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Vietnam Osteoporosis Workshop, HCMC 2006
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
A systematic skeleton disease characterized by:
- low bone mass
- microarchitectural deterioration of bone tissue
- consequent increase in bone fragility and susceptibility to fracture
Definition of OsteoporosisDefinition of Osteoporosis(WHO)(WHO)
Consensus Development Conference: Diagnosis, Prophylaxis, and Treatment of Osteoporosis, Am J Med 1993;94:646-650. WHO Study Group 1994.
Vietnam Osteoporosis Workshop, HCMC 2006
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)
Definition of OsteoporosisDefinition of Osteoporosis(NIH)(NIH)
Vietnam Osteoporosis Workshop, HCMC 2006
OsteoporosisOsteoporosis
Normal Osteopenia Osteoporosis
Vietnam Osteoporosis Workshop, HCMC 2006
OsteoporosisNormal bone
Vietnam Osteoporosis Workshop, HCMC 2006
5 15 25 35 45 55 65 75 85
Gain and loss of Bone throughout the lifespan
Age (Years)
Pubertal Growth Spurt Menopause
BMD
Resorption
Formation
Vietnam Osteoporosis Workshop, HCMC 2006
Gram of mineral per area
Bone architechture
Bone size &
geometry
Bone turnover
BONE QUALITYBONE MINERALDENSITY
BONE STRENGTH
Vietnam Osteoporosis Workshop, HCMC 2006
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)
Vietnam Osteoporosis Workshop, HCMC 2006
“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.
Vietnam Osteoporosis Workshop, HCMC 2006
Femoral neck BMD
Vietnam Osteoporosis Workshop, HCMC 2006
Lumbar spine BMD
Vietnam Osteoporosis Workshop, HCMC 2006
Hip BMD: Results
Vietnam Osteoporosis Workshop, HCMC 2006 (VN 2006, unpublished data)
Relationship between BMD and Age
Femoral neck BMD (g/cm2)
0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4
+1SD +2SD-1SD-2SD-2.5SD
mean (SD) = 0.91 (0.11)
Peak Bone Mass and SD
Vietnam Osteoporosis Workshop, HCMC 2006
T-score = 0.70 g/cm2 – 0.91 g/cm2
0.11 g/cm2
T-scores
Example: peak bone mass (AU) = 1.00 ± 0.12peak bone mass (VN) = 0.91 ± 0.11
= - 1.9
Patient’s BMD – Young-adult mean BMD
1 SD of Young-adult mean BMD
T-score = 0.70 g/cm2 - 1.00 g/cm2
0.12 g/cm2= - 2.5
Vietnam Osteoporosis Workshop, HCMC 2006
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
WHO Study Group, 1994
Vietnam Osteoporosis Workshop, HCMC 2006
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)
Vietnam Osteoporosis Workshop, HCMC 2006
Patient’s BMD – Age-Matched Mean BMD
1 SD of Age-Matched Mean BMD in g/cm2
Z-scores
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
Vietnam Osteoporosis Workshop, HCMC 2006
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
Vietnam Osteoporosis Workshop, HCMC 2006
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)
Vietnam Osteoporosis Workshop, HCMC 2006
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)
Vietnam Osteoporosis Workshop, HCMC 2006
WHO definition
• Derived from studies of White postmenopausal (PM) women and apply to them
• Currently, no standard for:
– non-white PM women
– men
Vietnam Osteoporosis Workshop, HCMC 2006
Femoral neck BMD (g/cm2)
0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1
Osteoporosis Osteopenia Normal
42.3%
51.2%
6.6%
Femoral neck BMD (g/cm2)
0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1
Osteoporosis Osteopenia Normal
16.7%
60.1%
23.2%
Prevalence of Osteoporosis
Using Vietnamese reference Using Caucasian reference
(VN 2006, unpublished data)
Vietnam Osteoporosis Workshop, HCMC 2006
BMD Values From Different Manufacturers Are Not Comparable
• Different dual energy methods
• Different calibration
• Different detectors
• Different edge detection software
• Different regions of interest
Vietnam Osteoporosis Workshop, HCMC 2006
Reference Device Women
N Mean SD Osteopenia Osteoporosis
(Looker, 1997) Hologic 409
Hip
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
(Nguyen, 1998) Lunar 37
Femoral neck 1.00 0.12 0.71-0.87 ≤ 0.70
Lumbar spine 1.20 0.12 0.89-1.01 ≤ 0.90
(Tenenhouse, 2000) 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
Cut-off thresholds for diagnosis of Osteoporosis (Women)
Vietnam Osteoporosis Workshop, HCMC 2006
Reference Men
N Mean SD Osteopenia Osteoporosis
(Looker, 1997) 382
Hip
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
(Nguyen, 1998) 37
Femoral neck 1.04 0.12 0.75-0.91 ≤ 0.74
Lumbar spine 1.2 0.12 0.89-1.01 ≤ 0.90
(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
Cut-off thresholds for diagnosis of Osteoporosis (Men)
Vietnam Osteoporosis Workshop, HCMC 2006
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.
Vietnam Osteoporosis Workshop, HCMC 2006
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: • 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
• Anorexia nervosa• Malabsorption syndromes• Primary Hyperparathyroidism• Post-transplantation• Chronic renal failure• Hyperthyroidism• Prolonged immobilisation• Cushing’s syndrome
(Source:Kanis JA, Lancet, 2002;359:1929-1936)
Indications For Bone Density Testing
Vietnam Osteoporosis Workshop, HCMC 2006
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:
All women ≥65 years
Younger postmenopausal women with one or more risk factors
Postmenopausal women who present with fractures
BMD testing for:
All women ≥65 years
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:
All women ≥65 years
For women at increased risk for fractures, begin screening at age 60
Vietnam Osteoporosis Workshop, HCMC 2006
Points 0 10 20 30 40 50 60 70 80 90 100
Age (y)35 45 55 65 75 85
Weight (kg)95 90 85 80 75 70 65 60 55 50 45 40 35 30
QUS (T-scores)4 3 2 1 0 -1 -2 -3 -4 -5
Total Points 0 40 80 120 160 200 240 280
Risk of Osteoporosis0.01 0.1 0.3 0.6 0.8 0.95 0.99
29
The risk for this woman developing of osteoporosis is ~ 60%
A woman of 65 yrs old,Weight = 45kg
QUS T-score = -2.5 What is the probability for her developing of osteoporosis?
6966
164
Nomogram for predicting of osteoporosis in Women
Source: Pongchaiyakul C and Nguyen TV 2006, unpublished data
Vietnam Osteoporosis Workshop, HCMC 2006
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
Vietnam Osteoporosis Workshop, HCMC 2006
Peripheral BMD TestingAccurate & 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.
Vietnam Osteoporosis Workshop, HCMC 2006
Perspective
• T-scores: arbitrary
Move away from T-scores, use absolute value and absolute risk.
Vietnam Osteoporosis Workshop, HCMC 2006
Lời Cảm tạ
• Chúng tôi xin chân thành cám ơn Công ty Dược phẩm Bridge Healthcare, Australia là nhà tài trợ cho hội thảo.
Vietnam Osteoporosis Workshop, HCMC 2006
Thank you!
Vietnam Osteoporosis Workshop, HCMC 2006
Vietnam Osteoporosis Workshop, HCMC 2006
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
Primary Secondary
Vietnam Osteoporosis Workshop, HCMC 2006
Femoral neck BMD (g/cm2)
0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4
+1SD +2SD-1SD-2SD-2.5SD
mean (SD) = 0.91 (0.11)
(VN 2006, unpublished data)
Peak Bone Mass and SD