Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry”2 Steven Steven

B Heymsfield, Rebecca Lichtman, Jack Wang,

Smith, Mary Aulet, andRichardNPierson,

Brooke Jr

Dual-photon absorptiometry (DPA) allows separation of body mass into bone mineral, fat, and fat-free soft tissue. This report evaluates the potential ofDPA to isolate appendages ofhuman subjects and to quantify extremity skeletal muscle mass(limb fat-free soft tissue). The method was evaluated in 34 healthy adults who underwent DPA study, anthropomety of the limbs, and estimation of whole-body skeletal muscle by models based on total body potassium (TBK) and nitrogen (TBN) and on fat-free body mass (FFM). DPA appendicular skeletal muscle (22.0 ± 3. 1 kg, I ± SD) represented ABSTRACT

38.7%

of FFM,

with

similar

proportions

in males

and

females.

There muscle

were strong correlations (all p < 0.00 1 ) between mass estimated by DPA and anthropometric limb cle areas (r = 0.82-0.92), TBK (r = 0.94), and total-body cle mass based on TBK-FFM (r = 0.82) and TBK-TBN =

0.82)

models.

Appendicular

skeletal

by DPA is thus a potentially quantifying human skeletal Clin Nutr 1990;52:2 14-8.

KEY WORDS ometry,

skeletal

practical muscle

and mass

mass

accurate method of in vivo. Am J

mass,

dual-photon

neutron-activation

absorptianalysis

Skeletal muscle represents the largest fraction of fat-free body mass. Depending on gender, age, and health status, between one-third and one-half of total body protein is within skeletal muscle (1). Despite the obvious significance ofskeletal muscle to physiology and nutrition, methods ofquantification in vivo remain Although

two

metabolic

end

products

released

from

myocytes, creatinine and 3-methyihistidine, have been used to estimate whole-body muscle mass, their application is beset with problems (2, 3). Long urine-collection intervals, the need for appropriate dietary intake, and concerns related to the metabolic origin and distribution of 3-methylhistidine and creatinine limit the use ofboth ofthese methods. At present the most widely accepted methods of evaluating skeletal muscle mass involve computerized axial tomography, magnetic-resonance imaging, and ultrasonography performed in multiple

sections

sent a technological 214

ofthe

advance,

body.

(DPA)

presents

a new opportunity

to quantify

skeletal

muscle

in vivo. Long recognized for its effectiveness at measuring bone density, the newly appreciated ability ofDPA to measure fat and lean components presents an equally significant promise to the field of body composition research. Because of the growing number of available whole-body instruments, extremely low radiation exposure, and ability to define total appendicular skeletal muscle and bone mass with high precision mass

(5, 6), these measurements will ingly, in this report we describe

DPA in estimating bration

data,

and

be widely

appendicular the

results

applicable.

Accord-

the theory behind the use of skeletal muscle mass, the cali-

ofinitial

patient

studies.

estimated

Introduction

limited.

ited instrument access, and concerns for accuracy are often cited as limitations ofone or the other techniques (4). The recent development of dual-photon absorptiometry

Methods Model

Body composition, muscle

muscle

limb musmus(r

Bensen,

Although

expense,

these

radiation Am

methods

ing differential attenuation of photons at two energy levels. These photons may be produced by ‘53Gd or by an x-ray source, and the underlying principle is identical in both cases. The DPA algorithm includes a measure of soft-tissue attenuation at the two energy levels referred to as the R. The R.,. correlates linearly with the proportion of soft tissue as fat (or lean). The fat content ofscanned soft tissue in vivo can be estimated by means of a calibration equation (6). This is accomplished by first scanning phantoms of known fat content and establishing the prediction equation for percent fat based on R5T . Chemically analyzed beefphantoms are used for this purpose. Typical regression lines during calibration are r = 0.960.98

Nuir

C

From

the Department

Physicians 2

we described

of Medicine,

Hospital

and Surgeons,

Address

4 1 1 West

I990;52:214-8.

study

this

calibration

pro-

and demonstrated excellent agreement between fat estiby DPA in healthy nonobese subjects and fat deterby such conventional methods as hydrodensitometry

Luke’s-Roosevelt

urn-

Downloaded from https://academic.oup.com/ajcn/article-abstract/52/2/214/4651407 by guest on 18 February 2018

(6, 7). In an earlier

cedure mated mined

repre-

exposure, J C/in

Whole-body DPA partitions body weight into two fractions, bone ash (calcium hydroxyapatite) and soft tissue, by measur-

reprint

Center,

to SB Heymsfield,

New York,

ReceivedJune 16, 1989. Accepted for publication October Printed

in USA.

Columbia

Research University

Center,

St

College

of

New York.

requests

1 14th Street,

Obesity

NY

Weight

Control

Unit,

10025.

1 1, 1989.

© 1990 American

Society

for Clinical

Nutrition

SKELETAL (r

(r

0.94,

=

SEE

0.95,

=

=

ofa

scan,

subregion

1 .82

=

SEE

kg)

skeletal

contains

a small

be ignored sume

and

amount

skin

and

a given

The

of marrow,

associated

minerals

(ash).

ofwet

skeletal

(50-52%)

Under

usual

weight,

with

in osteoporotic

subcutaneous

Limb

fat is estimated

toms

as described

tissue

determined

as percent

tal muscle oflimb

mass

Upon image

bone

ofthe

subject’s

landmarks

actual

and a cursor,

mass

limb

minus

is

Skele-

the sum

scan,

the DPA software generates an I). Using specific anatomic the DPA operator isolates the legs and 1 . Once isolated, the system software (Fig

RST,

and

bone

ash

lated

line.

RST calibration

muscle upper-

phanlimb

mass.

mass

ash X 1 .82) by subtraction

skeletal summed

beef

in the

by soft-tissue

region. Wet bone mass (bone from total limb mass, followed the

assumpash divided

R5T and

fat

to total

skeleton

arms as shown in Figure provides the total mass,

from

55% slightly

mass.

completion ofthe

negligi-

represents

bone

use ofthe

The

equal

are

decreasing

equals

fat multiplied

is then

fat and

ash

content

weight

through

above.

may

We also as-

(8, 9). A reasonable

wet bone by 1.82.

shaft

component. The deofwater, protein, and

circumstances mineral

patients

tion, therefore, is that by 0.55 or multiplied

or bone

for simplicity

composition.

ble in mass relative to the skeletal-muscle fatted and marrow-free bone is a mixture

or any

nonosseous

components-

skeleton

which

of limb

scan,

ash,

of three

fat.

215

MEASUREMENT

analysis

DPA

for bone

primarily

muscle,

in the evaluation

that

neutron-activation

Hence

be analyzed

can

lean tissue, and fat. The extremities consist skeleton,

and

1.68 kg) (6).

MUSCLE

This

for

the

is next

offat

result

mass

then

mass either separately for each and lower-limb muscle masses.

identified subtracted

calcu-

represents

limb

or for the

Protocol

The DPA muscle-mass subjects who underwent

method DPA,

was evaluated anthropometry,

counting for total body tron-activation analysis

potassium for total

(TBK), and body nitrogen

of the (n

=

subjects underwent 2) consecutive days

cient

of variation

(CV)

single trained observer the serial CV studies portion

of this

protocols

(6,

before

the

10).

view boards yen National

study the

is presented

Each

volunteer

which

was

signed

2) or 5 coeffi-

unrelated consent

institutional

and

re-

at Brookha-

WI)

regional bone scan required

tion,

phantoms

DPA scanner used to evaluate RST, and soft-tissue

1.7%,

respectively

ash, -‘-55

of known

mm.

For

fat

content

calibrawere

(6). The

radiation

exposure

is 0.02

mGy

per scan. Total

to derive dium

potassium.

TBK

iodide

( 1 1). The

detectors

Reconstruction of DPA scan demonstrating landmarks that body into six regions. The neck cut is made just below the rib cuts are made as close to, but not touching, the spine. The isolated by running a line through the humeral head. The is placedjust above the pelvic brim and the system computer draws the lower pelvic lines. The spine cut is placed just last pair ofribs coming out ofT 12.

for TBK whole-body counting is 2.4%. The system operawas described in detail previously (1 1). Total body nitrogen. Prompt -y-neutron-activation analysis was used to estimate TBN. This system, described by Vartsky CV

tion

et al ( I 2), uses

Whole-body Brookhaven

placed

above

#{176}K counting system consists and

below

the

was used of 54 so-

patient.

The

mounted

Downloaded from https://academic.oup.com/ajcn/article-abstract/52/2/214/4651407 by guest on 18 February 2018

above

the patient.

in nitrogen-containing

prompt and

a plutonium-beryllium

source

of neutrons

that

‘4N nuclei. The 1 735 0 prompt y decay of activated is then detected by two sodium iodide crystals that are

activates nitrogen 2.4%

bodi’

I.

was

scanned and the results were used to relate R5T to percent fat (6). The aforementioned procedures were then used to derive whole-body and appendicular bone ash, fat, and skeletal muscle. The between-day CV for bone ash and percent fat are 1.0% and

FIG

subdivide chin. The arms are pelvis cut automatically below the

A whole-body

Madison,

beef

earlier

by the

Hospital

absorptiometrv.

frozen

‘y-neuFour

=

an informed

approved

(DP4, Lunar Radiation, each patient’s total and mass. Each head-to-toe seven

on 4 (n between-day

in two

at St Luke’s-Roosevelt Laboratory.

Dual-photon

prompt (TBN).

for estimates of limb composition. A (RS) read all 34 initial DPA scans and were interpreted by investigator MA. A

database

study,

the DPA to establish

in 34 healthy whole-body

gamma

TBN

The

present

phantoms.

analysis

are

system

has a CV of

Additional

reviewed

details

in references

13.

The absolute

TBK

and TBN

were correlated

directly

against

of

12

HEYMSFIELD

216 TABLE

I

Subject

ET AL Statistical

characteristics

and

body

baseline

composition

methods

results*

Correlations Body

Age

Weight

3.

Females(n Males(n=

=

18)

Total(n

± 22.6

48.7±

15.9

59.7

52.3 ± 19.7

66.6

kg/rn?

± 10.2

72.7±

tion

index

kg

56.3

34)

=

22.4

10.3 ± 12.1

± 2.9

31.7

muscle

mass

(Statst,

Statsoft,

%

pressed

as mean

± SD.

23.1

26.3

± 8.4

estimated

kg)

by DPA.

is determined

(mmol)

and

TBN

In addition,

by

total-body

simultaneous

(g) by use ofthe =

SMM in which

(TBK

1.33

-

skele-

proposed by muscle mass

measurement following

Tulsa,

OK).

body

composi-

linear-regression

All group

results

are ex-

±

2 kg/rn2

of2l.4

- (TBK

was calculated

FFM

DPA

TBN)/51.2

(1)

(2)

- 48 FFM)/43

as body

weight

minus

DPA

limb

The

cle-plus-bone

area

from

was calculated

respective

circumference

and

skinfold

total

the results

ofthree

trials

were

averaged.

all units

TABLE 2 Limb composition

analyses

from

0. 1 18) and

Lower Bone

Skeletal

studies 2.4

did

tended

in males

on four

± 0.5%,

and

Skeletal No

females

for men

and

women

respectively.

ofthe 3.0

more

muscle definitive

(0.44).

to be higher (0.089

in lower(pooled

subjects

± 1.5%

resulted

(1±

SD)

in CVs for upper-

and

bone

The

for both 0.142)

ratio

upper

than

of bone

and

to skeletal

lower

in females

extremi-

(0.085

and

was present relative to skeletal muscle = 0. 135) than upper(0.094) extremities.

value

mass methods

are

available

for

quantifying

whole-

skeletal muscle mass in vivo. DPA was therefore evaluated in relation to available markers of skeletal muscle by simple linear-regression analysis. The results ofTBK and TBN estimates are presented in Table 3 along with calculated totalbody skeletal muscle mass (TBK, TBN, and FFM), anthropobody

thigh

metric

limb

muscle

areas,

and

combined

(upper

and

lower)

DPA limb muscle mass. TBK was highly correlated

with DPA extremity muscle mass pooled data for the 34 subjects (r = 0.94, p < 0.001 ; Table 4 and Fig 2). The correlation between DPA muscle and TBN was also significant (r = 0.78, p < 0.001) and ofsimilar magni-

(3)

fl

(16).

dual-photon

than

measure-

- (ir X skinfoid)]2/4ir

are in centimeters

0.57)

ties

skinfold was measured at the circumference site in the midsaggital plane on the anterior aspect of the thigh. Limb muscleplus-bone area was then calculated as [(circumference)

repeated ± 2.4%,

muscle

The

fat by DPA

composition

musand mid-

ments. A single trained observer made all ofthe measurements on the right side of standing patients (14). Midarm and midthigh were identified as being halfway between the acromial and olecranon processes ofthe scapula and the inferior margin ofthe ulna and the inguinal crease and proximal border of the patella, respectively. A calibrated tape measure was used to establish limb circumferences at each location. The triceps skinfold was then measured at the posterior aspect of the upper and

a percentage

extremity, lower-extremity, and combined-limb appendicular skeletal muscle masses, respectively. The bone, skeletal muscle, and fat content of the limbs as estimated by DPA is presented in Table 2. Males had more bone and skeletal muscle and less fat than did females for both lower and upper extremities. Males also had more upper-extremity than lower-extremity skeletal muscle (upper/lower =

The anthropometnc for upper midarm

measurements.

and

± 6.5% and 31.7 ± 6.8%,

of

relation:

fat.

Anthropometric

where

simple

There were 18 male and 16 female subjects (Table I) with average age for the pooled group of52.3 ± 19.7 (i± SD). Overall the group was relatively lean, with a body mass index of 23

This model assumes that K/N in skeletal muscle and nonskeletal muscle lean tissue is 9 1 and 47 mmol/kg, respectively. The second model replaces TBN with fat-free body mass(FFM, kg). Our approach in this study was to use the equation

midarm,

and other

Results

of7.0

thigh

mass by using

± 6.8

21.4±6.5

mass was calculated by two equations (14, 15). In the first model, skeletal

5MM

body

muscle

examined

Subjects

tal muscle Burkinshaw (5MM,

were

analysis

23.7±2.9 ± 2.8

between

estimates

Fat

SD.

S

TBK

16)

mass

absorptiometry* extremities

muscle

Upper Fat

Total

Bone

Skeletal

extremities

muscle

kg

Fat

Total

kg

Females

1.3±0.3

11.0±2.2

5.9±2.0

18.2±3.5

0.4±0.1

4.7±0.9

3.7±

Males Total

2.0±0.4 1.7±0.5

14.1±1.7 12.6±2.5

4.1±1.6 5.0±2.0

20.2±2.9 19.3±3.4

0.7±0.1 0.6±0.2

7.9±1.6 6.4±2.1

3.1±1.5 3.4±1.6

5i±SD.

Downloaded from https://academic.oup.com/ajcn/article-abstract/52/2/214/4651407 by guest on 18 February 2018

1.6

8.8±2.2

11.7±2.7 10.4±2.9

SKELETAL TABLE

3 ofbody

Results

composition TBK

TBN

5MM

mmo/

kg

kg

1.35±0.27

7.0±

5.9

3459±578 2844±823

1.78±0.25 1.58±0.34

21.4± 14.6±

8.0 10.1

I, SMM2,

and lower

and SMM3 extremity

are skeletal

5MM

muscle

estimated

5.0±4.6

(Eq 3). AMA

per

se is of intense

for a large

interest

and,

portion

moreover,

(73-75%)

oftotal

the

5.8 9.5 15.1

57.6± 45.5± respectively, muscle-plus-bone

Despite the obvious physiological relevance of quantifying skeletal muscle mass, no definitive whole-body in vivo method is yet available. The DPA technique described herein advances our measurement capability by providing a practical approach to estimating appendicular skeletal muscle mass. The extremaccount

cm2

from,

Discussion

pendages

cm

is arm

tude to the correlation between DPA muscle and body weight (r = 0.80, p < 0.001). Total body estimates of skeletal muscle mass (Eqs 1 and 2) were on average smaller than limb muscle mass estimated by DPA ( I 4.6 and 1 1 .4 kg, respectively, vs 1 9.0 kg). Although several negative values were observed in the former, both calculated muscle estimates were significantly correlated with DPA skeletal muscle (both r = 0.82, p < 0.00 1; Table 4). Anthropometric muscle-plus-bone areas were significantly (p < 0.001) correlated with DPA extremity muscle mass, with r = 0.82 for upper limb r = 0.88 for lower limb, and r = 0.92 for the sum of upper- plus lower-limb muscle-plus-bone areas. Thus two ofthe indirect markers ofskeletal muscle mass, TBK and anthropometric muscle-plus-bone areas, were highly correlated with DPA muscle mass. Significant but weaker associations were observed between DPA muscle and whole-body skeletal muscle derived by the TBK-TBN and TBK-FFM models.

ity muscle

TMA

31.9±

17.1 ±7.1 11.4±8.6

mass calculated

by DPA

AMA

kg

2152±394

SMM

SMM2

1

Males Total *

217

MEASUREMENT

studies*

Females

ofupper

MUSCLE

ap-

skeletal

TBK

muscle mass (17). for total extremity tassium.

(Eq

the

1), TBK

is thigh

such

DPA

SMM3 kg

168.3±31.4 227.1 ±36.3 199.3±44.9

(Eq 2), and the sum

and FFM

area.

CV for the method the range of other

as whole-body

approach

15.7±2.9 22.0±3.2 19.0±4.3

muscle-plus-bone

The between-day muscle) is within

techniques, Hence

brings

counting within

range

(3% body for

po-

the

ca-

pability of reproducibly estimating all but one-fourth of skeletal muscle mass. Skeletal muscle mass derived by DPA was highly correlated with other regional (anthropometry) and total-body (wholebody counting, neutron activation) estimates of muscle mass. These associations demonstrate the potential of using DPA to explore other methods ofquantifying muscle. For example, the sum ofanthropometric limb muscle-plus-bone areas showed a strong correlation (r = 0.92) with DPA total-extremity muscle mass, suggesting the potential for developing anthropometric limb-muscle-mass prediction equations. Another example is the demonstration that the neutron-activation and the wholebody counting models (Eqs 1 and 2) for partitioning FFM into muscle and nonmuscle components provides muscle estimates that on average are too low (1 1-15 kg vs 19 kg for DPA limb muscle), with negative values observed in some cases. These models therefore need to be reconsidered and perhaps revised in light ofthe present findings. The DPA skeletal-muscle-mass method has several possible limitations worthy of discussion. At present our gadolinium system has a long scan time (55 mm), restricting the study to patients with sufficient endurance. New x-ray-based dual-photon systems (DEXA) reduce scan time to 15 mm, thus partially alleviating this problem. The minimal radiation doses are < 0.01 of 1% ofannual background, or ‘--2 h background mdi-

TABLE

4 Correlations between DPA appendicular body composition estimates

and TBN

TMA

+

cm2

136.6±28.6 169.5±28.0 154.0±32.7

area; TMA

composition

AMA

30

skeletal

muscle

and other

0

.

Equation

r

SEE

Males Females

25

p DPA

Body

weight

0.29x

TBK

TBN

Skeletal Skeletal Arm

muscle I muscle 2t muscle-plus-bone

area

l0.06x+ 0.35x 0.41x

+ +

3.14 1 3.83 14.33

+ 8.25

0.80

2.7