Quantitative Ultrasound in Diagnosis of Metabolic Bone Diseases

Current Medical Imaging Reviews, 2005, 1, 67-74
67
Quantitative Ultrasound in Diagnosis of Metabolic Bone Diseases
Bogna Drozdzowska*1 and Wojciech Pluskiewicz2
1Dept. of Pathomorphology, Silesian School of Medicine in Katowice, 3 Maja 13/15 street, 41-800 Zabrze, Poland,
2Metabolic Bone Diseases Unit, Dept. & Clinic of Internal Diseases, Diabetology & Nephrology, Silesian School of
Medicine, 3-Maja 13/15 street, 41-800 Zabrze, Poland
Abstract: Currently, the diagnosis of osteoporosis is based on bone mineral density measurements using Dual Energy X-
ray Absorptiometry (DXA). DXA provides information about quantitative content of calcium hydroxyapatite in the
skeleton. From about 20 years Quantitative Ultrasound (QUS) measurements are used. QUS reveals both quantitative and
qualitative (elasticity and microstructure) features of bone tissue and was used in several pathologic and physiologic
conditions.
The most important are results of prospective studies showing the ability of QUS measurements to predict osteoporotic
fractures. QUS was used in monitoring skeletal changes during therapy on osteoporosis. In several studied QUS
measurements showed an ability to detect skeletal changes in children and adolescents and involutional changes at the
skeleton. QUS measurements were also used in order to follow bone changes during pregnancy and lactation,
glucocorticosteroid therapy, renal osteodystrophy, oncologic and rheumatic diseases, and prolonged immobilization.
Advantages of QUS are: lack of ionizing radiation, portability of devices and their relatively low cost.
Disadvantages of QUS include the lack of precise determination of measured bone features, measurements limited to
peripheral skeleton, relatively poor precision and the lack of unification of several devices.
Currently, despite these limitations QUS is a validated method in diagnostic armentarium in metabolic bone diseases.
Keywords: Metabolic bone diseases, quantitative ultrasound.
INTRODUCTION
lack of ionizing radiation, relatively low costs and small
sizes of equipment. QUS has also some disadvantages
Currently, densitometric methods are the most commonly
involving difficulty in precise determination of measured
used in order to assess skeletal status in metabolic bone
bone tissue features, skeletal sites limited only to peripheral
diseases. Early investigations were performed using ionizing
skeleton and relatively poor precision.
methods (single photon absorptiometry - SPA and dual
photon absorptiometry - DPA), and last years were a period
In the review, current data on the use of QUS are shown.
of the development of Dual Energy X-ray Absorptiometry
Commonly, in reviews concerning QUS [1,2] in the scope of
(DXA). DXA provides information on quantitative content
interest were mainly osteoporotic populations. It’s obvious
of hydroxyapatite calcium in measured bones. Thus, DXA
that osteoporosis is the most common metabolic bone
widely used in a clinical practice does not provide any data
disease but there are several other areas where is a necessity
on bone qualitative features. It is well known that
to follow bone status. Skeletal status changes during the
biomechanic competence of the skeleton is dependent both
whole life in physiologic (growth, involution) or pathologic
on bone mineral density (BMD) measured by DXA and
states (endocrine disorders, side effects of some medications
qualitative features of bone like elasticity or microarchite-
etc.). In further part of the review, an ability of QUS to
cture. The role of bone quality is currently widely accepted
detect bone changes is discussed.
and there is urgent need to develop new methods able to
CLINICAL ULTRASOUND BONE MEASUREMENTS
assess not only bone quantity.
SYSTEMS
Commercially available QUS machines measure several
peripheral skeletal sites: calcaneus, phalanges, patella, radius
Commercially available ultrasound systems measure
or tibia.
several skeletal sites like calcaneus, tibia, patella, forearm,
phalanges. The calcaneus is the most popular measurement
Some methods may give additional data on bone tissue
site for several reasons: calcaneus consisted of almost only
and among them are quantitative ultrasound (QUS) and high
active metabolically trabecular bone may early express
resolution quantitative computed tomography. QUS used
skeletal changes, is weight-bearing bone and is easily
since mid eighties shows several important advantages: an
accessible. Early devices as a coupling medium - in order to
ability to assess some qualitative features of bone tissue, the
allow a penetration of ultrasound waves - used a water bath
and currently a standard ultrasound gel is more popular.
*Adress correspondence to this author at the Dept. of Pathomorphology,
Some devices available use contact-free systems of
Silesian School of Medicine in Katowice, 3 Maja 13/15 street, 41-800
measurements. Fig. 1 and 2 show schematic representation
Zabrze, Poland; Tel/Fax: 00 48 32 2714994; E-mail:
of some ultrasound systems.
bognadr@poczta.onet.pl
1573-4056/05 $50.00+.00
©2005 Bentham Science Publishers Ltd.

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68 Current Medical Imaging Reviews, 2005, Vol. 1, No. 1
Drozdzowska and Pluskiewicz
Fig. (1). Contact method of QUS measurement.
Fig. (2). Method of QUS measurement.
Ultrasound is a traveling mechanical vibration and the
quality. It is well known that BMD is important but no sole
mechanical properties of the medium progressively alter the
determinant of biomechanical properties of skeleton [3].
shape, intensity (energy per second per unit area) and speed
Fundamental rules of biomechanics indicates that the
of the propagation wave [1]. Therefore, the nature of the
strength depends not only on material quantity but also on its
method being able to provide some qualitative bone features
internal structure, size and biomechanical properties. It
in addition to bone quantity seems to be especially
should be known that the risk of bone fracture depends on its
promising.
density, internal structure (mainly trabecular anisotrophy,
connectivity and porosity) and bone biomechanical
One of the most important features of devices used in
properties.
order to detect skeletal changes is their precision error. This
aspect is especially important in longitudinal studies when
QUS may provide some additional data on fracture risk
small changes ought to be precisely assessed. CV
because QUS parameters express both bone mass and bone
(coefficient of variation) does not express range of QUS
quality. QUS measures two parameters: speed of sound
parameter. CV% values range from 0.3% to 4%, and
(SOS) and broadband ultrasound attenuation (BUA). SOS is
standarized CV (SCV) defined as the percentage CV divided
believed to express elasticity and bone mass, and higher SOS
by the ratio of the range over the mean may be preferable.
values are obtained in denser and more elastic bone tissue
SCV values are almost 10%.
[4]. BUA is a function of absorption and dispersal of
ultrasound wave, and is associated with density and structure
QUALITY OF BONE ASSESSED BY QUS
of trabecular bone [4]. Studies in vitro confirm that SOS [5]
A potential of QUS to express qualitative features of
and BUA [6] depend on biomechanical features of bone
bone seems to be one the most important advantages of the
tissue expressed by Young modulus. Thus, QUS seems to be
method. Bone diseases may affect both bone quantity and
able to predict biomechanical properties of bone. In contrary

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Quantitative Ultrasound in Diagnosis of Metabolic Bone Diseases
Current Medical Imaging Reviews, 2005, Vol. 1, No. 1 69
to DXA method, QUS expresses anisotropic properties of
recommended as a diagnostic tool at least in screening
bone and internal structure of trabeculae [7]. Such data
procedures.
indicate that QUS may give some additional data to those
STUDIES IN MALES
given by densitometric evaluation of bone independent of
BMD [6,8]. Some researchers consider that common use of
Many studies using QUS measurements were performed
QUS and BMD measurements may better express
in female populations, and only some studies documented
biomechanical competence of bone than BMD measure-
possibility of the method to detect also skeletal changes in
ments alone [9], and others stated that QUS parameters are
males. Majority of them were conducted in normal, healthy
able to predict mechanical properties of bone independently
males [27-32], and some studies were aimed to discriminate
of bone density [10].
fractured from non-fractured males [33,34]. OR ranged from
It could be concluded that a potential of QUS to express
1.05 to 3.4 [33,34]. Sensitivity and specificity of ultrasound
some qualitative features of bones cannot be neglected. This
measurements were also established and AUC were from
ability of the method is the most promising area of future
0.66 to 0.81 [33,34]. Prospective fracture studies are not
studies and a combination of data on qualitative bone
available.
features and bone quantity would lead to wider clinical
Generally, QUS parameters showed comparable trends in
applications in the future.
age-related changes as in female populations (in bone growth
and bone involution) and were able to assess fracture
OSTEOPOROSIS
discrimination. Ultrasound measurements at the calcaneus
Assessment of fracture risk is a very important clinical
were able to discriminate between normal and osteoporotic
problem, and comparisons of groups with and without
male/female populations in a similar manner [35]. The most
fractures may show an ability to discriminate fractured and
important weakness concerns the lack of prospective fracture
non-fractured subjects. QUS was used in several case-control
studies confirming data from case-control studies, and
studies (subjects with fractures versus subjects without
further validation of QUS measurements in males are
fractures), and patients with past, low-energy fractures (due
urgently needed.
to minimal trauma caused by a fall from standing height or
THE EFFICACY OF PHARMACOLOGIC OSTEOPO-
less) had significantly lower QUS values [11-18]. In these
ROSIS MANAGEMENT
studies, fracture risk was assessed using Relative Risk (RR)
in longitudinal studies or Odds Ratio (OR) in cross-sectional
Currently, using available medications it is possible to
studies calculated as increasing risk per 1 standard deviation
treat osteoporosis and fracture risk is decreased. Several
decrease in measured QUS parameter. OR usually ranged
treatment options including bisphoshonates, PTH, estrogen
from to 1.5 do 4.0, and RR was close to 2.0.
receptor modulators, hormone replacement therapy (HRT),
The most important data on clinical utility of QUS in
strontium ranelate or calcitonin proved their efficacy in
osteoporosis provide longitudinal studies. In some such
fracture reduction in studies performed using rules of
studies the clinical utility of QUS was assessed [19-23], and
Evidence Based Medicine. It could be stated that these
calcaneal QUS measurements were able to predict future
medications reduce new fracture occurrence by approximat-
osteoporotic fracture.
ely 50%. Paralelly to fracture reduction, BMD increases only
by some percents what emphasizes that not only bone
The only one skeletal site besides calcaneus in fracture
quantity (=BMD), but also improvement in bone quality may
prediction were hand phalanges [24]. In some studies authors
contribute to fracture reduction. Bone quality is treated as an
compared the value of DXA and QUS measurements and
important factor influencing biomechanical competence of
authors stated that fracture discrimination or prediction may
bone so QUS may play a significant role as a method
be performed in a comparable manner using QUS and DXA
assessing bone quality. QUS measurements proved ability to
[20,21,23,25]. Clinical utility of QUS was also evaluated
monitor therapeutic efficacy of alendronate [36] and HRT at
using Receiving Operating Characteristic (ROC). ROC
the hand phalanges [14,37,38] and calcaneus [39]. One of the
analysis allows to assess how the method may discriminate
most important study was a prospective four-year
between subjects with and without fractures. ROC analysis
observation of a group of 27 females [37]. In 56% of them,
plots a sensitivity versus specificity curve and summarizes
an increase was observed, and in majority of controls QUS
the accuracy of used tool by estimating the area under the
parameters decreased. Other, important data were provided
ROC curve (AUC). A perfect tool which correctly classifies
by Hadji et al. [39], who noted in 611 females on HRT
individuals into a disease or no-disease state 100% of the
constant increase in QUS values while in 1395 controls a
time would have an AUC estimate of 1.0. AUC for QUS
decrease was observed.
parameter ranged from 0.62 [23] to 0.96 [15]. An interesting
algorithm how to use QUS in postmenopausal women was
Despite these promising results, relatively poor precision,
recently proposed by Gambacciani et al. [26] including
especially expressed by SCV limits the possibility of
several steps regarding current QUS results and clinical risk
longitudinal observation of bone changes and further use of a
factors for osteoporotic fractures. According to this proposal
method on this area would be dependent on precision
it is possible to select only a part of population for further
improvement.
DXA measurements, thus reducing the costs and limiting the
SKELETAL GROWTH
amount of patients exposed to ionizing radiation.
Many years ago C. Dent stated that osteoporosis is a
Concluding, QUS proved an utility in fracture risk
disease with roots in childhood and adolescence [40].
assessment in osteoporotic populations, and may be easily
Therefore, studies of skeletal growth are an important part of

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70 Current Medical Imaging Reviews, 2005, Vol. 1, No. 1
Drozdzowska and Pluskiewicz
knowledge on human bone physiology and pathology. QUS
also an ability to detect bone side effects in epileptic patients
seems to an excellent tool in assessment of skeletal status in
on long-term anticonvulsant therapy [59]. No prospective
young populations: it does not use ionizing radiation,
studies on the use of QUS in patients on therapy affecting
duration of bone scans is short, and devices are portable. The
bone status were published so far.
knowledge on rate of skeletal growth, determination of age
It seems that QUS could be especially fitted in patients
when this process is accelerated and age of peak bone mass
on glicocorticoids because additional to diminution in bone
achievement are essential factors in early prevention of
quantity deterioration of bone quality is present, and further
osteoporosis. QUS measurements were performed mainly at
studies ought to validate the role of QUS. Despite these
the hand phalanges [32,41-44]. Especially important is a
limitations it seems that yet published data allow to propose
possibility to reveal a rapid bone changes in adolescents.
QUS as a useful method expressing bone-side effects of
This process accelerates at the age of 10-11 years in girls and
some therapies.
two years later in boys, and phalangeal QUS measurements
very well express these changes. It could be stated that
- Renal Osteodystrophy
generally QUS gives comparable view of bone growth
processes as bone densitometry methods and may be easily
In a course of renal failure skeleton is commonly affected
used in children and adolescents.
and bone disturbances are called renal osteodystrophy. In
about 50% of patients with mild and moderate renal
INVOLUTION OF SKELETON
insufficiency, in bone tissue are shown histologic
abnormalities [40]. Renal osteodystrophy covers several
Age is one of the most important risk factor for
quantitative and qualitative disturbances of bone tissue, and
osteoporotic fracture [45] and understanding of nature of
QUS seems to be especially fitted to follow such changes. In
bone loss occurred due to ageing may improve patients’
several studies measurements of calcaneus [60-63], hand
management. Majority of QUS studies was based on heel
phalanges [61,64-69] and tibia [70], QUS measurements
measurements [13,27,35,46] but also other skeletal sites
were diminished in comparison to controls and correlated
were used [15,47,48]. One of the most important
with densitometric measurements. Some of yet published
contribution is given by multicentral European study on
studies were performed in children and adolescents [60-62],
QUS hand phalanges measurements [15]. In this study a total
and QUS due to the lack of ionizing is especially profitable
of 10,115 females aged up to 100 years were assessed and
in young subjects.
measured QUS parameter was able to express bone changes
over a whole period of observation. Generally, trends of
QUS could be especially useful in subjects with end-
changes in QUS parameters were comparable irrespective of
stage renal failure because deterioration of bone quality and
site of measurements. It ought to be taken into consideration
quantity are commonly present in such population. Further
that trends of changes in QUS variables do not differ
studies ought to validate the role of QUS in patients with
significantly from changes observed for DXA
renal failure, but it seems that yet published data allow to
measurements, and QUS may be successfully used to detect
propose the use of QUS especially in children and
bone changes over a whole period of life.
adolescents.
OTHER AREAS OF THE USE OF QUS
- Oncologic Diseases
- Pregnancy and Lactation
Prevalence of oncologic diseases increases steadily, and
improvement in patients management is associated with
Pregnancy and lactation may affect bone status. Due to
longer life duration. Among many possible side effects of
obvious ethic reasons during pregnancy any ionizing
therapeutic regimes also a skeleton may be affected and there
radiation cannot be accepted and QUS may be easily used. In
is urgent necessity to introduce methods which are able to
several studies QUS measurements at calcaneus [49,51,52]
detect them.
and hand phalanges [50,53] showed decreases during
pregnancy. Till now no studies on pregnancy-associated
QUS was used in order to detect and monitor skeletal
osteoporosis using QUS were published. Pregnancy-
changes during chemotherapy and radiotherapy in children
associated osteoporosis is probably diagnosed too rare, and
and adolescents with acute lymphoblastic leucaemia or other
QUS could be of special interest in pregnant females.
types of childhood malignancy [71-73]. In a prospective
study by Lequin et al. [72], in a group of 36 children
- Assessement of Bone Side Effects of Therapies
measured over a period of 3 years the most pronounced
The most important treatment affecting bone status is
decrease in tibial QUS parameter was observed in first 6
glicocorticotherapy, and in several studies QUS
months of therapy. After therapy completion slow process of
measurements showed an utility of calcaneal [54-57] and
improvement was noted. The study proved a possibility to
phalangeal measurements [58]. QUS variables were
monitor skeletal changes using QUS measurements. In other
decreased in a course of therapy. Calcaneus consisted of
longitudinal study hand measurements were performed in
almost only active metabolically trabecular bone seems to be
survivors of acute lymphoblastic leucaemia and 3 years after
better site of measurements in patients receiving
therapy completion skeletal status did not differ between
glicocorticoids but also hand phalanges showed an ability to
patients and controls [73]. It ought to be emphasized that the
follow bone changes [58]. Hand phalanges as a mainly
lack of ionizing radiation is especially important in young
cortical bone may be more prone to express bone changes
individuals with oncologic diseases and QUS could be used
due to secondary hyperparathyroidism commonly present
wider on this area.
under this therapy. Hand phalanges and calcaneus showed

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Quantitative Ultrasound in Diagnosis of Metabolic Bone Diseases
Current Medical Imaging Reviews, 2005, Vol. 1, No. 1 71
- Rheumatology
and environmental factors on bone status [90-92]. For
In patients with rheumatoid arthritis (RA), a prevalence
example, phalangeal QUS measurements showed correlation
of hip and spine fractures is high [74]. Therefore, skeletal
within pairs of monozygotic twins as high as 0.96-0.98, and
measurements in rheumatic patients may be important in
in dizygotic twins 0.92-0.93 [90]. Differences within pairs
order to assess fracture risk. Some studies have shown
increased with age what demonstrates the ability of the
possibilities of QUS in evaluation of skeletal status in such
method to follow changes due to environmental factors.
subjects. Martin and al. [75] proved that calcaneal QUS
QUS measurements in mother and their daughters
measurements were significantly lower in patients with RA
allowed to predict future QUS values in daughters [22]. In
than in controls. Similar data were given by phalangeal
the study were evaluated 21 fractured mothers, their 21
measurements [76,77]. It seems that phalanges may be
daughters and 27 non-fractured mothers and their 27
especially fitted in estimation of bone status because activity
daughters. As expected, mothers with past fractures had
of a disease is high within hand. Low calcaneal QUS values
lower QUS values than other mothers, and the same view
were also shown in patients with lupus erythematosus [78].
gave a comparison in daughters. Heritability of QUS values
in daughters of mothers with fracture ranged from 52 to
- Immobilization
76%, and only in their daughters future QUS values could be
Long-term immobilization is one of well established risk
predicted as shown by stepwise, multiple regression analysis.
factors of osteoporosis [79]. In stroke patients
Recently, calcaneal QUS measurements showed an
immobilization may lead to “hemiosteoporosis”. In this
ability to detect an influence of cigarette smoking on current
group of patients are common hip fractures; 4-15% of total
skeletal status what was not possible to obtain using DXA
number of subjects with hip fractures occur in patients after
[93]. This study suggests that QUS was able to express some
stroke, and 79-100% of hip fractures were present within
qualitative features of bone tissue what was not possible to
affected side [80,81]. Our yet unpublished data indicate that
obtain using routine densitometric measurements.
in patients being almost 3 years after a stroke, hand
phalangeal measurements were significantly lower in
In some studies QUS was used as a method evaluating
affected side in comparison to opposite side. Haddaway et
skeletal status in patients with genetic disorders and QUS
al. [82], in a group of 31 stroke patients being 1 month to 25
values were lower both in calcaneus [94] and hand phalanges
years (mean age is not given) did not observe differences
[95]. In 170 subjects with mental retardation QUS at the
between calcaneal QUS values in affected side versus results
calcaneus showed low values in comparison to 108 healthy
in opposite site. However, the authors observed a positive
controls. Low phalangeal QUS results were noted in patients
correlation of patients’ mobility and QUS parameters.
with Down syndrome, single-gene human defects and in
other rare abberations but subjects with Marfan-Mass
In a prospective study by Warden et al. [83], a rapid rate
phenotype did not differ from controls [95].
of a decrease in calcaneal QUS measurements was observed
An interesting data on strategy how to use QUS
in first two months following spine cord injury what proved
measurements in identification of women at high risk for hip
an ability of method to monitor bone changes due to
fracture were shown by EPIDOS prospective study [96]. The
immobilization. Also in subjects after brain injury
study population consisted of 5910 women and four
immobilized for long period calcaneal QUS values were
strategies to identify elderly women with risk for hip fracture
diminished by 40% [84].
greater than 20 per 100 woman-year were evaluated alone,
- Endocrinology
QUS followed by densitometric measurement or
densitometric measurement followed by clinical evaluation.
Disorders of endocrine system may significantly affect
The authors considered that a strategy including QUS
skeletal status. Among other methods also QUS was
followed by densitometric measurements allows to improve
successfully used in order to assess bone side effects [85-89].
identification of women at high risk.
QUS values were decreased in patients with Cushing
syndrome [85]. QUS was used to evaluate bone status in
In several studies QUS parameters were correlated with
girls treated by growth hormone [89], and in women on
DXA parameters and usually correlations between them
long-term therapy using non-supressive doses of thyroid
were weak to moderate [1,2]. The lack of strong
hormones QUS values at calcaneus were decreased in
relationships is obvious because QUS and DXA express, at
comparison to controls [88]. The latter observation seems of
least partly, different features of bone tissue. Therefore, QUS
clinical importance because the number of females taking
and DXA ought to be treated rather as complementary than
thyroid hormones is high and bone-side effects in this group
competitive methods.
of patients usually is not adequately estimated. An important
CONCLUSIONS
endocrinological risk factor for osteoporosis is primary
hyperparathyroidism, and in some studies calcaneal and
Results of the studies described in the current paper
phalangeal QUS was used to detect and monitor skeletal
indicate that a potential of QUS is really great. Despite
changes before and after surgery [85,87]. It was possible to
worldwide use of QUS, this method is not commonly
detect baseline low values and to follow a process of recover
recommended in a clinical practice for bone metabolic
after successful therapy.
diseases. What ought to be improved before acceptance of
the value of QUS:
- Other
- firstly, basic studies ought to provide an exact information
QUS served also to follow bone status in other groups. In
which bone features are measured by QUS (SOS or BUA
twins QUS proved an ability to assess an influence of genetic
only express some bone features),

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72 Current Medical Imaging Reviews, 2005, Vol. 1, No. 1
Drozdzowska and Pluskiewicz
- secondly, hip and spine could be measurable by QUS,
[21]
Bauer DC, Gluer CC, Cauley JA, et al. Broadband ultrasound
attenuation predicts fractures strongly and independently of
- thirdly, relatively poor precision needs corrections,
densitometry in older women: A prospective study. Study of
Osteoporotic Fractures Research Group. Arch Int Med 1997; 157:
If these conditions would be fulfilled, the nature of QUS
629-634.
measurements will be better understood and allowed for
[22]
Pluijm SMF, Graafmans WC, Bouter LM, et al. Ultrasound
wider clinical applications.
measurements for the prediction of osteoporotic fractures in elderly
people. Osteoporos Int 1999; 9: 550-556.
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Received: October 17, 2004
Accepted: October 22, 2004

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