Content uploaded by Glen Mervyn Blake
Author content
All content in this area was uploaded by Glen Mervyn Blake on Sep 28, 2017
Content may be subject to copyright.
CONTINUING EDUCATION
Different Approaches to Bone Densitometry*
Ignac Fogelman and Glen M. Blake
Department of Nuclear Medicine, Guy’s Hospital, London, United Kingdom
From 1990 to 2000, several effective new treatments were
introduced for the prevention of osteoporotic fractures; these
treatments were proven effective in large, international, clinical
trials. At the same time, there was rapid technologic innovation,
with the introduction of new radiologic methods for the noninva-
siveassessmentofpatients’bonedensitystatus.Thesedevelop-
ments led to the publication of guidelines for the clinical use of
bone densitometry that include criteria for the referral of patients
for investigation as well as recommendations for intervention
thresholds for the initiation of preventive treatment of osteoporo-
sis. Dual-energy x-ray absorptiometry scanning of the spine and
hip remains the technique of choice for bone densitometry
studies, although there is now a wider appreciation of the need
for smaller, cheaper devices for scanning the peripheral skeleton
if the millions of women most at risk of a fragility fracture are to be
identified and treated. This article reviews these developments,
concentrating in particular on the advantages and disadvantages
of the different types of equipment available for performing bone
densitometry investigations, the guidelines for the referral of
patients, and the principles for the interpretation of the scan
findings.
Key Words: bone densitometry; osteoporosis; dual-energy x-ray
absorptiometry; quantitative CT; quantitative ultrasound; radio-
graphic absorptiometry
J Nucl Med 2000; 41:2015–2025
Over the past decade, osteoporotic fractures have come
to be recognized as one of the most serious problems in
public health. For a 50-y-old white woman, the lifetime risk
of suffering a fragility fracture of the spine, hip, or forearm is
estimated to be 30%–40%, which compares with the percent-
ages for breast cancer and cardiovascular disease of 9%–
12% and 30%–40%, respectively (1). For men, the risk of an
osteoporotic fracture is about one third of that in women. In
the United States in 1995, the total health care costs
attributable to osteoporotic fractures exceeded $13 billion
(2), a figure that is expected to rise to between $30 and $40
billion by the year 2020 (3). Of these costs, about two thirds
are attributable to hip fractures. In addition to incurring
greater costs, hip fractures also cause greater morbidity and
mortality than other types of fractures. One quarter of
hip-fracture patients die within a year after their fracture (4),
and survivors frequently suffer sustained disability and loss
of independence (5). However, it should not be forgotten
that fractures at other sites may also cause substantial pain
and disability.
The increased recognition of the scale of morbidity and
mortality attributable to osteoporosis has led to a major
effort by the pharmaceutical industry to develop new
therapeutic strategies for the prevention of fractures (6–8).
Estrogen deficiency after menopause is one of the most
documented causes of osteoporosis and can be prevented by
hormone replacement therapy (HRT). However, although
HRT has additional benefits that include the prevention of
cardiovascular disease (9), it may also cause an increase, of
approximately 35%, in the risk of breast cancer in long-term
users (10). In addition to such fears, compliance with HRT
may also be a problem because of side effects such as
bleeding, weight gain, and breast tenderness. Consequently,
much effort has been devoted to developing alternative
treatments for osteoporosis. Among these treatments, bisphos-
phonates are becoming increasingly recognized as the
treatment of choice at the present time (11–13). Another new
class of therapeutic agents recently introduced is the selec-
tive estrogen receptor modulators (SERMs), which are
compounds that have a unique ability to mimic the beneficial
effects of HRT on osteoporosis and cardiovascular disease
while antagonizing the effects of estrogen on the breast and
uterus (14,15).
Associated with the growing awareness of the signifi-
cance of osteoporosis for public health and the development
of new treatments for its prevention, in the past decade there
has been a rapid evolution of new radiologic techniques for
the noninvasive assessment of skeletal integrity (Table 1)
(16,17). The technique most associated with the recent
growth in bone densitometry is dual-energy x-ray absorpti-
ometry (DXA) (18). DXA was developed in the mid-1980s
from the earlier technique of dual photon absorptiometry
(DPA) by replacing the 153Gd radionuclide source with an
x-ray tube. Because of the advantages of high precision,
short scan times, low radiation dose, and stable calibration,
DXA has proven to be appropriate in meeting the need for
scanning equipment to assist in the diagnosis of osteoporosis
and aid decisions about treatment.
Received Jun. 15, 2000; revision accepted Aug. 8, 2000.
Forcorrespondenceorreprintscontact: Ignac Fogelman,MD, Department of
Nuclear Medicine, Guy’s Hospital, St. Thomas St., London SE1 9RT, United
Kingdom.
*NOTE: FOR CE CREDIT, YOU CAN ACCESS THISACTIVITY THROUGH
THE SNM WEB SITE (http://www.snm.org) UNTIL JUNE 2001.
DIFFERENT APPROACHES TO BONE DENSITOMETRY •Fogelman and Blake 2015
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
THE DEFINITION OF OSTEOPOROSIS
The term ‘‘osteoporosis’’ is derived from the classical
Greek word ‘‘osteon,’’meaning bone, and ‘‘poros,’’ meaning
a small passage or pore. Thus, the term is descriptive of the
changes in bone tissue found in this generalized skeletal
disease. The modern definition of osteoporosis is ‘‘a sys-
temic skeletal disease characterized by low bone mass and
microarchitectural deterioration of bone tissue, with a conse-
quent increase in bone fragility and susceptibility to frac-
ture’’ (19). It should be noted that this definition does not
necessitate that an individual sustain a fracture before a
diagnosis of osteoporosis is made but introduces the concept
of low bone mass and its relationship to increased fracture
risk. Although it could be argued that it is wrong to define a
disease on the basis of what is essentially a risk factor (i.e.,
low bone density), there is nevertheless some logic to this
because fractures only occur late in the disease process when
skeletal integrity is already severely compromised. There-
fore, it is desirable to identify individuals at high risk for
osteoporosis, with the goal for beginning treatment early
enough to prevent fractures from occurring.
DEFINITION OF OSTEOPOROSIS USING BONE
MINERAL DENSITY
In recent years, the widespread availability of bone
densitometry systems has led to working definitions of
osteoporosis that are increasingly based on measurements of
bone mineral density (BMD). In particular, in 1994 a World
Health Organization (WHO) study group recommended a
definition of osteoporosis that was based on a BMD
measurement of the spine, hip, or forearm expressed in SD
units called T-scores (20,21). The WHO report also proposed
creating an intermediate category characterized by low bone
mass between the normal and osteoporotic states and
referred to as ‘‘osteopenia.’’
The T-score is calculated by taking the difference between
a patient’s measured BMD and the mean BMD of healthy
young adults, matched for gender and ethnic group, and
expressing the difference relative to the young adult popula-
tion SD:
T-score 5Measured BMD 2
young adult mean BMD/young adult SD.
Therefore, a T-score result indicates the difference between
the patient’s BMD and the ideal peak bone mass achieved by
a young adult.
The WHO definitions of osteoporosis and osteopenia are
based on T-score values such that an individual with a
T-score #22.5 at the spine, hip, or forearm is classified as
having osteoporosis; a T-score between 22.5 and 21is
classified as osteopenia; and a T-score $21 is regarded as
healthy.A fourth category of ‘‘established osteoporosis’’was
also proposed to denote osteoporosis as defined above but in
the presence of 1 or more documented fragility fractures,
usually of the wrist, spine, or hip.
The WHO study group definitions of osteoporosis, osteo-
penia, and healthy are intended to identify patients with
high, intermediate, and low risk of fracture, respectively
(Fig. 1). It is important to recognize that the WHO criteria
refer only to BMD measurements of the spine, hip, or
forearm. As is discussed later, these definitions cannot
automatically be applied to other BMD measurement sites or
to other technologies such as quantitative CT (QCT) or
quantitative ultrasound (QUS) (Table 1).
The rationale for the WHO definition of osteoporosis is
TABLE 1
Characteristics of Different Bone Densitometry Techniques
Technique Regions
of interest Units
reported Precision
(%CV)
Effective
dose
(µSv)
DXA PAspine BMD (g/cm2) 1% 1–10
Proximal femur 1%–2% 1–10
Total body 1% 3
QCT Spine BMD (g/cm3) 3% 50–500
pDXA Forearm BMD (g/cm2) 1%–2% 0.1
Calcaneus 1%–2% 0.1
pQCT Forearm BMD (g/cm3) 1%–2% 1–3
RA Phalanx BMD (g/cm2) 1%–2% 10
QUS Calcaneus BUA(dB/MHz) 2%–5% None
Calcaneus SOS (m/s) 0.1%–1% None
Tibia SOS (m/s) 1%–2% None
Multisite SOS (m/s) 1%–2% None
PA 5posteroanterior; BUA 5broadband ultrasonic attenuation;
SOS 5speed of sound.
FIGURE 1. Gradient-of-risk relationship between bone density
and fracture risk. Bone density is plotted in T-score units relative
to mean and SD of healthy young adult population. WHO
definitions of osteoporosis, osteopenia, and ‘‘normal’’ are in-
tended to identify patients at high, intermediate, and low risks of
fracture. In this figure, a decrease in T-score by 1 unit increases
fracture risk by a factor of 2.5. This approximates to relationship
between hip BMD and hip-fracture risk (see Figure 2).
2016 THE JOURNAL OF NUCLEAR MEDICINE •Vol. 41 •No. 12 •December 2000
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
that it captures approximately 30% of all white postmeno-
pausal women (1). As explained above, this figure approxi-
mates to the lifetime risk of fracture for a 50-y-old woman.
In comparison, it can be argued that the WHO definition of
osteopenia captures too high a percentage of women to be
clinically useful, and nowadays this term is being used less
often, particularly in the context of therapeutic decision
making. In contrast, the WHO definition of osteoporosis has
had a major influence on clinical practice, to the extent that if
the question is, ‘‘Does this patient have osteoporosis, yes or
no?’’, this is now regarded as aT-score issue.
In addition to the T-score, another useful way of express-
ing BMD measurements is in Z-score units (22). Like the
T-score, the Z-score is expressed in units of the population
SD. However, instead of comparing the patient’s BMD with
the young adult mean, it is compared with the mean BMD
expected for the patient’s peers: For example, for a healthy
subject matched for age, gender, and ethnic origin:
Z-score 5measured BMD 2
age-matched mean BMD/age-matched SD.
Although they are not as widely used as T-scores, Z-scores
nevertheless remain a useful concept because they express
the patient’s risk of sustaining an osteoporotic fracture
relative to his or her peers. Epidemiologic studies of the
relationship between BMD and fracture incidence are inter-
preted using a gradient-of-risk model in which fracture risk
increases exponentially with decreasing BMD (Fig. 1) (23).
The findings are expressed in terms of the relative risk (RR),
which is the increased risk factor for each 1-SD decrease in
BMD. Results for RR values by fracture site and BMD
measurement site derived in a recent meta-analysis of
prospective studies (24) are plotted in Figure 2. Typically,
every reduction of 1 SD in BMD equates to a 1.5–2.5
increase in the likelihood of fracture. It follows that patients
with a Z-score ,21 are at a substantially increased risk of
fracture compared with their peers.
TECHNIQUES AVAILABLE FOR BONE DENSITOMETRY
Table 1 lists the methods currently available for the
noninvasive assessment of the skeleton for the diagnosis of
osteoporosis or the evaluation of an increased risk of
fracture. These include DXA, QCT, peripheral DXA (pDXA),
peripheral QCT (pQCT), radiographic absorptiometry (RA),
and QUS. These techniques differ substantially in fundamen-
tal methodology, in clinical discrimination and use, and in
general availability and cost. Each is reviewed briefly below.
The reader can find further information about these tech-
niques in several comprehensive reviews (16,17,25,26).
DXA
Over the past decade, DXA has established itself as
the most widely used method of measuring BMD because
of its advantages of high precision, short scan times
and stable calibration in clinical use. DXA equipment (Fig.
3A) allows scanning of the spine and hip (Fig. 3B and 3C),
which are usually regarded as the most important measure-
ment sites because they are frequent sites of fractures that
cause substantial impairment of quality of life and increased
morbidity and mortality. A measurement of hip BMD has
been shown to be the most reliable way of evaluating the risk
of hip fracture (Fig. 2) (24,27). Also, because of the
metabolically active trabecular bone in the vertebral bodies,
the spine is regarded as the optimum site for monitoring
response to treatment (28).
The fundamental principle behind DXA is the measure-
ment of the transmission through the body of x-rays of 2
different photon energy levels (18). Because of the depen-
dence of the attenuation coefficient on atomic number and
photon energy, measurement of the transmission factors at 2
FIGURE 2. RR values for fractures at
differentskeletal sites for bone density mea-
surements in spine, calcaneus, distal ra-
dius, midradius, and hip. RR is defined as
increased risk of fracture for a 1-SD de-
crease in BMD. Data are taken from meta-
analysis of prospective studies collated by
Marshall et al. (
24
).
DIFFERENT APPROACHES TO BONE DENSITOMETRY •Fogelman and Blake 2017
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
FIGURE 3. (A) QDR4500 fanbeam DXA
scanner (Hologic, Bedford, MA). Densitom-
eters such as this are most frequently used
for measuring spine and hip BMD but can
also be used for total body, forearm, and
lateral projection studies of the spine. (B)
Portion of computer printout from DXA scan
of the spine. Printout shows (clockwise from
left): scan image of lumbar spine; patient’s
age and BMD plotted with respect to the
reference range; and BMD figures for indi-
vidual vertebrae and total spine (L1–L4)
with interpretation in terms of T-scores and
Z-scores. (C) Portion of computer printout
from a DXA scan of the hip. Printout shows
(clockwise from left): scan image of proxi-
mal femur; patient’s age and BMD for the
total femur ROI plotted with respect to the
NHANES III reference range; and BMD
figures for 5 ROIs in hip (femoral neck,
greater trochanter, intertrochanteric, total
femur, and Ward’s triangle) together with
interpretation in terms of T-scores and
Z-scores using the NHANES III reference
range.
2018 THE JOURNAL OF NUCLEAR MEDICINE •Vol. 41 •No. 12 •December 2000
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
energy levels enables the areal densities (i.e., the mass per
unit projected area) of 2 different types of tissue to be
inferred. In DXA scans, these are taken to be bone mineral
(hydroxyapatite) and soft tissue, respectively. Radiation
dose to the patient is very low (1–10 µSv) (29) and is
comparable with the average daily dose from natural back-
ground radiation of 7 µSv.
It is widely recognized that the accuracy of DXA scans is
limited by the variable composition of soft tissue. Because
of its higher hydrogen content, the attenuation coefficient of
fat is different from that of lean tissue. Differences in the soft
tissue composition in the path of the x-ray beam through
bone compared with the adjacent soft tissue reference area
cause errors in the BMD measurements, according to the
results of several studies (30,31). Svendsen et al. reported on
a cadaver study in which the effect of fat inhomogeneity on
the random accuracy errors for BMD measurements in the
spine, hip, and forearm were examined (31). The root mean
square accuracy errors were reported to be 3% for forearm,
5% for spine, and 6% for femoral neck and total hip BMD.
The first generation of DXA scanners used a pinhole
collimator, which produced a pencil beam coupled to a
single scintillation detector in the scanning arm. Since then,
the most significant development has been the introduction
of new systems that use a slit collimator to generate a
fanbeam coupled to a linear array of solid state detectors. As
a result, image resolution has improved, and scan times have
shortened from around 5–10 min for the early pencil beam
models to 10–30 s for the latest fanbeam systems. Radiation
dose to patients is higher for fanbeam systems compared
with pencil beam, and the resulting increased scatter dose to
technologists may require more active precautions to limit
exposure (32).
QCT
QCT has the advantage of determining the true 3-dimen-
sional (i.e., volumetric) bone density (units: mg/cm3) com-
pared with the 2-dimensional areal density measured by
DXA. QCT is usually applied to measure the trabecular bone
in the vertebral bodies (Fig. 4) (33). The measurement can
be performed on any clinical CT scanner, provided the
patient is scanned with an external reference phantom to
calibrate the CT numbers to bone equivalent values. Most
CT manufacturers provide a software package to automate
the placement of the regions of interest (ROIs) within the
vertebral bodies. Patient dose is much lower than for
standard CT scans, provided the examination is performed
correctly (34). QCT studies are generally performed using a
single kV setting (single-energy QCT), when the principal
source of error is the variable composition of the bone
marrow. However, a dual-kV scan (dual-energy QCT) is also
possible. This reduces the accuracy errors but at the price of
poorer precision and higher radiation dose. The advantage of
spinal QCT is the high responsiveness of the vertebral
trabecular bone to aging and disease (17,33). The principal
disadvantage is the cost of the equipment.
pDXA, pQCT, and RA
Despite the widespread popularity of spine and hip DXA,
there is continuing interest in the development of new
devices for assessing the peripheral skeleton (35). The first
bone densitometers were forearm scanners that used the
technique of single photon absorptiometry (SPA) that was
based on a 125I radionuclide source (36). A 25-y follow-up
period of patients after SPA studies has shown that forearm
bone density measurements can predict fracture risk (37). In
recent years, the technology has been updated by replacing
the radionuclide source with a low-voltage x-ray tube
(40–60 kVp) and using the principles of DXA to perform
BMD scans of the distal radius (Fig. 5) and the calcaneus.
The advantages of pDXA systems include the small foot-
print of the devices, relatively low cost, and extremely low
radiation dose (0.1 µSv (38)).
Just as pDXA devices were developed as an alternative to
DXA scanning of the central skeleton, small dedicated
pQCT systems are also available for measuring the forearm
(35). These devices have the advantage of separating the
FIGURE 4. Portion of computer printout from spinal QCT scan
showing transverse, sagittal, and coronal images of 2 lumbar
vertebrae. The study was analyzed using commercially available
QCT software package (Mindways Software, San Francisco,
CA).
DIFFERENT APPROACHES TO BONE DENSITOMETRY •Fogelman and Blake 2019
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
trabecular and cortical bone of the ultradistal radius and of
reporting volumetric density.Although widely used in some
countries in Europe, they have been primarily limited to
research studies in the United States.
RA is a technique that was developed many years ago for
assessing bone density in the hand, but the technique has
recently attracted renewed interest (35). It has the advantage
of using conventional x-ray equipment, usually with the
addition of a small aluminum wedge in the image field for
calibration. The radiographic image is captured on a per-
sonal computer and then processed automatically using a
specially developed software application to measure BMD
in the phalanges. The main advantage of RA is its potential
for general use on the basis of the widespread availability of
conventional film radiography.
Peripheral x-ray absorptiometry methods such as those
described above have obvious advantages when selecting
bone densitometry methodologies suitable for use in physi-
cians’ offices or in primary care. However, epidemiologic
studies have shown that the discriminatory ability of periph-
eral BMD measurements to predict spine and hip fractures is
probably lower than when spine and hip BMD measure-
ments are used (Fig. 2) (24,27). In addition, changes in
forearm BMD in response to HRT, bisphosphonates, and
SERMs are relatively small, making such measurements less
suitable than spine BMD for monitoring response to treat-
ment (39,40). Finally, although the radiation doses to patient
and operator are both extremely small, pDXA and pQCT
devices are subject to government regulatory requirements
controlling the use of x-ray equipment, including the
training of technologists and physicians in the principles of
radiation safety.
QUS
QUS is a technique for measuring the peripheral skeleton
that has raised considerable interest in recent years (26,35,41).
There is a wide variety of equipment available, with most
devices using the heel as the measurement site (Fig. 6). The
calcaneus is chosen because it encompasses a large volume
of trabecular bone between relatively flat faces and is readily
accessible for transmission measurements. The physical
principles of QUS measurements are outlined in Figure 7. A
sonographic pulse passing through bone is strongly attenu-
ated as the signal is scattered and absorbed by trabeculae.
Attenuation (measured in decibels) increases linearly with
frequency, and the slope of the relationship is referred to as
the broadband ultrasonic attenuation (BUA; units: dB/MHz)
(Fig. 7C). BUA is reduced in patients with osteoporosis,
because there are fewer trabeculae in the calcaneus to
attenuate the signal. In addition to BUA, most QUS systems
also measure the speed of sound (SOS) in the heel by
dividing the distance between the sonographic transducers
by the propagation time (units: m/s) (Fig. 7A). SOS values
are reduced in patients with osteoporosis because, with the
FIGURE 5. Computer printout from pDXA
scan of distal forearm. Scan was performed
on DTX-200 system (Osteometer Meditech,
Hawthorne, CA).
FIGURE 6. Achilles system for performing QUS measure-
ments in the heel (Lunar Corp., Madison, WI). Devices such as
this measure BUA and SOS in calcaneus. The 2 measurements
are combined into 1 index (‘‘Stiffness’’), which is supposed to
improve discrimination compared with BUA or SOS alone.
2020 THE JOURNAL OF NUCLEAR MEDICINE •Vol. 41 •No. 12 •December 2000
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
loss of mineralized bone, the elastic modulus of the bone is
decreased. Some manufacturers combine the BUA and SOS
values into a single parameter referred to as ‘‘stiffness’’ or
the Quantitative Ultrasound Index (QUI). These combina-
tions have no particular physical meaning but may improve
precision and discrimination by averaging out errors such as
those caused by temperature variations (42). With most
early-generation QUS devices, the patient’s foot was placed
in a water bath to couple the sonographic signal to the heel.
However, most recent devices are dry contact systems in
which rubber pads covered with sonographic gel are pressed
against the patient’s heel.
A major attraction of bone sonography devices is that they
do not use ionizing radiation and, therefore, avoid the
regulatory requirements for x-ray systems mentioned above.
In addition, the instrumentation is relatively inexpensive and
several devices, especially among the dry systems, are
designed to be portable. Therefore, sonography could be
more widely used than conventional DXA scanners, which
are largely restricted to hospital-based osteoporosis clinics.
Moreover, recent evidence from several large prospective
studies confirms that RR values for QUS measurements
predicting hip-fracture risk are comparable with DXA
(43–45).
There remain, however, several limitations to QUS mea-
surements. In general, the fracture studies mentioned above
were conducted in elderly populations who were older than
70 y, examined only hip-fracture risk, and used the earlier
generation of water-based calcaneal QUS systems. Thus, the
success of QUS in predicting fracture risk in younger
patients remains uncertain. Another difficulty with QUS
measurements is that they are not readily encompassed
within the WHO definitions of osteoporosis and osteopenia,
which, as emphasized above, should be applied only to
BMD measurements at the spine, hip, or forearm (46,47).
Recently, Kanis and Glu¨er proposed a more inclusive
paradigm in which a measurement of hip BMD would be
regarded as the gold standard for the definition of osteoporo-
sis (48). For the peripheral methodologies such as QUS,
intervention thresholds would be developed so that measure-
ments could be interpreted in terms of a fracture-risk
equivalent to that defined for hip DXA.
There are also several technical limitations to QUS. Many
devices use a foot support that positions the patient’s heel
between fixed transducers. Thus, the measurement site is not
readily adapted to different sizes and shapes of the calca-
neus, and the exact anatomic site of the measurement varies
from patient to patient. Furthermore, as a measurement site,
the calcaneus has the disadvantage of being particularly
sensitive to the amount of exercise the patient takes. The
former problem is avoided by imaging QUS systems that
perform a raster scan of the heel and ensure a more
consistent placement of the measurement site (49). Finally, it
is generally agreed that the relatively poor precision of QUS
measurements makes many devices unsuitable for monitor-
ing patients’ response to treatment (50). In part, this is
FIGURE 7. Physical principles behind measurement of BUA
and SOS. (A) Received pulse is digitized, and fourier analysis
used to determine the power spectrum. Pulse transit time is used
for SOS measurement. (B) Power spectrum of signal transmitted
through patient’s heel is compared with reference trace from
signaltransmittedthroughwater.Difference between the 2 traces
represents attenuation from patient’s heel. (C) When attenuation
throughpatient’sheelisplottedagainstfrequency,linearrelation-
ship is found at frequencies less than 1 MHz. BUA is defined as
slope of regression line and is measured in units of dB/MHz.
DIFFERENT APPROACHES TO BONE DENSITOMETRY •Fogelman and Blake 2021
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
because QUS technology is inherently less stable than DXA,
but in some devices this problem is compounded by a lack of
suitable anthropomorphic phantoms for adequate instrument
quality control.
RELATIONSHIP BETWEEN BONE
MEASUREMENT SITES
The spine and femur are generally regarded as the most
important BMD measurement sites because they are the sites
of the osteoporotic fractures that cause the greatest impair-
ment of quality of life, morbidity, and mortality. Many
would still consider spine BMD the optimum measurement
because of its sensitivity to the changes associated with
aging, disease, and therapy. However, spine BMD has the
disadvantage that, with advancing age, measurements are
often affected by the presence of degenerative changes that
lead to the artificial elevation of BMD values. This becomes
an increasing problem after the age of 70 y but can occur
earlier. Other clinicians would argue that hip BMD is the
most useful measurement, because it is the most predictive
of hip fracture (24,27), which is clinically the most impor-
tant fracture. In the research community, a consensus is
developing that the total femur should be the gold standard
for bone densitometry measurements (48). In practice, when
DXA measurements are performed, spine and hip BMD are
usually both available for evaluation.
Because osteoporosis is common and is a primary-care
disease, there is a need for a more simple evaluation of BMD
than DXA, which is generally found only in large hospitals.
There is therefore considerable interest in pDXA and QUS
devices, because such systems are smaller and cheaper than
DXA. Because osteoporosis is a systemic disease, bone loss
is not limited to the axial skeleton. However, correlation
coefficients between BMD measurements at different skel-
etal sites are typically around 0.6 to 0.7, and thus a
measurement at 1 site is far from being a perfect predictor of
that at any other. Furthermore, whatever intervention thresh-
old is chosen as the basis for initiating treatment, somewhat
different groups of patients are selected depending on the
measurement site.
The meta-analysis of prospective fracture studies pub-
lished by Marshall et al. (24) provides a basis for evaluating
the relative merits of different measurement sites for the
assessment of fracture risk (Fig. 2). The data show that,
although there is a strong indication that hip BMD measure-
ments are best at predicting hip fracture, the degree to which
spine BMD best predicts vertebral fracture or radius BMD
forearm fracture is weaker and less conclusive. Furthermore,
when assessed by the ability to predict fractures occurring at
any site, the RR values are closely comparable for the
different measurement sites. Thus, on the basis of the present
knowledge, and with the probable exception of hip fracture,
the differences between the various BMD measurement sites
for predicting future osteoporotic fractures are relatively
slight. As discussed above, recent studies now extend this
conclusion to include QUS measurements of the calcaneus
(43–45). In addition to BMD, the statistical models used to
analyze fracture studies also incorporate age as an indepen-
dent risk factor. In general, these studies show that, after
adjustment for BMD, each decade of age is associated with a
doubling of hip-fracture risk (27).
The fact that different patients may be selected for
treatment depending on the methodology used is conceptu-
ally more difficult, but it should be kept in mind that there is
no absolute fracture threshold (Fig. 1). There will always be
substantial overlap between measurements from fracture
and nonfracture patients, and absolute discrimination be-
tween these groups is not possible using any type of BMD
measurement. Bone densitometry studies provide a measure
of fracture risk that is analogous to assessment of blood
pressure with regard to the risk of stroke, or measurement of
cholesterol with regard to the risk of developing ischemic
heart disease. It is important to distinguish the concepts of
risk as applied to an individual and to a population. BMD
measurements are well suited to the study of populations,
where they are effective in identifying patients who have a
higher than average risk of fracture but are less accurate in
identifying those individuals who will later sustain a frac-
ture. This is at least partially explained by the fact that
although BMD may be the most important single risk factor
for fracture, osteoporotic fractures are nevertheless multifac-
torial and, in addition to low bone density, depend on other
issues such as accidents and the propensity to fall.
REFERENCE RANGES
If the WHO criterion of a T-score #22.5 is used to define
osteoporosis, then it is apparent that any errors in the mean
BMD or population SD of the reference group might lead to
significant differences in the apparent incidence of osteopo-
rosis when applied to other populations. The great majority
of centers that have a scanning service use reference ranges
provided by the equipment manufacturers, and issues over
the accuracy of these ranges have caused controversy in the
past (51). This continues to be a problematic area in view of
the large number of new devices that are being introduced
for the assessment of the skeleton. However, for DXA the
problem is now largely resolved after a report by the
International Committee for Standards in Bone Measure-
ment (ICSBM) (52), which recommended that hip BMD
measurements should be interpreted using the total femur
ROI and the hip BMD reference ranges derived from the
U.S. NHANES III study (53). The NHANES III project
studied a nationally representative sample of over 14,000
men and women with approximately equal numbers of
non-Hispanic white, non-Hispanic black, and Mexican
Americans. Data were gathered using Hologic QDR1000
densitometers operated from trailers so that subjects from all
regions of the United States could be included. The ICSBM
report recommends use of the total femur ROI instead of the
previously widely used femoral neck site because of its
improved precision and the fact that it is the hip region most
readily implemented on all manufacturers’ systems.
2022 THE JOURNAL OF NUCLEAR MEDICINE •Vol. 41 •No. 12 •December 2000
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
Many centers have already acted on these recommenda-
tions, and they are increasingly being used for scan report-
ing. It is important to note that these changes affect the
percentage of patients who are diagnosed as having osteopo-
rosis at the hip. Using the total femur ROI and the NHANES
III reference range, fewer patients will be diagnosed as
having osteoporosis than using the femoral neck ROI and
the manufacturer’s reference range (54). There is no definite
right or wrong answer in this situation. What is more
important is to have a consistent approach, and it is certainly
highly desirable to have universally accepted DXA BMD
criteria for the diagnosis of osteoporosis.
One advantage of presenting bone densitometry results in
terms of T- and Z-scores is that they avoid the confusion
caused by the raw BMD figures that differ for different
manufacturers’ equipment (55).The ICSBM Committee has
addressed this issue by publishing equations that allow each
manufacturer to express their BMD values on a consistent
scale in standardized units (sBMD: units mg/cm2)(52,56).
Their report also included figures for the NHANES III total
femur reference data converted into sBMD values.
CLINICAL DECISION MAKING
With the development of new treatments for preventing
osteoporosis and the wider availability of bone densitometry
equipment, much debate has centered on the issue of the
clinical indications for the diagnostic use of bone densitom-
etry and recommendations for the initiation of treatment on
the basis of the findings. In the United States, an influential
report was published by the National Osteoporosis Founda-
tion (NOF) (57). In Europe, similar reports have been issued
by the European Foundation for Osteoporosis (EFFO) (1),
and in the United Kingdom by the Royal College of
Physicians (RCP) (58).
The NOF report (57) included a sophisticated set of
guidelines for therapeutic intervention. Various nomograms
were developed that incorporate age, BMD, and 4 other risk
factors for osteoporosis (Table 2). An interesting aspect of
the NOF approach is that the calculations for therapeutic
intervention are based on the concept of a quality-adjusted
life year, which is approximated to be $30,000. This is a
relatively high value and one that would not be considered
appropriate for application in Europe. This implies that there
may have to be different BMD criteria for therapeutic
intervention in different countries. It also follows from the
NOF approach that there will be different thresholds for
intervention depending on the cost of treatment. Although
the NOF report is an extremely important document, with an
extensive review of the relevant background information, it
is nevertheless complex, and it is unlikely that primary care
physicians will instigate treatment on the basis of such a
scheme. The NOF subsequently published a physicians’
handbook with simplified recommendations that included
the availability of BMD measurements for all women over
the age of 65 y and in all postmenopausal women under the
age of 65 y in whom clinical risk factors are present (59).
Even if desirable, such a recommendation is simply not
feasible in Europe at the present time.
Clinical guidelines for the prevention and treatment of
osteoporosis in the United Kingdom were recently published
by the RCP (58). The authors concluded that at present, there
is no consensus for a policy of population screening using
BMD scans. Instead, a case-finding strategy is recom-
mended for referring patients for bone densitometry on the
basis of a list of widely accepted clinical risk factors (Table
3). The list is identical to that published in the EFFO report
(1). The RCP report also recommended a T-score of #22.5
as the basis for instigating therapy.
It is important to emphasize that the WHO definition of
osteopenia (22.5 ,T,21) is not useful in isolation with
regard to decisions about treatment, because it captures too
high a percentage of postmenopausal women and, in fair-
ness, was never intended to be used in this way. A
considerable body of evidence indicates that it is the patients
with the most severe disease who benefit most from
antiresorptive therapies such as bisphosphonates (60). Thus,
there seems to be a consensus supporting the use of a T-score
of #22.5 as the appropriate intervention threshold for
instigating treatment in white women. However, it is impor-
tant to take all the other relevant clinical factors into account
such as those listed in Tables 2 and 3. In particular, the age of
the patient and whether there is a history of previous fragility
fractures are important independent predictors of future
fracture risk.
No consensus has yet emerged on what intervention
thresholds are appropriate in men and other ethnic groups.
However, the revised guidelines recently published by Kanis
and Glu¨er (48) recommend that the same absolute BMD
thresholds applied to white women should also apply to
these other groups. There are also difficulties in applying the
WHO criterion in elderly persons, because, on the basis of a
T-score of 22.5, the majority of women will have osteoporo-
sis. It may be more appropriate to use Z-scores in elderly
persons, but at present there is no consensus on how this can
best be achieved.
SUMMARY AND CONCLUSION
In the 1990s, large international clinical trials proved the
effectiveness of several new treatments for the prevention of
osteoporosis, such as bisphosphonates and SERMs. In
addition to these developments, the pace of technologic
TABLE 2
Risk Factors for Osteoporosis, Additional toAge and BMD,
Incorporated in the NOF Guidelines for Therapeutic Intervention
ãHistory of fracture after age 40.
ãHistory of hip, wrist, or vertebral fracture in a first-degree relative.
ãBeing in lowest quartile for body weight (#57.8 kg [127 lb]).
ãCurrent cigarette smoking habit.
Data from NOF guidelines (
57,59
).
DIFFERENT APPROACHES TO BONE DENSITOMETRY •Fogelman and Blake 2023
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
innovation was rapid, with the introduction of new radio-
logic methods for the noninvasive assessment of patients’
bone density status. DXA scanning of the hip and spine
remains the gold standard, although there is now a wider
appreciation of the need for smaller, cheaper devices for
scanning the peripheral skeleton if the many millions of
women most at risk of a fragility fracture are to be identified
and treated. Several sets of guidelines for the clinical use of
bone densitometry have been published, and most have
included recommendations for intervention thresholds for
initiating treatment in white women. The WHO criterion of a
T-score #22.5 has been especially influential, although it
cannot automatically be applied to the newer peripheral
techniques such as QUS, or in men and patients from other
ethnic groups.
At the present time, most experts do not advocate mass
screening of the population for osteoporosis, and instead the
guidelines recommend a case-finding strategy that is based
on identifying patients with generally accepted clinical risk
factors. However, with the widespread availability of QUS
systems, this view may change. The advantages of QUS
outlined above mean that it may have a role in many
specialist departments and primary care facilities. However,
in view of the large number of commercial devices avail-
able, there are concerns about whether all the reference
ranges are accurate and appropriate. As emphasized above,
the WHO definition of a T-score of #22.5 cannot automati-
cally be applied to QUS, and there is a consensus emerging
toward defining intervention thresholds for peripheral de-
vices on the basis of estimates of absolute fracture risk. It
seems premature to advocate the routine use of QUS until
these issues have been resolved and appropriate clinical
strategies have been agreed on. Nevertheless, it is probable
that sonography will be widely used for the assessment of
the skeleton within the next 5 to 10 y, and at that point there
would effectively be screening for osteoporosis.
REFERENCES
1. Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D, on behalf of the
European Foundation for Osteoporosis and Bone Disease. Guidelines for diagno-
sis and treatment of osteoporosis. Osteoporosis Int. 1997;7:390–406.
2. Ray NF, Chan JK, Thamer M, Melton LJ. Medical expenditures for the treatment
of osteoporotic fractures in the United States in 1995: report from the National
Osteoporosis Foundation. J Bone Miner Res. 1997;12:24–35.
3. Chrischilles E, Shireman T, Wallace R. Costs and health effects of osteoporotic
fractures. Bone. 1994;15:377–386.
4. Jacobsen SJ, Goldberg J, Miles TP, et al. Race and sex differences in mortality
following fracture of the hip. Am J Public Health. 1992;82:1147–1150.
5. Koval KJ, Skovron ML, Ahanonoff GB, Meadows SE, Zuckerman JD. Ambula-
tory ability after hip fracture: a prospective study in geriatric patients. Clin
Orthop. 1995;310:150–159.
6. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3and calcium to prevent
fractures in elderly women. N Engl J Med. 1992;327:1637–1642.
7. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of the effect of
alendronate on risk of fracture in women with existing vertebral fractures. Lancet.
1996;348:1535–1541.
8. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in
postmenopausal women with osteoporosis treated with raloxifene: results from a
3-year randomized clinical trial. JAMA. 1999;282:637–645.
9. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and
prolong life in postmenopausal women. Ann Intern Med. 1992;117:1016–1037.
10. Collaborative group on hormonal factors in breast cancer. Breast cancer and
hormone replacement therapy: collaborative reanalysis of data from 51 epidemio-
logical studies of 52,705 women with breast cancer and 108,411 women without
breast cancer. Lancet. 1997;350:1047–1059.
11. Lin JH. Bisphosphonates: a review of their pharmacokinetic properties. Bone.
1996;18:75–85.
12. Liberman UA, Weiss SR, Bro¨ ll J, et al. Effect of oral alendronate on bone mineral
density and the incidence of fractures in postmenopausal osteoporosis. N Engl J
Med. 1995;333:1437–1443.
13. Mortensen L, Charles P, Bekker PJ, Digennaro J, Johnston CC. Risedronate
increases bone mass in an early postmenopausal population: two years of
treatment plus one year of follow-up. J Clin Endocrinol Metab. 1998;83:396–402.
14. Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifine on bone mineral
density, serum cholesterol concentrations, and uterine endometrium in postmeno-
pausal women. N Engl J Med. 1997;337:1641–1647.
15. Lufkin EG, Whitaker MD, Nickelsen T, et al. Treatment of established postmeno-
pausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res.
1998;13:1747–1754.
16. Genant HK, Engelke K, Fuerst T, et al. Noninvasive assessment of bone mineral
and structure: state of the art. J Bone Miner Res. 1996;11:707–730.
17. Grampp S, Genant HK, Mathur A, et al. Comparisons of non-invasive bone
mineral measurements in assessing age-related loss, fracture discrimination and
diagnostic classification. J Bone Miner Res. 1997;12:697–711.
18. Blake GM, Fogelman I. Technical principles of dual energy x-ray absorptiometry.
Semin Nucl Med. 1997;27:210–228.
19. Consensus Development Conference. Diagnosis, prophylaxis and treatment of
osteoporosis. Am J Med. 1993;94:646–650.
TABLE 3
Risk Factors Providing Indications for the Diagnostic
Use of Bone Densitometry
Category Risk factor
Presence of strong risk factors Estrogen deficiency
Premature menopause (age
,45 y)
Prolonged secondary amen-
orrhea (.1y)
Primary hypogonadism
Corticosteroid therapy
Prednisolone .7.5 mg/day for
1 y or more
Maternal family history of hip
fracture
Low body mass index (,19
kg/m2)
Other disorders associated with
osteoporosis
Anorexia nervosa
Malabsorption syndrome
Primary hyperparathyroidism
Post-transplantation
Chronic renal failure
Hyperthyroidism
Prolonged immobilization
Cushing’s syndrome
Radiographic evidence of osteo-
penia or vertebral deformity
Previous fragility fracture, espe-
cially of the hip, spine, or wrist
Loss of height, thoracic
kyphosis (after radiographic
confirmation of vertebral
deformities)
Data from RCP guidelines (
58
).
2024 THE JOURNAL OF NUCLEAR MEDICINE •Vol. 41 •No. 12 •December 2000
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
20. World Health Organization. WHO Technical Report Series 843. Assessment of
fracture risk and its application to screening for postmenopausal osteoporosis.
Geneva, Switzerland: World Health Organization, 1994.
21. Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of
osteoporosis. J Bone Miner Res. 1994;9:1137–1141.
22. Blake GM, Fogelman I. Interpretation of bone densitometry studies. Semin Nucl
Med. 1997;27:248–260.
23. Jergas M, Glu¨er C-C. Assessment of fracture risk by bone density measurements.
Semin Nucl Med. 1997;27:261–275.
24. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone
mineral density predict occurrence of osteoporotic fractures. Br Med J. 1996;312:
1254–1259.
25. Blake GM, Wahner HW, Fogelman I. The Evaluation of Osteoporosis: Dual
Energy X-Ray Absorptiometry and Ultrasound in Clinical Practice. 2nd ed.
London, England: Martin Dunitz, 1999.
26. Njeh CF, Hans D, Fuerst T, Glu¨er C-C, Genant HK. Quantitative Ultrasound:
Assessment of Osteoporosis and Bone Status. London, England: Martin Dunitz,
1999.
27. Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for
prediction of hip fractures. Lancet. 1993;341:72–75.
28. Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998;338:
736–746.
29. Njeh CF, Fuerst T, Hans D, Blake GM, Genant HK. Radiation exposure in bone
mineral assessment. Appl Rad Isotope. 1999;50:215–236.
30. Tothill P, Pye DW. Errors due to non-uniform distribution of fat in dual x-ray
absorptiometry of the lumbar spine. Br J Radiol. 1992;65:807–813.
31. Svendsen OL, Hassager C, Skodt V, Christiansen C. Impact of soft tissue on
in-vivo accuracy of bone mineral measurements in the spine, hip, and forearm: a
human cadaver study. J Bone Miner Res. 1995;10:868–873.
32. Patel R, Blake GM, Batchelor S, Fogelman I. Occupational dose to the
radiographer in dual x-ray absorptiometry: a comparison of pencil-beam and
fan-beam systems. Br J Radiol. 1996;69:539–543.
33. Cann CE. Quantitative CT for determination of bone mineral density: a review.
Radiology. 1988;166:509–522.
34. Kalender WA. Effective dose values in bone mineral measurements by photon
absorptiometry and computed tomography. Osteoporosis Int. 1992;2:82–87.
35. Glu¨er C-C, Jergas M, Hans D. Peripheral measurement techniques for the
assessment of osteoporosis. Semin Nucl Med. 1997;27:229–247.
36. Cameron JR, Sorensen JA. Measurement of bone mineral in vivo: an improved
method. Science. 1963;142:230–232.
37. Du¨ppe H, Ga¨rdsell P, Nilsson B, Johnell O. A single bone density measurement
can predict fractures over 25 years. Calcif Tissue Int. 1997;60:171–174.
38. Patel R, Blake GM, Fogelman I. Radiation dose to the patient and operator from a
peripheral dual x-ray absorptiometry system. J Clin Densitom. 1999;2:397–401.
39. Faulkner KG. Bone densitometry: choosing the proper skeletal site to measure. J
Clin Densitom. 1998;1:279–285.
40. Hoskings D, Chilvers CE, Christiansen C, et al. Prevention of bone loss in
postmenopausal women under 60 years of age. Early postmenopausal intervention
cohort study group. N Engl J Med. 1998;338:485–492.
41. Njeh CF, Boivin CM, Langton CM. The role of ultrasound in the assessment of
osteoporosis: a review. Osteoporosis Int. 1997;7:7–22.
42. Nicholson PH, Bouxsein ML. Influence of temperature on ultrasonic properties of
the calcaneus in situ [abstract]. J Bone Miner Res. 1999;14(suppl 1):S498.
43. Hans D, Dargent-Molina P, Schott AM, et al. Ultrasonographic heel measurements
to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet.
1996;348:511–514.
44. Bauer DC, Glu¨er C-C, Cauley JA, et al. Broadband ultrasonic attenuation predicts
fractures strongly and independently of densitometry in older women. Arch Intern
Med. 1997;157:629–634.
45. Pluijm SMF, Graafmans WC, Bouter LM, Lips P. Ultrasound measurements for
the prediction of osteoporotic fractures in elderly people. Osteoporosis Int.
1999;9:550–556.
46. Faulkner KG, VonStetton E, Miller P. Discordance in patient classification using
T-scores. J Clin Densitom. 1999;2:343–350.
47. Delmas PD. Do we need to change the WHO definition of osteoporosis?
Osteoporosis Int. 2000;11:189–191.
48. Kanis JA, Glu¨er C-C. An update on the diagnosis and assessment of osteoporosis
with densitometry. Osteoporosis Int. 2000;11:192–202.
49. Fournier B, Chappard C, Roux C, Berger G, Laugier P. Quantitative ultrasound
imaging at the calcaneus using an automatic region of interest. Osteoporosis Int.
1997;7:363–369.
50. Glu¨er C-C. Quantitative ultrasound techniques for the assessment of osteoporosis—
expert agreement on current status. J Bone Miner Res. 1997;12:1280–1288.
51. Faulkner KG, Roberts LA, McClung MR. Discrepancies in normative data
between Lunar and Hologic DXA systems. Osteoporosis Int. 1996;6:432–436.
52. Hanson J. Standardization of femur BMD [letter to the editor]. J Bone Miner Res.
1997;12:1316–1317.
53. Looker AC, Wahner HW, Dunn WL, et al. Updated data on proximal femur bone
mineral levels of US adults. Osteoporosis Int. 1998;8:468–489.
54. Chen Z, Maricic M, Lund P, Tesser J, Gluck O. How the new Hologic hip
reference values affect the densitometric diagnosis of osteoporosis. Osteoporosis
Int. 1998;8:423–427.
55. Genant HK, Grampp S, Glu¨er C-C, et al. Universal standardization for dual x-ray
absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res.
1994;9:1503–1514.
56. Steiger P. Standardization of spine BMD measurements [letter to the editor]. J
Bone Miner Res. 1995;10:1602–1603.
57. National Osteoporosis Foundation. Osteoporosis: review of the evidence for
prevention, diagnosis, and treatment and cost-effectiveness analysis. Osteoporosis
Int. 1998;8(suppl 4):S7–S80.
58. Royal College of Physicians. Osteoporosis: Clinical Guidelines for Prevention
and Treatment. London, England: Royal College of Physicians, 1999.
59. National Osteoporosis Foundation. Physicians Guide to Prevention and Treatment
of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 1998.
60. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of
fracture in women with low bone density but without vertebral fracture: results
from the Fracture Intervention Trial. JAMA. 1998;280:2077–2082.
DIFFERENT APPROACHES TO BONE DENSITOMETRY •Fogelman and Blake 2025
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
2000;41:2015-2025.J Nucl Med.
Ignac Fogelman and Glen M. Blake
Different Approaches to Bone Densitometry*
http://jnm.snmjournals.org/content/41/12/2015
This article and updated information are available at:
http://jnm.snmjournals.org/site/subscriptions/online.xhtml
Information about subscriptions to JNM can be found at:
http://jnm.snmjournals.org/site/misc/permission.xhtml
Information about reproducing figures, tables, or other portions of this article can be found online at:
(Print ISSN: 0161-5505, Online ISSN: 2159-662X)
1850 Samuel Morse Drive, Reston, VA 20190.
SNMMI | Society of Nuclear Medicine and Molecular Imaging
is published monthly.The Journal of Nuclear Medicine
© Copyright 2000 SNMMI; all rights reserved.
by on September 28, 2017. For personal use only. jnm.snmjournals.org Downloaded from
