- Email: [email protected]
Bone Mineral Density, Hip Bone Geometry, and Calcaneus Trabecular Bone Texture in Obese and Normal-Weight Children
Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 16, no. 2, 244e249, 2013 Ó Copyright 2013 by The International Society for Clinical Densitometry 1094-6950/16:244e249/$36.00 http://dx.doi.org/10.1016/j.jocd.2013.02.001
Original Article
Bone Mineral Density, Hip Bone Geometry, and Calcaneus Trabecular Bone Texture in Obese and Normal-Weight Children Emilie Rocher,1,2 Rawad El Hage,*,3 Christine Chappard,4 Hugues Portier,1 Ga€el Y. Rochefort,1 and Claude-Laurent Benhamou1 1
EA 4708eI3MTO, Regional Hospital, Orleans, France; 2Danone, Danone Research, Palaiseau, France; 3Laboratoire de physiologie et de biomecanique de la performance motrice, Universite de Balamand, Al Koura, Liban; and 4B2OA, UMR 7052 CNRS, Universite Paris Diderot, Sorbonne Paris Cite, Paris, France
Abstract Our study aimed at comparing bone mineral density (BMD), geometric indices of hip bone strength, and indices of trabecular bone texture at the calcaneus in obese and normal-weight children. Fifty-three obese children (10.3 1.4 yr) and 24 normal-weight children (10.4 1.5 yr) participated in this study. Body composition, bone mineral content, and BMD at whole body (WB), lumbar spine (L2eL4), total forearm, and proximal femur (total hip [TH] and femoral neck [FN]) were measured by dual-energy X-ray absorptiometry (DXA). Bone geometry of the hip was evaluated by the hip structure analysis (HSA) program. DXA scans were analyzed at the FN at its narrowest region and the femoral shaft (FS) by the HSA program. Cross-sectional area (CSA) and section modulus (Z ) were measured from hip BMD profiles. Texture analysis was performed on digitized radiographs of the calcaneus to assess trabecular bone microarchitecture, and the result was expressed as Hmean. WB BMD, L2eL4 BMD, TH BMD, and FN BMD were significantly higher in obese children compared with normal-weight peers ( p ! 0.05). FN Z and FS Z were not significantly different between the 2 groups, whereas Hmean parameter was significantly lower in obese children compared with normal-weight peers ( p ! 0.001). After adjustment for body weight, obese children displayed lower WB BMD, FN CSA, FN Z, FS CSA, and FS Z compared with normal-weight children. This study suggests that BMD of WB and geometric indices of hip bone strength are not adapted to the increased body weight in obese children. Key Words: Bone geometry; bone mass; fat mass; physical activity; texture analysis.
greater (10,11), or equivalent (13) bone mass than healthy weight children. These differences could be related to differing approaches for the assessment of 2-dimensional (2D) projected DXA bone measures relative to age, bone size, and body size (10,11). Furthermore, the influence of being obese on bone parameters in growing children may be influenced by gender and maturity (10,11). Although bone mineral density (BMD) is a strong predictor of fracture risk, it only explains a part of bone strength (14,15). In reality, the organization of the trabecular bone (microarchitecture), shape and geometry of bones (macroarchitecture), and intrinsic properties of the matrix (mineral and collagen) also contribute to bone strength (14,15). Interestingly, Benhamou et al (16) have validated an approach to evaluate bone microarchitecture from radiographs by
Introduction Childhood obesity has been linked to an increase in fracture risk at the upper extremities (1e3). Dual-energy X-ray absorptiometry (DXA) is an accurate method to assess body composition and bone mass in normal-weight and obese children (4,5). To date, several studies have aimed at studying the skeleton of obese children and adolescents (6e13). It has been shown that obese children have either lower (6e9), Received 06/21/12; Revised 01/31/13; Accepted 02/05/13. *Address correspondence to: Rawad El Hage, PhD, Faculty of Arts and Social Sciences, Division of Physical Education, University of Balamand, P.O. Box: 100 Tripoli, Lebanon. E-mail: rawadelhage21@ hotmail.com
244
Bone Status in Obese Children measuring the Hmean parameter determining the fractal dimension. Hmean measurement is related to trabecular bone structure properties, such as porosity, connectivity, and bone strength (16e20). This method has also been used in children (19). Bone strength is also related to bone geometry (21e23). Proximal femur DXA scan images have been used to assess femoral bone geometry using the method previously described by Martin and Burr (21) and later modified by Beck et al (22). We have recently demonstrated that proximal femur bone geometry is well adapted to body weight in overweight adolescent boys but not in obese adolescent boys (24). However, the influence of being obese on BMD, bone geometry, and microarchitecture in prepubertal children and early pubertal is not completely understood. The aim of this study was to compare BMD, geometric indices of hip bone strength, and indices of trabecular bone texture at the calcaneus in obese and normal-weight children.
Materials and Methods Subjects and Study Design The study participants were recruited from primary schools in Orleans area, France, via information meetings, flyers, or newspaper advertisements. Inclusion criteria were male or female from 7 to 11 yr, Tanner stages I or II, being without endocrine or genetic abnormalities, no diagnosis of comorbidity, and no history of fracture. These criteria were checked during a previous medical examination. The subjects were not under any medication known to affect bone metabolism. Children were divided into a group of obese (n 5 53; 22 boys and 31 girls) and a group of control children (n 5 24; 11 boys and 13 girls). The diagnosis of obesity was defined using international cut offs for body mass index (BMI) (25). The study was approved by the regional ethics committee. Informed written consent was obtained from the children and their parents.
Anthropometric Measurements Height (cm) was measured in the upright position to the nearest 1 mm with a Seca standard stadiometer, and weight (kg) was measured on a Seca mechanic scale with a precision of 100 g (Seca 709, Hamburg, Germany). Children were weighed wearing only underclothes. BMI was calculated as body weight divided by height squared (kg/m2).
Pubertal Assessment Pubertal development was assessed according to the method of Tanner by a self-assessment form (26,27). A radiograph of the nondominant hand was taken for all children. The skeletal age was assessed using the method described by Greulich and Pyle (28).
Bone Mineral and Body Composition Measurements Body composition was assessed by DXA (Delphi QDRÒ Series; Hologic Inc., Waltham, MA). BMD (g/cm2) and Journal of Clinical Densitometry: Assessment of Skeletal Health
245 bone mineral content (BMC, g) were measured at whole body (WB), lumbar spine (L2eL4), nondominant forearm, and nondominant hip. The reproducibility of DXA measurements in our laboratory has been previously published (9,29).
Physical Activity Questionnaire Physical activity of the past year was assessed with a validated questionnaire for French children (30). Time spent watching TV or playing video games, an index of inactivity, was also assessed. Total annual physical activity was expressed as a mean in h/wk and as a mean in metabolic equivalent of task/wk (31).
Hip Structure Analysis Measurements We used the method described by Martin and Burr (21) and later modified by Beck et al (22). We studied 2 regions: the narrow neck across the narrowest segment of the femoral neck (FN) and femoral shaft (FS). For each region, we measured 2 parameters: cross-sectional area (CSA, cm2) and section modulus (Z, cm3). In mechanical terms, CSA is an indicator of resistance to loads directed along the bone axis (21,22). Section modulus (Z ) is an indicator of strength of the bone to resist bending and torsion (21,22).
Texture Analysis Parameters Fractal analysis is a statistical texture analysis. It expresses the roughness of the texture and characterizes the selfsimilarity of the texture gray-level variations over different scales. Fractal analysis of calcaneus radiographs was performed following a standardized protocol. The detailed procedure has already been described (16,32). To minimize the precision errors because of the digitization of X-ray film, we used a direct digital X-ray device (D3A Medical SystemÒ) to obtain radiographs of calcaneus. Hmean, co-occurrence, and run-lengths parameters were measured as previously described (33e35).
Dietary Habits Assessment Parents were asked to complete with the help of their child a 4-d food record. The current daily nutrient intake was calculated using the software Prodiet 5.2a (Proform, France).
Laboratory Methods Fasting blood samples were taken between 07:30 AM and 09.00 AM to avoid diurnal variation. Serum leptin was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (interassay coefficient of variation [CV] !9%). Serum adiponectin was measured using a commercial ELISA kit (interassay CV !8.5%). Bone formation was assessed by serum osteocalcin measured by ELISA (interassay CV !6.5%). Bone resorption was assessed by serum cross-laps (CTX) and measured by ELISA (interassay CV !8.2%). Serum 25-hydroxyvitamin D (serum 25(OH)D) level was measured using a commercial radioimmunoassay (interassay CV !11%). Volume 16, 2013
246 Statistical Analysis Basic data are presented as means standard deviations. Chi-squared tests were performed for testing gender and Tanner stage (1 or 2) distributions between the 2 groups (obese and controls). There were no interactions between these 2 factors and groups. Comparisons between obese and control groups were made after checking for Gaussian distribution. If Gaussian distribution was found, parametric unpaired t-tests were used. If not, Mann-Whitney U tests were used. Correlation coefficient was used to study the relationship between clinical characteristics and bone variables using Pearson test if Gaussian distribution was found or Spearman test if not. To determine which anthropometric characteristics (total body weight, total lean mass, total fat mass, or percent of fat mass) are the most related to BMD, principal component analysis was performed. The variables most highly correlated with BMD were included as parameters of adjustment. As a consequence, DXA, bone microarchitecture, and bone macroarchitecture values were compared after adjustment for total body weight and total lean mass using a 1-way analysis of covariance. Data were analyzed using number cruncher statistical system 2001 (NCSS; Kaysville, UT). A level of significance of p ! 0.05 was used.
Results Subject Characteristics and Body Composition
Rocher et al. Table 1 Clinical Characteristics of the Study Population Variable Gender (no. of boys/girls) Tanner stage (no. 1/2) Age (yr) Bone age (yr) Body weight (kg) Height (cm) Fat mass (%) Fat mass (kg) Lean mass (kg) BMI (kg.m 2) DCI (mg/d) Serum 25(OH)D (mg/L) CTX (ng/L) Osteocalcin (mg/L) Leptin (ng/mL) Adiponectin (mg/L) Energy expenditure (METs/wk) Physical practice in club (h/wk) Screen time (h/d)
Obese (n 5 53)
Controls (n 5 24)
p-Value
22/31
11/13
0.72
33/20
19/5
0.14
10.3 10.9 54.5 144.9 38.7 21.4 31.2 25.6 894 22.30
1.4 10.4 1.5 1.3 10.5 1.3 14.8 33.3 5.6 9.6 141.8 8.5 4.7 20.7 5.4 8.3 7.0 2.6 6.9 25.0 3.7 4.3 16.5 2.0 247 981 279 13.06 21.12 10.41
1268 32.08 15.3 11.2 124.7
338 5.12 15.1 3.9 32.9
1505 35.47 3.5 10.1 127.7
224 4.03 1.8 2.6 37.8
0.73 0.22 !0.001 0.17 !0.001 !0.001 !0.001 !0.001 0.17 0.74 0.01 0.01 0.003 0.20 0.74
1.4 1.5
1.9 1.8
0.25
16.6 7.6
8.2 4.8
!0.001
Gender distribution, Tanner stage, age, bone age, height, total energy expenditure, time spent in the sport club, daily calcium intake (DCI), and serum 25(OH)D were not statistically different between the 2 groups. Body weight, fat mass, fat mass percentage, lean mass, BMI, and serum leptin were significantly higher in obese children compared with controls. Serum osteocalcin and cross-laps (CTX) were significantly lower in obese children compared with controls (Table 1).
Note: Values are means standard deviation; p ! 0.05: obese significantly different from controls, using a parametric unpaired t-test, Mann-Whitney U test, or chi-squared test. Abbr: BMI, body mass index; CTX, serum cross-laps; DCI, daily calcium intake; METs, metabolic equivalent of tasks; Serum 25(OH) D, serum 25-hydroxyvitamin D.
DXA Measurements
different between the 2 groups after adjustment for lean mass, whereas only TH BMC was significantly higher in controls compared with obese children ( p ! 0.05).
WB BMD, L2eL4 BMD, total hip (TH) BMD, and FN BMD were significantly higher in obese children compared with normal-weight children (Table 2). In the whole population, weight, lean mass, fat mass, BMI, and fat mass percentage were positively correlated to WB BMD, L2eL4 BMD, TH BMD, and FN BMD (r 5 0.26e0.75; all p ! 0.05). Physical activity (h/week), sitting time, DCI, osteocalcin, and CTX levels were not correlated to BMD values. After adjustment for body weight, WB BMC, L2eL4 BMC, TH BMC, FN BMC, and total forearm BMC were lower in obese children compared with controls, whereas BMD values at all sites were not statistically different between the 2 groups except for the WB where BMD was significantly lower in obese children compared with controls (Table 3). After adjustment for lean mass, there were no significant differences in BMD values between the 2 groups. WB BMC, L2eL4 BMC, FN BMC, and TF BMC were not significantly Journal of Clinical Densitometry: Assessment of Skeletal Health
Hip Structure Analysis Variables FN CSA was significantly higher in obese children compared with normal-weight peers. FN Z, FS CSA, and FS Z were not significantly different between the 2 groups (Table 2). In the whole population, weight and lean mass were positively correlated to FN CSA (r 5 0.67; p ! 0.001 and r 5 0.73; p ! 0.001), FN Z (r 5 0.60; p ! 0.001 and r 5 0.63; p ! 0.001), FS CSA (r 5 0.51; p ! 0.001 and r 5 0.58; p ! 0.001), and FS Z (r 5 0.35; p ! 0.01 and r 5 0.39; p ! 0.001). After adjustment for body weight, obese children displayed lower CSA and Z values at the FN and FS compared with normal-weight children (Table 3). After adjustment for lean mass, there were no significant differences regarding hip structure analysis (HSA) variables between the 2 groups. Volume 16, 2013
Bone Status in Obese Children
247
Table 2 Crude Bone Variables in the 2 Groups Variable
Obese (n 5 53)
Controls (n 5 24)
Table 3 Bone Variables Adjusted for Body Weight in the 2 Groups p-Value
WB BMD 0.883 0.069 0.845 0.052 0.01 (g.cm 2) WB BMC (g) 1313.4 292.7 1066.6 194.1 !0.001 L2eL4 BMD 0.683 0.093 0.594 0.068 !0.001 (g.cm 2) L2eL4 BMC (g) 23.38 5.34 20.06 3.52 0.002 TH BMD 0.773 0.103 0.704 0.088 0.004 (g.cm 2) TH BMC (g) 20.00 5.40 17.34 4.57 0.03 FN BMD 0.742 0.108 0.670 0.098 0.006 (g.cm 2) FN BMC (g) 3.38 0.75 2.93 0.66 0.01 TF BMD 0.439 0.044 0.423 0.041 0.14 (g.cm 2) TF BMC (g) 3.93 0.95 3.29 0.78 0.006 2.02 0.56 1.76 0.47 0.04 FN CSA (cm2) FN Z (cm3) 1.04 0.57 0.87 0.39 0.13 FS CSA (cm2) 1.88 0.53 1.71 0.48 0.15 FS Z (cm3) 0.595 0.357 0.570 0.304 0.75 Hmean 0.572 0.031 0.606 0.030 !0.001 Co-occurrence 2.63 0.37 2.74 0.10 0.04 Run lengths 2.15 0.20 2.23 0.08 0.008 Note: Values are means standard deviation; p ! 0.05: obese significantly different from controls, using a parametric unpaired t-test or a Mann-Whitney U test. Abbr: BMC, bone mineral content; BMD, bone mineral density; CSA, cross-sectional area; FN, femoral neck; FS, femoral shaft; TF, total forearm; TH, total hip; WB, whole body; Z, section modulus.
Bone Texture Indices at the Calcaneus Hmean, co-occurrence, and run lengths were significantly lower in obese children compared with controls (Table 2). After adjustment for total body weight, Hmean, co-occurrence, and run lengths were not significantly different between the 2 groups (Table 3). After adjustment for lean mass, H mean and run lengths were lower in obese children compared with controls ( p ! 0.05). In the whole population, Hmean was negatively correlated to body weight (r 5 0.58; p ! 0.001), BMI (r 5 0.58; p ! 0.001), lean mass (r 5 0.51; p ! 0.001), fat mass (r 5 0.58; p ! 0.001), and fat mass percentage (r 5 0.53; p ! 0.001), and positively but weakly correlated to DCI (r 5 0.27; p ! 0.05).
Dietary Intake Total daily energy intake was lower in obese children in comparison to controls (1822 320 vs 1997 229 intake Kcal, p ! 0.05). In the whole population, DCI was negatively correlated to BMI and fat mass (r 5 0.28; p ! 0.05 and r 5 0.26; p ! 0.05, respectively). Journal of Clinical Densitometry: Assessment of Skeletal Health
Obese (n 5 53)
Variable WB BMD (g.cm 2) WB BMC (g) L2eL4 BMD (g.cm 2) L2eL4 BMC (g) TH BMD (g.cm 2) TH BMC (g) FN BMD (g.cm 2) FN BMC (g) TF BMD (g.cm 2) TF BMC (g) FN CSA (cm2) FN Z (cm3) FS CSA (cm2) FS Z (cm3) Hmean Co-occurrence Run lengths
Controls (n 5 24)
p-Value
0.861 0.006 0.893 0.010 0.04 1192 18 1333 26 !0.001 0.654 0.009 0.657 0.013 0.85 21.4 0.742 17.92 0.708 3.13 0.429 3.54 1.82 0.863 1.74 0.520 0.579 2.69 2.18
0.4 0.010 0.45 0.014 0.07 0.005 0.08 0.05 0.054 0.06 0.042 0.003 0.01 0.008
24.4 0.770 21.92 0.744 3.49 0.442 4.09 2.19 1.25 2.02 0.734 0.590 2.70 2.19
0.6 0.002 0.016 0.26 0.67 !0.001 0.017 0.17 0.11 0.03 0.008 0.34 0.12 0.008 0.07 0.003 0.081 0.002 0.08 0.04 0.063 0.03 0.005 0.20 0.01 0.75 0.012 0.46
Note: Values are means standard error; p ! 0.05: obese significantly different from controls, using a 1-way analysis of covariance. Abbr: BMC, bone mineral content; BMD, bone mineral density; CSA, cross-sectional area; FS, femoral shaft; FN, femoral neck; TF, total forearm; TH, total hip; WB, whole body; Z, section modulus.
Laboratory Methods Leptin, adiponectin, vitamin D, osteocalcin, and CTX circulating levels were not significantly correlated to bone variables in the whole population.
Discussion In this study, we showed that obese children displayed lower WB BMD, FN CSA, FN Z, FS CSA, and FS Z values compared with normal-weight children after adjustment for body weight. Thus, this study suggests that BMD of WB and geometric indices of hip bone strength are not adapted to the increased body weight in obese children. In our study, obese children had significantly lower CTX and osteocalcin levels compared with normal-weight peers. Thus, it seems that pediatric obesity slows bone remodeling process. This is in line with a recent study conducted on obese and control children (36). Crude BMD values for WB, lumbar spine, TH, and FN were higher in obese children compared with controls. These results are in accordance with those of previous studies (10,11). It has been suggested that the effects of overweight on BMD of weight-bearing bones may be because of overloading; the mechanical strain producing an osteogenic stimulus similar to the influence of physical activity (37). In spite of these likely adaptations, recent studies indicated that obese Volume 16, 2013
248 children had lower WB BMD compared with normal-weight peers after adjustment for body weight (7,9). Moreover, previous reports showed a decrease of spinal density for body weight in obese children (6). Nagasaki et al (12) also found a negative correlation between BMD and fat mass in obese boys who were 12 yr and older. Indeed, it has been shown that there is an inadequate adaptation between body weight and BMD in overweight and obese children, which raises their predisposition to sustain fractures (1). After adjustment for body weight, WB BMC, lumbar spine BMC, TH BMC, FN BMC, and WB BMD of obese children were significantly lower than in controls in our study. There was no difference in BMD at any site of analysis after adjustment for total lean mass. Consequently, we found that WB BMD adaptation of the obese children seems to be insufficient to cope with the excess of body weight applied to their skeleton. We showed that FN CSA was higher in obese children compared with controls, whereas narrow neck and FS Z values were similar between the 2 groups. However, when we adjusted our HSA data for body weight, CSA and Z values became lower in obese compared with controls. These data suggest that obese children have an insufficient adaptation of their femoral geometry to their body weight excess. Specker et al (38) showed that children with the higher percent of body fat had lower WB BMC and tibial cortical bone area than their leaner counterparts. In a recent study using peripheral quantitative computed tomography, Pollock et al (39) showed that, after controlling for muscle CSA, overweight late adolescent females had significantly lower bone measures at the tibia cortical site than controls. We have chosen to examine trabecular bone microarchitecture in obese children by a bone texture analysis (17,19). Hmean, co-occurrence matrices, and run lengths were significantly lower in obese children. However, after adjustment for total body weight, there were no significant differences between the 2 groups regarding Hmean, co-occurrence matrices, and run-length values. It has been previously shown in a population of adults that Hmean decreases with aging (40). Our study suggests that obese children have poorer texture of trabecular bone at the calcaneus than controls despite a higher body weight. Further prospective studies are necessary to demonstrate the validity of the 2 methods (texture analysis and HSA) in obese children. Limitations of our study include its cross-sectional design that limits our ability to infer causal relationships among the variables. The second limitation is the use of 2D images to study bone strength and bone trabecular microarchitecture although these techniques have already shown their good reliability (22,41). Third, the proximal femur is not an ideal site for measurement of BMD in children because of significant variability in skeletal development and lack of reproducible regions of interest (41). Our study provides evidence of negative effects of obesity on bone status in children. In fact, the BMD results showed that in obese children, WB BMD was not increased enough to fully compensate for their excessive weight. Moreover, Journal of Clinical Densitometry: Assessment of Skeletal Health
Rocher et al. our results suggest that geometric properties of the proximal femur are not adapted to the excess of body weight in obese children. Implementing strategies to reduce excess fat mass may be necessary to reduce fracture risk in this population.
Acknowledgments We thank the Danone Institute and The Foundation for the Medical Research for their financial support. Conflicts of interest: Claude-Laurent Benhamou has regularly worked with several pharmaceutical laboratories on different topics (clinical research, conferences, postuniversity teaching, and boards): Amgen, GSK, Lilly, Merck Sharp Dohme, Novartis, Roche/Roche Chugai, Servier, UCB Pharma, and Wyeth. Besides, Claude Laurent Benhamou has directed the PhD thesis of Emilie Rocher that has been sponsored by Danone Research till November 20, 2007, date of PhD viva at Orleans University, France.
References 1. Goulding A, Jones IE, Taylor RW, et al. 2000 More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. J Bone Miner Res 15: 2011e2018. 2. Davidson P, Goulding A, Chalmers D. 2003 Biomechanical analysis of arm fracture in obese boys. J Paediatr Child Health 39:657e664. 3. Manias K, McCabe D, Bishop N. 2006 Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass. Bone 39:652e657. 4. Goran MI. 1998 Measurement issues related to studies of childhood obesity: assessment of body composition, body fat distribution, physical activity, and food intake. Pediatrics 101: 505e518. 5. Thomas SR, Kalkwarf HJ, Buckley DD, et al. 2005 Effective dose of dual-energy X-ray absorptiometry scans in children as a function of age. J Clin Densitom 8:415e422. 6. McCormick DP, Ponder SW, Fawcett D, et al. 1991 Spinal bone mineral density in 335 normal and obese children and adolescents: evidence for ethnic and sex differences. J Bone Miner Res 6:507e513. 7. Goulding A, Taylor RW, Jones IE, et al. 2000 Overweight and obese children have low bone mass and area for their weight. Int J Obes Relat Metab Disord 24:627e632. 8. Dimitri P, Bishop N, Walsh JS, et al. 2012 Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 50:457e466. 9. Rocher E, Chappard C, Jaffre C, et al. 2008 Bone mineral density in prepubertal obese and control children: relation to body weight, lean mass and fat mass. J Bone Miner Metab 26:73e78. 10. Ellis KJ, Shypailo RJ, Wong WW, et al. 2003 Bone mineral mass in overweight and obese children: diminished or enhanced? Acta Diabetol 40:274e277. 11. El Hage R, Moussa E, Jacob C. 2010 Femoral neck geometry in overweight and normal weight adolescent girls. J Bone Miner Metab 28:595e600. 12. Nagasaki K, Kikuchi T, Hiura M, et al. 2004 Obese Japanese children have low bone mineral density after puberty. J Bone Miner Metab 22:376e381. 13. Hasanoglu A, Bideci A, Cinaz P, et al. 2000 Bone mineral density in childhood obesity. J Pediatr Endocrinol Metab 13: 307e311. Volume 16, 2013
Bone Status in Obese Children 14. Felsenberg D, Boonen S. 2005 The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27:1e11. 15. Wren TA, Gilsanz V. 2006 Assessing bone mass in children and adolescents. Curr Osteoporos Rep 4:153e158. 16. Benhamou CL, Lespessailles E, Jacquet G, et al. 1994 Fractal organization of trabecular bone images on calcaneus radiographs. J Bone Miner Res 9:1909e1918. 17. Pothuaud L, Benhamou CL, Porion P. 2000 Fractal dimension of trabecular bone projection texture is related to three-dimensional microarchitecture. J Bone Miner Res 15:691e699. 18. Lespessailles E, Jullien A, Eynard E. 1998 Biomechanical properties of human os calcanei: relationships with bone density and fractal evaluation of bone microarchitecture. J Biomech 31:817e824. 19. Ianc D, Serbescu C, Bembea M, et al. 2006 Effects of an exercise program and a calcium supplementation on bone in children: a randomized control trial. Int J Sport Nutr Exerc Metab 16:580e596. 20. Lespessailles E, Gadois C, Lemineur G, et al. 2007 Bone texture analysis on direct digital radiographic images: precision study and relationship with bone mineral density at the os calcis. Calcif Tissue Int 80:97e102. 21. Martin R, Burr D. 1984 Non-invasive measurement of long bone cross-sectional moment of inertia by photon absorptiometry. J Biomech 17:195e201. 22. Beck TJ, Ruff CB, Warden KE, et al. 1990 Predicting femoral neck strength from bone mineral data: a structural approach. Invest Radiol 68:205e210. 23. Petit MA, Beck TJ, Shults J, et al. 2005 Proximal femur bone geometry is appropriately adapted to lean mass in overweight children and adolescents. Bone 36:568e576. 24. El Hage R. 2012 Geometric indices of hip bone strength in obese, overweight and normal-weight adolescent boys. Osteoporos Int 23:1593e1600. 25. Cole TJ, Bellizzi MC, Flegal KM, et al. 2000 Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1e6. 26. Duke PM, Litt IF, Gross RT. 1980 Adolescents’ self-assessment of sexual maturation. Pediatrics 66:918e920. 27. Tanner JM. 1962 Growth at adolescence. 2nd ed. Oxford, UK: Blackwell. 28. Greulich WW, Pyle SI. 1959 Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, CA: Stanford University Press.
Journal of Clinical Densitometry: Assessment of Skeletal Health
249 29. Courteix D, Jaffre C, Lespessailles E, et al. 2005 Cumulative effect of calcium supplementation and physical activity on bone accretion in premenarchal children: a double-blind randomised placebo-controlled trial. Int J Sports Med 26:332e338. 30. Deheeger M, Rolland-Cachera MF, Fontevieille AM. 1997 Physical activity and body composition in 10 year old French children: linkages with nutritional intake? Int J Obes 21:372e379. 31. Ainsworth BE, Haskell WL, Leon AS, et al. 1993 Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 25:71e80. 32. Benhamou CL, Poupon S, Lespessailles E, et al. 2001 Fractal analysis of radiographic trabecular bone texture and bone mineral density: two complementary parameters related to osteoporotic fractures. J Bone Miner Res 6:697e704. 33. Haralick R. 1986 Statistical image texture analysis. In: Handbook of Pattern Recognition and Image Processing. Orlando, FL: Academic Press, 86: 247e279. 34. Chappard D, Guggenbuhl P, Legrand E, et al. 2005 Texture analysis of X-ray radiographs is correlated with bone histomorphometry. J Bone Miner Metab 23:24e29. 35. Guggenbuhl P, Bodic F, Hamel L, et al. 2006 Texture analysis of X-ray radiographs of iliac bone is correlated with bone microCT. Osteoporos Int 17:447e454. 36. Dimitri P, Wales JK, Bishop N. 2011 Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signalling resulting in reduced bone mass. Bone 48: 189e196. 37. Barr SI, McKay HA. 1998 Nutrition, exercise, and bone status in youth. Int J Sport Nutr 8:124e142. 38. Specker BL, Johannsen N, Binkley T, et al. 2001 Total body bone mineral content and tibial cortical bone measures in preschool children. J Bone Miner Res 16:2298e2305. 39. Pollock NK, Laing EM, Baile CA, et al. 2007 Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females. Am J Clin Nutr 86:1530e1538. 40. Lespessailles E, Poupon S, Niamane R, et al. 2002 Fractal analysis of trabecular bone texture on calcaneus radiographs: effects of age, time since menopause and hormone replacement therapy. Osteoporos Int 13:366e372. 41. Gordon CM, Bachrach LK, Carpenter TO, et al. 2008 Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 11:43e58.
Volume 16, 2013
Original Article
Bone Mineral Density, Hip Bone Geometry, and Calcaneus Trabecular Bone Texture in Obese and Normal-Weight Children Emilie Rocher,1,2 Rawad El Hage,*,3 Christine Chappard,4 Hugues Portier,1 Ga€el Y. Rochefort,1 and Claude-Laurent Benhamou1 1
EA 4708eI3MTO, Regional Hospital, Orleans, France; 2Danone, Danone Research, Palaiseau, France; 3Laboratoire de physiologie et de biomecanique de la performance motrice, Universite de Balamand, Al Koura, Liban; and 4B2OA, UMR 7052 CNRS, Universite Paris Diderot, Sorbonne Paris Cite, Paris, France
Abstract Our study aimed at comparing bone mineral density (BMD), geometric indices of hip bone strength, and indices of trabecular bone texture at the calcaneus in obese and normal-weight children. Fifty-three obese children (10.3 1.4 yr) and 24 normal-weight children (10.4 1.5 yr) participated in this study. Body composition, bone mineral content, and BMD at whole body (WB), lumbar spine (L2eL4), total forearm, and proximal femur (total hip [TH] and femoral neck [FN]) were measured by dual-energy X-ray absorptiometry (DXA). Bone geometry of the hip was evaluated by the hip structure analysis (HSA) program. DXA scans were analyzed at the FN at its narrowest region and the femoral shaft (FS) by the HSA program. Cross-sectional area (CSA) and section modulus (Z ) were measured from hip BMD profiles. Texture analysis was performed on digitized radiographs of the calcaneus to assess trabecular bone microarchitecture, and the result was expressed as Hmean. WB BMD, L2eL4 BMD, TH BMD, and FN BMD were significantly higher in obese children compared with normal-weight peers ( p ! 0.05). FN Z and FS Z were not significantly different between the 2 groups, whereas Hmean parameter was significantly lower in obese children compared with normal-weight peers ( p ! 0.001). After adjustment for body weight, obese children displayed lower WB BMD, FN CSA, FN Z, FS CSA, and FS Z compared with normal-weight children. This study suggests that BMD of WB and geometric indices of hip bone strength are not adapted to the increased body weight in obese children. Key Words: Bone geometry; bone mass; fat mass; physical activity; texture analysis.
greater (10,11), or equivalent (13) bone mass than healthy weight children. These differences could be related to differing approaches for the assessment of 2-dimensional (2D) projected DXA bone measures relative to age, bone size, and body size (10,11). Furthermore, the influence of being obese on bone parameters in growing children may be influenced by gender and maturity (10,11). Although bone mineral density (BMD) is a strong predictor of fracture risk, it only explains a part of bone strength (14,15). In reality, the organization of the trabecular bone (microarchitecture), shape and geometry of bones (macroarchitecture), and intrinsic properties of the matrix (mineral and collagen) also contribute to bone strength (14,15). Interestingly, Benhamou et al (16) have validated an approach to evaluate bone microarchitecture from radiographs by
Introduction Childhood obesity has been linked to an increase in fracture risk at the upper extremities (1e3). Dual-energy X-ray absorptiometry (DXA) is an accurate method to assess body composition and bone mass in normal-weight and obese children (4,5). To date, several studies have aimed at studying the skeleton of obese children and adolescents (6e13). It has been shown that obese children have either lower (6e9), Received 06/21/12; Revised 01/31/13; Accepted 02/05/13. *Address correspondence to: Rawad El Hage, PhD, Faculty of Arts and Social Sciences, Division of Physical Education, University of Balamand, P.O. Box: 100 Tripoli, Lebanon. E-mail: rawadelhage21@ hotmail.com
244
Bone Status in Obese Children measuring the Hmean parameter determining the fractal dimension. Hmean measurement is related to trabecular bone structure properties, such as porosity, connectivity, and bone strength (16e20). This method has also been used in children (19). Bone strength is also related to bone geometry (21e23). Proximal femur DXA scan images have been used to assess femoral bone geometry using the method previously described by Martin and Burr (21) and later modified by Beck et al (22). We have recently demonstrated that proximal femur bone geometry is well adapted to body weight in overweight adolescent boys but not in obese adolescent boys (24). However, the influence of being obese on BMD, bone geometry, and microarchitecture in prepubertal children and early pubertal is not completely understood. The aim of this study was to compare BMD, geometric indices of hip bone strength, and indices of trabecular bone texture at the calcaneus in obese and normal-weight children.
Materials and Methods Subjects and Study Design The study participants were recruited from primary schools in Orleans area, France, via information meetings, flyers, or newspaper advertisements. Inclusion criteria were male or female from 7 to 11 yr, Tanner stages I or II, being without endocrine or genetic abnormalities, no diagnosis of comorbidity, and no history of fracture. These criteria were checked during a previous medical examination. The subjects were not under any medication known to affect bone metabolism. Children were divided into a group of obese (n 5 53; 22 boys and 31 girls) and a group of control children (n 5 24; 11 boys and 13 girls). The diagnosis of obesity was defined using international cut offs for body mass index (BMI) (25). The study was approved by the regional ethics committee. Informed written consent was obtained from the children and their parents.
Anthropometric Measurements Height (cm) was measured in the upright position to the nearest 1 mm with a Seca standard stadiometer, and weight (kg) was measured on a Seca mechanic scale with a precision of 100 g (Seca 709, Hamburg, Germany). Children were weighed wearing only underclothes. BMI was calculated as body weight divided by height squared (kg/m2).
Pubertal Assessment Pubertal development was assessed according to the method of Tanner by a self-assessment form (26,27). A radiograph of the nondominant hand was taken for all children. The skeletal age was assessed using the method described by Greulich and Pyle (28).
Bone Mineral and Body Composition Measurements Body composition was assessed by DXA (Delphi QDRÒ Series; Hologic Inc., Waltham, MA). BMD (g/cm2) and Journal of Clinical Densitometry: Assessment of Skeletal Health
245 bone mineral content (BMC, g) were measured at whole body (WB), lumbar spine (L2eL4), nondominant forearm, and nondominant hip. The reproducibility of DXA measurements in our laboratory has been previously published (9,29).
Physical Activity Questionnaire Physical activity of the past year was assessed with a validated questionnaire for French children (30). Time spent watching TV or playing video games, an index of inactivity, was also assessed. Total annual physical activity was expressed as a mean in h/wk and as a mean in metabolic equivalent of task/wk (31).
Hip Structure Analysis Measurements We used the method described by Martin and Burr (21) and later modified by Beck et al (22). We studied 2 regions: the narrow neck across the narrowest segment of the femoral neck (FN) and femoral shaft (FS). For each region, we measured 2 parameters: cross-sectional area (CSA, cm2) and section modulus (Z, cm3). In mechanical terms, CSA is an indicator of resistance to loads directed along the bone axis (21,22). Section modulus (Z ) is an indicator of strength of the bone to resist bending and torsion (21,22).
Texture Analysis Parameters Fractal analysis is a statistical texture analysis. It expresses the roughness of the texture and characterizes the selfsimilarity of the texture gray-level variations over different scales. Fractal analysis of calcaneus radiographs was performed following a standardized protocol. The detailed procedure has already been described (16,32). To minimize the precision errors because of the digitization of X-ray film, we used a direct digital X-ray device (D3A Medical SystemÒ) to obtain radiographs of calcaneus. Hmean, co-occurrence, and run-lengths parameters were measured as previously described (33e35).
Dietary Habits Assessment Parents were asked to complete with the help of their child a 4-d food record. The current daily nutrient intake was calculated using the software Prodiet 5.2a (Proform, France).
Laboratory Methods Fasting blood samples were taken between 07:30 AM and 09.00 AM to avoid diurnal variation. Serum leptin was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (interassay coefficient of variation [CV] !9%). Serum adiponectin was measured using a commercial ELISA kit (interassay CV !8.5%). Bone formation was assessed by serum osteocalcin measured by ELISA (interassay CV !6.5%). Bone resorption was assessed by serum cross-laps (CTX) and measured by ELISA (interassay CV !8.2%). Serum 25-hydroxyvitamin D (serum 25(OH)D) level was measured using a commercial radioimmunoassay (interassay CV !11%). Volume 16, 2013
246 Statistical Analysis Basic data are presented as means standard deviations. Chi-squared tests were performed for testing gender and Tanner stage (1 or 2) distributions between the 2 groups (obese and controls). There were no interactions between these 2 factors and groups. Comparisons between obese and control groups were made after checking for Gaussian distribution. If Gaussian distribution was found, parametric unpaired t-tests were used. If not, Mann-Whitney U tests were used. Correlation coefficient was used to study the relationship between clinical characteristics and bone variables using Pearson test if Gaussian distribution was found or Spearman test if not. To determine which anthropometric characteristics (total body weight, total lean mass, total fat mass, or percent of fat mass) are the most related to BMD, principal component analysis was performed. The variables most highly correlated with BMD were included as parameters of adjustment. As a consequence, DXA, bone microarchitecture, and bone macroarchitecture values were compared after adjustment for total body weight and total lean mass using a 1-way analysis of covariance. Data were analyzed using number cruncher statistical system 2001 (NCSS; Kaysville, UT). A level of significance of p ! 0.05 was used.
Results Subject Characteristics and Body Composition
Rocher et al. Table 1 Clinical Characteristics of the Study Population Variable Gender (no. of boys/girls) Tanner stage (no. 1/2) Age (yr) Bone age (yr) Body weight (kg) Height (cm) Fat mass (%) Fat mass (kg) Lean mass (kg) BMI (kg.m 2) DCI (mg/d) Serum 25(OH)D (mg/L) CTX (ng/L) Osteocalcin (mg/L) Leptin (ng/mL) Adiponectin (mg/L) Energy expenditure (METs/wk) Physical practice in club (h/wk) Screen time (h/d)
Obese (n 5 53)
Controls (n 5 24)
p-Value
22/31
11/13
0.72
33/20
19/5
0.14
10.3 10.9 54.5 144.9 38.7 21.4 31.2 25.6 894 22.30
1.4 10.4 1.5 1.3 10.5 1.3 14.8 33.3 5.6 9.6 141.8 8.5 4.7 20.7 5.4 8.3 7.0 2.6 6.9 25.0 3.7 4.3 16.5 2.0 247 981 279 13.06 21.12 10.41
1268 32.08 15.3 11.2 124.7
338 5.12 15.1 3.9 32.9
1505 35.47 3.5 10.1 127.7
224 4.03 1.8 2.6 37.8
0.73 0.22 !0.001 0.17 !0.001 !0.001 !0.001 !0.001 0.17 0.74 0.01 0.01 0.003 0.20 0.74
1.4 1.5
1.9 1.8
0.25
16.6 7.6
8.2 4.8
!0.001
Gender distribution, Tanner stage, age, bone age, height, total energy expenditure, time spent in the sport club, daily calcium intake (DCI), and serum 25(OH)D were not statistically different between the 2 groups. Body weight, fat mass, fat mass percentage, lean mass, BMI, and serum leptin were significantly higher in obese children compared with controls. Serum osteocalcin and cross-laps (CTX) were significantly lower in obese children compared with controls (Table 1).
Note: Values are means standard deviation; p ! 0.05: obese significantly different from controls, using a parametric unpaired t-test, Mann-Whitney U test, or chi-squared test. Abbr: BMI, body mass index; CTX, serum cross-laps; DCI, daily calcium intake; METs, metabolic equivalent of tasks; Serum 25(OH) D, serum 25-hydroxyvitamin D.
DXA Measurements
different between the 2 groups after adjustment for lean mass, whereas only TH BMC was significantly higher in controls compared with obese children ( p ! 0.05).
WB BMD, L2eL4 BMD, total hip (TH) BMD, and FN BMD were significantly higher in obese children compared with normal-weight children (Table 2). In the whole population, weight, lean mass, fat mass, BMI, and fat mass percentage were positively correlated to WB BMD, L2eL4 BMD, TH BMD, and FN BMD (r 5 0.26e0.75; all p ! 0.05). Physical activity (h/week), sitting time, DCI, osteocalcin, and CTX levels were not correlated to BMD values. After adjustment for body weight, WB BMC, L2eL4 BMC, TH BMC, FN BMC, and total forearm BMC were lower in obese children compared with controls, whereas BMD values at all sites were not statistically different between the 2 groups except for the WB where BMD was significantly lower in obese children compared with controls (Table 3). After adjustment for lean mass, there were no significant differences in BMD values between the 2 groups. WB BMC, L2eL4 BMC, FN BMC, and TF BMC were not significantly Journal of Clinical Densitometry: Assessment of Skeletal Health
Hip Structure Analysis Variables FN CSA was significantly higher in obese children compared with normal-weight peers. FN Z, FS CSA, and FS Z were not significantly different between the 2 groups (Table 2). In the whole population, weight and lean mass were positively correlated to FN CSA (r 5 0.67; p ! 0.001 and r 5 0.73; p ! 0.001), FN Z (r 5 0.60; p ! 0.001 and r 5 0.63; p ! 0.001), FS CSA (r 5 0.51; p ! 0.001 and r 5 0.58; p ! 0.001), and FS Z (r 5 0.35; p ! 0.01 and r 5 0.39; p ! 0.001). After adjustment for body weight, obese children displayed lower CSA and Z values at the FN and FS compared with normal-weight children (Table 3). After adjustment for lean mass, there were no significant differences regarding hip structure analysis (HSA) variables between the 2 groups. Volume 16, 2013
Bone Status in Obese Children
247
Table 2 Crude Bone Variables in the 2 Groups Variable
Obese (n 5 53)
Controls (n 5 24)
Table 3 Bone Variables Adjusted for Body Weight in the 2 Groups p-Value
WB BMD 0.883 0.069 0.845 0.052 0.01 (g.cm 2) WB BMC (g) 1313.4 292.7 1066.6 194.1 !0.001 L2eL4 BMD 0.683 0.093 0.594 0.068 !0.001 (g.cm 2) L2eL4 BMC (g) 23.38 5.34 20.06 3.52 0.002 TH BMD 0.773 0.103 0.704 0.088 0.004 (g.cm 2) TH BMC (g) 20.00 5.40 17.34 4.57 0.03 FN BMD 0.742 0.108 0.670 0.098 0.006 (g.cm 2) FN BMC (g) 3.38 0.75 2.93 0.66 0.01 TF BMD 0.439 0.044 0.423 0.041 0.14 (g.cm 2) TF BMC (g) 3.93 0.95 3.29 0.78 0.006 2.02 0.56 1.76 0.47 0.04 FN CSA (cm2) FN Z (cm3) 1.04 0.57 0.87 0.39 0.13 FS CSA (cm2) 1.88 0.53 1.71 0.48 0.15 FS Z (cm3) 0.595 0.357 0.570 0.304 0.75 Hmean 0.572 0.031 0.606 0.030 !0.001 Co-occurrence 2.63 0.37 2.74 0.10 0.04 Run lengths 2.15 0.20 2.23 0.08 0.008 Note: Values are means standard deviation; p ! 0.05: obese significantly different from controls, using a parametric unpaired t-test or a Mann-Whitney U test. Abbr: BMC, bone mineral content; BMD, bone mineral density; CSA, cross-sectional area; FN, femoral neck; FS, femoral shaft; TF, total forearm; TH, total hip; WB, whole body; Z, section modulus.
Bone Texture Indices at the Calcaneus Hmean, co-occurrence, and run lengths were significantly lower in obese children compared with controls (Table 2). After adjustment for total body weight, Hmean, co-occurrence, and run lengths were not significantly different between the 2 groups (Table 3). After adjustment for lean mass, H mean and run lengths were lower in obese children compared with controls ( p ! 0.05). In the whole population, Hmean was negatively correlated to body weight (r 5 0.58; p ! 0.001), BMI (r 5 0.58; p ! 0.001), lean mass (r 5 0.51; p ! 0.001), fat mass (r 5 0.58; p ! 0.001), and fat mass percentage (r 5 0.53; p ! 0.001), and positively but weakly correlated to DCI (r 5 0.27; p ! 0.05).
Dietary Intake Total daily energy intake was lower in obese children in comparison to controls (1822 320 vs 1997 229 intake Kcal, p ! 0.05). In the whole population, DCI was negatively correlated to BMI and fat mass (r 5 0.28; p ! 0.05 and r 5 0.26; p ! 0.05, respectively). Journal of Clinical Densitometry: Assessment of Skeletal Health
Obese (n 5 53)
Variable WB BMD (g.cm 2) WB BMC (g) L2eL4 BMD (g.cm 2) L2eL4 BMC (g) TH BMD (g.cm 2) TH BMC (g) FN BMD (g.cm 2) FN BMC (g) TF BMD (g.cm 2) TF BMC (g) FN CSA (cm2) FN Z (cm3) FS CSA (cm2) FS Z (cm3) Hmean Co-occurrence Run lengths
Controls (n 5 24)
p-Value
0.861 0.006 0.893 0.010 0.04 1192 18 1333 26 !0.001 0.654 0.009 0.657 0.013 0.85 21.4 0.742 17.92 0.708 3.13 0.429 3.54 1.82 0.863 1.74 0.520 0.579 2.69 2.18
0.4 0.010 0.45 0.014 0.07 0.005 0.08 0.05 0.054 0.06 0.042 0.003 0.01 0.008
24.4 0.770 21.92 0.744 3.49 0.442 4.09 2.19 1.25 2.02 0.734 0.590 2.70 2.19
0.6 0.002 0.016 0.26 0.67 !0.001 0.017 0.17 0.11 0.03 0.008 0.34 0.12 0.008 0.07 0.003 0.081 0.002 0.08 0.04 0.063 0.03 0.005 0.20 0.01 0.75 0.012 0.46
Note: Values are means standard error; p ! 0.05: obese significantly different from controls, using a 1-way analysis of covariance. Abbr: BMC, bone mineral content; BMD, bone mineral density; CSA, cross-sectional area; FS, femoral shaft; FN, femoral neck; TF, total forearm; TH, total hip; WB, whole body; Z, section modulus.
Laboratory Methods Leptin, adiponectin, vitamin D, osteocalcin, and CTX circulating levels were not significantly correlated to bone variables in the whole population.
Discussion In this study, we showed that obese children displayed lower WB BMD, FN CSA, FN Z, FS CSA, and FS Z values compared with normal-weight children after adjustment for body weight. Thus, this study suggests that BMD of WB and geometric indices of hip bone strength are not adapted to the increased body weight in obese children. In our study, obese children had significantly lower CTX and osteocalcin levels compared with normal-weight peers. Thus, it seems that pediatric obesity slows bone remodeling process. This is in line with a recent study conducted on obese and control children (36). Crude BMD values for WB, lumbar spine, TH, and FN were higher in obese children compared with controls. These results are in accordance with those of previous studies (10,11). It has been suggested that the effects of overweight on BMD of weight-bearing bones may be because of overloading; the mechanical strain producing an osteogenic stimulus similar to the influence of physical activity (37). In spite of these likely adaptations, recent studies indicated that obese Volume 16, 2013
248 children had lower WB BMD compared with normal-weight peers after adjustment for body weight (7,9). Moreover, previous reports showed a decrease of spinal density for body weight in obese children (6). Nagasaki et al (12) also found a negative correlation between BMD and fat mass in obese boys who were 12 yr and older. Indeed, it has been shown that there is an inadequate adaptation between body weight and BMD in overweight and obese children, which raises their predisposition to sustain fractures (1). After adjustment for body weight, WB BMC, lumbar spine BMC, TH BMC, FN BMC, and WB BMD of obese children were significantly lower than in controls in our study. There was no difference in BMD at any site of analysis after adjustment for total lean mass. Consequently, we found that WB BMD adaptation of the obese children seems to be insufficient to cope with the excess of body weight applied to their skeleton. We showed that FN CSA was higher in obese children compared with controls, whereas narrow neck and FS Z values were similar between the 2 groups. However, when we adjusted our HSA data for body weight, CSA and Z values became lower in obese compared with controls. These data suggest that obese children have an insufficient adaptation of their femoral geometry to their body weight excess. Specker et al (38) showed that children with the higher percent of body fat had lower WB BMC and tibial cortical bone area than their leaner counterparts. In a recent study using peripheral quantitative computed tomography, Pollock et al (39) showed that, after controlling for muscle CSA, overweight late adolescent females had significantly lower bone measures at the tibia cortical site than controls. We have chosen to examine trabecular bone microarchitecture in obese children by a bone texture analysis (17,19). Hmean, co-occurrence matrices, and run lengths were significantly lower in obese children. However, after adjustment for total body weight, there were no significant differences between the 2 groups regarding Hmean, co-occurrence matrices, and run-length values. It has been previously shown in a population of adults that Hmean decreases with aging (40). Our study suggests that obese children have poorer texture of trabecular bone at the calcaneus than controls despite a higher body weight. Further prospective studies are necessary to demonstrate the validity of the 2 methods (texture analysis and HSA) in obese children. Limitations of our study include its cross-sectional design that limits our ability to infer causal relationships among the variables. The second limitation is the use of 2D images to study bone strength and bone trabecular microarchitecture although these techniques have already shown their good reliability (22,41). Third, the proximal femur is not an ideal site for measurement of BMD in children because of significant variability in skeletal development and lack of reproducible regions of interest (41). Our study provides evidence of negative effects of obesity on bone status in children. In fact, the BMD results showed that in obese children, WB BMD was not increased enough to fully compensate for their excessive weight. Moreover, Journal of Clinical Densitometry: Assessment of Skeletal Health
Rocher et al. our results suggest that geometric properties of the proximal femur are not adapted to the excess of body weight in obese children. Implementing strategies to reduce excess fat mass may be necessary to reduce fracture risk in this population.
Acknowledgments We thank the Danone Institute and The Foundation for the Medical Research for their financial support. Conflicts of interest: Claude-Laurent Benhamou has regularly worked with several pharmaceutical laboratories on different topics (clinical research, conferences, postuniversity teaching, and boards): Amgen, GSK, Lilly, Merck Sharp Dohme, Novartis, Roche/Roche Chugai, Servier, UCB Pharma, and Wyeth. Besides, Claude Laurent Benhamou has directed the PhD thesis of Emilie Rocher that has been sponsored by Danone Research till November 20, 2007, date of PhD viva at Orleans University, France.
References 1. Goulding A, Jones IE, Taylor RW, et al. 2000 More broken bones: a 4-year double cohort study of young girls with and without distal forearm fractures. J Bone Miner Res 15: 2011e2018. 2. Davidson P, Goulding A, Chalmers D. 2003 Biomechanical analysis of arm fracture in obese boys. J Paediatr Child Health 39:657e664. 3. Manias K, McCabe D, Bishop N. 2006 Fractures and recurrent fractures in children; varying effects of environmental factors as well as bone size and mass. Bone 39:652e657. 4. Goran MI. 1998 Measurement issues related to studies of childhood obesity: assessment of body composition, body fat distribution, physical activity, and food intake. Pediatrics 101: 505e518. 5. Thomas SR, Kalkwarf HJ, Buckley DD, et al. 2005 Effective dose of dual-energy X-ray absorptiometry scans in children as a function of age. J Clin Densitom 8:415e422. 6. McCormick DP, Ponder SW, Fawcett D, et al. 1991 Spinal bone mineral density in 335 normal and obese children and adolescents: evidence for ethnic and sex differences. J Bone Miner Res 6:507e513. 7. Goulding A, Taylor RW, Jones IE, et al. 2000 Overweight and obese children have low bone mass and area for their weight. Int J Obes Relat Metab Disord 24:627e632. 8. Dimitri P, Bishop N, Walsh JS, et al. 2012 Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 50:457e466. 9. Rocher E, Chappard C, Jaffre C, et al. 2008 Bone mineral density in prepubertal obese and control children: relation to body weight, lean mass and fat mass. J Bone Miner Metab 26:73e78. 10. Ellis KJ, Shypailo RJ, Wong WW, et al. 2003 Bone mineral mass in overweight and obese children: diminished or enhanced? Acta Diabetol 40:274e277. 11. El Hage R, Moussa E, Jacob C. 2010 Femoral neck geometry in overweight and normal weight adolescent girls. J Bone Miner Metab 28:595e600. 12. Nagasaki K, Kikuchi T, Hiura M, et al. 2004 Obese Japanese children have low bone mineral density after puberty. J Bone Miner Metab 22:376e381. 13. Hasanoglu A, Bideci A, Cinaz P, et al. 2000 Bone mineral density in childhood obesity. J Pediatr Endocrinol Metab 13: 307e311. Volume 16, 2013
Bone Status in Obese Children 14. Felsenberg D, Boonen S. 2005 The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther 27:1e11. 15. Wren TA, Gilsanz V. 2006 Assessing bone mass in children and adolescents. Curr Osteoporos Rep 4:153e158. 16. Benhamou CL, Lespessailles E, Jacquet G, et al. 1994 Fractal organization of trabecular bone images on calcaneus radiographs. J Bone Miner Res 9:1909e1918. 17. Pothuaud L, Benhamou CL, Porion P. 2000 Fractal dimension of trabecular bone projection texture is related to three-dimensional microarchitecture. J Bone Miner Res 15:691e699. 18. Lespessailles E, Jullien A, Eynard E. 1998 Biomechanical properties of human os calcanei: relationships with bone density and fractal evaluation of bone microarchitecture. J Biomech 31:817e824. 19. Ianc D, Serbescu C, Bembea M, et al. 2006 Effects of an exercise program and a calcium supplementation on bone in children: a randomized control trial. Int J Sport Nutr Exerc Metab 16:580e596. 20. Lespessailles E, Gadois C, Lemineur G, et al. 2007 Bone texture analysis on direct digital radiographic images: precision study and relationship with bone mineral density at the os calcis. Calcif Tissue Int 80:97e102. 21. Martin R, Burr D. 1984 Non-invasive measurement of long bone cross-sectional moment of inertia by photon absorptiometry. J Biomech 17:195e201. 22. Beck TJ, Ruff CB, Warden KE, et al. 1990 Predicting femoral neck strength from bone mineral data: a structural approach. Invest Radiol 68:205e210. 23. Petit MA, Beck TJ, Shults J, et al. 2005 Proximal femur bone geometry is appropriately adapted to lean mass in overweight children and adolescents. Bone 36:568e576. 24. El Hage R. 2012 Geometric indices of hip bone strength in obese, overweight and normal-weight adolescent boys. Osteoporos Int 23:1593e1600. 25. Cole TJ, Bellizzi MC, Flegal KM, et al. 2000 Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1e6. 26. Duke PM, Litt IF, Gross RT. 1980 Adolescents’ self-assessment of sexual maturation. Pediatrics 66:918e920. 27. Tanner JM. 1962 Growth at adolescence. 2nd ed. Oxford, UK: Blackwell. 28. Greulich WW, Pyle SI. 1959 Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, CA: Stanford University Press.
Journal of Clinical Densitometry: Assessment of Skeletal Health
249 29. Courteix D, Jaffre C, Lespessailles E, et al. 2005 Cumulative effect of calcium supplementation and physical activity on bone accretion in premenarchal children: a double-blind randomised placebo-controlled trial. Int J Sports Med 26:332e338. 30. Deheeger M, Rolland-Cachera MF, Fontevieille AM. 1997 Physical activity and body composition in 10 year old French children: linkages with nutritional intake? Int J Obes 21:372e379. 31. Ainsworth BE, Haskell WL, Leon AS, et al. 1993 Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 25:71e80. 32. Benhamou CL, Poupon S, Lespessailles E, et al. 2001 Fractal analysis of radiographic trabecular bone texture and bone mineral density: two complementary parameters related to osteoporotic fractures. J Bone Miner Res 6:697e704. 33. Haralick R. 1986 Statistical image texture analysis. In: Handbook of Pattern Recognition and Image Processing. Orlando, FL: Academic Press, 86: 247e279. 34. Chappard D, Guggenbuhl P, Legrand E, et al. 2005 Texture analysis of X-ray radiographs is correlated with bone histomorphometry. J Bone Miner Metab 23:24e29. 35. Guggenbuhl P, Bodic F, Hamel L, et al. 2006 Texture analysis of X-ray radiographs of iliac bone is correlated with bone microCT. Osteoporos Int 17:447e454. 36. Dimitri P, Wales JK, Bishop N. 2011 Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signalling resulting in reduced bone mass. Bone 48: 189e196. 37. Barr SI, McKay HA. 1998 Nutrition, exercise, and bone status in youth. Int J Sport Nutr 8:124e142. 38. Specker BL, Johannsen N, Binkley T, et al. 2001 Total body bone mineral content and tibial cortical bone measures in preschool children. J Bone Miner Res 16:2298e2305. 39. Pollock NK, Laing EM, Baile CA, et al. 2007 Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females. Am J Clin Nutr 86:1530e1538. 40. Lespessailles E, Poupon S, Niamane R, et al. 2002 Fractal analysis of trabecular bone texture on calcaneus radiographs: effects of age, time since menopause and hormone replacement therapy. Osteoporos Int 13:366e372. 41. Gordon CM, Bachrach LK, Carpenter TO, et al. 2008 Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 11:43e58.
Volume 16, 2013