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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 59:B796-B800 (2004)
© 2004 The Gerontological Society of America

Dual-Energy X-Ray Absorptiometry-Measured Lean Soft Tissue Mass: Differing Relation to Body Cell Mass Across the Adult Life Span

Marie-Pierre St-Onge1, Jack Wang1, Wei Shen1, ZiMian Wang1, David B. Allison2, Stanley Heshka1, Richard N. Pierson, Jr.1 and Steven B. Heymsfield1,

1 St. Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York.
2 Department of Biostatistics, University of Alabama at Birmingham.

Address correspondence to Steven B. Heymsfield, MD, Weight Control Unit, 1090 Amsterdam Ave., 14th Floor, New York, NY 10025. E-mail: sbh2{at}columbia.edu


   Abstract
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 Abstract
Methods
 Participants
 Results
 Discussion
 References
 
Lean soft tissue (LST) measured by dual-energy X-ray absorptiometry (DEXA) is used as a metabolic measure in aging research despite evidence of extracellular fluid expansion and a corresponding reduction in body cell mass (BCM) in older participants. We investigated the hypothesis that the fraction of LST as BCM is smaller with greater age. Men and women (n = 2043) had DEXA and 40K-counting for body potassium and BCM measured on the same day. Both BCM and LST were lower with greater age but the relative lowering was larger for BCM. A multiple linear regression model was fitted with BCM/LST as the dependent variable, and age, sex, and interaction terms as independent variables. Men had a mean BCM/LST greater (p <.001) than women; quadratic and cubic age terms were also significant or approached significance. Thus, the fraction of LST as BCM is smaller in older adults, a finding that has implications for the interpretation of DEXA results.

AGING is associated with loss of lean tissue mass and bone with a corresponding relative increase in fat mass (1). The decline in lean tissue mass, notably skeletal muscle, and associated function are collectively referred to as sarcopenia (2). The presence of sarcopenia is a risk factor for functional limitation (3) and potentially for morbidity and mortality (4).

Dual-energy X-ray absorptiometry (DEXA) is increasingly available to investigators and clinicians as a means of quantifying and tracking changes in body composition (5). DEXA provides rapid and accurate estimates of three components that comprise body mass, lean soft tissue (LST), bone mineral, and fat (5). DEXA estimates of LST are now widely incorporated into clinical studies as a measure of age-related changes in skeletal muscle and other metabolically active and functional components (6).

Several earlier studies demonstrated both cross-sectional and longitudinal changes in body cell mass (BCM) and extracellular fluid (ECF) (1,7–10) with aging. As LST, as measured by DEXA, represents the sum of whole body BCM and ECF with a small extracellular solids (ECS) contribution (11), the possibility exists that the fraction of LST as protoplasmic mass (i.e., BCM) declines with aging. If valid, this hypothesis suggests that DEXA LST estimates do not reflect functionally equivalent components across the adult life span. That is, these earlier studies suggest that the LST compartment has a smaller fraction of BCM and a larger fraction of ECF in old participants compared to their younger counterparts. The rate of decline in LST with aging may therefore not represent the actual rate of active cell mass loss.

The aim of the present study was to test the hypothesis that the fraction of LST as BCM is smaller in magnitude with greater age.


   METHODS
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 Abstract
 Methods
Participants
 Results
 Discussion
 References
 
Design and Protocol
We carried out a cross-sectional study examining the associations between LST mass as measured by DEXA, BCM as measured by whole body 40K counting for total body potassium (TBK), and age. Each participant had LST and 40K measured on the same day. A pencil-beam whole body DEXA system was used to estimate total LST mass (11). Whole body counting for 40K was used to quantify TBK using a 4 {pi} system (12,13). Body cell mass (in kg) was derived as 0.0092 x TBK (mmol) as reported by Wang and colleagues (14). Using these measures, we then tested the hypothesis that the fraction of DEXA-measured LST as BCM is lower with greater age in healthy adults.


   PARTICIPANTS
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 Abstract
 Methods
 Participants
Results
 Discussion
 References
 
Participants were healthy adults, aged 18 years or older, who participated in a large cross-sectional body composition study (13). Each participant was prescreened for health by telephone interview. Those participants without serious chronic illnesses (e.g., diagnosed malignancies, congestive heart failure, and so forth) or recent weight change (± 3 kg/6 months) were then evaluated by medical history, physical examination, and screening blood studies. DEXA estimates are less reliable when body mass index (BMI) exceeds 35 kg/m2, and we therefore limited enrollment into this project to individuals with BMI < 35 kg/m2. Participants without any newly diagnosed medical conditions were included in the participant pool that forms the basis of this report. The participants included five race/ethnic groups as follows: non-Hispanic black, non-Hispanic white, Hispanic, Asian, and other. The study was approved by the St. Luke's-Roosevelt Hospital Institutional Review Board, and all participants signed an informed consent prior to evaluation.

Body Composition
Anthropometric measurements.-- Anthropometric measurements were made with all participants clothed in a hospital gown. The participant's body weight was then measured to the nearest 0.01 kg using a Weight-Tronix electronic scale (Scale Electronics Development, NY). Standing height was measured without shoes to the nearest 1 mm with a wall-mounted Holtain stadiometer (Crosswell, Wales, U.K.).

Dual-energy X-ray absorptiometry.-- DEXA was used to measure LST, bone mineral, and fat mass (11). The sum of these three components represents total body mass. The scan was completed with a whole-body pencil beam DEXA system (DPX, Lunar Radiation Corp., Madison, WI); detailed methods for image acquisition and analysis are described elsewhere (11,14). The within-participant coefficient of variation is 1.2% for lean soft tissue, 1.28% for bone mineral, and 3%–4% for fat (15).

Whole-body counting.-- The St. Luke's 4 {pi} whole-body counter was used to detect the natural 1.46 MeV {gamma}-ray of 40K as previously reported (12,13). The 40K counts accumulated over 9 minutes were adjusted for body size on the basis of a 42K calibration formula (12). Total-body potassium was then calculated as 40K/0.000118 (1). The technical error in our laboratory for repeated counting of a 40K phantom is 2.4% (14).

Statistical Methods
Group mean values and standard deviations were calculated for men, women, and pooled participants. The statistical significance of baseline characteristics and body composition differences between men and women were tested with t tests for independent samples.

The amount of LST, of BCM, and the fraction of LST as BCM (BCM/LST) were plotted against age for men and women separately, and a locally weighted scatter-plot smoothing line was fitted (SAS PROC LOESS). The shape of the smoothed line for BCM/LST was used to guide subsequent multiple regression modeling of the curve of BCM/LST with age, age2, and age3. Residuals were checked for normality and homoscedasticity. Regression analyses with BCM as the dependent variable and LST, age, the LST by age interaction, and higher powers of age were also carried out within each sex group to determine whether conclusions would differ from those reached with BCM/LST as the dependent variable. Statistical analysis was carried out using SAS (SAS Institute, Cary, NC), and p <.05 was considered a significant result, although some nearly significant (p <.10) associations were also investigated.


   RESULTS
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 Abstract
 Methods
 Participants
 Results
Discussion
 References
 
Participants
The total sample consisted of 2043 participants: 847 men and 1196 women (Table 1). All race/ethnic groups had good representation, with the largest number being non-Hispanic white [822] followed by non-Hispanic black [454], Hispanic [340], Asian [373], and other [54]. Women were significantly (p <.001) older than the men, 52.8 ± 19.3 versus 49.4 ± 19.8 years (Table 1). The distribution of age was similar in women and men (age < 20 years/20–29/30–39/40–49/50–59/60–69/>70: n = 25, 26/136, 148/190, 151/144, 126/204, 118/219, 133/278, 145). The BMI was also similar in men (25.4 ± 3.8 kg/m2) and women (25.0 ± 5.2 kg/m2) as was the distribution of participants into normal weight (52.0%/57.9%), overweight (37.1%/27.4%), and obese (10.8%/14.6%) groups.


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  		Table 1. Baseline Characteristics and Body Composition of Participants.

 
Body Composition
Men were significantly taller, weighed more, and had more LST and bone mineral than the women (all p <.001) (Table 1). Women had significantly more fat than did the men (p <.001). Men had a significantly larger BCM and LST than did the women, and BCM/LST was also significantly larger in men (0.59 ± 0.07) than in women (0.54 ± 0.06) (all p <.001) (Table 1).

BCM/LST Regression Models
The smoothed scatter-plots of LST, BCM, and BCM/LST against age for men and women are shown in Figures 1 and 2. The figures show an unmistakable decline over the age range as a whole with the likelihood of a quadratic and possibly a cubic component to the LST/BCM decline for both men and women.



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  		Figure 1. Lean soft tissue (LST, solid line) and body cell mass (BCM, broken line) by age in men and women. The lines are a locally weighted smoothing of the scatter-plot of individual data points (not shown)

 


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  		Figure 2. Body cell mass/lean soft tissue (BCM/LST) versus age in men (upper panel) and women (lower panel). The lines are a locally weighted smoothing of the scatter-plot

 
A multiple linear regression model was fitted to the full dataset with BCM/LST as the dependent variable and age, age2, age3, sex, and sex by age, age2, and age3 interaction terms. Sex was coded as 0 for women, 1 for men. The results showed a main effect for sex with men having a mean BCM/LST ratio 0.057 (SE [standard error] 0.005; p <.001) greater than women; however, a significant sex by age interaction (–0.00026; SE 0.0001; p =.007) indicated that the magnitude of the sex difference decreased with increasing age. No higher order interaction terms of age with sex were significant. The quadratic term for age was significant (–0.000044; SE 0.000018; p =.016) and the cubic term was nearly statistically significant (2.04 x 10–7; SE 1.12 x 10–7; p =.069). The model R2 was.46.

Because of the sex by age interaction, we also applied regression models within each sex group to clarify the importance of the higher powers of the age variable in describing the BCM/LST versus age relationship. In the female subsample, age3 (p =.044) and age2 (p =.016) both reached conventional significance, and the linear effect of age was nearly significant (p =.064), indicating the simultaneous and independent presence of all three components in the relationship. In the male subsample, the linear component was clearly nonsignificant and added virtually nothing beyond the effects of age2 (p <.001) and age3 (p =.078).

The separate equations are:


{grna-59-08-14-eq1}

For both men and women, the regression of BCM on LST alone yielded nonsignificant intercepts indicating that the use of BCM/LST as a dependent variable is appropriate. Also, regression models similar to those above using BCM rather than BCM/LST as the dependent variable confirmed the results of the previous analyses, with the exception that, in the male subgroup, the linear and quadratic components of age were significant, whereas the cubic was not.


   DISCUSSION
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 Abstract
 Methods
 Participants
 Results
 Discussion
References
 
Dual-energy X-ray absorptiometry is increasingly being used to evaluate cross-sectional and longitudinal age-related changes in body composition across the life span. Total body and regional LST estimates provided by DEXA are often used as measures of metabolically active tissue (16,17), devoid of storage fat and structural bone mineral mass. The present study, carried out in a large and ethnically diverse participant group, shows that the cell mass portion of LST varies with age in adults, being at a maximum relative level in young adults and reaching low levels in older adults. Our findings also indicate that men have a larger fraction of LST as BCM than women, although the size of the difference decreases with age. Our findings extend earlier reports of age and sex differences in the associations between BCM and FFM, a component similar to that of LST (18).

An important implication of these findings is that LST and BCM cannot be considered interchangeable measures of metabolically active tissue. Our observations suggest that the fraction of LST in young adults as BCM is greater than that in older adults. Correspondingly, the fraction of LST as ECF and ECS (i.e., ~LST–BCM), components of low metabolic activity, are greater in old adults than in young adults. Resting metabolic rate, other metabolic measures, and mechanical function of organs and tissues that are primarily related to intracellular processes and LST estimates, particularly in elderly persons, should be cautiously interpreted when used as a marker or denominator for these processes, especially when making comparisons with young adults. Moreover, since the protein content of extracellular and intracellular fluid differ (19), older participants also may have a lower protein/LST fraction.

Lean soft tissue or related FFM estimates are often used as metabolic predictor variables in resting metabolic rate regression models (16,17). Both sex and age enter these models as additional resting metabolic rate predictors, leading to the interpretation of higher LST energy flux in men and in younger participants. Our findings support an alternative theory: that LST and FFM are heterogeneous with respect to cell mass, and that sex and age in resting metabolic rate prediction equations capture variation in the cellularity of LST. Additionally, heterogeneity exists in the fractional contributions of various organs and tissues to total BCM (20), and this also may account for some of the observed sex and age-dependence of resting metabolic rate after controlling for LST or FFM.

An important question is: What potential mechanisms account for the differing relations between LST and BCM across sex and age groups? Each organ and soft tissue, devoid of fat, can be considered "lean soft tissue." There is a large variation in the fraction of organs and tissues as BCM, ranging from a low of 0.44 in placenta to a high of 0.85 in skeletal muscle (Figure 3) (21). Adipose tissue also has a low BCM relative to fat-free lean soft tissue (21). Our observations suggest a whole-body BCM/LST of ~0.59 in men and ~0.54 in women, reflecting the integrated BCM and LST from all organs and tissues. The larger BCM/LST in men than in women likely represents the greater fraction of body mass as skeletal muscle, which has a BCM/LST of 0.85, in men. A smaller adipose tissue mass in men would also contribute to a higher BCM/LST than in women. In support of the muscle hypothesis, Wang and colleagues reported a larger fraction of FFM as skeletal muscle in men than in women (22).



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  		Figure 3. Body cell mass/lean soft tissue (BCM/LST) for adult human organs and tissues. Data are from Lentner (20). SM = skeletal muscle

 
Additionally, with aging, the loss of skeletal muscle exceeds those of most other organs and tissues while adiposity increases (23), and this may account for our observation of a lower BCM/LST in older participants. This view is also supported in the study of Wang and colleagues that reported a lower skeletal muscle/FFM and greater relative adipose tissue mass in both older men and women compared with their younger counterparts (22). An explanation for lower BCM/LST in older participants is that, as organs atrophy with age, the fraction of organs as ECF and collagen increases and the fraction as cell mass declines. Thus, two possible explanations for the lower BCM/LST observed in older participants in our study are a relatively large age-related reduction in skeletal muscle mass with greater adiposity and a lowering in the BCM/LST of each organ and tissue. However, since our data were cross-sectional, it cannot be undoubtedly inferred that BCM/LST decreases within an individual as he or she ages.

The presence of linear, quadratic, and cubic components that were identified in the BCM/LST curves cannot be unequivocally related to physiological processes, although the roles that each of the terms plays in shaping the final curve is clear. For women, for example, the positive linear coefficient accounts for the increase in BCM/LST seen in the early part of the curve. The influence of the negative quadratic coefficient then becomes dominant in the middle and higher age range, accounting for the increasing rate of decrease until, finally, the moderating effect of the positive cubic coefficient begins to slow the rate of decline at the upper end of the age range. While it may be possible to speculate about specific physiological processes that increase or decrease the ratio at various periods in the life span and that correspond to these components, it would be beyond the scope of this article.

While DEXA can be considered a major advance in body composition methodology, our findings show the limitation of LST estimates as a marker of age-related changes in BCM and thus potentially functional outcomes. Although disease is also likely to alter the relationship of BCM to LST, our findings suggest BCM/LST in otherwise healthy participants might be a useful biomarker of aging. Although TBK is not a widely available measure, a similar BCM/LST model could be developed by combining DEXA measurements with bromide dilution (24); BCM is approximately the difference between LST and ECF with a small adjustment for nonbone mineral ECS. A useful future study would be to compare BCM estimates by TBK and the combination of DEXA and bromide dilution.

In sum, our findings strongly support the hypothesis that the fraction of LST as BCM is lower with greater age in both men and women. These observations have implications for the application and interpretation of DEXA LST estimates.


   Acknowledgments
 
Supported by National Institutes of Health grants RR00645, DK056336, and NIDDK 42618.

Dr. St-Onge is supported by a Fellowship from the Canadian Institutes of Health Research, Ottawa, Ontario.


   Footnotes
 
Decision Editor: James R. Smith, PhD

Received January 13, 2004

Accepted March 11, 2004


   References
Top
 Abstract
 Methods
 Participants
 Results
 Discussion
 References
 

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