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DOI 10.1007/s00774-015-0708-9

1 3


Association between bone indices assessed by DXA, HR‑pQCT
and QCT scans in post‑menopausal women

Anne Kristine Amstrup1 · Niels Frederik Breum Jakobsen1 · Emil Moser1 ·
Tanja Sikjaer1 · Leif Mosekilde1 · Lars Rejnmark1

Received: 30 January 2015 / Accepted: 22 July 2015 / Published online: 21 August 2015
© The Japanese Society for Bone and Mineral Research and Springer Japan 2015

weak to moderate. Our data suggest that the various tech-
niques measure different characteristics of the bone, and
may therefore be used in addition to rather than as a replac-
ment for imaging in clinical practice.

Keywords aBMD · vBMD · QCT · DXA · HR-pQCT


Osteoporosis is a metabolic disorder resulting from
changes in bone mineral density, bone geometry and micro-
structure that leads to an increased susceptibility to frac-
tures. Currently, diagnosis of osteoporosis is based on areal
bone mineral density (aBMD; g/cm2) values gained from
2D techniques (dual X-ray absorptiometry or DXA scans).
However, aBMD has been shown to be only a partial pre-
dictor of fracture risk [1, 2]. This may in part be due to the
fact that 2D measures do not fully reflect the distribution
of bone mass, including the relative contribution from cor-
tical and trabecular bone or the microarchitecture of the
bone matrix. For these aspects, imaging techniques such
as quantitative computed tomography (QCT) and high-
resolution pQCT (HR-pQCT) may present much better
alternatives. QCT techniques enable measurements at cen-
tral sites such as lumbar spine and hip [3] and are consid-
ered to measure true volumetric BMD (vBMD; mg/cm3).
HR-pQCT, an improved detector technique combined with
beam acquisition originally designed for micro-computed
tomography, permits in vivo assessment of trabecular and
cortical architecture and vBMD at distal sites such as the
tibia and radius [4]. In addition, these images can be used
for microstructural finite element analysis (FEA) that inte-
grates BMD with bone geometry and structure to estimate
bone strength under various loading conditions [4].

Abstract Quantitative computed tomography (QCT),
high-resolution peripheral QCT (HR-pQCT) and dual
X-ray absorptiometry (DXA) scans are commonly used
when assessing bone mass and structure in patients with
osteoporosis. Depending on the imaging technique and
measuring site, different information on bone quality
is obtained. How well these techniques correlate when
assessing central as well as distal skeletal sites has not
been carefully assessed to date. One hundred and twenty-
five post-menopausal women aged 56–82 (mean 63) years
were studied using DXA scans (spine, hip, whole body
and forearm), including trabecular bone score (TBS), QCT
scans (spine and hip) and HR-pQCT scans (distal radius
and tibia). Central site measurements of areal bone mineral
density (aBMD) by DXA and volumetric BMD (vBMD)
by QCT correlated significantly at the hip (r = 0.74,
p < 0.01). Distal site measurements of density at the radius
as assessed by DXA and HR-pQCT were also associated
(r = 0.74, p < 0.01). Correlations between distal and cen-
tral site measurements of the hip and of the tibia and radius
showed weak to moderate correlation between vBMD by
HR-pQCT and QCT (r = −0.27 to 0.54). TBS correlated
with QCT at the lumbar spine (r = 0.35) and to trabecu-
lar indices of HR-pQCT at the radius and tibia (r = −0.16
to 0.31, p 120 µmol/l),
diagnosed with malignant disease within 2 years, intestinal
malabsorption, abuse of alcohol, medical condition known
to affect bone including drugs with effects on calcium
homeostasis and bone metabolism. None of the study sub-
jects were on treatment with experimental drugs at the time
of investigations.

All subjects studied were recruited to the respective
studies by a mailed letter send to a random sample of the
general background population inviting them to participate
in the studies.

All subjects provided informed consent prior to par-
ticipation in the studies. All studies were approved by the
regional ethics committee (#M-2010-0296; #M2012-252-
12; #M2011-0260).

The following measurements were conducted as a part
of an integrated study program for the subjects; i.e. all
scans were performed within 2 weeks of each other.

Osteodensitometry by DXA

We measured areal bone mineral density (aBMD; g/cm2)
on the right forearm, lumbar spine (L1–L4), the left hip
region, and whole body (sub-total) using a Hologic Discov-
ery scanner (Hologic, Inc., Waltham, MA, USA). The fore-
arm included radius + ulnaris (total, ultra-distal, one-third
and mid). For each scan, the system automatically calcu-
lates the region of interest (ROI). When evaluating the fore-
arm, the ROI is based on the length of the forearm divided
by three, plus 10 mm to allow for the ultra-distal region.

According to the product information, the total radia-
tion dose was a maximum of 0.95 mSV, equal to approx.
120 days of normal background radiation in Denmark [16].


At the distal tibia and distal radius, we measured volu-
metric bone mineral density (vBMD; mg/cm3), geometry,
microarchitecture, and strength on the right side using
a high-resolution pQCT scanner (Xtreme CT scanner,
Scanco Medical AG, Brüttisellen, Switzerland). Each scan
comprised 110 slices corresponding to a 9.02-mm axial 3D
representation with an isotropic voxel size of 82 µm. The
tibia and radius were immobilized in a carbon fibre cast
during the measurements. A scout view was used to define
the measurement region, using an offset from the endplate
of the radius and tibia by 9.5 and 22.5 mm, respectively.
Daily and weekly phantom scans were performed.

640 J Bone Miner Metab (2016) 34:638–645

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According to the manufacturer’s default methods (by
Xtreme CT scanner, Scanco Medical AG), trabecular bone
density (Dtrab) was calculated as an average mineral den-
sity within the trabecular region assuming a density of fully
mineralized bone of 1.2 mg hydroxyapatite (HA)/cm3,
thereby calculating trabecular bone volume per tissue vol-
ume (BT/BV) [17].

Trabecular architecture was assessed as trabecular num-
ber (Tb.N), which was obtained using a model-independent
distance transformation method; trabecular thickness (Tb.
Th) and trabecular spacing (Tb.Sp) were then derived from
BV/TV and Tb.N [Tb.Th = (BV/TV)/Tb.N; Tb.Sp = (1−
BV/TV)/Tb.N]. Cortical thickness (Ct.Th) was measured
according to the manufacturer’s standard patient protocol.

In addition, HR-pQCT images were used for FEA [18].
Model solving was performed by Scanco FEA software
v1.13. The evaluation is described in detail by Hansen et al.
[19]. In short, bone voxels are converted into equally-sized
square elements resulting in approx. two and five billion
element models for radius and tibia, respectively. Accord-
ing to the product information from the manufacturer, the
radiation dose of each scan was <0.0030 mSV, which is
approximately equal to half a day of background radiation
[16]. The parameter of interest was failure load.

Quantitative computed tomography (QCT)

We measured vBMD (mg/cm3) at the lumbar spine (L1–
L2) and proximal femur by QCT using a Philips Brilliance
40-slice multidetector helical CT scanner (Phillips, Eind-
hoven, The Netherlands). We scanned with a dose modulation
tool (Z-DOM, Phillips) at a voltage of 120 kV. Slice thickness
and slice spacing were 3 mm. The field of view was 360 mm
and collimation was 40 × 0.625 mm. According to the manu-
facturer, the total radiation dose was a maximum of 2.75 mSV,
equal to less than 1 year of background radiation [16]. The
vBMD was determined using QCTPro (version 4.2.3, Mind-
ways Software, Inc., Austin, TX, USA) in conjunction with a
solid-state CT calibration phantom (Model 3, Mindways Soft-
ware), which was scanned simultaneously with the patients.
We performed analysis of the proximal femur by automatic
bone segmentation including the total hip and femoral neck
[20]. The separation algorithm for cortical bone was pre-set at
350 mg/cm3.

The reproducibility [coefficient of variation (CV%)] of
the analyses by QCTPro was calculated by repeating eval-
uation analyses of ten subjects’ data, showing a CV from
vBMD of 0.8 % at the total hip and 1.1 % at L1 + L2.

Trabecular bone score (TBS)

Lumbar spine TBS was extracted from DXA images using
iNsight software (Medimaps, France). The score was

evaluated by determination of the grey-level variations of
the anterior−posterior DXA image of the lumbar spine
[21]. A higher score indicates a better microstructure (high
trabecular number and connectivity and low trabecular sep-
aration). The mean value of each vertebra (L1–L4) was col-
lected into a single score.

Statistical analysis

We report results as mean ± standard deviation (SD) or
median with interquartile range (IQR 25–75 %) unless
otherwise stated. Associations between variables were
assessed by linear regression analyses calculating Pearson’s
correlation coefficient (r) and the regression coefficient
(β) with 95 % confidence interval (95 % CI). p < 0.05 was
considered statistically significant. We used IBM SPSS Sta-
tistics version 21 (IBM, New York, USA) for the statistical


Descriptive data are shown in Table 1. The mean age of the
participants was 63 years (range 56–82).


Correlations between TBS, aBMD values at different
skeletal sites, and indices of HR-pQCT at distal radius
and tibia are shown in Table 2. Significant correlations
were observed, and at distal sites, in particular at the dis-
tal radius, moderate to strong (r = 0.48–0.75) associations
were seen in relation to aBMD at the ultra-distal forearm.
Furthermore, moderate correlations were observed between
geometric indices of cortical area by tibia (r = 0.55) and
radius (r = 0.63), and aBMD at distal forearm (data not

Failure load of radius and tibia correlated significantly
with all skeletal sites (p < 0.01), and a strong correlation
(r = 0.80) was present between aBMD at the distal forearm
and failure load of distal radius by HR-pQCT. Overall, TBS
showed only weak correlation to trabecular indices of the
radius and tibia (r = −0.16 to 0.31, p < 0.01).

Adjusting the correlations for age did not change the
results (data not shown).


Table 3 shows correlations between peripheral HR-pQCT
measurements of radius and tibia and central vBMD
measurements by QCT at the lumbar spine and total hip.
At the radius and tibia, vBMD total bone density by HR-
pQCT correlated moderately with integral total hip vBMD

641J Bone Miner Metab (2016) 34:638–645

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(r = 0.54, r = 0.50, respectively). Cortical vBMD by
HR-pQCT and QCT showed correlation coefficients of
r = −0.39 at radius and r = −0.27 at tibia, while indi-
ces of trabecular vBMD correlated by r = 0.37 at radius
and r = 0.44 at tibia. Adjusting for age did not change the
results (data not shown).

Geometric indices of tibia and radius correlated weakly
to moderately with QCT sites (r = 0.19–0.48, data not
shown). The correlations with microstructural architecture
showed significance, although weak, at several measure-
ment sites.

Failure load at both tibia and radius showed weak or no
correlations with QCT vBMD.


Table 4 shows correlations between aBMD at different
skeletal sites and central sites of vBMD by QCT. At most
sites, significant correlations were present. A moderate to
strong correlation was seen between vBMD integral total
hip and aBMD total hip (r = 0.74). Integral vBMD at
femoral neck correlated significantly with aBMD at fem-
oral neck (r = 0.64). TBS showed weak correlation with
vBMD, with the highest value measured at the lumbar
spine (r = 0.35, p < 0.01).


In the present study we compared TBS, aBMD, vBMD,
geometry, microstructure and strength as measured by DXA,
QCT and HR-pQCT at central sites (hip and lumbar spine)
and peripheral sites (tibia and radius) on the same subjects.

Significant correlations were found at multiple skeletal
sites between aBMD and vBMD as measured by DXA and
HR-pQCT. In particular, distal site associations showed
agreement between aBMD at the ultra-distal forearm and
distal radius vBMD and failure load. Central site meas-
urements of the hip and femoral neck between integral
vBMD by QCT and aBMD by DXA reflected each other
with moderate to strong correlations. Peripheral and cen-
tral site measurements of vBMD by QCT and HR-pQCT
corresponded weakly to moderately in terms of total bone
density. TBS showed weak correlation with trabecular indi-
ces of peripheral as well as central sites by HR-pQCT and

In accordance with our study, Liu et al. [12] investigated
the association between DXA, HR-pQCT and QCT in pre-
menopausal women (N = 69, mean age 37.5 years). The
authors showed central site associations of the hip in agree-
ment with our results, although we demonstrated a stronger
association at distal sites compared to the study by Liu
et al. (r = 0.63–0.74 vs. r = 0.33–0.45). Compared to our
results, the authors reported stronger correlations between
central and distal sites measurements along with a stronger
association at the lumbar spine between aBMD and vBMD.

These differences may be due to the age differences and
menopausal status, as the mean age in the present study is
63 years. By age, osteoarthritis is known to affect DXA

Table 1 Descriptive data

Median with 25–75 % interquartile range

HA hydroxyapatite

Median (IQR)

Age (years), mean (range) 63 (56–82)

Height (cm) 165.0 (161.0–169.6)

Weight (kg) 67.1 (60.5–76.0)

BMI (kg/m2) 24.8 (22.2–27.5)

Smokers, n (%) 6 (5 %)

DXA BMD (n = 125)
Lumbar spine (g/cm2) 0.857 (0.808–0.952)

Hip, total (g/cm2) 0.795 (0.740–0.848)

Hip, neck (g/cm2) 0.654 (0.620–0.707)

Forearm, ultradistal (g/cm2) 0.319 (0.295–0.351)

Whole body, subtotal (g/cm2) 0.851 (0.810–0.907)

QCT (n = 98)
Spine, trabecular vBMD (mg/cm3) 98 (81–114)

Total hip, integral vBMD (mg/cm3) 253 (234–282)

Total hip, cortical vBMD (mg/cm3) 909 (878–938)

Total hip, trabecular vBMD (mg/cm3) 132 (120–142)


Distal radius (n = 118)
Total bone density (mg HA/cm3) 264 (220–302)

Cortical bone density (mg HA/cm3) 839 (782–881)

Trabecular bone density (mgHA/cm3) 125 (98–149)

Ct.Th (mm) 0.64 (0.49–0.74)

Tb.Th (mm) 0.06 (0.05–0.06)

Tb.N (mm−1) 1.80 (1.50–2.03)

Tb.Sp (mm) 0.50 (0.43–0.61)

TrBV/TV (mm) 0.10 (0.08–0.12)

Tb.N.SD (mm) 0.24 (0.18–0.34)

Failure load (N) 3038 (2708–3417)

Distal tibia (n = 123)
Total bone density (mg HA/cm3) 249 (216–278)

Cortical bone density (mg HA/cm3) 819 (784–851)

Trabecular bone density (mg HA/cm3) 149 (123–168)

Ct.Th (mm) 0.91 (0.75–1.06)

Tb.Th (mm) 0.07 (0.06–0.08)

Tb.N (mm−1) 1.69 (1.48–1.91)

Tb.Sp (mm) 0.52 (0.46–0.59)

TrBV/TV (mm) 0.12 (0.10–0.14)

Tb.N.SD (mm) 0.24 (0.20–0.31)

Failure load (N) 8579 (7891–9690)

642 J Bone Miner Metab (2016) 34:638–645

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measurements [22] especially in the spine, which may
explain our weak correlation. Furthermore, although our
results did not differ after adjusting for age, the correla-
tions may still be affected by age, as multiple factors such
as hormonal changes and bone loss rates change following
menopause [23].

The present study showed agreement between distal
site measuring techniques in terms of aBMD by DXA and
vBMD by HR-pQCT. This is most likely explained by the

area of interest being closely situated in the two techniques,
and our findings are in accordance with other studies [24–
26]. Furthermore, in both scanning techniques, the right
forearm was the primary arm chosen for the scans, making
the correlation more precise, as small differences between
right and left may exist [27].

In general, central site measurements corresponded weakly
to moderately to distal sites, which indicates that peripheral
measures do not completely reflect the bone composition of

Table 2 Correlation between
indices assessed by DXA and
HR-pQCT scans. Pearson’s
correlation coefficient (r)

HA hydroxyapatite

* p < 0.05; ** p < 0.01



spine, aBMD

Total hip,

forearm, aBMD




Total bone density
(mg HA/cm3)

0.19* 0.17* 0.44** 0.74** 0.33**

Cortical bone
density (mg HA/

0.07 0.08 0.37** 0.48** 0.19*

Trabecular bone
density (mg HA/

0.31** 0.31** 0.31** 0.75** 0.35**


Ct.Th (mm) 0.08 0.12 0.39** 0.57** 0.24**

Tb.Th (mm) 0.17* 0.09 0.20* 0.46** 0.15*

Tb.N (mm−1) 0.25** 0.27** 0.16* 0.54** 0.24**

Tb.Sp (mm) –0.24** −0.23** −0.11 −0.43** −0.18*
TrBV/TV (mm) 0.31** 0.30** 0.28** 0.73** 0.30**

Tb.N.SD (mm) −0.21* −0.18* −0.09 −0.33** −0.11

Failure load (N) 0.29** 0.43** 0.47** 0.80** 0.40**



Total bone density
(mg HA/cm3)

0.10 0.14 0.43** 0.63** 0.28**

bone density
(mg HA/cm3)

0.10 0.17* 0.29** 0.44** 0.17*

bone density
(mg HA/cm3)

0.12 0.11 0.36** 0.62** 0.31**


Ct.Th (mm) 0.06 0.12 0.35** 0.46** 0.26**

Tb.Th (mm) 0.06 −0.09 0.05 0.36** 0.08
Tb.N (mm−1) 0.09 0.24** 0.40** 0.46** 0.30**

Tb.Sp (mm) −0.09 −0.17* –0.35** −0.46** −0.26**
TrBV/TV (mm) 0.13 0.11 0.36** 0.62** 0.31**

Tb.N.SD (mm) −0.16* −0.13 –0.30** −0.33** −0.18*

Failure load (N) 0.20* 0.38** 0.45** 0.66** 0.46**

643J Bone Miner Metab (2016) 34:638–645

1 3

the central sites. This is further supported by Tsurusaki et al.
[25], suggesting that correlation values are influenced by the
measurement area as different bone loss patterns are seen in
trabecular and cortical compartments, and between weight-
bearing and non-weight-bearing portions. In addition, despite
demonstrating similar aBMD at the spine, Kazakia et al. [24]
showed a large heterogeneity in peripheral site measurements
in 52 post-menopausal women. HR-pQCT measurements of
tibia and radius showed completely different bone structures,

and in particular values of microarchitecture differed by
50–100 % between the subjects [24].

In line with other studies, we found moderate to strong
correlations between central site measurements of the total
hip and femoral neck [12, 28]. Our results indicated that
DXA aBMD of the hip may only to some extent provide an
indication of bone health and fracture risk, and the addition
of 3D images with their information on bone distribution is
still needed.

On the basis of our data, we suggest that further stud-
ies on the ability of the scanning modalities are still needed
to predict the fracture risk and treatment response in osteo-
porotic patients. Owing to its cost, effectiveness and acces-
sibility, DXA is still the first choice when evaluating bones.
As HR-pQCT scanners are easy to use and radiation dose
is low, this is an attractive additional measuring technique
that will most likely become more widespread. Despite the
additional information gained from central site QCT scans,
the radiation dose is high compared to the other techniques.

When used in clinical practice it must be emphasized
that despite the various techniques available, the imagin-
ing techniques may be used in addition to rather than in
replacement of each other.

The relationship between TBS and QCT, and HR-pQCT
has only been sparsely investigated. A study by Silva et al.
[13] investigated these correlations in 115 pre- and post-
menopausal women, and in partial accordance with our
results the authors demonstrated weak to moderate associa-
tions with TBS. The results were further supported by Popp
et al. [29] in 72 healthy pre-menopausal women, showing
similar correlations. As TBS reflects the heterogeneity of
trabecular structures of lumbar vertebrae, it is taken into
account in the descriptions of its correlations that it should
correlate more strongly with trabecular indices than with
cortical parameters. The relatively weak correlations, how-
ever, may suggest that TBS reflects other properties of bone
than traditional density measurements. This is further sup-
ported by Silva et al. [13], explaining the findings due to
differences in trabecular microstructure between central
and peripheral sites.

There are several strengths to the study. This is, to our
knowledge, the first study of its kind among post-meno-
pausal women to demonstrate the correlations between
aBMD, vBMD, microstructure and strength at central and
peripheral sites using DXA, QCT and HR-pQCT. The fact
that our study group consisted of post-menopausal women
heightens its importance, as the major bone changes appear
around menopause.

There are, however, limitations to our study. Our popula-
tion was heterogenic and consisted of normal, osteopenic
and osteoporotic women, resulting in a very wide spectrum
of BMDs.

Table 3 Correlations between indices assessed by HR-pQCT and
QCT scans. Pearson’s correlation coefficient (r)

HA hydroxyapatite

* p < 0.05; ** p < 0.01


HR-pQCT Lumbar

Total hip

Trabecular Integral Cortical Trabecular



Total bone density
(mg HA/cm3)

0.32** 0.54** −0.37** 0.44**

Cortical bone density
(mg HA/cm3)

0.29** 0.49** −0.39** 0.33**

Trabecular bone den-
sity (mg HA/cm3)

0.18* 0.29** −0.19* 0.37**


Ct.Th (mm) 0.32** 0.48** −0.37** 0.34**
Tb.Th (mm) 0.18* 0.30** −0.07 0.20*
Tb.N (mm−1) 0.11 0.11 −0.12 0.27**
Tb.Sp (mm) −0.01 −0.05 0.13 −0.18*
TrBV/TV (mm) 0.18* 0.29** −0.19* −0.37**
Tb.N.SD (mm) −0.00 −0.07 0.14 −0.14


Failure load (N) 0.25** 0.28** −0.26** 0.27**
Tibia (mg HA/cm3)


Total bone density 0.30** 0.50** −0.32** 0.51**
Cortical bone density

(mg HA/cm3)
0.25** 0.39** −0.27** 0.28**

bone density
(mg HA/cm3))

0.24** 0.32** −0.17* 0.44**


Ct.Th (mm) 0.25** 0.44** −0.37** 0.36**
Tb.Th (mm) 0.15 0.21* −0.08 0.23*
Tb.N (mm−1) 0.15 0.18* −0.14 0.31**
Tb.Sp (mm) −0.17* −0.18* 0.10 −0.30**
TrBV/TV (mm) 0.24** 0.32** −0.17* 0.44**
Tb.N.SD (mm) −0.18* −0.24** 0.14 −0.30**


Failure load (N) 0.18 0.17 −0.18* 0.26**

644 J Bone Miner Metab (2016) 34:638–645

1 3

In conclusion, there was moderate to strong agreement
between measuring techniques in terms of DXA, HR-
pQCT and QCT when assessing the same area in post-
menopausal women. However, when assessing correla-
tions between central and distal sites, the associations were
only weak to moderate. Our data suggest that the various
techniques measure different characteristics of bone, and
in clinical practice they can only supplement rather than
replace each other. In addition, the study calls for further
research on the ability of the different scanning modalities,
alone or in combination, to predict risk of fractures and
responses to treatment of patients with osteoporosis.

Acknowledgments Acquisition of the XtremeCT scanner was sup-
ported by the Karen Elise Jensens Foundation, A.P. Møller og hus-
tru Chastine MC-Kinney Møllers Foundation, the Central Denmark
Region, the Danish Osteoporosis Patient Union and Toyota Founda-
tion, Denmark.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of
interests regarding the publication of this paper.


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