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Applicability of Quantitative Ultrasonography of the Radius and Tibia in
HIV-Infected Children and Adolescents
Stefano
1
Mora ,
Laura
2
Cafarelli ,
Giulia
2
Pattarino ,
Vania
Gianvincenzo
2
Zuccotti ,
Chiara
Alessandra
2
Cerini ,
Valentina
2
Fabiano ,Clara
3
Gabiano ,
2
Viganò
Department of Pediatrics
L. Sacco Hospital
Via G.B. Grassi 74
20157 Milano
Italy
Phone +39-0239042253
Fax: +39-0239042254
Raffaele Scientific Institute, Milan, Italy, 2L. Sacco Hospital, University of Milan, Italy, and 3Regina Margherita Hospital, University of Turin, Italy.
ABSTRACT
Background. Bone health assesment is becoming an emerging issue in HIVinfected children and adolescents. Dual-energy x-ray absorptiometry (DXA) has
become the most commonly employed method for the assessment of bone health
worldwide. However its wide implementation in growing individuals is hampered by
cost, radiation exposure and size dependency of the measurements. Quantitative
ultrasonography (QUS) has a special appeal for studying bone in children because
of its speed, low cost, lack of ionizing radiation and use of portable devices. To
assess the applicability of QUS measurements in HIV-infected children, we related
QUS bone measurements with those obtained by DXA.
Methods. We studied 88 HIV-infected youths, aged 4.8 to 22.1 years (43 boys and
45 girls). Seventy % of the patients had undetectable HIV viral load. Seventy-six
patients were receiving a protease inhibitor or non-nucleoside reverse transcriptase
inhibitor-based HAART, six patients were receiving a double nucleoside reverse
transcriptase inhibitor regimen and six patients were naïve to antiretroviral
treatment. Speed of sound (SOS) was measured at the mid-shaft of the tibia and at
the distal radius of non-dominant limb using a Sunlight Omnisense 7000 device.
Bone mineral content (BMC) and density (BMD) of the lumbar spine, the whole
skeleton, and the mid-shaft of the tibia were measured by DXA (DPX-L, GELunar).
Results. The mean of SOS measurements at the radius was 3896 (15) m/s, while
the mean SOS of the tibia was 3797 (16) m/s. SOS of the radius correlated to
lumbar spine BMC (r=0.48) and BMD (r=0.54), whole body BMC (r=0.37) and
BMD (r=0.45) and SOS of the tibia correlated to lumbar spine BMC (r=0.63) and
BMD (r=0.65), whole body BMC (r=0.58) and BMD (r=0.62). BMC and BMD of
the mid-shaft of the tibia correlated with corresponding SOS measurements
(r=0.44 and r=0.50, respectively).
Conclusions. The correlations between DXA and QUS indicate that the latter may
be an additional diagnostic tools available to the pediatrician in the study of HIVinfected youths. Although the use of ultrasound to predict fracture risk is still
debated, there is evidence that SOS measurements are lower in children with
fractures compared to non-fractured controls. Therefore, QUS could be a valid
alternative in resource and non resource limited setting were more complex devices
for bone health assessment in pediatric HIV are not available.
INTRODUCTION
Bone health assesment is becoming an emerging issue in HIVinfected children and adolescents. Dual-energy x-ray
absorptiometry (DXA) is the most commonly employed
method for the assessment of bone mass worldwide. However
its wide implementation in growing individuals is hampered by
cost, radiation exposure and size dependency of the
measurements. Quantitative ultrasonography (QUS) has a
special appeal for studying bone in children because of its
speed, low cost, lack of ionizing radiation and use of portable
devices. To assess the applicability of QUS measurements in
HIV-infected children, we related QUS bone measurements
with those obtained by DXA in HIV-infected youths.
SUBJECTS
Bone mass measurements have been obtained in 88 HIV-infectd
children and adolescents (78 of Caucasian ancestry and 10 of
African ancestry). Forty patients showed asymptomatic or mild
disease, while 48 cases hade moderate or severe disease. The
great majority (70%) of the patients included in the study had
undetectable HIV viral load while 30% of the patients showed
detectable HIV viral load (ranging from 1000 to >10000
copies/ml). Characteristics of the patients are shown in Table 1.
TABLE 1 Description of the 88 HIV-infected pediatric
patients included in the study.
TABLE 2 QUS and DXA measurements of 88 HIV-infected
children and adolescents.
TABLE 3 Relationships between QUS and DXA bone
measurements.
Sex (Boys/Girls)
Variable
QUS Radius vs. Lumbar spine BMC
BMD
Total Body
BMC
BMD
r=0.48
r=0.54
r=0.37
r=0.45
P<.0001
P<.0001
P=.0004
P<.0001
QUS Tibia
r=0.63
r=0.65
r=0.58
r=0.62
r=0.44
r=0.50
P<.0001
P<.0001
P<.0001
P<.0001
P<.0001
P<.0001
43/45
Mean (SEM)
Age (years)
13.9 (0.5)a
Radius SOS (m/s)
3896 (15)
Weight (kg)
45.8 (1.7) a
Tibia SOS (m/s)
3797 (16)
Height (cm)
151.5 (2.1)a
Lumbar spine BMC (g)
32.6 (1.6)
BMI (kg/m2)
19.2 (0.4)a
Lumbar spine BMD (g/cm2)
Pubertal development (n)
Stage I: 20
Total body BMC (g)
Stages II-III: 22
Total body BMD (g/cm2)
0.932 (0.022)
1824 (75)
1.028 (0.02)
Stages IV-V: 45
CD4 number (cell/µl)
CD4 %
a
795 (15-1946)
FIGURE 1. Reproducibility of QUS bone measurements
31.5 (2-72)
expressed as coefficient of variation (CV). No differences were
observed between two operators.
Data are expressed as mean (SEM).
vs. Lumbar spine BMC
BMD
Total Body
BMC
BMD
Midshaft tibia BMC
BMD
FIGURE 4. Relationships between QUS measurements
of the tibia and DXA measurements of the total body
(Panel A) and midshaft of the tibia (Panel B).
METHODS
Speed of sound (SOS) was measured
(Sunlight Omnisense 7000, Tel Aviv,
Israel) at the mid-shaft of the tibia of the
non-dominant leg and on the distal
radius of non-dominant arm. The midtibial location was determined using
special calipers measuring the knee-sole
length and the distal radius was measured
at a point halfway between the elbow and
the end of the middle finger.
DXA bone measurements of the lumbar spine and the total body
were obtained using a Lunar DPX-L scanner. To explore the
relationship between the measurements obtained with QUS in the
tibia and the corresponding region measured by DXA, we selected
manually a region of interest placed at the mid-shaft tibia of the
non-dominant leg on the total body scan. BMC and BMD values
were calculated for each tibial region by the same operator (LC).
The coefficient of variation was calculated for repeated
measurements as the standard deviation divided by the mean of
the measurements, and expressed as percentage. The relationships
between QUS and DXA measurements were explored by simple
correlation analyses. Paired t-test were performed to assess
differences between Z-scores.
RESULTS
The values of QUS and DXA bone measurements are shown in
table 2. The reproducibility od QUS measurements (Figure 1) was
good. Z-scores of QUS and DXA measurements are shown in
Figure 2, and their distribution in Figure 3.
%
FIGURE 2. Distribution of QUS and DXA Z-scores. Red
circles represent the maximum values, purple circles the
minimum, and the orange circles the median. Spine Z-scores
were significantly different (P<.0001) from those of QUS
measurements, as evaluated by paired analyses.
Z-scores
1San
2
Giacomet ,
CONCLUSIONS
FIGURE 3. Prevalence of low QUS and DXA bone
measurements within the 88 patients studied. No significant
differences in prevalence were observed.
Number of patients
596
SD
SD
The current study indicate good agreement between QUS
and DXA bone measurements. In particular, total body
DXA measurements not only correlated with SOS, but they
also showed no differences with QUS measurements when
expressed as Z-scores. This is likely due to the fact that both
measurements are targeted to cortical bone.
Our data suggest that QUS may be an additional diagnostic
tool for the study of cortical bone mass in HIV-infected
youths.
QUS could be an alternative tool in resouce-limited settings
where more expensive devices for bone mass measurement
are not available.