Association of Lean Tissue and Fat Mass with Bone Mineral Content in Children and Adolescents

Transcription

1 Association of Lean Tissue and Fat Mass with Bone Mineral Content in Children and Adolescents Angelo Pietrobelli,* Myles S. Faith,* Jack Wang,* Paolo Brambilla, Giuseppe Chiumello, and Steven B. Heymsfield* Submitted for publication April 17, Accepted for publication in final form September 25, *Obesity Research Center, St. Luke s-roosevelt Hospital, Columbia University, College of Physicians and Surgeons, New York, New York; and Endocrine Unit, Department of Pediatrics, Scientific Institute H. San Raffaele, University of Milan, Milan, Italy. Address correspondence to Dr. Angelo Pietrobelli, Pediatric Unit, Verona University, Policlinico GB. Rossi, Via delle Menegone, 10, Verona, Italy. Copyright 2002 NAASO Abstract PIETROBELLI, ANGELO, MYLES S. FAITH, JACK WANG, PAOLO BRAMBILLA, GIUSEPPE CHIUMELLO, AND STEVEN B. HEYMSFIELD. Association of lean tissue and fat mass with bone mineral content in children and adolescents. Obes Res. 2002;10: Objectives: There has been uncertainty in the adult body composition literature about whether fat mass (FM) or fat free mass is a better predictor of bone mineral content and bone mineral density. This issue has recently also been raised in the pediatric literature. Based on suggested skeletal muscle bone relationships, this study tested the hypothesis that in children and adolescents lean tissue mass (LTM) is a better predictor of total bone mineral content (TBMC) than is FM. Research Methods and Procedures: Subjects were 133 Italian children and adolescents, 5 to 17 years of age, undergoing a routine medical screen. FM (kilograms), LTM (kilograms), and TBMC (kilograms) were measured by DXA. Multiple regression analyses tested the independent association of FM and LTM with bone mineral content. Results: Regression analyses, adjusting for pubertal status and other covariates, showed that FM and LTM were independently associated with TBMC. These associations were similar for boys and girls. TBMC was more strongly associated with LTM than FM. Discussion: These observations support the hypothesis that in children and adolescents a close association exists between LTM, a measure of skeletal muscle, and skeletal characteristics. Key words: pediatric age, DXA, fat, lean tissue mass, bone Introduction Studies in the adult body composition literature document associations of lean tissue mass (LTM) with total bone mineral content (TBMC) and total bone mineral density (TBMD). These correlations are presumably due to skeletal characteristics, the mechanical load, and force placed on bones by increased LTM and related skeletal muscle (1,2). What has been less clear is the extent to which fat mass (FM) is associated with TBMC or TBMD after adjusting for LTM and the reasons for such an association (3). Recent data suggest that greater FM is related to greater TBMC and TBMD, albeit to a lesser degree than LTM (4,5). This association may be due to the additional mechanical load on bone conferred by increased FM (4,6) and increased estrogen production (7). Similar questions have been raised in the pediatric literature (8 10), although data are limited. Nelson et al. (8) demonstrated that greater body weight in children is associated with greater bone mass, although this study did not partition FM and LTM. Courteiux et al. (11) tested the independent associations of FM and LTM with TBMC and TBMD, respectively, although their sample was restricted to prepubertal girls. This study examined a model relating the body composition components (i.e., LTM and FM) linked with TBMC in a sample of children and adolescents. The development of such models might assist in a better understanding of how variation in nutritional status and physical activity relates to bone development. The adult human literature suggests a link between mechanical load, force (i.e., LTM as skeletal 56 OBESITY RESEARCH Vol. 10 No. 1 January 2002

2 Table 1. Physical characteristics of the study sample Girls Boys Total Number Age (years) Weight (kg) Height (cm) Body mass index (kg/m 2 ) * Fat mass (%) Fat mass (kg) * Lean tissue mass (kg) Total bone mineral content (kg) Data are shown as mean SD. * p p 0.01 for Student s unpaired t test girls vs. boys. muscle attached to bone), and skeletal characteristics. We hypothesized a significant association of LTM with TBMC. In addition, we predicted that FM would be associated with TBMC even after controlling for LTM and other covariates, such as age, sex, and puberty status. Research Methods and Procedures Subjects The subjects were 133 children and adolescents, 5 to 17 years old, including 70 boys and 63 girls. All subjects were white, living in the Milan area (Italy), recruited after a routine medical evaluation, and seen consecutively during the period of September through December The subjects had no history of endocrine, nutritional, growth, or renal problems and were not receiving pharmacological treatment, and secondary obesity was excluded. Pubertal stages were assessed according to Tanner developmental staging (12). The characteristics of the study population are shown in Table 1. This study was approved by the Ethical Committee of the Scientific Institute H. San Raffaele. Parents and subjects signed an informed consent before the evaluation. Methods Anthropometry and DXA were performed on the same day. A single experienced physician made all measurements. Weight was measured with minimal clothing on a balance-beam scale. Height was measured on a standard laboratory stadiometer. Body mass index was computed as weight/square height, where weight is expressed in kilograms and height in meters. DXA total body analysis was performed on a Lunar DPX-L scanner 1.5E (Lunar Corp., Madison, WI) equipped with pediatric software (version 1.5e). The characteristics and physical concepts of DXA are described elsewhere (13,14). All metal objects (jewelry, snaps, and belts) were removed before the scan. Measurements were taken with the subject positioned supine on the scanning table, beginning at the top of the head moving, in a rectilinear pattern, down the body to the feet. None of the children required sedation. The subjects were scanned in a medium scan mode or in a fast scan mode, according to their size as suggested by the manufacturer. FM and LTM were expressed in kilograms. TBMC was expressed as total mass (kilograms). Daily quality assurance tests were performed according to the manufacturer s directions, and all scans were performed and analyzed by the same operator. The coefficient of variation for repeated tests of the DXA scanner was 0.6% for plastic and water phantoms. Statistical Analyses Descriptive analyses are presented as mean SD, with gender differences analyzed using Student s t test. The relationships of FM and LTM with TBMC were evaluated by multiple regression analysis controlling for age and sex. A single analysis was conducted using TBMC as the dependent variable. Nonlinear effects and interactions were explored in model development. Significance levels were based on two-tail tests, and was set at p Results TBMC was significantly correlated to FM (r 0.70 in girls and r 0.71 in boys, respectively) and LTM (r 0.91 in girls and r 0.94 in boys, respectively; p in both sexes). Age was positively correlated in boys and girls with TBMC (p ). Older subjects, thus, tended to OBESITY RESEARCH Vol. 10 No. 1 January

3 Table 2. Summary table for total bone mineral content (kilograms) regression model Total bone mineral content variable 1 SE p Overall R 2 SE p model Sex Age Fat mass Lean tissue mass Constant refers to the unstandardized regression coefficient. have greater TBMC than did younger subjects. Age was also positively related with FM (r 0.32, p in boys and r 0.39, p in girls) and LTM (both p ). Figure 1: Lean tissue mass (LTM) on the ordinate and total bone mineral content (TBMC) on the abscissa in 70 boys and 63 girls. Univariate line for the total population is shown. Multiple Regression Analyses TBMC was regressed onto FM, LTM, age, and sex (Table 2), yielding a highly significant model (p , R ). TBMC was significantly associated with both FM (p 0.003) and LTM (p ), although the association with LTM was stronger. Specifically, a 1-kg increase in LTM was associated with a 0.04-kg increase in TBMC on average, whereas a 1-kg increase in FM was associated with only a kg increase in TBMC. The association of TBMC with LTM is depicted in Figure 1. Age and sex did not contribute significantly to the model. In addition, interactions between LTM and either sex or age were not significant. Finally, results did not substantially change when adjusted for puberty status (i.e., Tanner stage 1 vs. stages 2 to 5). Discussion Two main findings emerge from this study. First, LTM was independently associated with TBMC. This association was similar for boys and girls, as indicated by the lack of interactions with gender in the regression model. Second, and consistent with the adult literature (2,3), TBMC was more strongly associated with LTM than with FM. A number of adult body composition studies have attempted to disentangle the independent relationships of FM and LTM with bone using laboratory methods (2 6). These studies have generally found that TBMC and TBMD are associated with LTM and, to a lesser extent, with FM (4). The few pediatric studies that have tested these associations have primarily estimated FM and LTM from body density using the equation of Siri (11,15). This study used DXA to develop a model relating bone mass to FM and LTM. In other studies that used DXA for similar purposes, analyses were limited to prepubescent girls (11) and premenopausal (6) or postmenopausal women (4,5). Alekel et al. (16) reported that fat free mass was the parameter most strongly correlated with vertebral and femoral bone mineral density in premenopausal women, a result that is not surprising because fat free mass is the sum of LTM and bone mass. The development of DXA to provide precise, simultaneous measurement of bone content and soft tissue mass, yielded evidence of the inter-relationship between fat, lean tissue components, and bone mineral content (17). Our findings are in line with Courteix et al. (11) who found a significant correlation between LTM and bone mineral content in a group of prepubertal girls. Mechanisms underlying these associations are currently unclear and remain an important avenue for subsequent studies. Potential mechanisms for the positive associations between LTM and 58 OBESITY RESEARCH Vol. 10 No. 1 January 2002

4 TBMC include a greater mechanical load (4,6) and increased estrogen production (7), among other factors (18). Because lean body mass reflects skeletal muscle mass, and bone and skeletal muscle form an operational unit (19), our data are consistent with the notion that skeletal muscle development is linked to skeletal development (20). Indeed, some agents (e.g., growth hormone, androgens, and calcium) that directly influence bone cells also affect muscle mass (21). Twin studies offer an informative approach for better understanding the basis for these correlations, including genetic and environmental influences. This approach was recently taken by Maes et al. (22) in a sample of adult twins. Another important component is the role of physical activity, which promotes greater bone density in children and adolescents (23). Gutin et al. demonstrated in a group of obese children that physical activity leads to greater reduction in the percentage of fat and increases fat free soft tissue, bone mineral content, and bone density during periods of physical training compared with no training (24), whereas Akisaka et al. (25) showed that girls involved in an exercise program had significantly higher bone density than did controls. Finally, these results and those by Courteix et al. (11) raise interesting questions about weight loss among overweight, obese, and anorectic children and adolescents. One report indicted that, in overweight and obese pediatric subjects, TBMC and bone density were low for body weight (26). In a separate study of anorectic adolescents, lower bone density was associated with severe weight loss (27). To the extent that reductions in FM and LTM confer differential reductions in TBMC, this may be clinically informative and suggests the importance of FM but not LTM loss for obese children. Using DXA in the context of controlled interventions may be useful for assessing long-term changes in bone density and mineral that occur with weight loss among children (28). In summary, these results support the hypothesis linking skeletal muscle and bone, and to a lesser extent fat and bone, in children and adolescents. The mechanistic basis of these observations remains to be elucidated. Acknowledgments This study was supported in part by National Institutes of Health Grant K08MH We thank our departmental colleagues and collaborators for stimulating discussions and suggestions. This article is based on the presentation we did at the meeting Nutrition, Foods and Health, Milan, Italy, November References 1. Doyle FH, Brown J, LaChance C. Relation between bone mass and muscle weight. Lancet. 1970;1: Chen Z, Lohman TG, Stini WA, Ritenbaugh C, Aickin M. Fat or lean tissue: which one is the major determinant of bone mineral mass in healthy postmenopausal women? J Bone Miner Res. 1997;12: Aloia JF, Vaswani A, Ma R, Flaster E. To what extent is bone mass determined by fat-free or fat mass? Am J Clin Nutr. 1995; 61: Reid IR, Ames R, Evans MC, et al. Determinants of total body and regional bone mineral density in normal postmenopausal women a key role for fat mass. J Clin Endocrinol Metab. 1992;75: Compston JE, Bhambhani M, Laskey MA, Murphy S, Khaw KT. Body composition and bone mass in postmenopausal women. J Clin Endocrinol. 1992;37: Reid IR, Plank LD, Evans MC. Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endocrinol Metab. 1992;75: Grodin JM, Siiteri PK, MacDonald PC. Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab. 1973;36: Nelson DA, Barondess DA. Whole body bone, fat and lean mass in children: comparison of three ethnic groups. Am J Physiol Anthropol. 1997;103: Gutin B, Litaker M, Islam S, Manos T, Smith C, Treiber F. Body composition measurement in 9 11-y-old children by dual-energy X-ray absorptiometry, skinfold-thickness measurements, and bioimpedance analysis. Am J Clin Nutr. 1996; 63: Faulkner RA, Bailey DA, Drinkwater DT, Wilkinson AA, Houston CS, Mckay HA. Regional and total body mineral content, bone mineral density, and total body tissue composition in children 8 16 years of age. Calcif Tissue Int. 1993; 53: Courteix D, Lespessailles E, Loiseau-Peres S, Obert P, Ferry B, Benhamou CL. Lean tissue mass is a better predictor of bone mineral content and density than body weight in prepubertal girls. Rev Rhum. 1998;65: Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity and weight velocity and stages of puberty. Arch Dis Child. 1976;51: Chan GM. Performance of dual energy X-ray absorptiometry in evaluating bone, lean body mass and fat in pediatric subjects. J Bone Miner Res. 1992;4: Pietrobelli A, Formica C, Wang ZM, Heymsfield SB. Dual energy X-ray absorptiometry body composition model: review of physical concepts. Am J Physiol. 1996;271: Siri WE. Body composition from fluid spaces and density. In: Brozec J, Hanschels A, eds. Techniques for Measuring Body Composition. Washington, DC: National Academy of Science, National Research Council; 1961, pp Alekel L, Clasey JL, Fehling PC, et al. Contributions of exercise, body composition and age to bone mineral density in premenopausal women. Med Sci Sports Exerc. 1995;27: OBESITY RESEARCH Vol. 10 No. 1 January

5 17. Pritchard JE, Nowson CA, Wark JD. Bone loss accompanying diet-induced or exercise-induced weight loss: a randomized controlled study. Int J Obes Relat Metab Disord. 1996;20: Lanyon LE. Using functional loading to influence bone mass and architecture: objectives, mechanisms, and relationship with estrogen of the mechanically adaptive process in bone. Bone 1996;18:37S 43S. 19. Frost HM, Schonau E. The muscle-bone unit in children and adolescents: a 2000 overview. J Pediatr Endocrinol Metab. 2000;13: Schonau E, Werhahn E, Schiedermaier U, et al. Influence of muscle strength on bone strength during childhood and adolescence. Horm Res. 1996;45: Frost HM. Muscle, bone and the Utah paradigm: a 1999 overview. Med Sci Sports Exerc. 2000;32: Maes HHM, Neale M, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27: Branca F. Physical activity, diet and skeletal health. Public Health Nutr. 1999;2: Gutin B, Owens S, Okuyama T, Riggs S, Ferguson M, Litaker M. Effect of physical training and its cessation on percent fat and bone density of children with obesity. Obes Res. 1999;7: Akisaka M, Zakouji H, Ariizumi M. A study of bone density and lifestyles of high school girls. Nipp Eiseig Zass. 1997;52: Goulding A, Taylor RW, Lones IE, McAuley KA, Manning PJ, Williams SM. Overweight and obese children have low bone mass and area for their weight. Int J Obes Relat Metab Disord. 2000;24: Iketani T, Kiriike N, Nakanishi S, Nakasuji T. Effects of weight gain and resumption of menses on reduced bone density in patients with anorexia nervosa. Biol Psychiatry. 1995; 37: Castro J, Lazaro L, Pons F, Halperin I, Toro J. Predictors of bone mineral density reduction in adolescents with anorexia nervosa. J Am Acad Child Adolesc Psychiatry. 2000;39: OBESITY RESEARCH Vol. 10 No. 1 January 2002