JOURNAL OF BONE A N D MINERAL RESEARCH Volume 7, Number 4, 1992 Mary Ann Liebert, Inc., Publishers
Performance of Dual-Energy X-ray Absorptiometry in Evaluating Bone, Lean Body Mass, and Fat in Pediatric Subjects GARY M. CHAN
ABSTRACT We studied the performance of the dual-energy x-ray absorptiometry method in evaluating bone mineral, fat, and lean soft tissue mass. This method was accurate in quantifying known small amounts of calcium, lard, and lean tissue mass. I t was also accurate in evaluating small animal ashed bones, fat, and muscle mass. The analytic sensitivity o f the method was 40 mg for calcium, 180 mg for fat, and 270 mg for lean tissue mass. The method was highly correlated to the single-photon absorptiometry method i n measuring bone mineral content at the radius bone in 32 children, r = 0.998. There was a difference between the two methods in older children. Long-term precision for a small bone phantom was 2.0%. Total-body, lumbar, and radial bone scans were performed on 14 newborn infants whose gestational ages ranged from 28 to 41 weeks. Both total-body bone mineral and far mass increased with gestational age and weight. The infant’s totalbody calcium was also associated with length and lumbar and radial bone densities. The lumbar bone density was associated with birth weight, gestational age, length, body mass index, body fat, and radial bone density. Male infant’s lumbar bone density to total-body calcium ratio was higher than female infant’s lumbar bone density ratio. Dual-energy x-ray absorptiometry may be used in pediatrics with high accuracy, sensitivity, and precision.
INTRODUCTION
T
HE ASSESSMENT of body composition in pediatric subjects is limited. The traditional methods of measuring anthropometric indices, such as skinfold thickness, arm circumference, and height, only indirectly evaluate the child’s body composition and may be invalid in determining body composition.(ll Both neutron activation and computed tomography expose the pediatric subject to unnecessary high radiation. Single-beam photon (SPA) absorptiometry has been used to measure bone mineral content, but only at the peripheral limb site.(21Total-body electrical conductivity and bioelectrical impedance may be used to assess body fat mass and fat-free masses, but their validity in a wide range of pediatric subjects requires confirmation. (3-6) Conventional dual-photon absorptiometry has been
used widely in adult research and clinical practice. However, this technique has been used very little in pediatrics because of the long scan times required (50 minutes for a body scan) and the poor resolution on smaller subjects. Now, with the replacement of the gadolinium 153 source with an x-ray source, the scan times are more rapid and the resolution is better (0.5 versus 1 mm). The purpose of this study is to evaluate the performance of this dual x-ray technique for pediatric use and to report correlation analyses of total-body calcium and lumbar bone mineral density with important variables, such as gestational age, body weight, and body mass.
M A T E R I A L S A N D METHODS We tested a commercial x-ray bone densitometer (XR26; Norland Corporation, Fort Atkinson, W1) that uses
Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City. 369
CHAN
370 an x-ray tube operating at constant potential 100 k V and 1.0 mA coupled with a samarium filter ( k edge, 46.8 keV), which effectively separates the spectrum into two energy peaks. The x-ray detector consists of two sodium iodide scintillation detectors that measure the transmitted x-ray beam intensities at the two energies. The principle of dualenergy absorptiometry in determining bone and soft tissue mass has been described.(’-*) Essentially, as the x-ray beam passes through the subject, the beam undergoes attenuation by the tissues. The amount of attenuation at the two energies is dependent on both the amount and the type of tissue. The intensity information from the detectors for each 0.5 x 0.5 mm pixel in the scan region is received and stored by the computer system. The computer then uses a series of complex algorithms to determine the amount of bone and lean and fat mass in each pixel. The totals from all the pixels can then be calculated. The radiation dose for the whole-body scan ranges from 0.005 to 0.10 mrems, depending on subject’s size and scan speed. Accuracy was tested two different ways: ( 1 ) the evaluations of known quantities of calcium, lard, and lean soft tissue mass, and (2) measurements of bone mineral content, fat, and lean soft tissue mass in small chicken parts. Comparison between single-beam photon and dual-energy x-ray absorptiometry (DEXA) in assessing the bone mineral content in children was made. Different known quantities of calcium phosphate hydroxide, which is similar to calcium hydroxyapatite (Sigma Chemical H-0252, St. Louis, MO), and lard were weighed and then measured by DEXA. A solution of 20% protein and 60 mM potassium chloride was made to represent fat-free or lean tissue mass.(’O.l’lAnalytic sensitivities for bone, fat, and lean tissue mass were assessed by noting the minimal amount of detection by DEXA method. Seven individual fresh chicken parts containing the breast or femoral bones were measured by DEXA for bone mineral content, fat, and lean tissue mass. Bones, fat, and muscle were then dissected from chicken parts carefully. The fat and muscle were weighed. The bones were ashed‘”) and weighed. The actual weights of the ashed bones, fat, and muscle were then compared to the weight determined by DEXA. The results on 32 children using DEXA were compared to those using single-beam photon bone densitometer (Lunar Radiation, Madison, WI) at the right distal radius bone. All measurements for both SPA and DEXA occurred at the child’s distal third left radius bone site. The site measured was the same for both methods and was tested on the same day. Using the DEXA method, the distal bone was scanned at 1 x 1 mm resolution and 60 mm/s speed. The study protocol was reviewed and approved by our institutional review board, and informed consent was obtained from the parents of the subjects. Precision was measured by making repeated measurements on small bone phantom (a precision-bored plastic chamber containing a 6 mm diameter Lucite tube) and commercially available spine phantom weekly for 6 months. The values of bone mineral content in grams were tabulated, and a coefficient of variation was determined. Intrauterine body composition was determined by select-
ing 14 infants with gestational ages 28-41 weeks. All infant weights and length were recorded. Total-body and lumbar scans were evaluated by the DEXA method and the infants’ distal radius bone by the SPA method. All infants were appropriate for size as determined by the clinical examination and maternal dates. All infants were less than 5 days old when the body measurements were made. Infants were healthy, white, and free of major congenital illness. This study was approved by our institutional review board, and informed consent was obtained from the mothers of our subjects. Standard regression analyses were used in a linear model. Correlation coefficients were employed to assess the best relationship. Student’s t-test was used to evaluate differences between groups. Paired t-tests were employed in a comparison of two methods on the same subject.
RESULTS The associations of the known weights of calcium phosphate, lard, and the solution representing lean soft tissue mass and the determined weights by DEXA were highly correlated and linear (Fig. 1). The sensitivities of the CALCIUM PHOSPHATE
700 ljoo
-
‘5W
-
JW
-
100
-
200
-
0
= .
y
100
1224
+ 1051
r
z
OD97
200
500
300 400 A C T U A L W E I G H T (MC)
600
FAT
800
=
y
mo -
50.55
+
0.871
r
=
0.997
700
‘300
-
Goo-
-
:lo0
100
200
300
400 500 600 ACTUAL WEIGHT (MG)
700
800
LEAN SOFT TISSUE y
20
z
.
0.22
+ 0.831
r
=
1.00
-
0
10
20
30
40
A C T U A L W E I G H T (C)
1. Associations of known quantities of calcium phosphate, lean soft tissue, and fat with weights determined by DEXA. Correlation coefficients were high at 0.997-1 .00.
37 1
DEXA USE IN PEDIATRICS DEXA method were the following: calcium phosphate, 40 mg; fat, 180 mg; and lean soft tissue mass, 270 mg. The total mean accuracy error in determining the actual weight for calcium, fat, and lean mass was 4.5%. The chicken parts weighed from 67 to 293 g. The DEXA-measured bone ( r = 0.99), muscle ( r = 0.99), and fat ( r = 0.98) weights were highly related to the actual weight (Fig. 2). In comparing the single-beam method with DEXA, 32 children were scanned at the distal radius bone by both methods. The correlation coefficient was 0.998 (Fig. 3). There were no differences in bone mineral content of the radius bone between the two methods from birth to 6 months of age. In older children, however, there was a difference between the two methods (Table 1). The short-term precision of the phantoms was 0.7% for the spine and 1.7% for the small bone for weekly determined means. The long-term precision error (monthly determined means) for spine phantom was 1% and for the small bone phantom was 2%. A group of 14 infants were measured for total-body composition. Infant scans require on the average 15 minutes. All infants were asleep during the scan and did not receive sedative drugs. All body scans were accomplished at 3 x 3 mm resolution at a scan speed of 60 or 80 mm/s. The lumbar bones (L2-4) were scanned at 1 x 1 mm resolution at a scan speed of 60 mm/s. The total-body mineral content increased with gestational age and weight ( r = 0.84-0.87, p < 0.001; Fig. 4). The total-body calcium was also associated with length and lumbar and radial bone densities (Table 2). The percentage body fat increased with gestational age but the lean body mass decreased. The preterm (28-35 weeks of gestation) infant body fat ranged from 2 to 8%. The term infant body fat ranged from 9 to 22%. Infant body fat was associated with gestational age ( r = 0.80, P = 0.001) and birth weight ( r = 0.80, P = 0.001) but not with body mass index or weight/length3 ( r = 0.43, P > 0.05). The lumbar bone density was associated with birth weight, gestational age, length, body mass index, body fat, and radial bone density (Table 3). N o difference between male and female radial bone density/ weight or lumbar bone density/weight was noted. However, both the lumbar and radial bone density/total-body calcium ratios were higher in the male infants (0.003 f 0.0003, mean t SD, standard deviation, and 0.003 f 0.001) than females (0.0026 t 0.0005 and 0.002 k 0.0004; t-test, p = 0.03).
BONES
A W E D WEIGHT ( C )
MUSCLE
d
200
100
ACTUAL WEIGHT ( C )
FAT
0
10
20 30 ACTUAL WEIGHT (G)
40
50
FIG. 2. Associations of actual weights of fresh chicken parts to the weight of bones, fat, and muscle determined by DEXA. Correlation coefficients were high at 0.98-0.99.
0.8
,
I 06 0 U
I m
a 04 Y
5
a cc Iyi
:0 2 a 0 x
DISCUSSION From our data, the accuracy of the DEXA method was excellent for small quantities of bone, fat, or lean soft tissue mass. The DEXA-determined weights were highly associated ( r = 0.98-0.99) with the actual weights of chicken bones, muscle, and fat. The absolute values were different, however, as a result of the differences in methods and limits of sensitivity of the methods employed. We found that the DEXA method was linear to decreasing amounts of calcium phosphate. Other researchers found that the
00 0.0
0 2
0.6
0.4
SPA-DETERMINED
C
8
BMC, G i C M
FIG. 3. Association of DEXA-determined BMC and SPA-determined BMC in 32 children's distal radius bone. The correlation coefficient was 0.998.
372
CHAN TABLE1. COMPARISON OF SPA A N D DEXA ON THE RADIUSBONEMINERAL CONTENT G/CM,MEAN f SD" Age
n
SPA
DEXA
P
Birth-6 months 3-8 years 10-12 years
10 10 12
0.057 f 0.026 0.418 f 0.135 0.533 f 0.116
0.059 f 0.029 0.396 f 0.131 0.520 ? 0.114
NS 0.001 0.003
aAssociation of SPA and DEXA. r
=
0.99. NS, not significant.
TABLE2 . CORRELATION COEFFICIENT r FOR TOTAL-BODY CALCIUM VERSUSDIRECTLY MEASURED AND DERIVED VARIABLES x FOR INFANTS
lZO1
loo
0
1 X
"
I
1000
2000
3000
4000
BIRTH WEIGHT. G
0
GESTATIONAL
AGE ( W E E K S )
FIG. 4. The relation of total-body bone mineral content in 14 newborn infants with gestational age and birth weight. Total-body calcium increases with both gestation and birth weight. The 95% confidence bands are presented with the regression line.
DEXA method was also linear to increasing amounts of calcium hydroxyapatite. ( I 3 ) There was a high correlation of the bone mineral content values obtained by the singlephoton and the DEXA methods in children. We found a difference between the two methods as the child became older. This difference is probably due to the improved accuracy of DEXA over the SPA method and differing calibration and algorithms between the two The high analytic sensitivities of the DEXA method for these specific components of body composition make this technique applicable to very small animals and subjects in vivo.
Birth weight Gestational age Length Ponderal index, wt//, Radial bone density Lumbar bone density
r
P
0.91 0.88 0.93 0.45 0.67 0.83
0.001 0.001 0.001 NS 0.01 0.001
In adults the precision of total-body bone density using the DEXA method was 0.5% in vitro and in vivo. Totalbody bone mineral density correlated highly with dualphoton absorptiometry Using the single-photon absorptiometry method on small bones, the long-term precision was 2.1V0.''~) Our short-term precision was 1.7 and 2.0% for long-term precision on a small bone phantom. The precisions reported in this study are similar to others using the DEXA method.''" The body composition results from the infants are similar from those of other researchers using different techniques. From o u r preliminary data, we found that the total-body bone mineral content increased with gestational age and birth weight. The infant total-body calcium was also highly associated with length and radial and lumbar bone densities. By chemical analyses of a fetus that died before birth, the skeletal accretion of calcium increases during the last Using the single-beam photon absorptiometry method, a similar intrauterine bone mineralization was derived. Both bone mineral content and bone width of the distal radial bone site correlated with gestational age. (1b.18-*o) The major advantage of the DEXA method over the SPA is the ability to evaluate the metabolic active trabecular bones, as in the lumbar region. Lumbar bone mineral density showed a high degree of association with birth weight, gestational age, length, and body mass index (weight/length3) in infants. These associations of the infant's lumbar bone density are similar to those found in older In this study we found that the male newborn infants had a higher lumbar bone mineral content (BMC) than females. This sex dimorphism in BMC has been reported as early as 2 weeks of age in term infants.'221 Other researchers found a sex difference in bone mineral
373
DEXA USE IN PEDIATRICS TABLE3. CORRELATION COEFFICIENT I‘ FOR LUMBAR BONEDENSITY VERSUSDIRECTLY MEASURED A N D DERIVED x VARIABLES
3. 4.
X
Birth weight Gestational age Length Ponderal index, wt/l, Total body calcium Body fat, Yo Radial bone density
r
P
0.93 0.93 0.86 0.68 0.83 0.82 0.87
0.001 0.001
5.
O.(X)I
0.0 10 0.001 0.001 0.001
6.
7.
8.
status in older infants and children, but this has not been a consistent finding. L 1 7 . 2 2 ) We found this difference by using 9. the lumbar bone density to total-body calcium ratio. In evaluating pediatric subjects, bone density determinations must be adjusted for body size and growth. The ratio of the lumbar or radial bone density to total-body calcium 10. may be useful in comparing subgroups. Other researchers II. have recommended a similar bone mineral density index in children aged 5-19 years.‘21) Both body fat and lean soft tissue mass correlated with 12. gestational age and birth weight. As the fetus became more mature, there was more body fat and less soft tissue mass. The body fat content of human fetuses determined by 13. chemical analysis and by total-body electrii.,!l ~~~~iiLiiictivity is similar to our value^.(^^'^) By using the ci! . < i !:,\ionab14. sorptiometry method on 51 newborn intaiil,, ICAI body mass was determined. Preterm infants had a11 Ican body mass and no fat; term infants have an averape ot 13% lean 15. body fat.(23)These results are similar to o u r findings in which our preterm infants had body fat from 2 to 8% and our term infant body fat ranged from 9 to 22% using the 16. DEXA method. In conclusion, the DEXA method appears to be suited for pediatric use because of its high accuracy, precision, and sensitivity. This technique may thus be useful in iden17. tifying, treating, and following infants and children with nutritional problems.
ACKNOWLEDGMENTS We thank Tom Sanchez and Russ Nord of Norland Corporation for their technical support and encouragement. This work was supported in part from grants from Ross Laboratories and the National Dairy Council.
REFERENCES
18.
19.
20.
21.
1. Heymsfield SB, Casper K 1987 Anthropometric assessment
of the adult hospitalized patient. J Parenter Enter Nutr 11: 36s-41s. 2. Chan GM 1989 Calcium and bone mineral status in infant’s and children’s nutrition. In: Lebenthal E (ed), Textbook of
22.
Gastroenterology and Nutrition in Infancy. Raven Press, New York, pp. 403-412. Cohn SH 1985 How valid are bioelectrical impedance in body composition studies. Am J Clin Nutr 42889-890. Fiorotto ML, Cochran, Klish WJ 1987 Fat-free mass and total body water of infants estimated from total body electrical conductivity measurements. Pediatr Res 22417-421. Cochran WJ, Klish WJ, Wong WW, Klein P D 1986 Total body electrical conductivity used t o determine body composition in infants. Pediatr Res 20:561-564. Klish WJ, Cochran W J , Fiorotto ML 1987 The bioelectrical measurement of body composition during infancy. Hum Biol 59:319-327. Mazess RB, Barden HS, Bisek J P , Hanson J 1987 Dual energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition. Am J Clin Nutr 51:1l06-lI12. Mazess RB, Peppler WW, Gibbons M 1984 Total body composition by dual-photon (153 Gd) absorptiometry. Am J Clin Nutr 405334-839. Peppler WW, Mazess RB 1981 Total body bone mineral and lean body mass by dual-photon absorptiometry. Calcif Tissue Int 33:353-359. Garrow JS 1982 New approaches t o body composition. Am J Clin Nutr 35:1152-1158. Womersley J , Durnin JVGA, Boddy K , Mahaffy ML 1976 Influence of muscular development, obesity, and age on the fat-free mass of adults. J Appl Physiol 41:223-229. Cruess RL, Hong KC 1979 The effect of long term estrogen administration on the bone metabolism in the female rat. Endocrinology 104:1188-1193. Mazess RB, Collick B, Tempe J , Barden H, Hanson J 1989 Performance evaluation of a dual-energy x-ray bone densitometer. Calcif Tissue Int 44:228-232. Goodwin PN 1987 Methodologies for the measurement of bone density and their precision and accuracy. Semin Nucl Med 17:293-304. Wahner HW, Dunn WL, Brown ML, Morin RL. Riggs BL 1988 Comparison 0 1 dual-energy x-ray absorptiometry for bone mineral measurements of the lumbar spine. Mayo Clin Proc 63:1075-1084. Greer FR, Lane J, Weiner S, Mazess RB 1983 An accurate and reproducible absorptiometric technique for determining bone mineral content in newborn infants. Pediatr Res 17: 259-262. Glastre C , Braillon P, David L, Cochat P, Meunier P J , Delmas P D 1990 Measurement of bone mineral content of the lumbar spine by dual energy x-ray absorptiometry in normal children: Correlations with growth parameters. J Clin Endocrinol Metab 70:1330-1333. Ziegler EE, O’Donnell AM, Nelson SE, Foman SJ 1976 Body composition of reference fetus. Growth 40:329-335. Minton SD, Steichen J J , Tsang RC 1979 Bone mineralization in term and preterm appropriate for gestational age infants. J Pediatr 95:1037-1041. Chan GM, Mileur I>. Hansen JW 1986 Effects of increased calcium and phosphorus formulas and human milk on bone mineralization in preterm infants. J Pediatr Gastroenterol Nutr 5:444-449. McCormick DP, Ponder SW, Fawcett HD, Palmer JL, McKernan MG, Brouhard BH 1991 Spinal bone mineral density in 335 normal and obese children and adolescents: Evidence for race and sex differences. J Bone Miner Res 6:507-513. Chan GM, Roberts CC, Folland D, Jackson R 1982 Growth and bone mineralization of normal breast-fed infants and the effects of lactation on maternal bone mineral status. Am J Clin Nutr 36:438-443.
374
CHAN
23. Petersen S, Gotfredsen A, Knudsen FU 1988 Lean body mass in small for gestational age and appropriate for gestational age infants. J Pediatr 113:886-889.
Address reprint requests to: Gary M. Chan, M.D. Department of Pediatrics, 2A230 50 North Medical Drive Salt Lake City, U T 84/32 Received for publication December 10, 1990; in revised form August 12, 1991; accepted November IS, 1991.
Performance of Dual-Energy X-ray Absorptiometry in Evaluating Bone, Lean Body Mass, and Fat in Pediatric Subjects GARY M. CHAN
ABSTRACT We studied the performance of the dual-energy x-ray absorptiometry method in evaluating bone mineral, fat, and lean soft tissue mass. This method was accurate in quantifying known small amounts of calcium, lard, and lean tissue mass. I t was also accurate in evaluating small animal ashed bones, fat, and muscle mass. The analytic sensitivity o f the method was 40 mg for calcium, 180 mg for fat, and 270 mg for lean tissue mass. The method was highly correlated to the single-photon absorptiometry method i n measuring bone mineral content at the radius bone in 32 children, r = 0.998. There was a difference between the two methods in older children. Long-term precision for a small bone phantom was 2.0%. Total-body, lumbar, and radial bone scans were performed on 14 newborn infants whose gestational ages ranged from 28 to 41 weeks. Both total-body bone mineral and far mass increased with gestational age and weight. The infant’s totalbody calcium was also associated with length and lumbar and radial bone densities. The lumbar bone density was associated with birth weight, gestational age, length, body mass index, body fat, and radial bone density. Male infant’s lumbar bone density to total-body calcium ratio was higher than female infant’s lumbar bone density ratio. Dual-energy x-ray absorptiometry may be used in pediatrics with high accuracy, sensitivity, and precision.
INTRODUCTION
T
HE ASSESSMENT of body composition in pediatric subjects is limited. The traditional methods of measuring anthropometric indices, such as skinfold thickness, arm circumference, and height, only indirectly evaluate the child’s body composition and may be invalid in determining body composition.(ll Both neutron activation and computed tomography expose the pediatric subject to unnecessary high radiation. Single-beam photon (SPA) absorptiometry has been used to measure bone mineral content, but only at the peripheral limb site.(21Total-body electrical conductivity and bioelectrical impedance may be used to assess body fat mass and fat-free masses, but their validity in a wide range of pediatric subjects requires confirmation. (3-6) Conventional dual-photon absorptiometry has been
used widely in adult research and clinical practice. However, this technique has been used very little in pediatrics because of the long scan times required (50 minutes for a body scan) and the poor resolution on smaller subjects. Now, with the replacement of the gadolinium 153 source with an x-ray source, the scan times are more rapid and the resolution is better (0.5 versus 1 mm). The purpose of this study is to evaluate the performance of this dual x-ray technique for pediatric use and to report correlation analyses of total-body calcium and lumbar bone mineral density with important variables, such as gestational age, body weight, and body mass.
M A T E R I A L S A N D METHODS We tested a commercial x-ray bone densitometer (XR26; Norland Corporation, Fort Atkinson, W1) that uses
Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City. 369
CHAN
370 an x-ray tube operating at constant potential 100 k V and 1.0 mA coupled with a samarium filter ( k edge, 46.8 keV), which effectively separates the spectrum into two energy peaks. The x-ray detector consists of two sodium iodide scintillation detectors that measure the transmitted x-ray beam intensities at the two energies. The principle of dualenergy absorptiometry in determining bone and soft tissue mass has been described.(’-*) Essentially, as the x-ray beam passes through the subject, the beam undergoes attenuation by the tissues. The amount of attenuation at the two energies is dependent on both the amount and the type of tissue. The intensity information from the detectors for each 0.5 x 0.5 mm pixel in the scan region is received and stored by the computer system. The computer then uses a series of complex algorithms to determine the amount of bone and lean and fat mass in each pixel. The totals from all the pixels can then be calculated. The radiation dose for the whole-body scan ranges from 0.005 to 0.10 mrems, depending on subject’s size and scan speed. Accuracy was tested two different ways: ( 1 ) the evaluations of known quantities of calcium, lard, and lean soft tissue mass, and (2) measurements of bone mineral content, fat, and lean soft tissue mass in small chicken parts. Comparison between single-beam photon and dual-energy x-ray absorptiometry (DEXA) in assessing the bone mineral content in children was made. Different known quantities of calcium phosphate hydroxide, which is similar to calcium hydroxyapatite (Sigma Chemical H-0252, St. Louis, MO), and lard were weighed and then measured by DEXA. A solution of 20% protein and 60 mM potassium chloride was made to represent fat-free or lean tissue mass.(’O.l’lAnalytic sensitivities for bone, fat, and lean tissue mass were assessed by noting the minimal amount of detection by DEXA method. Seven individual fresh chicken parts containing the breast or femoral bones were measured by DEXA for bone mineral content, fat, and lean tissue mass. Bones, fat, and muscle were then dissected from chicken parts carefully. The fat and muscle were weighed. The bones were ashed‘”) and weighed. The actual weights of the ashed bones, fat, and muscle were then compared to the weight determined by DEXA. The results on 32 children using DEXA were compared to those using single-beam photon bone densitometer (Lunar Radiation, Madison, WI) at the right distal radius bone. All measurements for both SPA and DEXA occurred at the child’s distal third left radius bone site. The site measured was the same for both methods and was tested on the same day. Using the DEXA method, the distal bone was scanned at 1 x 1 mm resolution and 60 mm/s speed. The study protocol was reviewed and approved by our institutional review board, and informed consent was obtained from the parents of the subjects. Precision was measured by making repeated measurements on small bone phantom (a precision-bored plastic chamber containing a 6 mm diameter Lucite tube) and commercially available spine phantom weekly for 6 months. The values of bone mineral content in grams were tabulated, and a coefficient of variation was determined. Intrauterine body composition was determined by select-
ing 14 infants with gestational ages 28-41 weeks. All infant weights and length were recorded. Total-body and lumbar scans were evaluated by the DEXA method and the infants’ distal radius bone by the SPA method. All infants were appropriate for size as determined by the clinical examination and maternal dates. All infants were less than 5 days old when the body measurements were made. Infants were healthy, white, and free of major congenital illness. This study was approved by our institutional review board, and informed consent was obtained from the mothers of our subjects. Standard regression analyses were used in a linear model. Correlation coefficients were employed to assess the best relationship. Student’s t-test was used to evaluate differences between groups. Paired t-tests were employed in a comparison of two methods on the same subject.
RESULTS The associations of the known weights of calcium phosphate, lard, and the solution representing lean soft tissue mass and the determined weights by DEXA were highly correlated and linear (Fig. 1). The sensitivities of the CALCIUM PHOSPHATE
700 ljoo
-
‘5W
-
JW
-
100
-
200
-
0
= .
y
100
1224
+ 1051
r
z
OD97
200
500
300 400 A C T U A L W E I G H T (MC)
600
FAT
800
=
y
mo -
50.55
+
0.871
r
=
0.997
700
‘300
-
Goo-
-
:lo0
100
200
300
400 500 600 ACTUAL WEIGHT (MG)
700
800
LEAN SOFT TISSUE y
20
z
.
0.22
+ 0.831
r
=
1.00
-
0
10
20
30
40
A C T U A L W E I G H T (C)
1. Associations of known quantities of calcium phosphate, lean soft tissue, and fat with weights determined by DEXA. Correlation coefficients were high at 0.997-1 .00.
37 1
DEXA USE IN PEDIATRICS DEXA method were the following: calcium phosphate, 40 mg; fat, 180 mg; and lean soft tissue mass, 270 mg. The total mean accuracy error in determining the actual weight for calcium, fat, and lean mass was 4.5%. The chicken parts weighed from 67 to 293 g. The DEXA-measured bone ( r = 0.99), muscle ( r = 0.99), and fat ( r = 0.98) weights were highly related to the actual weight (Fig. 2). In comparing the single-beam method with DEXA, 32 children were scanned at the distal radius bone by both methods. The correlation coefficient was 0.998 (Fig. 3). There were no differences in bone mineral content of the radius bone between the two methods from birth to 6 months of age. In older children, however, there was a difference between the two methods (Table 1). The short-term precision of the phantoms was 0.7% for the spine and 1.7% for the small bone for weekly determined means. The long-term precision error (monthly determined means) for spine phantom was 1% and for the small bone phantom was 2%. A group of 14 infants were measured for total-body composition. Infant scans require on the average 15 minutes. All infants were asleep during the scan and did not receive sedative drugs. All body scans were accomplished at 3 x 3 mm resolution at a scan speed of 60 or 80 mm/s. The lumbar bones (L2-4) were scanned at 1 x 1 mm resolution at a scan speed of 60 mm/s. The total-body mineral content increased with gestational age and weight ( r = 0.84-0.87, p < 0.001; Fig. 4). The total-body calcium was also associated with length and lumbar and radial bone densities (Table 2). The percentage body fat increased with gestational age but the lean body mass decreased. The preterm (28-35 weeks of gestation) infant body fat ranged from 2 to 8%. The term infant body fat ranged from 9 to 22%. Infant body fat was associated with gestational age ( r = 0.80, P = 0.001) and birth weight ( r = 0.80, P = 0.001) but not with body mass index or weight/length3 ( r = 0.43, P > 0.05). The lumbar bone density was associated with birth weight, gestational age, length, body mass index, body fat, and radial bone density (Table 3). N o difference between male and female radial bone density/ weight or lumbar bone density/weight was noted. However, both the lumbar and radial bone density/total-body calcium ratios were higher in the male infants (0.003 f 0.0003, mean t SD, standard deviation, and 0.003 f 0.001) than females (0.0026 t 0.0005 and 0.002 k 0.0004; t-test, p = 0.03).
BONES
A W E D WEIGHT ( C )
MUSCLE
d
200
100
ACTUAL WEIGHT ( C )
FAT
0
10
20 30 ACTUAL WEIGHT (G)
40
50
FIG. 2. Associations of actual weights of fresh chicken parts to the weight of bones, fat, and muscle determined by DEXA. Correlation coefficients were high at 0.98-0.99.
0.8
,
I 06 0 U
I m
a 04 Y
5
a cc Iyi
:0 2 a 0 x
DISCUSSION From our data, the accuracy of the DEXA method was excellent for small quantities of bone, fat, or lean soft tissue mass. The DEXA-determined weights were highly associated ( r = 0.98-0.99) with the actual weights of chicken bones, muscle, and fat. The absolute values were different, however, as a result of the differences in methods and limits of sensitivity of the methods employed. We found that the DEXA method was linear to decreasing amounts of calcium phosphate. Other researchers found that the
00 0.0
0 2
0.6
0.4
SPA-DETERMINED
C
8
BMC, G i C M
FIG. 3. Association of DEXA-determined BMC and SPA-determined BMC in 32 children's distal radius bone. The correlation coefficient was 0.998.
372
CHAN TABLE1. COMPARISON OF SPA A N D DEXA ON THE RADIUSBONEMINERAL CONTENT G/CM,MEAN f SD" Age
n
SPA
DEXA
P
Birth-6 months 3-8 years 10-12 years
10 10 12
0.057 f 0.026 0.418 f 0.135 0.533 f 0.116
0.059 f 0.029 0.396 f 0.131 0.520 ? 0.114
NS 0.001 0.003
aAssociation of SPA and DEXA. r
=
0.99. NS, not significant.
TABLE2 . CORRELATION COEFFICIENT r FOR TOTAL-BODY CALCIUM VERSUSDIRECTLY MEASURED AND DERIVED VARIABLES x FOR INFANTS
lZO1
loo
0
1 X
"
I
1000
2000
3000
4000
BIRTH WEIGHT. G
0
GESTATIONAL
AGE ( W E E K S )
FIG. 4. The relation of total-body bone mineral content in 14 newborn infants with gestational age and birth weight. Total-body calcium increases with both gestation and birth weight. The 95% confidence bands are presented with the regression line.
DEXA method was also linear to increasing amounts of calcium hydroxyapatite. ( I 3 ) There was a high correlation of the bone mineral content values obtained by the singlephoton and the DEXA methods in children. We found a difference between the two methods as the child became older. This difference is probably due to the improved accuracy of DEXA over the SPA method and differing calibration and algorithms between the two The high analytic sensitivities of the DEXA method for these specific components of body composition make this technique applicable to very small animals and subjects in vivo.
Birth weight Gestational age Length Ponderal index, wt//, Radial bone density Lumbar bone density
r
P
0.91 0.88 0.93 0.45 0.67 0.83
0.001 0.001 0.001 NS 0.01 0.001
In adults the precision of total-body bone density using the DEXA method was 0.5% in vitro and in vivo. Totalbody bone mineral density correlated highly with dualphoton absorptiometry Using the single-photon absorptiometry method on small bones, the long-term precision was 2.1V0.''~) Our short-term precision was 1.7 and 2.0% for long-term precision on a small bone phantom. The precisions reported in this study are similar to others using the DEXA method.''" The body composition results from the infants are similar from those of other researchers using different techniques. From o u r preliminary data, we found that the total-body bone mineral content increased with gestational age and birth weight. The infant total-body calcium was also highly associated with length and radial and lumbar bone densities. By chemical analyses of a fetus that died before birth, the skeletal accretion of calcium increases during the last Using the single-beam photon absorptiometry method, a similar intrauterine bone mineralization was derived. Both bone mineral content and bone width of the distal radial bone site correlated with gestational age. (1b.18-*o) The major advantage of the DEXA method over the SPA is the ability to evaluate the metabolic active trabecular bones, as in the lumbar region. Lumbar bone mineral density showed a high degree of association with birth weight, gestational age, length, and body mass index (weight/length3) in infants. These associations of the infant's lumbar bone density are similar to those found in older In this study we found that the male newborn infants had a higher lumbar bone mineral content (BMC) than females. This sex dimorphism in BMC has been reported as early as 2 weeks of age in term infants.'221 Other researchers found a sex difference in bone mineral
373
DEXA USE IN PEDIATRICS TABLE3. CORRELATION COEFFICIENT I‘ FOR LUMBAR BONEDENSITY VERSUSDIRECTLY MEASURED A N D DERIVED x VARIABLES
3. 4.
X
Birth weight Gestational age Length Ponderal index, wt/l, Total body calcium Body fat, Yo Radial bone density
r
P
0.93 0.93 0.86 0.68 0.83 0.82 0.87
0.001 0.001
5.
O.(X)I
0.0 10 0.001 0.001 0.001
6.
7.
8.
status in older infants and children, but this has not been a consistent finding. L 1 7 . 2 2 ) We found this difference by using 9. the lumbar bone density to total-body calcium ratio. In evaluating pediatric subjects, bone density determinations must be adjusted for body size and growth. The ratio of the lumbar or radial bone density to total-body calcium 10. may be useful in comparing subgroups. Other researchers II. have recommended a similar bone mineral density index in children aged 5-19 years.‘21) Both body fat and lean soft tissue mass correlated with 12. gestational age and birth weight. As the fetus became more mature, there was more body fat and less soft tissue mass. The body fat content of human fetuses determined by 13. chemical analysis and by total-body electrii.,!l ~~~~iiLiiictivity is similar to our value^.(^^'^) By using the ci! . < i !:,\ionab14. sorptiometry method on 51 newborn intaiil,, ICAI body mass was determined. Preterm infants had a11 Ican body mass and no fat; term infants have an averape ot 13% lean 15. body fat.(23)These results are similar to o u r findings in which our preterm infants had body fat from 2 to 8% and our term infant body fat ranged from 9 to 22% using the 16. DEXA method. In conclusion, the DEXA method appears to be suited for pediatric use because of its high accuracy, precision, and sensitivity. This technique may thus be useful in iden17. tifying, treating, and following infants and children with nutritional problems.
ACKNOWLEDGMENTS We thank Tom Sanchez and Russ Nord of Norland Corporation for their technical support and encouragement. This work was supported in part from grants from Ross Laboratories and the National Dairy Council.
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18.
19.
20.
21.
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Address reprint requests to: Gary M. Chan, M.D. Department of Pediatrics, 2A230 50 North Medical Drive Salt Lake City, U T 84/32 Received for publication December 10, 1990; in revised form August 12, 1991; accepted November IS, 1991.
