1. Using Quantitative Ultrasound (QUS) measurements of the calcaneus to
predict vertebral bone mineral density (BMD) and fracture risk.
Quantitative Ultrasound
Quantitative Ultrasound (QUS) is used to identify changes in bone tissue bought about by
aging, menopause and osteoporosis as well as changes in activity levels and nutrition.
Measurements of Broadband Ultrasound Attenuation (BUA) and Speed of Sound (SOS) can
provide clinicians and researchers with information that can be used to determine fracture
risk, monitor skeletal changes and the efficacy of treatments and interventions and, also, as
a basis for comparison with normative data from a given population.
Fig. 1: Brandi, M. (2009) Microarchitecture, the key to bone quality. Rheumatology. 48, iv3-iv8.
A mechanical wave is passed through the bone with a frequency between 20 kHz-150MHz.
The shape, intensity and speed of the wave are altered by the physical and mechanical
properties of the bone. The velocity and attenuation of the wave are measured in metres
per second (m/s) and decibels per megahertz (dB/Mhz) respectively. The values measured
are dependent on the bone mineral content (BMC), microstructure and elasticity of the
mineralized bone matrix (Babatunde & Forsyth, 2013). Studies obtained post-mortem on 20
elderly human calcanei have shown a significant relationship between BUA and density and
that BUA of the calcaneus is a good predictor of the elasticity (R2
= 75.7%) and compressive
strength (R2
= 73.6%) of cancellous bone (Langton, Njeh, Hodgkinson & Currey, 1996).
Normal bone:
Trabecular architecture
Osteoporotic bone:
Trabecular architecture
Fig. 2: Relationship between apparent
density and nBUA of cancellous bone
samples. Linear data.
Langton, Njeh, Hodgkinson & Currey, (1996)
Prediction of mechanical properties of the human
calcaneus by broadband ultrasonic attenuation.
Bone. 18 (6), 495-503.

2. Whilst it has been shown that in increase in the mineralisation of cancellous bone improves
it’s stiffness (Follet, Boivin, Rumelhart and Meunier, 2004) the sound waves are absorbed,
scattered and travel in such a manner that depends not just on the stiffness but on the
elasticity, volume and density of the material as well (Gregg et al., 1997) therefore QUS
values are influenced by BMD and bone structure or bone architecture (Njeh, Fuerst, Diessel
& Genant, 2001).
QUS and Precision
Graafmans, Lingen, Ooms, Bezemer & Lips (1996) studied the precision of QUS
measurements of the calcaneus and found that no significant differences between readings
of BUA and SOS in short-term (5 consecutive measurements in 1 hour) and long-term (6
within 6 months) measurements. They also found that QUS measurements of the calcaneus
correlated well with BMD at the same site.
It is recommended that a manufacturer supplied ‘phantom’ is used as a diagnostic tool prior
to measuring in order to check correct function of the scanning device. The probes should
also be clean, the foot being scanned should be still and in exactly the same position on
each subsequent occasion and ultrasound gel should be used taking care to remove any
remaining old gel beforehand. Ambient temperature should also be taken and ideally be the
same for subsequent measurements (Guglielmi & de Terlizzi, 2009).
Frost, Blake & Fogelman (1999) examined the precision of QUS in a study consisting of 422
healthy women with no risk factors associated with osteoporosis and 93 women with one or
more vertebral fractures. They suggested that changes in the mechanical loading of the
calcaneus may be due to a change in dynamic posture bought about by the pain associated
with vertebral fractures. They also suggested that bone structure would change due to
immobility.
Fig. 3: For a given deficit of 10% in trabecular density,
the loss of strength is greater when this is caused by
reduced trabecular number than by reduced
trabecular thickness.
Seeman, E. (2008). Bone quality: the material and
structural basis of bone strength. Journal of Bone and
Mineral Research. 26, 1-8.

3. BUA measurements can be positively affected by certain activities. Jones, Hardman, Hudson
& Norgan (1991) have shown that brisk walking increases BUA at the calcaneus through the
osteogenic effect of the heel-strike which causes strain related remodeling.
QUS measurements at the calcaneus are commonly taken in the mediolateral direction
along the transverse axes. This method shows good correlations between all ultrasonic
measurements and BMD (Nicholson et al., 1998).
Applications of QUS
QUS appears to perform similarly in men and women (Moayyeri et al., 2012) and is at least
comparable to DXA in the prediction of fractures in the elderly (Moayyeri et al., 2009).
Lifestyle factors such as physical activity, alcohol consumption and smoking can affect QUS
measurements (Pye et al., 2010) and modification of these factors may help reduce the risk
of fracture (Pye et al., 2010). A review of cross-sectional studies suggests that lower QUS
values are related to an increased risk of fractures and low bone mass (Gregg et al., 1997)
and the EPIC-Norfolk study of 14,824 men and women aged 42-82 years showed that
quantitative calcaneum ultrasound predicts total and hip fracture risk in men and women
(Khaw, Reeve, Luben, Bingham, Welch, et al., 2004).
Unlike DXA QUS does not measure Bone Mineral Density (BMD) directly however QUS can
provide indirect information on BMD as well as more direct information on bone micro-
architecture. Bone micro-architecture (trabecular number, connectivity and orientation) is
an important component of bone quality and therefore bone strength. Recent studies have
looked at combining Trabecular Bone Score (TBS) with BMD in order to ascertain fracture
risk (Roux, Wegryzn, Boutroy, Bouxsein, Hans & Chapurlat, 2013; Hans, Goertzen, Krieg &
Leslie, 2011) because BMD alone cannot provide sufficient information to determine bone
quality. An increase in BMD may not necessarily result in an improvement in bone strength
as the improved area may be the discontinuous end of a bony trabeculum as opposed to
strengthening a joined trabecular structure (Khan et al., 2001).
E., Chappard, D., Pascaretti, C., DuQuenne, M., Krebs, S. Rohmer,
V. & Basle, M. (2000) Trabecular Bone Microarchitecture, Bone
Mineral Density and Vertebral Fractures in Male Osteoporosis.
Journal of Bone and Mineral Research. 15 (1), 13-19.
Fig.3: When BMD alone is not enough, the combinationof BMD +
TBS enables to identify patients with high risk of fracture likely to
have fractures whereas the patients are in the osteopenic zone

4. In osteoporosis there is a decline in the compressive strength of the vertebrae bought about
by changes on the trabecular density which increases the risk of fracture (Briggs , Greig,
Wark, Fazzalri, Bennell. 2004). Whilst QUS has been officially declared as an alternative
technique for assessment of osteoporosis (Gluer, 1997) Dual X-Ray Absorptiometry (DXA) is
the current preferred method for assessing osteoporosis (National Osteoporosis Society,
2001). However QUS has many benefits over DXA. It is comparatively inexpensive to run,
easy to use, requires no expensive preparation of the testing area, has no ionizing radiation
and is very portable.
BUA is determined trabecular structure and density and SOS is influenced by BMD and bone
elasticity. There is a linear relationship between BMD and BUA and SOS. (Hans, Fuerst and
DuBoeuf, 1997). With the values for BMD and SOS stiffness can be calculated using the
equation (0.67 x BUA + 0.28 x SOS) – 420 (Yamamoto, Kishimoto and Katagiri, 1997). Bone
stiffness of the calcaneus has been shown to be a good indicator of risk of vertebral fracture
(Frediani et al., 2006).
The most popular site for QUS measurements is the calcaneus. The calcaneus is
approximately 90% cancellous bone (Yamamoto, Kishimoto and Katagiri, 1997) with
relatively flat sides providing easy access and good contact areas. It is also thought to
accurately reflect the condition of the proximal femur and the spine in terms of
environmental mechanical stress and particularly the vertebrae which also has a very high
percentage of cancellous bone. Changes in bone mass are greater and occur earlier in
trabecular bone than in bones that are primarily corticol.
QUS and Bone Mineral Density
BMD measurements are used to assess osteoporosis A reduction in BMD of 1 SD of the
population is associated with 2-4 times higher fracture risk. However decreased BMD is only
one of several factors influencing bone fragility. (Hans, Fuerst and DuBoeuf, 1997). Changes
in bone quality, which QUS measures, are stronger predictors of fracture risk than clinical
risk factors (National Osteoporosis Society, 2001). In a study of 654 women Yamamoto,
Kishimoto and Katagiri (1997) demonstrated that QUS measurements were more sensitive
than BMD in diagnosing vertebral fracture and for evaluating fracture risk. 89 women
(14.7%) had vertebral fracture 42 (9.3%) of the 451 healthy women and 47 (23.2%) of the
osteoporotic women). In the osteoporotic group QUS values decreased after 1 year even
though BMD had increased suggesting QUS parameters represent bone properties other
than BMD. An increase in BMD may not always be accompanied by an increase in bone
strength. In a study of 91 female subjects (aged 56.9 + 9.6 years) 30 categorised as normal,
38 oseopenic and 23 osteoporotic Langton & Langton (2000) found that QUS calcaneal
measurements and BMD as measured by DXA were comparable in their discriminatory
ability to identify osteoporotic or osteopenic subjects.

5. QUS and Bone Micro-Architechture
Gonnelli S, Cepollaro C, Agnusdei D, Palmieri R, Rossi S, Gennari C. (1995) Found that SOS,
BUA and Stiffness were all independent predictors of fracture risk. Cheng et al. (1997) took
spinal BMD measurements using DXA and QCT and calcaneal measurements using DXA and
QUS of 62 adult cadavers and found calcaneal DXA, BMD, bone velocity and BUA correlated
well with each other (r2
– 0.67-0.76) but less so when compared with DXA and QCT
measurements of the vertebra. Their data also suggested that about 40% of the variability
of vertebral strength is unaccounted for by BMD measurements. They concluded that
ultrasound measurements of the calcaneus may reflect more fracture risk than bone
fragility.
Nicholson and Alkalay (2007) also found the predictive performance of QUS measurements
of vertebral bodies comparable to or greater than BMD when predicting vertebral failure
load. Mezaros et al. (2007) have reached a more specific conclusion. Their results suggest
that BUA values are closely related to BMD but that SOS values are able to predict fractures.
They found no connection between BUA and vertebral fracture risk but a strong positive
association between SOS and vertebral fracture risk. SOS is thought to be influenced by
mineral density and the elastic characteristics of bone and BUA is thought to be influenced
by the structural characteristics of bone and by bone mass (Mezaros, et al. 2007).
In a study of 463 women aged 20-39 and 2,374 women aged 55-79 Gluer et al., (2004) found
that QUS of the calcaneus worked as well as central DXA for identification of women at high
risk for prevalent osteoporotic vertebral fractures. Mariconda et al., 2004 studied 117
patients with low back pain and found that evidence of degenerative changes and stenosis
in the lumbar spine correlated with ultrasonographic parameters (SOS and stiffness) of the
calcaneus, p = 0.019 for SOS and p = 0.039 for stiffness.
Pluijm, Graafmans, Bouter & Lips, (1999) studied 132 men and 578 women aged 70 years
and older (mean age + SD: 82.8 + 5.9) over a 1 year period and found that low BUA values
and immobility were the strongest predictors of hip fracture as well as any other fracture
including pelvic and femoral fractures.
QUS can provide information on the ‘non-mass’ characteristics of bone. In a study of 108
men LeGrand et al., (2000) found that bone trabecular micro-architecture is a major
determinant of vertebral fractures in middle-aged men with severe osteopenia. They
concluded that the biomechanical competence of bone is not dependent on BMD alone but
also its three-dimensional configuration. A meta-analysis by Marin, Gonzalez-Macias, Diez-
perez, Palm & Delgado-Rodriguez (2006) found that the values of the parameters measured
by QUS at the calcaneus are lower in women with a history of osteoporotic fracture
regardless of the BMD values determined by DXA.

6. QUS and Vertebral Fracture
Since a significant proportion of vertebral fractures are asymptomatic (Mezaros et al., 2007)
QUS measurements could be an easy to use, inexpensive and quick method to better
distinguish between those who are more likely to benefit from a more expensive DXA or
QCT scan. A low QUS reading may also highlight those who are asymptomatic but who could
be suffering from a vertebral fracture or who are more at risk of suffering any fracture
including a vertebral one and this would allow better targeting of preventative care. Frost,
Blake & Fogelman (1999) found that contact ultrasound can detect age and menopause
related changes in bone status in women and that it can also distinguish between healthy
women and women with a vertebral fracture.
QUS measurements of the calcaneus have been shown to predict the risk of hip and non-
spine fracture in men (Bauer et al., 2007) and predict risk of vertebral fracture in
postmenopausal women in vivo (Bauer, Gluer, Genant & Stone, 1995) although one study
has shown that QUS measurements of the calcaneus in vitro are poor predictors of vertebral
strength (Cheng et al, 1997). In a study of 566 postmenopausal women (mean age 74 + 5)
QUS measurements of the calcaneus have been shown to predict vertebral deformity and
that spine BMD measurements provided no additional information (Ross, Huang, Imose,
yates, Vogel & Wasnich, 1995). In a retrospective, cross-sectional study looking specifically
at the relationship between calcaneal ultrasonometry and vertebral fracture risk Frediani et
al., (2006) selected 764 post-menopausal women with non-traumatic vertebral fractures
and 770 women with normal morphometry as a control group and found that QUS stiffness
measurements of the calcaneus were valid and reliable predictors of vertebral fracture even
when correcting for confounding factors such as age, weight, height and years since
menopause and they concluded that QUS of the calcaneus is an excellent substitute for
BMD of the axial skeleton by DXA. Huopio et al., (2004) found that calcaneal QUS is able to
predict early postmenopausal fractures as well as or even better than axial BMD. They
found a 1SD decrease in BUA values increased the risk of future fracture by 43% equalling
the risk of 1SD decrease in spinal BMD however only QUS measurements were able to
predict risk of fracture when allowing for confounding variables.
Conclusion
QUS measurements of BUA and SOS at the calcaneus can provide useful information on
bone quality of the calcaneus. Research shows that these measurements can help predict
total fracture risk including hip and vertebral fracture risk in men and pre and post-
menopausal women. QUS measurement of the calcaneus is a relatively inexpensive,
portable, easy to use and quick to administer test that requires no special environmental
adaptations since there is no ionizing radiation. Measuring bone quality may be an adequate

7. if not better substitute for measuring BMD. QUS measurements may help to identify those
at risk of fracture without incurring significant costs.
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