Dual-energy X-ray absorptiometry
(DXA) and other techniques used
to measure bone
Ann Laskey
U3AC 2017
Bone measurements
These are used to:
1. Diagnose osteoporosis
2. Predict risk
3. Monitor the effects of
treatment
Techniques need to be:
1. Accurate
2. Precise
Accuracy and Precision
Accuracy
• How closely a measurement agrees with the
“true” value
• Bone measurements compared to bone
phantoms or ashed bones
• “True” value difficult to obtain
Precision
• Measure of repeatability (reproducibility)
• Important for longitudinal studies
• Depends on equipment, subject, skeletal site and
person performing the scans
• Expressed as:
standard deviation (SD)
coefficient of variation (%CV=SDx100%/mean)

Accurate and precise

Precise but not accurate

Accurate but not precise

????
NOT accurate or precise
Imaging techniques used to measure bone
Non-ionizing techniques (not involving radiation)
 Quantitative ultrasound (QUS)
 Magnetic resonance imaging (MRI)
Ionizing techniques (involving radiation)
 X-rays
 Computed tomography (CT)
 Peripheral quantitative computed tomography (pQCT)
 Micro-CT
 Single-photon absorptiometry (SPA)
 Dual-photon absorptiometry (DPA)
 Dual-energy X-ray absorptiometry (DXA)
NB: These measure different parameters that may be
related to bone strength
Quantitative Ultrasound (QUS)
High frequency sound waves are beamed into
the body. The reflected sound (broadband
ultrasound attenuation) and/or rate of
transmission (velocity of ultrasound) are
measured at heel and/or wrist and can be used
to build up an electronic image
Advantages
 Inexpensive, portable
 May be predictive of wrist fracture in
population studies of postmenopausal women
Disadvantages
 Poor precision and accuracy
 Results from different QUS systems
unrelated
 Results unrelated to DXA and cannot be
used to diagnose/monitor osteoporosis
 What is ultrasound measuring?
Magnetic resonance
imaging (MRI)
• 1977: First MRI of human body
• Uses magnetism, radio-waves and a
computer to produce detailed images of
tissue
• Provides good contrast between
different soft tissues so widely used to
image brain, heart, spine and cancers
• Measures 3-dimensionsal bone
architecture in vivo and vitro and used to
detect skeletal problems
• Not used for detecting/monitoring
osteoporosis
• Research/clinical potential?
Ionising Radiation and X-rays
•
X-rays, like light, are a form of electromagnetic radiation
•
Everyone is exposed to natural sources of radiation (e.g. rocks, cosmic rays)
•
X-rays have higher energy than light and can pass through the body
•
When X-rays pass thro’ body, energy is dissipated and can cause DNA damage
•
Potentially harmful as may result in an increased risk of cancer and/or damage
the germ cells (eggs/sperm) leading to problems in next generation
Radiation doses and risk
Effective dose used to compare different radiation doses: unit = Sv
•
•
•
•
•
DXA scan = 1-10µSv
Chest x-ray = 20-50µSv
Computed tomography scans = 200-6000µSv
Lumbar spine x-ray = 800-1500µSv
Background radiation in Cambridge is 6µSv/day (2.2mSv per year)
Measurement of risk
•
•
•
Risk = Number of injuries or death/Number of people exposed to hazard
Micromort is unit of risk measuring one-in-a million probability of death
Risks greatest with higher radiation doses, but no totally “safe” dose
Activities carrying similar risk of death as a DXA scan
•
•
•
•
Smoking one cigarette
Travelling 30 miles by car
Travelling 1500 miles by plane
Being a woman aged 50 years for 1 hour
•
•
Risk of fatal cancer from radiation is 1 in 20,000,000/µSv (very low risk)
Natural risk of developing a fatal cancer is 1 in 4 (very high)
X-rays
• Used to detect broken bones
•Can detect gross changes in bone density
• Bone loss not visible until 40% of bone lost
• X-rays still used to identify fractures, assess
vertebral shape and alignment
X-ray of spine
Computed tomography (CT)
• Quantitative computed tomography
• Peripheral quantitative computed tomography
(pQCT)
• Micro-CT
Quantitative computed tomography (QCT)
• Imaging method that uses x-rays to create
pictures of cross-sections (slices) of the body
• X-ray source rotates around patient.
Narrow beam of X-rays pass through
sections of the body from different directions
• A computer generates multiple crosssectional images of the inside of the body.
Images “stacked” to form a 3-dimensional
image
• Can visualize nearly all parts of the body.
Widely used for detecting cancers, head
injuries, heart and lung disease, complex
fractures etc
• Rarely used to measure BMD but
measures true volumetric BMD and potential
for investigation of bone architecture
• High radiation dose (200-5000µSv)
CT image
Peripheral quantitative computer tomography (pQCT)
• Measures peripheral sites:
forearm (radius) and lower
leg (tibia)
• Low radiation dose (<1Sv
for set of measurements)
• Peripheral measurements
may not reflect changes at
clinically important sites of
osteoporotic fracture (spine
and hip)
pQCT Image through lower leg
Can visualize and
quantify:
• Bone (tibia)
• Muscle
• Fat
pQCT measurements
Trabecular bone
Thin cortical
shell
Separate measurements of trabecular and
cortical bone
Measurements include:
• True volumetric BMD (g/cm3)
• BMC (g)
• Cross-sectional area of bone (cm2)
Cortical bone
• Cortical thickness (mm)
• Periosteal and endosteal circumference
(mm)
• Strength strain index: Density-weighted
section modulus (reflects bending strength)
pQCT sites: Can select different positions of arms/legs
Male
100%
66%
Female
Tibia and fibula
• 33-66%: mainly
cortical bone
33%
14%
4%
0%
• 4% (ankle):
mainly trabecular
bone
NB: more fat in
females
The Gambia and bone shape
Keneba in The Gambia: a poor rural African village
• Low areal BMD (DXA) but osteoporotic fractures rare despite
low Ca intake
• Exercise/activity: tends to be frequent but smooth and sedate.
Heavy loads routinely carried on head and children on back
• Loading influences bone shape (Mechanostat theory)
• Studies show tibia more circular in Gambians than in
Cambridge
• New software developed to quantify shape differences
• More circular/symmetrical bones may make Gambians more
able to cope with unusual loading (e.g. falls)
Gambian
Cambridge
Micro-CT
• Assesses 3-dimensional micro-architecture of
trabecular bone
• In vitro (biopsies) and in vivo technology
• Spacial resolution 5-100m
• Potential to calculate:
 trabecular thickness
 trabecular separation
 indices of connectivity and orientation
 mineralization
• Starting to be used in clinical and volunteer
studies to understand what is really happening
inside a bone
Early Absorptiometry techniques
Single-energy Photon Absorptiometry (SPA)
• Introduced in 1963
• Used isotope to produce radiation with
single energy level
• Measured bone in arm and heel bone
Dual-energy Photon Absorptiometry (DPA)
• Used radioactive isotope to produce
radiation with 2 energies
• Bone measured at clinically important
sites (spine and hip)
• Poor precision, long measurement time,
isotope (gadolinium) decays and needs
regular/expensive replacement
SPA in use in The Gambia
Dual-Energy X-ray Absortiometry (DXA)
• Introduced 1989
• Now replaced SPA
and DPA
DXA: How it works
• X-rays of 2 different energies,
generated from X-ray tube under
scan bed, travel through subject’s
bone and soft tissue
• X-rays attenuated more by bone
than soft tissue
• Transmitted X-rays are measured
by detector above DXA scan bed
• The differential attenuation of high
and low energy X-rays is used to
quantify body composition
(bone+fat+lean)
Transm
issionof X-rays throughTissue
Bone
X-rays incident
M
uscle
Lung
X-rays transm
itted
What DXA measures
• Projected area of bone = BA (cm2)
• Bone mineral content = BMC (g)
• Areal bone mineral density (aBMD)
= BMC/BA (g/cm2)
NB True volumetric density = g/cm3
(This cannot be measured as depth of
bone unknown)
• Sites: spine, forearm, hip and whole
body
Lumbar spine
• High trabecular bone
content
• Therefore high rates of
bone turnover
(resorption/formation)
• Major site of osteoporotic
fractures
• Most precise site (CV<1%)
and can monitor small
changes with confidence
28-year-old white female
Forearm (radius and ulna)
• Measures trabecular-rich
(UD=ultra-distal) and
cortical site (33% shaft)
• Similar regions measured
by SPA and pQCT
• Infrequently measured
now and cannot be used to
diagnose osteoporosis
43-year-old white female
Femur (hip bone)
•Major site of osteoporotic fracture
• Measures different hip regions
with varying amounts of cortical
and trabecular bone:
 neck*
 trochanter (mainly trabecular)
 shaft (mainly cortical)
 total hip*
 Ward’s triangle
• Sites have different response
to physiological and pathological
situations
• Poor precision (2-3%)
• Most difficult region to scan and
analyse
51-year-old white female
Whole body
• Measures total body BMD,
BMC and BA
• Provides the TOTAL story
• Measures body composition
(fat and lean tissue). Useful for
obesity/anorexia studies
• Results influenced by depth
of subject (especially obese)
• Scan time longer than for
other sites
Scan of 28-year-old man
T and Z-scores
• These scores compare BMD results with appropriate
ethnic/sex-matched reference ranges
• These reference ranges are compiled by
manufacturers using measurements from many “normal”
subjects of different ages
• Different ranges for males and females and different
countries/ethnic groups
• Comparisons can be age-matched (Z) or matched to
young normals (peak-bone mass) (T)
Z-score = BMD of subject - mean BMD of age-matched
SD for age-matched normals
Used to compare subjects of same age
T-score = BMD of subject - mean BMD of young normals
SD for young normals
Used to diagnose osteoporosis
Spine data for UK females
Standard deviation (SD)
• Normal distribution of BMD (bell curve)
• By definition
68% of subjects will fall between +1 and -1SD
95% will fall between +2 and -2SD
5% will be outside this range, 2.5% above and 2.5% below
T and Z-scores very different for elderly subjects
Can be normal for age
(Z-score=0.5)
BUT have osteoporosis
(T-score= -2.5)
WHO definition of osteoporosis
•
NORMAL: T-scores above +1 to -1 SD
Blue region: fracture risk low
•
OSTEOPAENIA: T-score of -1 to -2.5 SD
Green region: 4x risk of fracture
compared to normal BMD
•
OSTEOPOROSIS: T-score of -2.5 SD or below
Yellow/red region: 8x risk of fracture compared to normal BMD
•
SEVERE OSTEOPOROSIS: T-score of -2.5 SD or below and 1 or
more fragility fracture
Red region: 20x risk of fracture compared to normal BMD
Can BMD at one site predict BMD at other?
• Hip BMD is best predictor of hip fractures (RR 2.4, vertebral RR= 1.5)
• Spine BMD is best predictor of vertebral fractures (RR 2.2, hip RR= 1.9)
• No site predicts all fractures
• T-scores of subject can vary within the body. May have low BMD at one
site but normal at other
Is a high BMD
always good news?
Spine DXA results for 64-year–old man
•This appears to indicate a
superb spine
•Spine (L2-L4) T-score = +2.3
•Look more carefully!!
•T-scores for individual
vertebrae very different (0.6
to 3.7)
•What does this mean?
This is not a healthy spine
• Spine shows degenerative changes
• This is very common in the elderly
• Look out for:
a) Osteophytes (dense areas of
calcified bone often associated
with arthritis)
b) Crush fractures
c) Scoliosis (curvature of the spine)
These all result in increased BMD
• High BMD does not always indicate
healthy bone
• It can indicate degeneration
Important to look at image as well as T-score
64-year-old white man
Artefacts effecting DXA results
Artefacts on subject
(These should be removed before scanning)
• Jewellery (watches, body piercings in unexpected places)
• Metal fastenings (e.g. zips, buttons)
• Coins and other items in pockets
Artefacts within subjects
(These cannot be removed)
• Metal implants (hip replacements)
• Breast implants
• Aortic calcifications
• Osteophytes
• Crush fractures
• Medical tests (barium meals)
• Pacemaker
• Plaster casts
• Geophagy
• Etc, etc
34
Geophagy
Geophagy: deliberate ingestion of
soil
•
• Occurs in nutritionally vulnerable
populations of Africa and other
countries
• Most common in children and
pregnant women
• 5% pre-adolescent Gambian
children had 11-50g of soil in gut
but 2 had more than 500g
• The soil will allay hunger and
minimize irritation from intestinal
parasites
• Moderate ingestion of soil may
reflect ancient medical practice for
treatment of diarrhea, absorption of
toxins, acid indigestion (pregnant
women) and act as source of
minerals (e.g. iron)
Dense region conforming to shape of small bowel
in 11-year-old Gambian boy
NB: BMD zero as artifacts (soil) denser than bone
Copyright © 2011 Journal of Pediatric Gastroenterology and Nutrition. Published by Lippincott Williams & Wilkins.
35
DXA: Accuracy and precision
Precision: measure of repeatability
• DXA is precise: CV=1-3% for ‘normal’ subjects
• Precision best for subjects with healthy bones and normal size
• Precision worst for osteoporotic and obese subjects
• Good precision allows DXA to be used for monitoring changes in bone but problem when
bones start to degenerate
Accuracy: how closely a measured result is to true value
• DXA is NOT accurate
• Different DXA manufacturers use different calibrations
• 10-30% difference in BMD between two most widely used DXA systems (Hologic and
Lunar)
• Manufacturers collect data from many “normal healthy” subjects of different ages. This
reference data (and SD) must be accurate for diagnosis of osteoporosis (T and Z-scores)
• It is “normal” for elderly subjects to have osteoporosis but not “healthy”
• Reference data from different manufacturers now give similar T/Z-scores for patients
Areal BMD and size-related artefacts
DXA cannot measure true volumetric density
X-ray beam
X-ray beam
BMC (g)
Projected area(cm2)
Areal BMD (g/cm2)
16
4
4
54
9
6
Volume (cm3)
Volumetric BMD (cm3)
8
2
27
2
• Two bones with same
volumetric density (BMC/
Volume g/cm3)
• Small bone has lower
areal BMD (BMC/BA)
New Developments: the Lunar I (Intelligent) DXA
Manufacturers state:
• Greater precision, clearer images so can identify vertebral
deformities
• Larger scan table so better for tall and obese subjects
• Can quantify visceral body fat distribution
• Suitable for paediatric and small animal scanning
Bone strength
• Bone strength determined by many factors (not just BMD):
bone mass, structural geometry, shape, micro-architecture etc
• Structural geometry is the architectural arrangement of bone
around the bone axis
• The further the mineral mass is located from centre of bone,
the stronger the bone
• Hip structural analysis uses DXA data to determine bone
geometry
• An increase in bone width with same bone mass (BMC),
leads to decrease in BMD but increase in bone strength
• Bone diameter of femoral neck expands with age. This
reduces BMD but helps to maintain bone strength as we age
• If you have limited building materials get
a good architect!
BMD, age and fracture risk
Age is an excellent predictor of fracture risk
How can we improve prediction of fracture risk?
Subjects in purple will
have a fragility fracture
within the next ten years
BMD and age are
important. What else?
Ten-year fracture prediction (FRAX)
•
Low BMD is useful risk factor for fracture. However, some people with low BMD
will never fracture and others with higher BMD will fracture. BMD comparable
to blood pressure prediction of stroke
•
Predictive value of BMD improved by including clinical risk factors
•
A fracture risk assessment tool (FRAX) is a diagnostic tool that provides 10year probability of major osteoporotic fracture and integrates clinical risk factors
and BMD at femoral neck for different populations across the world
•
Risk factors include: age, sex, height/weight, prior fragility fracture, parent hipfracture history, smoking, excess alcohol use, use of glucocorticords,
rheumatoid arthritis, etc
•
The combination of clinical risk factors with BMD more accurately predicts
individuals who will fracture and hence improves the cost-effectiveness of
treatment
Summary of bone measurements
• Fracture risk is determined by many parameters, not
just aBMD as measured by DXA
• These include true vBMD, bone size, geometry, shape,
trabecular micro-architecture, muscle and fat mass,
collagen structure etc
• There is not a “one size fits all”
We can do better than this but still scope for improvements