Vol. 85, Issue 4, 1578-1582, October 1998
SPECIAL COMMUNICATION
Determining bone and total body mineral content from body density
and bioelectrical response spectroscopy
Steven F.
Siconolfi1,
Randal J.
Gretebeck2,
William W.
Wong3,
Sheril S.
Moore4, and
John H.
Gilbert III5
1 Neurosciences' Neuromuscular
Laboratory, SD3/Space and Life Sciences Research Laboratories, National
Aeronautics and Space Administration Johnson Space Center, Houston
77058; 3 Stable Isotope
Program, United States Department of Agriculture/Agricultural
Research Service Children's Nutrition Research Center, Department of
Pediatrics, Baylor College of Medicine, Houston 77030;
4 University Space Research
Association, Houston 77058;
5 Aerospace Consultant
Enterprises, Houston, Texas 77059; and
2 Department of Foods and
Nutrition, Purdue University, West Lafayette, Indiana 47907
 |
ABSTRACT |
We hypothesized that one could assess total body
mineral (TBM) and bone mineral content (BMC) from measurements of body
density and bioelectrical response spectroscopy (BRS)-determined total body water by using a three-compartment (3C) model. We compared TBM and
BMC computed from measurements of water
(2H2O
dilution or BRS) and body density (underwater weighing) with [4-compartment (4C)] and without (3C) mineral (dual X-ray
absorptiometry) in 15 women and 16 men. BRS used multifrequency or
single-frequency estimates of water. Mean differences between the 3C
and 4C models ranged from 
6.1 to 2.2%. Correlations between
models were 0.82-0.91. Standard errors of the estimate of
8.5-9.3% were within the range of those previously reported,
i.e., 4.9-13%. Use of BRS did not significantly decrease the
strength of the correlations between the models. A significant mean
difference (only in women) was found only with 3C single-frequency BRS
estimates of TBM and BMC. We concluded that investigators can assess
TBM and BMC 3C multifrequency BRS estimates in men and women.
multicompartment models; body composition; underwater weighing; osteoporosis
| |
INTRODUCTION |
SPACEFLIGHT INDUCES physiological adaptations that
include decreases in bone mineral content (BMC) (15). Monitoring of BMC with bone densitometers is not possible during spaceflight because of
the size and power requirements of present instrumentation. Siconolfi
et al. (17) reported that one could assess total body mineral
[TBM; 82.4% of which is bone (2)] from measurements of
body density and water. During spaceflight, assessing body density is
possible because it is the ratio of body mass (available since Skylab)
to body volume (portable air-displacement volumometry) (16). The
problem is the assessment of total body water on a real-time basis.
One possible solution uses bioelectrical response spectroscopy (BRS) to
assess total body water. BRS comprises the impedance, phase-angle, capacitance, and inductance responses of the human body to
a multifrequency input current. A common problem observed with BRS is
that the body's impedance shifts as fluid compartments exchange water,
such as that observed when a subject moves from a standing to a supine
position. The water shift between compartments may take up to 30 min to
stabilize. Consequently, estimates of total body water were only valid
for the amount of time the subject maintained the position used in the
original research study. Siconolfi et al. (18) reported a
new approach that eliminated this problem. They showed BRS assessment
of total body water to be valid after 0 and 40 min of supine rest. This
new BRS, combined with body density, would make remote monitoring of
TBM and BMC feasible during spaceflight or in other research studies,
such as field evaluation of BMC. However, we must know the effect of
using water assessed by BRS on the validity of the Siconolfi et al.
(17) model. This study evaluated the validity of the Siconolfi et al. estimates of TBM and BMC from measurements of body density
(Db) and water by using BRS. We
evaluated the validity for all subjects (n = 31) and subjects by gender (men
n = 16 and women
n = 15).
| |
METHODS |
Subjects.
Thirty-one subjects (16 men and 15 women) participated in this study.
All subjects had passed an Air Force Class III physical or its
equivalent and were briefed on the study. After all questions about the
study were answered, subjects signed an approved informed consent
statement. Table 1 lists subject
characteristics.
Total body water by dilution.
This method has been described in detail elsewhere (17). Briefly,
subjects reported to the Johnson Space Center in the morning, after an
overnight fast, for collection of baseline urine samples. They then
drank an oral dose of water containing 4 g of 99.8 atom percent
2H2O
(Icon Services, Summit, NJ) diluted to 100 g total volume with tap
water. Urine samples collected 3, 4, and 5 h after administration of
the dose were stored frozen in cryogenically stable tubes at 20°C until analysis. We prepared samples according to the
procedures of Wong et al. (21) for
2H:1H
isotope-ratio measurements by gas-isotope-ratio mass spectrometry. The
precision in our laboratory for water is <1% (on the basis of the
difference between 4- and 5-h samples from 50 subjects).
Total body water by BRS.
The full BRS model is described in detail elsewhere (18). Briefly, we
recorded BRS from a Hewlett-Packard model 4284A Precision LCR Meter
through electrodes placed on the hand, wrist, ankle, and foot at
standard locations, before the subject assumed the supine position. BRS
uses an average input current of ~250 µA (at frequencies of 5, 50, 67, 85, 100, 150, 166, 200, 250, and 300 kHz). Subjects reclined in a
supine position, and a computer recorded the BRS immediately.
We used the Siconolfi et al. (18) parallel electric circuit model to
determine water. We regressed (3rd-order least squares regression) each
subject's impedance and resistance values on frequency. The mean
(±SD) of the correlations for the individualized regressions was
0.99 ± 0.2. The resistance of the total circuit (RT) was the
resistance at the frequency where impedance changed by only 1% with a
frequency increase of 25 kHz. We used the 1% limit because it is an
industry standard for high-precision resistors (12). Our laboratory (4)
reported that this approach was better than the statistically derived
values of the Cole-Cole method. RT estimated water by using the
following equation (18)
model
R = 0.987; SE of estimate (SEE) = 1.26 kg, where Ht is the subject's height (cm), RT is the resistance (
)
of the circuit, and BM is body mass (kg).
We also evaluated other BRS estimates of water on the basis of
single-frequency responses. The gender-specific equations by Kushner
and Schoeller (7) estimated water from
Ht2/R
(resistance at 50 kHz) and BM by using the following gender-specific equations
men:
model R = 0.988; SEE = 1.658 kg, and
women:
model R = 0.975; SEE = 0.884 kg.
Body density.
This protocol is described in a previously published study (17).
Briefly, we determined the subject's mass on a beam balance scale and
volume by underwater weighing (19). In our laboratory we used a harness
and snorkel system that maintains the subject at ~2.5 cm below the
water surface during the weighing procedures. This reduces the effects
of the water acting on the thorax. Water is thought to affect the
subject's ability to reach the same residual volume observed outside
the tank (3). We found no difference between residual volumes measured
in subjects in this position in the water and those measured in a
separate group of subjects before weighing. Therefore, we chose not to
measure the residual volume during the weighing procedures in this
study. The precision (±SD of the difference between 2 measurements)
in our laboratory for body density is 0.0015 g/ml (50 subjects were
weighed twice).
BMC.
We assessed BMC with a Hologic QDR 2000 whole body densitometer that
employs the technique of dual-energy X-ray absorptiometry (DEXA). The
test subject removed all metal (i.e., jewelry) or clothes containing
metal before the scan. Subjects wore medical scrubs or other suitable
clothing. The technician performing the scans positioned the subject in
the supine position on the densitometer for each scan and instructed
the subject to remain still during the scan. The Hologic scanned the
subject's whole body in the pencil-beam mode.
The standard analysis software provided by Hologic (version 5.64)
analyzed the scans and reported BMC. Within our laboratory, the
precision of the whole body scan is 0.6% (21 subjects were scanned 3 times over 5 days). The same individual performed all scans and scan
analyses to avoid interoperator sources of precision error.
Many studies report that DEXA measurements of BMC systematically
underestimate in vivo neutron activation or chemical analysis values
(5, 6, 8, 10, 13, 14, 20). Sabin et al. (14) examined the BMC of three
lumbar spines
(L2-L4)
from 12 cadavers with DEXA and by ashing at 250°C for 60 h,
followed by an additional 24 h of ashing at 500°C. They reported
that DEXA systematically underestimated (14%) the ashed BMC. Ho et al.
(6) also reported a systematic underestimation of BMC by DEXA. They reported the Hologic BMC to be 5.2% lower than individually ashed (n = 31) lumbar spines (11 cadavers),
and the regression had a SEE of 8.9%. Sabin et al. suggested that the
difference between their results and the Ho et al. results were due to
the different temperatures used for ashing the bone. Sabin et al. ashed
eight additional vertebrae at the same temperature as did Ho et al. and
found a result (6.7%) similar to that of Ho et al.
Sabin et al. suggested that the higher temperatures used by Ho et al. may have "led to chemical changes in the hydroxapatite" that
account for the smaller mineral content in the ashed vertebrae.
Louis et al. (10) reported that neutron activation analysis also
underestimated bone mineral ash (3.9%). This difference between the
osseous mineral and ashed mineral was similar to that reported by
Mendez et al. (4.3%) (11). Louis et al. also reported that DEXA was
2.2% lower than neutron activation analysis. This yielded a net 6%
underestimation of DEXA BMC for the Louis et al. data. Tothill et al.
(20) compared BMC from a phantom measured on Hologic, Norland, and
Lunar instruments. These authors found Hologic to be 6.7% lower than
the phantom (provided by Norland). They also compared BMC of humans
across instruments. Hologic and Lunar BMCs were well correlated
(r = 0.974, Hologic = 1.006*Lunar 201.2) but had significantly different means. This suggests that a correction factor should be used when the accuracy of BMC is
compared with ashing or neutron activation analyses, when investigators use different bone densitometers.
Two of the cadaver studies (6, 10) scanned individual lumbar spines.
The BMC of these individual vertebrae are small, ~10-15 g.
Lapillone et al. (8) examined the accuracy of Hologic estimates of BMC
in small (~10 g mineral) bone tablets (Ossopan) and reported that the
Hologic BMC was 2.6 ± 10.9% lower than expected. This
high degree of variability makes the extrapolation to whole humans
difficult. Sabin et al. (14) used the
L2-L4
values as one measurement to avoid this error. Lapillone et al. noted
that, as the BMC increased above 10 g, the error decreased from
±10.9 to ±3.5%. This suggests that the results of Sabin et al.
could be useful as a correction factor.
Heymsfield et al. (5) and Pierson et al. (13) compared in vivo neutron
activation with Lunar DEXA-determined BMC. We can compare the accuracy
of DEXA with this instrument after correcting the Lunar BMC to an
equivalent Hologic BMC by using the regression of Tothill et al. (20).
Comparing in vivo neutron activation estimate of osseous mineral by
Heymsfield et al. to their DEXA data, we found that Lunar DEXA was
underestimated by 3.7%. Adjusting their mean Lunar data to an
equivalent Hologic response increased the underestimation to 10.8%.
Lunar-determined BMC overestimated the in vivo neutron activation value
of Pierson et al. by 3.7%. Adjusting their mean Lunar data to an
equivalent Hologic response yielded an underestimation of
12.5%. The ashing and neutron activation studies show a range
of underestimation of BMC by Hologic DEXA of 5.2-14%. The Heymsfield
et al., Pierson et al., and Sabin et al. (14) studies produce a
composite correction factor of 11.9% (adjusted for sample size).
We applied each correction factor plus the adjusted mean factor to the
BMC from the three-compartment (3C) dilution model (3CD). A repeated-measures ANOVA
between the DEXA BMC and corrected 3CD estimates
(n = 31) showed that only the Ho et
al. (6) and Louis et al. (10) correction factors produced significant
differences from the Hologic BMC (Table 2).
The adjusted mean correction to the three 3C estimates
[3CD, multifrequency BRS
(3CMB), and single-frequency BRS
(3CSB)] were not
significantly different (0.3, 1.4, and 3.0%,
respectively) from the Hologic BMC for our subjects (Table 2).
Therefore, we chose to use the 11.9% correction factor.
TBM.
Brozek et al. (2) reported that osseous mineral was 82.4% of the TBM
content. We followed the suggestion by Lohman (9) and Heymsfield et al.
(5) that TBM could be obtained by dividing the corrected BMC by 0.824.
3C model assessment of TBM and BMC.
Body density and total body water (with
3CD,
3CMB, or
3CSB) estimated percent body fat
with the following equation (9)
where
w is total body water expressed as a
fractional component of body mass. This estimate, in combination with
body mass, yielded body fat. Fat-free mass (FFM) was the difference
between body mass and fat mass. The density of the FFM was computed by using (17)
We
used the equation by Siconolfi et al. (17) to determine mineral FFM
(mFFM)
Multiplying
mFFM by FFM
resulted in TBM. BMC was 82.4% of TBM.
Statistical analyses.
Good validity was present when 1)
mean differences between the four-compartment (4C) and 3C values were
not significant (repeated-measures ANOVA with Scheffé's post hoc
analyses); 2) there was a strong Pearson product-moment correlation;
3) there was a low SEE
[expressed as a percentage of the 4C mean (SEE%)]; and
4) there were nonsignificant correlations between the residuals and the averaged values (1), indicating no systematic reason for differences between the methods. Validity was evaluated for all subjects
(n = 31) and for subjects by gender
subgroups.
| |
RESULTS |
The means and SDs of the TBM and BMC for 4C and 3C models are presented
in Table 3. Only the validity results for
BMC are presented in Table 4. The TBM
statistical data were not included in Table 4 because it is a function
of BMC and the mean differences, correlations, SEE%, and residual
correlations (1) were identical to the BMC data. A key result was the
lack of a significant decrease in Pearson product-moment correlations
by substituting 3CMB
(r = 0.90) or
3CSB
(r = 0.91) estimates of total body
water for dilution (r = 0.91) for all
subjects. Male and female subgroups (Table 4) had similar results. The
correlations of residuals (1) (0.08 to 0.36) were not
significant, suggesting no systematic over- or underestimation of BMC
(Table 4) for all, male, and female subjects. The substitution of the
3CSB model estimates of total body
water did produce significantly (P < 0.05) lower BMC values (6.1%) only for female subjects.
The single-frequency BRS model estimates of total body water had
excellent correlations (all 0.95; men 0.92; women 0.96) with dilution
values but were significantly (P < 0.05) larger for all (3.9%), male (4.0%), and female (3.8%)
subjects. The multifrequency BRS model estimates of total body water
had both excellent correlations (all 0.96; men 0.93; women 0.97) and no
significant mean differences for all (1.1%), male (1.0%), and female
(1.3%) subjects. SEE% for both methods were similar (4.4-6.7%).
| |
DISCUSSION |
The effects of the single and multifrequency BRS estimates of total
body water on the validity of 3CMB and 3CSB
determined TBM and BMC were similar. However, the single frequency BRS
model estimate of total body water underestimated the 3CSB
determined TBM and BMC for the 15 female subjects in the
3CSB model. This underestimation was due to the
significantly larger (3.8%) value for water from single frequency BRS
compared with the isotopic dilution in our female subjects. The
increase in estimated total body water increases the relative
percentage of water in the FFM because FFM mass has not changed. This
increase in the percentage of water in the FFM is at the expense of the
percentage available for mineral and protein. The decrease in the
percentage of mineral in the FFM yields smaller values for TBM and BMC.
For example, if a person with an actual FFM of 60 kg (consisting of
43.5 kg of water and 16.5 kg of mineral and protein) had an estimated water content of 45.2 kg (~4% larger than actual), the estimated residual mass decreases by ~10% (14.8 kg). Assuming the percent decrease is proportionally (~27% mineral and 73% protein based on
mean female data from Table 1) distributed between mineral and
proteins, the reported mineral value would be 2.7% lower than the
actual mineral value. The difference between the
3CD and
3CSB models for the female
subjects was 2.5%.
This study also evaluated the validity of the 3C methods in male
subjects. The 3C estimates of BMC were not significantly larger than
were the Hologic BMC. The validity for men was equivalent for the three
3C BRS models, despite a 4% overestimation of water with the
3CSB method. This may have been
due to the nonsignificant overestimation of the
3CD, which was decreased by the
nonsignificant expansion of water.
High correlations, small or nonsignificant mean differences, and no
systematic error (evident by no significant residual correlations) are
only part of the evaluation. The SEE of the 3C methods also must be
examined. We expressed the SEEs as a percentage of the mean so that we
could compare them to SEEs reported in the literature. Our SEEs ranged
from 8.5 to 9.3%. This range of accuracy was within the range reported
in the literature (4.9-13%) when DEXA BMC is compared with either
ashing (of lumbar spines) or to in vivo neutron activation analysis of
humans. Given the error associated with estimating total
body water [~5.6% from multifrequency BRS and ~6.6% from
single-frequency BRS (18)] and the 8.8% error in the 3C estimate
of BMC (17), the propagated error of using the BRS in the 3C method
would be from 10.4 to 10.9%. All of the mean differences and SEEs in
this study were less than these expected errors. This suggests that the
estimate of BMC from the 3CMB
model would be acceptable.
The combined methods of a portable air-displacement volumometer (15),
calibrated scale, and the BRS instrumentation can permit the assessment
of TBM and BMC (~82.4% of TBM) during spaceflight. These methods
also could be used during Earth-based research, such as epidemiologic
studies of osteoporosis. These instruments could easily be used in a
portable laboratory (trailer) or taken into a subject's home. The
total cost of the instruments would be minimal (<$15,000) compared
with the cost of bone densitometers and magnetic resonance imagers. We
concluded that investigators can assess TBM and BMC from the
3CMB model in men and women.
| |
ACKNOWLEDGEMENTS |
We thank Elisabeth Spector for work with the bone densitometer and
Dr. Alan D. Moore for assistance in underwater weighing.
| |
FOOTNOTES |
Address for reprint requests: S. F. Siconolfi, 121 Shapero Hall/College
of Pharmacy and Allied Health Professions, Wayne State University,
Detroit, MI 48202.
Received 3 April 1997; accepted in final form 15 June 1998.
| |
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Top
Abstract
Introduction
![D<SUB>FFM</SUB> = (1 − %fat)/[(1/D<SUB>b</SUB>) − (%fat/0.9007)]](/content/vol85/issue4/fulltext/1578/img005.gif)
of 3C
estimates of BMC