Bone Mineral Density According to Age, Bone Age, and Pubertal Stages in Korean Children and Adolescents

Bone Mineral Density According to Age, Bone Age, and Pubertal Stages in Korean Children and Adolescents

Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 13, no. 1, 68e76, 2010 Ó Copyright 2010 by The International Society for Clinica...

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Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 13, no. 1, 68e76, 2010 Ó Copyright 2010 by The International Society for Clinical Densitometry 1094-6950/10/13:68e76/$36.00 DOI: 10.1016/j.jocd.2009.09.006

Original Article

Bone Mineral Density According to Age, Bone Age, and Pubertal Stages in Korean Children and Adolescents Jung Sub Lim,*,1 Jin Soon Hwang,2 Jun Ah Lee,1 Dong Ho Kim,1 Kyung Duk Park,1 Gi Jeong Cheon,3 Choong Ho Shin,4 and Sei Won Yang4 1

Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Republic of Korea; 2Department of Pediatrics, Ajou University School of Medicine, Suwon, Republic of Korea; 3Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea; and 4Department of Pediatrics, College of Medicine, Seoul National University, Seoul, Republic of Korea

Abstract To determine whether bone age (BA)ebased bone mineral density (BMD) reference values are more accurate than chronological ageebased BMD values in predicting the BMD of children who have a discrepancy between their chronological age and BA; we calculated BMD reference values for 514 healthy Korean children (262 girls and 252 boys) aged 5e20 yr by dual-energy X-ray absorptiometry. We found that children with BA chronological age discrepancy fitted better to the BA BMD reference curve than to the chronological age BMD reference curve. In contrast, most children without BAechronological age discrepancy fitted well to both BA and chronological age BMD reference curves, because the 2 reference curves are very similar. In the linear regression analysis, BAebased equations for BMD had a higher R2 value and lower standard error of estimate than chronological ageebased equations. These results indicate that BAebased BMD values are more accurate in predicting BMD in children who have a discrepancy between their BA and chronological age. Key Words: Bone age; bone mineral density; children and adolescents; DXA; Korean.

Healthy children with low BMD have a high risk of fracture, as do adults with osteoporosis (5,6). Children with chronic disease have a lower BMD than their healthy counterparts (7,8). Some of these children treated with specific medications, such as corticosteroid, anticonvulsants, and chemotherapeutic drugs, do not acquire adequate BMD and, thus, have an increased risk of fractures in later life (9e11). One problem in assessing BMD in children with chronic disease (whether taking a medication or not) is that they have a discrepancy between their chronological age and bone age BA (12e14). Even in healthy children, this discrepancy has been reported (15,16). Children with pituitary hormonal deficiency are often diagnosed with severe BMD deficit, because they commonly have a delayed BA (12). One solution may be to use BA (as an indicator of) in assessing BMD in children with chronic disease, because BMD is closely related to muscle mass and pubertal maturation (3,12,17). Bone age is also closely related to growth spurts and pubertal maturation compared with chronological age.

Introduction Bone mineral density (BMD) differs according to age, gender, race, ethnicity, and lifestyle. Therefore, appropriate normal BMD reference values should be used for specific ethnicity, particularly in children and adolescents (1). Normal BMD reference values are important for assessing adequate peak bone mass during childhood and adolescence, which is an important factor for determining the risk of osteoporosis in adult life (2). It is also important for evaluating skeletal health in these age groups (3,4). Received 04/18/09; Revised 09/18/09; Accepted 09/18/09. This study was supported by the Korean Society of Pediatric Endocrinology Research Fund. *Address correspondence to: Jung Sub Lim, PhD, MD, Department of Pediatrics, Korea Cancer Center Hospital, Gongneungdong 215, Nowon-gu, Seoul 139-706, Republic of Korea. E-mail: [email protected]

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Bone Mineral Density of Korean Children However, to our knowledge, there were no BAebased BMD reference values. Therefore, the purpose of this study was to provide chronological agee and BAespecific BMD reference values for healthy Korean children and adolescents. For this study, we evaluated the efficacy of BAebased BMD reference values over chronological ageebased BMD values in predicting the BMD of children who had a discrepancy between chronological age and BA.

Subjects and Methods Subjects A total of 514 Koreans aged 5e20 yr were enrolled between June 2007 and July 2008 (262 girls and 252 boys). The participants were recruited from Seoul and Kyungi-do area, in which 50% of the Korean population resides. All the participants were of Korean ethnicity, their parents had all originated from various Korean provinces, and their heights and weights were within normal range in Korean anthropometric reference for their age (18). The subjects were excluded by interview and a physical examination if they had 1 of the following: (1) a history of chronic disease that affects bone growth and metabolism; (2) a prior history of medication affecting bone growth and metabolism, such as corticosteroids and anticonvulsants; (3) a history of 2 or more recurrent fractures; (4) a history and physical findings of endocrine diseases, including precocious puberty; and (5) whose expected height by BA is not within normal range of the Korean adult standard height. The Ethics Committee of the Korea Cancer Center Hospital approved the study protocol. Written informed consent was obtained from all individual participants, and if participants’ ages were less than 17 yr, consent was obtained from their parents too.

Anthropometric and Dual-Energy X-Ray Absorptiometry Measurements Anthropometric measurements were performed immediately before dual-energy X-Ray absorptiometry (DXA). The height was measured without shoes to the nearest 0.1 cm using a stadiometer (DS-102; Dong Sahn Jenix Co., Ltd., Seoul, Republic of Korea), and weight was measured to the nearest 0.1 kg on an electronic scale (150A; Cas Co., Ltd., Seoul, Korea). The measurements were duplicated, and the average values were used in the analysis. The body mass index (BMI) was calculated by dividing the weight (in kg) by the height squared (kg/m2). Among the 514 participants, 442 agreed to pubertal assessments by 1 pediatric endocrinologist, and the BA was measured. Pubertal development was evaluated according to the method reported by Tanner. Bone age was assessed by 1-yr interval (except for BA 13.5 yr in girls) according to the method reported by Greulich and Pyle by a pediatric endocrinologist (19). For example, if the subject’s BA was between 12 and 13 yr, the most probable BA was assessed. Hence, if BA is assessed as 13 yr, the subject’s BA is between 12.6 Journal of Clinical Densitometry: Assessment of Skeletal Health

69 and 13.4 yr, theoretically. Advanced BA was defined as BA minus chronological age being more than 1 yr. Delayed BA was defined as BA minus chronological age being more than 1 yr. All the participants who did not have their BA taken were older than 17 yr, and their pubertal stage was assessed by a picture of the Tanner stage (TS). The BMDs of the lumbar spine (BMDLS), both femur neck (BMDFN), and total body (BMDTB) were measured serially by Lunar Prodigy Advance DXA bone densitometry (Lunar Corporation, General Electric, Madison, WI) with pediatric software (ver. enCore 2005 9.15.010, GE Lunar Corporation, Madison, WI). The same technician took all the measurements according to the manufacturer’s standards, including the positioning of each region of interest (ROI). Quality control was carried out daily with a phantom according to the manufacturer’s instructions. The data obtained were analyzed using software encore 10x (GE Lunar Corporation, General Electric, Madison, WI). The software encore 10x provided each ROI result of the BMD, bone mineral content (BMC), and bone area. For volumetric BMD of the lumbar spine, the apparent BMD (BMAD) was calculated using the model of the spine BMADLS (g/cm3) 5 BMDLS  [4/(p  width)] (20). Width is the mean width of the first to the fourth lumbar vertebral body. The BMD of the total body less head (BMDTBLH) was calculated using the sum BMC of the trunk, upper limbs, and lower limbs divided by the same area. The coefficients of variation (CV) for the BMDLS, BMDFN, BMDTB, and BMDTBLH of 30 subjects with repeated measurements were 1.20%, 1.99%, 0.87%, and 0.77%, respectively. The mean net differences between the left and right BMDFN were 0.030  0.030 and 0.030  0.037 g/cm2 in girls and boys, respectively. The CV of both the femur neck BMD was 3.41%. Hence, we used only left BMDFN in the following analysis.

Statistical Analyses The anthropometric and BMD data are expressed as the mean and standard deviation (SD). The age group was defined as follows: for example, age group 8 contained those aged 8.0e8.9 yr. The BA group was defined as previously described. The difference between the groups was tested using an analysis of variance. Subsequently, difference between 2 age groups was tested by independent t-test in both chronological age and BA group. The difference between girls and boys in the same age group was also tested by independent t-test. Partial correlation analysis was performed to determine the relationship between anthropometric values, such as height and chronological age (or BA), controlling the other variables. Linear regression analysis for each ROI BMD was carried out to compare chronological age and BA as an independent variable. Curve fitting was carried out using tri-weight log estimation according to chronological age and BA. All statistical analyses and curve fitting was performed using SPSS 15.0 (SPSS, Chicago, IL). In all analyses, a p value of less than 0.05 was considered significant. Volume 13, 2010

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Lim et al. Table 1 Clinical Characteristics of the Study Population

Variables Age (yr) Bone age (yr)a Height (cm)a Height percentile Weight (kg)a Weight percentile BMI (kg/m2)a BMI percentile

Girls (n 5 262) 12.3  4.1 0.49  1.13 145  17 52.9  18.7 41.7  14.1 52.9  17.8 19.0  3.3 53.3  29.2

Tanner stage 1 2 3 4 5

70 33 27 40 92

Boys (n 5 252) 12.3  4.1 0.14  1.42 150  21 56.0  18.3 47.6  19.0 54.3  17.9 20.1  3.9 57.0  28.7 106 30 16 28 72

Values are mean  SD. Abbr: BMI, body mass index; SD, standard deviation. a Statistically significant difference between boys and girls at p ! 0.01. No specific differences are observed in height, weight, and BMI SD.

Results Clinical Characteristics The mean height, weight, and BMI of the subjects are described in Table 1. Among the 514 children and adolescents, 74 girls (32.3%) and 71 boys (33.2%) had an advanced BA of more than 1 yr (girls: 1.7  0.5 yr; boys: 1.8  0.6 yr). In addition, 33 girls (14.4%) and 50 boys (23.4%) had a delayed BA of more than 1 yr (girls: 1.7  0.4 yr; boys: 1.7  0.5 yr).

However, BMDFN, BMDTBLH, and BMDTB values of boys were higher than those of girls from BA of 6 to 11 yr ( p ! 0.05) and after BA of 17 yr ( p ! 0.05).

Tanner StageeBased Bone Mineral Density In each ROI, the BMD value increased according to TS. BMADLS values of girls were higher than those of boys at TS 1, 2, and 4. BMDFN, BMDTBLH, and BMDTB values of boys were higher than those of girls in all TS ( p ! 0.05). However, BMDLS values did not differ between girls and boys. After controlling for age, height, and weight, all BMD values correlated strongly with the TS in boys (all p ! 0.01 except BMAD with p ! 0.05), but only BMDLS and BMADLS correlated with the TS in girls ( p ! 0.01).

Comparison of Chronological Agee and Bone AgeeBased Bone Mineral Density In general, the shapes of both the chronological age and the BA fitting curves were not different, because mean BMD values according to chronological age and BA were not different. However, girls’ BA fitting curve was shifted farther right than chronological age fitting curve. Boys’ BA fitting curve was shifted right after the age of 12 yr (Fig. 2). In linear regression equations for BMD at each ROI using the independent variables of either chronological age or BA, BAebased equations for each ROI showed a higher R2 value and lower standard error of estimates (Table 4). Bone age also had a closer relationship with anthropometric values than the chronological age (R of BA vs chronological age: height, 0.932 vs 0.903; weight, 0.868 vs 0.826; BMI, 0.576 vs 0.532dall p ! 0.01). After controlling for chronological age, BA showed high correlation with height (R 5 0.477, p ! 0.001). However, after controlling for BA, chronological age had little correlation with height (R 5 0.297, p ! 0.001). TS correlated only with BA after controlling for chronological age (R 5 0.493, p ! 0.001).

Discussion Chronological AgeeBased Bone Mineral Density In each ROI, the BMD value increased with respect to the chronological age in both genders (Table 2). BMDLS and BMADLS values of girls were higher than those of boys. Girls showed a higher BMDLS (Fig. 1). Girls had a smaller lumbar spine area (39.3  10.0 vs. 42.3  13.3 cm, p ! 0.01) but the same BMCLS (girls: 38.2  17.1 g; boys: 40.2  21.5 g, p 5 0.25). However, after age of 15 yr, BMDFN, BMDTBLH, and BMDTB values of boys were higher than those of girls ( p ! 0.05), and after the age of 19 yr, the BMDTB of boys was higher than that of girls ( p ! 0.01).

Bone AgeeBased Bone Mineral Density In each ROI, the BMD value increased according to BA in both genders (Table 3). In all ROI, BMD values had plateaus and small increases after BA of 15 yr in girls and 17 yr in boys. BMDLS and BMADLS values of girls were higher than those of boys from BA of 11 to 16 yr ( p ! 0.05). Journal of Clinical Densitometry: Assessment of Skeletal Health

This study provides chronological agee and BAespecific DXA BMD reference values for healthy Korean children and adolescents. In addition, we showed that BAebased BMD reference values are more accurate than chronological ageebased BMD values in predicting the BMD of children who have a discrepancy between their chronological age and BA.

The Bone Mineral Density Values of Koreans Compared with other studies that used lunar DXA, we have found that Korean children and adolescents have earlier BMD acquisition but similar trends according to age. Koreans showed the highest increase in BMDLS between age groups 11 and 12 in girls and between age groups 12 and 13 in boys. Dutch children showed the highest increase in BMDLS a year later (21). The reason for the earlier BMD acquisition in Korean children compared with Dutch children is not certain. The reason might simply Volume 13, 2010

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Table 2 BMDLS, BMDFN, BMDTB, BMDTBLH (g/cm2), and BMADLS (g/cm3) According to Gender and Age Group (Mean  SD) BMDLS Age (yr) Girls 5e5.9 6e6.9 7e7.9 8e8.9 9e9.9 10e10.9 11e11.9 12e12.9 13e13.9 14e14.9 15e15.9 16e16.9 17e17.9 18e18.9 19e20 Total Boys 5e5.9 6e6.9 7e7.9 8e8.9 9e9.9 10e10.9 11e11.9 12e12.9 13e13.9 14e14.9 15e15.9 16e16.9 17e17.9 18e18.9 19e20 Total

BMADLS

BMDFN

BMDTB

BMDTBLH

n

Mean

SD

Mean

SD

Mean

SD

Mean

SD

Mean

SD

13 14 15 15 32 25 24 18 14 16 13 15 15 18 15

0.644 0.665 0.664 0.733a 0.779a 0.813 0.871 0.964a 1.038 1.095 1.124 1.117 1.155 1.154 1.183

0.108 0.063 0.081 0.064 0.072 0.101 0.137 0.118 0.153 0.138 0.087 0.101 0.068 0.120 0.124

0.273 0.273 0.272 0.281 0.291 0.294 0.311 0.333 0.350 0.373 0.372 0.381 0.387 0.380 0.385

0.041 0.021 0.029 0.029 0.024 0.030 0.058 0.041 0.051 0.055 0.037 0.032 0.019 0.042 0.045

0.625 0.649 0.618 0.710b 0.737 0.765 0.786 0.848 0.924 0.947 0.943 0.960 0.989 0.994 0.980

0.068 0.044 0.055 0.062 0.072 0.089 0.102 0.108 0.118 0.094 0.118 0.081 0.106 0.098 0.126

0.778 0.784 0.797 0.841b 0.858 0.867 0.913a 0.950 1.006a 1.037 1.062 1.061 1.083 1.091 1.106

0.052 0.036 0.038 0.036 0.035 0.063 0.070 0.062 0.077 0.067 0.060 0.057 0.042 0.066 0.070

0.618 0.642 0.658 0.708b 0.742a 0.772a 0.815a 0.852 0.909a 0.924 0.943 0.942 0.964 0.963 0.988

0.041 0.036 0.039 0.040 0.046 0.068 0.076 0.063 0.070 0.064 0.058 0.039 0.047 0.061 0.072

262

0.923

0.213

0.327

0.058

0.825

0.156

0.940

0.124

0.823

0.130

15 14 19 14 19 17 18 27 19 16 19 12 12 18 13

0.607 0.656 0.644 0.715a 0.737 0.754 0.790 0.820 0.954b 1.001 1.108a 1.114 1.180 1.154 1.216

0.057 0.071 0.062 0.090 0.082 0.087 0.100 0.098 0.161 0.141 0.137 0.071 0.120 0.098 0.125

0.252 0.261 0.244 0.260 0.272 0.270 0.275 0.273 0.307b 0.312 0.335 0.337 0.342 0.340 0.361

0.028 0.030 0.029 0.034 0.030 0.039 0.044 0.031 0.048 0.039 0.043 0.027 0.038 0.036 0.043

0.660 0.732b 0.697 0.721 0.772 0.765 0.821a 0.842 0.996b 1.008 1.068 1.070 1.125 1.106 1.152

0.064 0.073 0.066 0.069 0.084 0.096 0.064 0.087 0.127 0.171 0.174 0.114 0.120 0.119 0.095

0.779 0.816a 0.820 0.842 0.857 0.884 0.921 0.933 0.999 1.052 1.110 1.103 1.174 1.130 1.200a

0.038 0.038 0.041 0.049 0.049 0.067 0.060 0.053 0.088 0.104 0.111 0.069 0.112 0.071 0.077

0.607 0.660b 0.672 0.706a 0.738 0.780a 0.810 0.844 0.921b 0.981 1.031 1.022 1.093 1.045 1.114a

0.035 0.042 0.043 0.044 0.055 0.064 0.070 0.073 0.093 0.103 0.107 0.070 0.112 0.068 0.074

252

0.883

0.223

0.293

0.050

0.889

0.192

0.964

0.147

0.859

0.172

Abbr: BMD, bone mineral density; BMDLS, BMD of lumbar spine; BMDFN, BMD of femur neck; BMDTB, BMD of total body; BMDTBLH, BMD of total body less head; BMADLS, bone mineral apparent density of lumbar spine; SD, standard deviation. a Significant difference compared with the previous age group by independent t-test at p ! 0.05. b Significant difference compared with the previous age group by independent t-test at p ! 0.01.

be the ethnic difference. One explanation might be the difference in BA or sexual maturation, as sexual maturation differs according to race (22). We assume that Korean children might have advanced BA although it needs further study. Korean girls showed BMDLS increase significantly at chronological age of 7e10 yr whereas at BA of 10 yr. When compared with Korean adults, the BMDLS and BMDFN values for girls older than 18 yr and boys older than 19 yr were same as in 20- to 30-yr-old Koreans Journal of Clinical Densitometry: Assessment of Skeletal Health

(23). Therefore, Koreans achieve almost the peak BMD in the lumbar spine and femur neck late in the second decade of life. However, late teenagers from The Netherlands showed slightly lower BMD values than adults, about 1.6e6.6% lower, depending on the ROI (20). Similarly, 5e12% BMD gains were reported during the third decade in the study of Caucasian women (24). In a multirace longitudinal study, Asians reached a plateau of BMD earlier than other races (25). Volume 13, 2010

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Fig. 1. Bone mineral density (BMD) of the lumbar spine (A), femur neck (C), and the total body less head (TBLH); (D) as well as bone mineral apparent density (BMAD; g/cm3) of the lumbar spine (B) according to gender and age. The bold lines and filled squares represent boys, and the dotted lines and emptied squares represent girls. During puberty, Koreans had a similar increase in BMDLS as in other ethnic groups. The BMDLS acquisitions of Koreans between TS 1 and TS 5 were 65% in girls and 66% in boys. The BMDLS acquisitions of other ethnicities were 51e67% in girls and 67e70% in boys (21,26). Koreans also had higher trabecular bone mass (BMDLS) acquisition than cortical bone mass (BMDFN and BMDTBLH) acquisition during puberty, as previously reported (27). The BMDFN increased by 47% in girls and 53% in boys between TS1 and TS5. The BMDTBLH increased to 43% in girls and 51% in boys. Korean girls also showed an earlier BMD plateaus than boys did. The plateaus of the BMDLS, BMADLS, BMDFN, BMDTB, and BMDTBLH in girls occurred at ages 15, 16, 14, 17, and 17 yr, respectively. The plateaus of all ROI BMDs in boys occurred in age group 17.

Bone Age vs Chronological Age Although, all participants in this study were within normal range of Korean National Growth Charts (18) and their expected height was within normal range of adult height, Journal of Clinical Densitometry: Assessment of Skeletal Health

about 32.3% of girls and 33.2% of boys had an advanced BA of more than 1 yr. In addition, 14.4% of girls and 23.4% of boys had a delayed BA of more than 1 yr. The evidence for the fact that BAebased BMD reference values are more accurate than chronological ageebased BMD values in predicting the BMD is that children who had advanced BA fitted better to the BA BMDLS reference curve than to the chronological age BMDLS reference curve. Most children with advanced BA showed increased BMD values according to chronological age BMDLS reference curve. Children, who had delayed BA, showed decreased BMD values according to chronological age BMDLS reference curve. Children without a BAechronological age discrepancy fitted well to both BA and chronological age BMDLS reference curves, because both reference curves were very similar. This tendency was true in other ROIs, including BMDFN, BMDTB, and BMDTBLH (data not shown). Similarly, BA was reported to predict the spine BMD more accurately by DXA in healthy Caucasian children (28e30). Thus, in the interpretation of BMD of children who had Volume 13, 2010

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Table 3 BMDLS, BMDFN, BMDTB, BMDTBLH (g/cm2), and BMADLS (g/cm3) According to Gender and BA (Mean  SD) BMADLS

BMDLS

BMDFN

BMDTB

BMDTBLH

Age (yr)

n

Mean

SD

Mean

SD

Mean

SD

Mean

SD

Mean

SD

Girls 5 6 7 8 9 10 11 12b 13 13.5 14 15 16 17 18

9 9 20 10 16 14 35 20 9 9 8 18 17 12 22

0.612 0.619 0.680 0.690 0.716 0.769b 0.799 0.863a 0.950a 0.990 1.064a 1.083 1.111 1.158 1.137

0.071 0.068 0.082 0.067 0.054 0.059 0.047 0.074 0.058 0.166 0.118 0.102 0.064 0.055 0.116

0.264 0.262 0.275 0.271 0.279 0.288 0.290 0.307b 0.327 0.353 0.366 0.359 0.370 0.391 0.389

0.033 0.030 0.033 0.028 0.018 0.023 0.025 0.028 0.037 0.065 0.039 0.040 0.035 0.030 0.043

0.634 0.571 0.646a 0.684 0.671 0.734a 0.747 0.800a 0.863 0.851 0.945 0.932 0.937 0.981 1.001

0.042 0.042 0.055 0.052 0.058 0.040 0.063 0.068 0.118 0.088 0.124 0.090 0.094 0.067 0.111

0.780 0.776 0.792 0.809 0.830 0.853 0.864 0.901a 0.946b 0.958 1.006b 1.035 1.059 1.084 1.072

0.027 0.046 0.051 0.031 0.030 0.024 0.034 0.047 0.036 0.077 0.060 0.050 0.047 0.053 0.071

0.614 0.616 0.653b 0.686a 0.684 0.728a 0.768a 0.810a 0.854b 0.859 0.912 0.927 0.934 0.960 0.960

0.022 0.037 0.040 0.027 0.031 0.026 0.029 0.051 0.045 0.073 0.076 0.052 0.042 0.047 0.059

Total

228

0.888

0.200

0.320

0.056

0.803

0.150

0.919

0.116

0.803

0.124

Boys 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

3 15 18 17 16 16 11 13 15 16 17 10 7 12 12 16

0.539 0.596 0.665a 0.686 0.699 0.700 0.789a 0.750 0.782 0.850a 0.938a 0.975 1.005 1.140 1.146 1.182

0.033 0.052 0.051 0.066 0.074 0.076 0.075 0.059 0.053 0.069 0.104 0.103 0.073 0.134 0.126 0.102

0.213 0.248 0.259 0.256 0.259 0.255 0.277 0.263 0.272 0.289 0.302 0.305 0.311 0.344 0.339 0.352

0.019 0.031 0.027 0.032 0.026 0.031 0.039 0.037 0.029 0.036 0.035 0.038 0.032 0.046 0.035 0.028

0.623 0.664 0.727b 0.726 0.720 0.731 0.813b 0.788 0.826 0.862 0.919 0.964 0.993 1.146 1.096 1.131

0.034 0.075 0.065 0.066 0.069 0.087 0.072 0.058 0.079 0.051 0.108 0.171 0.086 0.128 0.149 0.117

0.743 0.786 0.814b 0.831 0.845 0.841 0.896 0.893 0.922b 0.955a 0.990 1.005 1.054 1.136 1.125 1.161b

0.027 0.041 0.032 0.034 0.049 0.051 0.041 0.037 0.038 0.046 0.066 0.085 0.056 0.100 0.099 0.091

0.574 0.608 0.669a 0.690b 0.706 0.723 0.791a 0.785 0.814 0.867a 0.921a 0.941 0.982 1.062 1.042 1.079b

0.023 0.033 0.026 0.036 0.044 0.049 0.041 0.042 0.043 0.043 0.065 0.089 0.048 0.096 0.094 0.093

Total

214

0.840

0.205

0.285

0.047

0.856

0.180

0.936

0.125

0.827

0.161

Abbr: BMD, bone mineral density; BMDLS, BMD of lumbar spine; BMDFN, BMD of femur neck; BMDTB, BMD of total body; BMDTBLH, BMD of total body less head; BMADLS, bone mineral apparent density of lumbar spine; SD, standard deviation. a Significant difference compared with the previous bone age group by independent t-test at p ! 0.01. b Significant difference compared with the previous bone age group by independent t-test at p ! 0.05.

multihormonal pituitary deficiency, BAebased, not chronological ageebased, interpretation was recommended, because hormone-deficient children have delayed BA (12). Further evidence for BAebased BMD reference values being more accurate is that BAebased BMD reference values also had smaller SDs than chronological ageebased BMD reference values. In linear regression analysis, BAebased equations had a higher R2 value and lower standard error of Journal of Clinical Densitometry: Assessment of Skeletal Health

estimates than the chronological ageebased equations. Bone age correlated more closely with anthropometric values, such as height, weight, and TS, in this study population. After controlling for BA, chronological age did not correlate with TS, which is important for assessing development and BMD. The height, weight, and TS are all known to be closely related to BMD (16,29). Even in single-ethnicity studies, the timing of individual development of height, weight, and TS Volume 13, 2010

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Fig. 2. Both advanced BA subjects (A, B) and delayed BA subjects (C, D) showed a better fit to the BA reference than to the chronological age reference. Solid lines represent boys, and dotted lines represent girls. are different (15,16). In a single-ethnicity population, contemporaneous children showed earlier developmental maturation than did their historical counterparts (15). This earlier maturation is associated with advanced BAs relative to the chronological age. In this study of Korean children, although the participants were selected within normal height according to age and although expected heights were within normal adult range, about half of the subjects enrolled showed a discrepancy of more than 1 yr between chronological age and BA. Therefore, considering that normal biological maturation is closely related to BA, a BAebased reference might be useful for evaluating the BMD for a single-ethnic group, as previously recommended (17).

Limitation of Study The major limitations of this study are the cross-sectional nature and the small number of subjects within each age/gender group. Further prospective study is needed to confirm characteristic Korean BMD development and the BA influence on BMD. This study has 2 minor limitations. First, the Journal of Clinical Densitometry: Assessment of Skeletal Health

BA atlas has no reference for BA above 18 yr in girls and 19 yr in boys. Therefore, the BA above 18 yr in girls and 19 yr in boys no longer represents skeletal maturation. Second, a range of BMD values is presented within the same BA, because the BA interval is 1 yr, and there may be a range of anthropometric values, such as height and weight, which would affect BMD. In conclusion, this study provides chronological agee and BAespecific BMD reference values for healthy Korean children and adolescents. To our knowledge, this is the first study of BAespecific BMD reference values in a range of skeletal sites with a large sample size, diverse age group, and equal gender representation in healthy children and adolescents of a single-ethnic group. We also found that although both reference values are similar in a single-ethnic group, BAebased BMD reference values are more accurate than chronological ageebased BMD values in predicting the BMD of children. These results suggest that BMD interpretation according to BA base might be more accurate in children with BAe chronological age discrepancy because of various chronic diseases. Volume 13, 2010

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Table 4 Linear Regression Equations for BMDLS, BMADLS, BMDFN, BMDTB, and BMDTBLH Using the Independent Variables of Either Chronological Age or Bone Age R2

SEE

BA-based regression equation

R2

SEE

Girls BMDLS 5 (372 þ 45  age)/103 BMADLS 5 (199 þ 10  age)/103 BMDFN 5 (457 þ 30  age)/103 BMDTB 5 (607 þ 27  age)/103 BMDTBLH 5 (476 þ 28  age)/103

0.729 0.532 0.606 0.777 0.778

0.110 0.039 0.098 0.059 0.061

BMDLS 5 (259 þ 50  BA Wt)/103 BMADLS 5 (177 þ 12  BA)/103 BMDFN 5 (388 þ 35  BA)/103 BMDTB 5 (576 þ 29  BA)/103 BMDTBLH 5 (427 þ 32  BA)/103

0.823 0.613 0.708 0.821 0.869

0.084 0.035 0.082 0.049 0.045

Boys BMDLS 5 (304 þ 47  age)/103 BMADLS 5 (192 þ 8  age)/103 BMDFN 5 (430 þ 37  age)/103 BMDTB 5 (582 þ 31  age)/103 BMDTBLH 5 (393 þ 38  age)/103

0.751 0.450 0.621 0.746 0.806

0.111 0.037 0.119 0.074 0.076

BMDLS 5 (361 þ 42  BA)/103 BMADLS 5 (199 þ 7  BA)/103 BMDFN 5 (465 þ 34  BA)/103 BMDTB 5 (626 þ 27  BA)/103 BMDTBLH 5 (434 þ 34  BA)/103

0.798 0.481 0.661 0.777 0.859

0.091 0.034 0.106 0.063 0.061

Chronological ageebased regression equation

Abbr: BMD, bone mineral density; BMDLS (g/cm2), BMD of lumbar spine L1e4; BMADLS (g/cm3), bone mineral apparent density of lumbar spine L1e4; BMDFN, BMD of femur neck (g/cm2); BMDTB (g/cm2), BMD of total body; BMDTBLH (g/cm2), BMD of total body less head; BA, bone age; SEE, standard error of estimate. BA-based equation shows stronger correlation and lower SEE.

Acknowledgments The authors wish to express their gratitude to all the volunteers. The authors also thank Jin Seong Jeong for measuring the BMD by DXA and Qi Q. Zhou for the technical support in analyzing the DXA results.

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