Vietnam Osteoporosis Workshop, HCMC 2006 Interpretation of Bone mineral density Tuan Van Nguyen and...

Vietnam Osteoporosis Workshop, HCMC 2006

Interpretation of Bone mineral density

Tuan Van Nguyen and Nguyen Dinh Nguyen

Garvan Institute of Medical Research

Sydney, Australia


Overview

• Definitions

• Bone strength and quality

• DXA and BMD

• T-scores and interpretations

• Clinical applications


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.


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)


OsteoporosisOsteoporosis

Normal Osteopenia Osteoporosis


OsteoporosisNormal bone


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


Gram of mineral per area

Bone architechture

Bone size &

geometry

Bone turnover

BONE QUALITYBONE MINERALDENSITY

BONE STRENGTH


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)


“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.


Femoral neck BMD


Lumbar spine BMD


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Vietnam Osteoporosis Workshop, HCMC 2006 (VN 2006, unpublished data)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


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


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


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)


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


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


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)


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


3 F 0.710 -2.4 Osteopenia


* Calculated based on young adult mean: 1.00 +/- 0.12 (g/cm2)


WHO definition

• Derived from studies of White postmenopausal (PM) women and apply to them

• Currently, no standard for:

– non-white PM women

– men



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%


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)


BMD Values From Different Manufacturers Are Not Comparable

• Different dual energy methods

• Different calibration

• Different detectors

• Different edge detection software

• Different regions of interest


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)


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)


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.


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


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


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:


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


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


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


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.


Perspective

• T-scores: arbitrary

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


Lời Cảm tạ

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


Thank you!


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



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

Vietnam Osteoporosis Workshop, HCMC 2006 Interpretation of Bone mineral density Tuan Van Nguyen and...

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