Interpretation of Bone mineral density

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 199394646-650. 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 285785-95 2001)
5
Osteoporosis
6
Osteoporosis
Normal bone
7
Gain and loss of Bone throughout the lifespan
Pubertal Growth Spurt
Menopause
BMD
Resorption
Formation
Age (Years)
8
BONE STRENGTH
BONE MINERAL DENSITY
BONE QUALITY
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
Peak Bone Mass and SD
Relationship between BMD and Age
(VN 2006, unpublished data)
15
T-scores
Patients 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
- 1.9
- 2.5
16
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
17
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.
199491137)
18
Z-scores
Patients 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 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)
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   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
26
Cut-off thresholds for diagnosis of Osteoporosis
(Men)
Reference     Men    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
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

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 lt45 y.
• Maternal family history of hip fracture
• Long-term secondary amenorrhoea gt1y.
• Low body mass index (lt19 Kg/m2)
• Primary hypogonadism
• Other disorder associated with osteoporosis

• Anorexia nervosa
• Malabsorption syndromes
• Primary Hyperparathyroidism
• Post-transplantation
• Chronic renal failure
• Hyperthyroidism
• Prolonged immobilisation
• Cushings syndrome

(SourceKanis JA, Lancet, 20023591929-1936)
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 OsteoporosisBone 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
31
Nomogram for predicting of osteoporosis in Women
29
69
66
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 patients 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 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.

34
Perspective

• T-scores arbitrary
• ? Move away from T-scores, use absolute value and
  absolute risk.

35
L?i C?m t?

• Chúng tôi xin chân thành cám on Công ty Du?c ph?m
  Bridge Healthcare, Australia là nhà tài tr? cho
  h?i th?o.

36
Thank you!
37
(No Transcript)
38
Osteoporosis Primary and Secondary
Primary
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)