
mean (SD) = 0.91 (0.11)
0.4
0.5
-2.5SD -2SD
-1SD
0.6
0.8
0.7
+1SD
0.9
1.0
+2SD
1.1
1.2
1.3
1.4
Femoral neck BMD (g/cm2)
Vietnam Osteoporosis Workshop, HCMC 2006
(VN 2006, unpublished data)
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
= - 1.9
0.11 g/cm2
0.70 g/cm2 - 1.00 g/cm2
T-score =
0.12 g/cm2
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= - 2.5
Diagnostic Classification
Classification
T-scores
Normal
≥-1
Osteopenia
Between -1 and -2.5
Osteoporosis
≤ -2.5 or less
Severe Osteoporosis ≤ -2.5 and fragility fracture
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WHO Study Group, 1994
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)
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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
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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
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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)
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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
F
0.690
-2.5
Osteoporosis
3
F
0.710
-2.4
Osteopenia
4
F
0.705
-2.5
Osteoporosis
* Calculated based on young adult mean: 1.00 +/- 0.12 (g/cm2)
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WHO definition
• Derived from studies of White
postmenopausal (PM) women and apply
to them
• Currently, no standard for:
– non-white PM women
– men
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Prevalence of Osteoporosis
Osteoporosis Osteopenia
Normal
Osteoporosis
60.1%
51.2%
0.5
0.6
42.3%
23.2%
16.7%
0.4
0.7
Osteopenia Normal
0.8
0.9
1.0
1.1
0.4
Femoral neck BMD (g/cm2)
Using Vietnamese reference
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0.5
0.6
6.6%
0.7
0.8
0.9
1.0
1.1
Femoral neck BMD (g/cm2)
Using Caucasian reference
(VN 2006, unpublished data)
BMD Values From Different
Manufacturers Are Not Comparable
• Different dual energy methods
• Different calibration
• Different detectors
• Different edge detection software
• Different regions of interest
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Cut-off thresholds for diagnosis of
Osteoporosis (Women)
Reference
Device
Women
N
Mean
SD
Osteopenia
Osteoporosis
femoral neck
0.86
0.12
0.57-0.73
≤ 0.56
trochanter
0.71
0.099
0.47-0.60
≤ 0.46
intertrochanter
1.09
0.142
0.75-0.94
≤ 0.74
total femur
0.94
0.122
0.65-0.81
≤ 0.64
Femoral neck
1.00
0.12
0.71-0.87
≤ 0.70
Lumbar spine
1.20
0.12
0.89-1.01
≤ 0.90
(Looker, 1997)
Hologic
409
Hip
(Nguyen, 1998)
(Tenenhouse, 2000)
Lunar
37
Hologic
Femoral neck
95
0.857
0.125
0.55-0.72
≤ 0.54
Lumbar spine
432
1.042
0.121
0.75-0.91
≤ 0.74
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Cut-off thresholds for diagnosis of
Osteoporosis (Men)
Reference
Men
N
Mean
SD
Osteopenia
Osteoporosis
femoral neck
0.93
0.137
0.60-0.78
≤ 0.59
trochanter
0.78
0.118
0.50-0.65
≤ 0.49
intertrochanter
1.21
0.172
0.79-1.02
≤ 0.78
total femur
1.04
0.144
0.69-0.89
≤ 0.68
Femoral neck
1.04
0.12
0.75-0.91
≤ 0.74
Lumbar spine
1.2
0.12
0.89-1.01
≤ 0.90
(Looker, 1997)
382
Hip
(Nguyen, 1998)
37
(Tenenhouse, 2000)
Femoral neck
101
0.91
0.125
0.61-0.78
≤ 0.60
Lumbar spine
366
1.058
0.127
0.75-0.92
≤ 0.74
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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.
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Indications For Bone Density Testing
1. All women age 65+ and men age 70+
2. Radiographic evidence of osteopenia or vertebral
deformity or both
3. Adult with previous fragility fracture
4. Loss of height, thoracic kyphosis
(after radiographic confirmation of vertebral deformities)
5. 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;359:1929-1936)
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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
Vietnam Osteoporosis Workshop, HCMC 2006
Screening for Osteoporosis:
Bone Density Testing Guidelines
NOF1
AACE2
USPSTF3
BMD testing for:
BMD testing for:
Screening for:
 All women ≥65 years
 All women ≥65 years
 All women ≥65 years
 Younger
postmenopausal
women with one or
more risk factors
 Pre- and
postmenopausal women
who have risk factors for
fracture
 For women at
increased risk for
fractures, begin
screening at age 60
 Postmenopausal
women who present
with fractures
 All women ≥40 years
who have sustained a
fracture
 Women beginning or
receiving long-term
glucocorticoid therapy
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Nomogram for predicting of
osteoporosis in Women
66 69
29
0
10
20
30
40
50
60
70
80
90
100
Points
Age (y)
35 A woman
45
55
Weight (kg)
QUS (T-scores)
75 old,
85
of6565 yrs
Weight = 45kg
QUS T-score = -2.5
95 90 85 80 75 70 65 60 55 50
What is the probability for her
developing of osteoporosis?
4
3
2
1
0
-1
45 40 35 30
-2
-3
-4
-5
164
Total Points
0
40
80
120
160
200
240
280
Risk of Osteoporosis
0.01
0.1 0.3 0.6 0.8 0.95 0.99
The risk for this woman developing of osteoporosis is ~ 60%
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Source: Pongchaiyakul C and
Nguyen TV 2006, unpublished data
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
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Peripheral BMD Testing
Accurate & Precise
• What it can do
– Predict fracture risk
– Tool for osteoporosis education
• What it cannot do
– Diagnose osteoporosis
– Monitor therapy
1. A “normal” peripheral test does not necessarily mean
that the patient does not have osteoporosis.
2. WHO criteria do not apply to peripheral BMD testing.
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Perspective
• T-scores: arbitrary
•  Move away from T-scores, use absolute
value and absolute risk.
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Lời Cảm tạ
• Chúng tôi xin chân thành cám
ơn Công ty Dược phẩm
Bridge Healthcare, Australia là
nhà tài trợ cho hội thảo.
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Thank you!
Vietnam Osteoporosis Workshop, HCMC 2006
Vietnam Osteoporosis Workshop, HCMC 2006
Osteoporosis: Primary and Secondary
Primary
• Bone loss that
occurs with:
Secondary
• Bone loss caused,
at least in part by:
– age
– other diseases
– and sex steroid
deficiency
– and/or medications
Vietnam Osteoporosis Workshop, HCMC 2006
Peak Bone Mass and SD
mean (SD) = 0.91 (0.11)
0.4
0.5
-2.5SD -2SD
-1SD
0.6
0.8
0.7
+1SD
0.9
1.0
+2SD
1.1
1.2
1.3
1.4
Femoral neck BMD (g/cm2)
Vietnam Osteoporosis Workshop, HCMC 2006
(VN 2006, unpublished data)