CLINICAL TRIALS
Relation Between Serum Osteocalcin Levels and Body Composition in Obese Children
Jing-Wen Wang, Qing-Ya Tang, Hui-Juan Ruan, and yWei Cai
ABSTRACT Overweight and obesity may contribute to bone fractures in children; however, the mechanism involved is not clear. In this study, we assessed the relation between serum osteocalcin levels and body composition in obese children. A total of 79 children (ages 7–12 years) were recruited. Serum osteocalcin levels were negatively correlated with fat percentage and visceral fat area (r ¼ 0.24 and r ¼ 0.46, respectively, P < 0.05); however, no statistically significant association was found between obesity degree and serum osteocalcin levels (r ¼ 0.29, P ¼ 0.052). Serum osteocalcin levels were positively correlated with lean body mass, fat-free mass, and fat-free mass index (r ¼ 0.24, 0.23, and 0.31, respectively; P < 0.05). In addition, serum osteocalcin levels were significantly lower in severely obese (44.46 9.73 mg/mL) and moderately obese (48.72 10.82 mg/mL) children than in mildly obese (55.43 12.4 mg/mL) and overweight (54.36 11.96 mg/mL) children (P ¼ 0.02). These findings indicate that body composition is related to serum osteocalcin levels in overweight and obese children. Key Words: bone metabolism, children, obesity, osteocalcin
(JPGN 2014;58: 729–732)
O
besity rates are rapidly increasing in adults and children (1). The World Health Organization (WHO) defines obesity as a chronic disease with serious health consequences, including hypertensive, cardiovascular, and metabolic diseases (2). Several studies have reported that fracture rates are common in overweight and obese children and that fractures are associated with lower bone mass and narrow bones (3–7). The effect of obesity on the development of the musculoskeletal system is still poorly understood in children; however, Chan and Chen have suggested that obesity affects both the function and structure of the locomotor system in this group of the population (8). Osteocalcin, a bone-specific noncollagenous protein secreted by osteoblasts, is a marker of bone formation (9). Lee et al reported associations among osteocalcin, obesity, and insulin resistance (IR) (9,10). In their study, mice lacking the osteocalcin gene (osteocalcin/) had an abnormal amount of visceral fat, glucose Received and accepted November 9, 2013. From the Department of Clinical Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, and the yShanghai Institute for Pediatric Research, Shanghai, China. Address correspondence and reprint requests to Qing-Ya Tang, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (e-mail: [email protected]). This study was supported by the Program of Shanghai Public Health Promotion (2011–2013) and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition (grant no 11DZ2260500). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000243
JPGN
Volume 58, Number 6, June 2014
intolerance, IR, and impaired insulin secretion. Recently, Kanazawa et al (11) and Zhou et al (12) reported that obesity and type 2 diabetes mellitus are associated with significantly lower osteocalcin levels in humans. The objective of this study was to assess the associations among obesity, body composition, and serum osteocalcin levels in obese children.
METHODS In this study, 79 children (ages 7–12 years), who visited the Obesity Clinic at the Department of Clinical Nutrition of Xinhua Hospital, were recruited. Subjects were eligible for enrollment if they had a body mass index (BMI) 85th percentile (defined as being overweight) or 95th percentile (defined as being obese) for their age and sex according to WHO standards (13). Exclusion criteria included the presence of certain medical conditions that contribute to obesity (eg, hypothyroidism, Prader-Willi syndrome, single-gene defects), type 1 diabetes mellitus, obesity treatments or medications, significant learning difficulties, significant mental health problems, and psychological or psychiatric treatments or medications. Height was measured using a rigid stadiometer. Weight, fat mass (FM), the percentage of body fat (PBF), lean body mass (LBM), visceral fat area (VFA), and fat-free mass (FFM) were assessed by bioelectrical impedance analysis using Inbody 720 (Biospace, Seoul, South Korea) in an upright position following bladder emptying. Speed of ultrasound (SOS) at the calcaneus was measured by quantitative ultrasonography (QUS; IEC 601–1 Class II Type BF. IPXO, Sahara Bone Densitometer, Hologic, Bedford, MA). Serum osteocalcin and parathyroid hormone levels were measured by enzyme-linked immunosorbent assay. BMI, fat mass index (FMI), fat-free mass index (FFMI), and degree of obesity were calculated with the following formulas: BMI ¼ body weight (kg)/height (m2); FMI ¼ FM (kg)/height (m)2; FFMI ¼ FFM (kg)/height (m)2; obesity degree (%) ¼ (actual weight [kg ideal weight kg]) 100/ideal weight (kg). The degree of obesity was determined by the amount by which the actual body weight exceeded the ideal weight. Subjects with obesity degrees of 10% to 20%, 20% to 30%, 30% to 50%, or >50% were classified as being overweight, mildly obese, moderately obese, or severely obese, respectively (14). We used Tanner pubertal staging method to determine sexual maturation through self-assessment techniques for breast development in girls (B1, B2, B3, B4, and B5) and genitalia development in boys (G1, G2, G3, G4, and G5) (15).
Statistical Analyses Data were expressed as mean and standard deviation. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc, Chicago, IL). The normality of data distribution was assessed using the Kolmogorov-Smirnov test. Differences among groups (ie, overweight, mildly obese, moderately obese, and severely obese) were analyzed by analysis of variance. Correlation
729
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Wang et al
JPGN
coefficients (r) were calculated according to the Pearson or the Spearman rank correlation coefficient tests. Statistical significance was set at P < 0.05.
RESULTS In this study, 79 children (55 boys and 24 girls) with an average age of 9.47 2.09 years were enrolled. Study parameters, including body height and weight, body composition, osteocalcin, and parathyroid hormone levels, are shown in Table 1. The results revealed no significant differences in body composition and osteocalcin levels between boys and girls (Table 2).
Body Composition and Osteocalcin Levels Based on the degree of obesity, we divided the subjects into 4 groups: 8 children belonged to the overweight group, 13 belonged to the mildly obese group, 23 belonged to the moderately obese group, and 35 belonged to the severely obese group. The 4 groups were not significantly different in age and sex. The moderately and severely obese groups had significantly higher BMI, body weight, waist-tohip ratio, PBF, FMI, and VFA and significantly lower FFM% and LBM% than the other 2 groups (P < 0.05). In addition, serum osteocalcin levels were significantly lower in the severely obese (44.46 9.73 mg/mL) and moderately obese (48.72 10.82 mg/ mL) groups than in the mildly obese (55.43 12.4 mg/mL) and overweight (54.36 11.96 mg/mL) groups (P ¼ 0.02); however, there were no significant differences in SOS among the 4 groups (P ¼ 0.62) (Table 3).
Relation Among Obesity Degree, Body Composition, and Serum Osteocalcin Levels Osteocalcin levels were negatively correlated with PBF (r ¼ 0.24, P < 0.05) and VFA (r ¼ 0.46, P < 0.05); however, there was no significant correlation between obesity degree and
Volume 58, Number 6, June 2014
serum osteocalcin levels (r ¼ 0.29, P ¼ 0.052). Serum osteocalcin levels were positively correlated with LBM, FFM, and FFMI (r ¼ 0.24, 0.23, and 0.31, respectively; P < 0.05). After correcting for pubertal stage and sex, PBF and VFA were still negatively correlated with serum osteocalcin levels (r ¼ 0.28, P ¼ 0.013 and r ¼ 0.22, P ¼ 0.05, respectively). Consequently, serum osteocalcin levels were related with LBM, FFM, and FFMI (r ¼ 0.37, P ¼ 0.01; r ¼ 0.37, P ¼ 0.001; and r ¼ 0.37, P ¼ 0.001, respectively).
DISCUSSION As a result of global economic changes, which affect dietary intake and lifestyle, obesity has become a worldwide public health problem. Overweight and obesity rates in children have increased in the last years (16). Childhood obesity impairs normal growth and development, contributes to glucolipid metabolic disorders (eg, metabolic syndrome) (17,18), and negatively affects bone health. Recent studies have reported a relation among obesity, bone osteoporosis (19), and cardiovascular diseases (20). Some studies reported that overweight and obese children have a higher risk of fractures than their normal-weight counterparts (3,4). The results of our study revealed that the SOS values in the overweight and mildly obese groups were higher than those in the moderately and severely obese groups. There is increasing evidence that there is a bidirectional regulation between energy metabolism and bone tissue (21,9). On the contrary, several studies have reported that fractures are more common in overweight and obese children and that fractures are associated with lower bone mass and narrow bones (3–7). The effect of obesity on the development of the musculoskeletal system is still poorly understood in children; however, Chan and Chen (8) have suggested that obesity affects both the function and structure of the locomotor system. Osteocalcin, an osteoblast-specific protein, is a marker of bone formation and osteoblast activity, osteoblast function, and
TABLE 1. Characteristics of the 4 groups
Age, y Height, cm Weight, kg BMI, kg/m2 Obesity degree, % Waist-to-hip ratio FM, kg PBF, % FMI, kg FFM kg FFM, % FFMI, kg/m2 LBM, kg LBM, % VFA, m2 BMC, kg BMR, kcal SOS, m/s BUA OC, mg/mL PTH, pg/mL
Overweight, n ¼ 8
Mildly obese, n ¼ 13
Moderately obese, n ¼ 23
Severely obese, n ¼ 35
P
9.36 1.66 135.86 6.99 35.33 4.96 19.06 0.98 16.51 2.14 0.89 0.02 9.90 1.71 28.25 4.88 5.43 0.89 25.43 4.46 71.75 4.96 13.68 1.28 23.89 4.25 67.4 4.88 23.56 12.19 1.54 0.22 919.26 96.3 1560.2 19.67 64.07 23.58 55.43 12.4 32.19 8.53
8.3 0.78 134.68 7.33 35.83 4.38 19.68 0.48 24.33 2.28 0.9 0.02 10.34 2.21 28.73 4.69 5.68 0.97 25.18 3.63 70.18 3.7 13.81 0.8 23.67 3.43 65.95 3.6 33.56 23.65 1.52 0.2 914.06 78.4 1556.56 20.51 53.00 9.65 54.36 11.96 28.96 15.71
9.69 2.07 142.17 8.56 47.71 10.07 23.35 2.14 41.84 4.89 0.91 0.04 17.27 4.87 36.08 4.32 8.51 1.64 30.45 5.86 64.07 4.32 14.92 1.15 28.66 5.52 60.29 4.15 76.30 26.46 1.79 0.33 1027.66 126.35 1549.12 22.41 54.74 7.91 48.72 10.82 25.86 10.27
9.78 2.42 147.21 14.0 63.83 21.71 28.55 4.55 71.42 17.88 0.95 0.04 26.37 10.73 41.18 4.26 11.76 2.92 37.39 12.17 58.91 4.27 16.74 2.29 35.27 11.47 55.58 4.04 93.41 43.76 2.12 0.69 1177.24 262.87 1547.54 24.82 69.54 22.8 44.46 9.73 22.76 8.04
0.086 0.07
Relation Between Serum Osteocalcin Levels and Body Composition in Obese Children
Jing-Wen Wang, Qing-Ya Tang, Hui-Juan Ruan, and yWei Cai
ABSTRACT Overweight and obesity may contribute to bone fractures in children; however, the mechanism involved is not clear. In this study, we assessed the relation between serum osteocalcin levels and body composition in obese children. A total of 79 children (ages 7–12 years) were recruited. Serum osteocalcin levels were negatively correlated with fat percentage and visceral fat area (r ¼ 0.24 and r ¼ 0.46, respectively, P < 0.05); however, no statistically significant association was found between obesity degree and serum osteocalcin levels (r ¼ 0.29, P ¼ 0.052). Serum osteocalcin levels were positively correlated with lean body mass, fat-free mass, and fat-free mass index (r ¼ 0.24, 0.23, and 0.31, respectively; P < 0.05). In addition, serum osteocalcin levels were significantly lower in severely obese (44.46 9.73 mg/mL) and moderately obese (48.72 10.82 mg/mL) children than in mildly obese (55.43 12.4 mg/mL) and overweight (54.36 11.96 mg/mL) children (P ¼ 0.02). These findings indicate that body composition is related to serum osteocalcin levels in overweight and obese children. Key Words: bone metabolism, children, obesity, osteocalcin
(JPGN 2014;58: 729–732)
O
besity rates are rapidly increasing in adults and children (1). The World Health Organization (WHO) defines obesity as a chronic disease with serious health consequences, including hypertensive, cardiovascular, and metabolic diseases (2). Several studies have reported that fracture rates are common in overweight and obese children and that fractures are associated with lower bone mass and narrow bones (3–7). The effect of obesity on the development of the musculoskeletal system is still poorly understood in children; however, Chan and Chen have suggested that obesity affects both the function and structure of the locomotor system in this group of the population (8). Osteocalcin, a bone-specific noncollagenous protein secreted by osteoblasts, is a marker of bone formation (9). Lee et al reported associations among osteocalcin, obesity, and insulin resistance (IR) (9,10). In their study, mice lacking the osteocalcin gene (osteocalcin/) had an abnormal amount of visceral fat, glucose Received and accepted November 9, 2013. From the Department of Clinical Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, and the yShanghai Institute for Pediatric Research, Shanghai, China. Address correspondence and reprint requests to Qing-Ya Tang, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (e-mail: [email protected]). This study was supported by the Program of Shanghai Public Health Promotion (2011–2013) and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition (grant no 11DZ2260500). The authors report no conflicts of interest. Copyright # 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0000000000000243
JPGN
Volume 58, Number 6, June 2014
intolerance, IR, and impaired insulin secretion. Recently, Kanazawa et al (11) and Zhou et al (12) reported that obesity and type 2 diabetes mellitus are associated with significantly lower osteocalcin levels in humans. The objective of this study was to assess the associations among obesity, body composition, and serum osteocalcin levels in obese children.
METHODS In this study, 79 children (ages 7–12 years), who visited the Obesity Clinic at the Department of Clinical Nutrition of Xinhua Hospital, were recruited. Subjects were eligible for enrollment if they had a body mass index (BMI) 85th percentile (defined as being overweight) or 95th percentile (defined as being obese) for their age and sex according to WHO standards (13). Exclusion criteria included the presence of certain medical conditions that contribute to obesity (eg, hypothyroidism, Prader-Willi syndrome, single-gene defects), type 1 diabetes mellitus, obesity treatments or medications, significant learning difficulties, significant mental health problems, and psychological or psychiatric treatments or medications. Height was measured using a rigid stadiometer. Weight, fat mass (FM), the percentage of body fat (PBF), lean body mass (LBM), visceral fat area (VFA), and fat-free mass (FFM) were assessed by bioelectrical impedance analysis using Inbody 720 (Biospace, Seoul, South Korea) in an upright position following bladder emptying. Speed of ultrasound (SOS) at the calcaneus was measured by quantitative ultrasonography (QUS; IEC 601–1 Class II Type BF. IPXO, Sahara Bone Densitometer, Hologic, Bedford, MA). Serum osteocalcin and parathyroid hormone levels were measured by enzyme-linked immunosorbent assay. BMI, fat mass index (FMI), fat-free mass index (FFMI), and degree of obesity were calculated with the following formulas: BMI ¼ body weight (kg)/height (m2); FMI ¼ FM (kg)/height (m)2; FFMI ¼ FFM (kg)/height (m)2; obesity degree (%) ¼ (actual weight [kg ideal weight kg]) 100/ideal weight (kg). The degree of obesity was determined by the amount by which the actual body weight exceeded the ideal weight. Subjects with obesity degrees of 10% to 20%, 20% to 30%, 30% to 50%, or >50% were classified as being overweight, mildly obese, moderately obese, or severely obese, respectively (14). We used Tanner pubertal staging method to determine sexual maturation through self-assessment techniques for breast development in girls (B1, B2, B3, B4, and B5) and genitalia development in boys (G1, G2, G3, G4, and G5) (15).
Statistical Analyses Data were expressed as mean and standard deviation. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc, Chicago, IL). The normality of data distribution was assessed using the Kolmogorov-Smirnov test. Differences among groups (ie, overweight, mildly obese, moderately obese, and severely obese) were analyzed by analysis of variance. Correlation
729
Copyright 2014 by ESPGHAN and NASPGHAN. Unauthorized reproduction of this article is prohibited.
Wang et al
JPGN
coefficients (r) were calculated according to the Pearson or the Spearman rank correlation coefficient tests. Statistical significance was set at P < 0.05.
RESULTS In this study, 79 children (55 boys and 24 girls) with an average age of 9.47 2.09 years were enrolled. Study parameters, including body height and weight, body composition, osteocalcin, and parathyroid hormone levels, are shown in Table 1. The results revealed no significant differences in body composition and osteocalcin levels between boys and girls (Table 2).
Body Composition and Osteocalcin Levels Based on the degree of obesity, we divided the subjects into 4 groups: 8 children belonged to the overweight group, 13 belonged to the mildly obese group, 23 belonged to the moderately obese group, and 35 belonged to the severely obese group. The 4 groups were not significantly different in age and sex. The moderately and severely obese groups had significantly higher BMI, body weight, waist-tohip ratio, PBF, FMI, and VFA and significantly lower FFM% and LBM% than the other 2 groups (P < 0.05). In addition, serum osteocalcin levels were significantly lower in the severely obese (44.46 9.73 mg/mL) and moderately obese (48.72 10.82 mg/ mL) groups than in the mildly obese (55.43 12.4 mg/mL) and overweight (54.36 11.96 mg/mL) groups (P ¼ 0.02); however, there were no significant differences in SOS among the 4 groups (P ¼ 0.62) (Table 3).
Relation Among Obesity Degree, Body Composition, and Serum Osteocalcin Levels Osteocalcin levels were negatively correlated with PBF (r ¼ 0.24, P < 0.05) and VFA (r ¼ 0.46, P < 0.05); however, there was no significant correlation between obesity degree and
Volume 58, Number 6, June 2014
serum osteocalcin levels (r ¼ 0.29, P ¼ 0.052). Serum osteocalcin levels were positively correlated with LBM, FFM, and FFMI (r ¼ 0.24, 0.23, and 0.31, respectively; P < 0.05). After correcting for pubertal stage and sex, PBF and VFA were still negatively correlated with serum osteocalcin levels (r ¼ 0.28, P ¼ 0.013 and r ¼ 0.22, P ¼ 0.05, respectively). Consequently, serum osteocalcin levels were related with LBM, FFM, and FFMI (r ¼ 0.37, P ¼ 0.01; r ¼ 0.37, P ¼ 0.001; and r ¼ 0.37, P ¼ 0.001, respectively).
DISCUSSION As a result of global economic changes, which affect dietary intake and lifestyle, obesity has become a worldwide public health problem. Overweight and obesity rates in children have increased in the last years (16). Childhood obesity impairs normal growth and development, contributes to glucolipid metabolic disorders (eg, metabolic syndrome) (17,18), and negatively affects bone health. Recent studies have reported a relation among obesity, bone osteoporosis (19), and cardiovascular diseases (20). Some studies reported that overweight and obese children have a higher risk of fractures than their normal-weight counterparts (3,4). The results of our study revealed that the SOS values in the overweight and mildly obese groups were higher than those in the moderately and severely obese groups. There is increasing evidence that there is a bidirectional regulation between energy metabolism and bone tissue (21,9). On the contrary, several studies have reported that fractures are more common in overweight and obese children and that fractures are associated with lower bone mass and narrow bones (3–7). The effect of obesity on the development of the musculoskeletal system is still poorly understood in children; however, Chan and Chen (8) have suggested that obesity affects both the function and structure of the locomotor system. Osteocalcin, an osteoblast-specific protein, is a marker of bone formation and osteoblast activity, osteoblast function, and
TABLE 1. Characteristics of the 4 groups
Age, y Height, cm Weight, kg BMI, kg/m2 Obesity degree, % Waist-to-hip ratio FM, kg PBF, % FMI, kg FFM kg FFM, % FFMI, kg/m2 LBM, kg LBM, % VFA, m2 BMC, kg BMR, kcal SOS, m/s BUA OC, mg/mL PTH, pg/mL
Overweight, n ¼ 8
Mildly obese, n ¼ 13
Moderately obese, n ¼ 23
Severely obese, n ¼ 35
P
9.36 1.66 135.86 6.99 35.33 4.96 19.06 0.98 16.51 2.14 0.89 0.02 9.90 1.71 28.25 4.88 5.43 0.89 25.43 4.46 71.75 4.96 13.68 1.28 23.89 4.25 67.4 4.88 23.56 12.19 1.54 0.22 919.26 96.3 1560.2 19.67 64.07 23.58 55.43 12.4 32.19 8.53
8.3 0.78 134.68 7.33 35.83 4.38 19.68 0.48 24.33 2.28 0.9 0.02 10.34 2.21 28.73 4.69 5.68 0.97 25.18 3.63 70.18 3.7 13.81 0.8 23.67 3.43 65.95 3.6 33.56 23.65 1.52 0.2 914.06 78.4 1556.56 20.51 53.00 9.65 54.36 11.96 28.96 15.71
9.69 2.07 142.17 8.56 47.71 10.07 23.35 2.14 41.84 4.89 0.91 0.04 17.27 4.87 36.08 4.32 8.51 1.64 30.45 5.86 64.07 4.32 14.92 1.15 28.66 5.52 60.29 4.15 76.30 26.46 1.79 0.33 1027.66 126.35 1549.12 22.41 54.74 7.91 48.72 10.82 25.86 10.27
9.78 2.42 147.21 14.0 63.83 21.71 28.55 4.55 71.42 17.88 0.95 0.04 26.37 10.73 41.18 4.26 11.76 2.92 37.39 12.17 58.91 4.27 16.74 2.29 35.27 11.47 55.58 4.04 93.41 43.76 2.12 0.69 1177.24 262.87 1547.54 24.82 69.54 22.8 44.46 9.73 22.76 8.04
0.086 0.07
