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Jan 30, 2013 - Age trends of bone mineral density and percentile curves in healthy Chinese children and adolescents. Bin Guo • Yi Xu • Jian Gong •. Yongjin ...
J Bone Miner Metab (2013) 31:304–314 DOI 10.1007/s00774-012-0401-1

ORIGINAL ARTICLE

Age trends of bone mineral density and percentile curves in healthy Chinese children and adolescents Bin Guo • Yi Xu • Jian Gong Yongjin Tang • Hao Xu



Received: 4 May 2012 / Accepted: 14 October 2012 / Published online: 30 January 2013 Ó The Japanese Society for Bone and Mineral Research and Springer Japan 2013

Abstract The clinical utility of dual-energy X-ray absorptiometry (DXA) measurement requires appropriate normative values, designed to be diverse with respect to age, gender and ethnic background. The purpose of this study was to generate age-related trends for bone density in Chinese children and adolescents, and to establish a gender-specific reference database. A total of 1,541 Chinese children and adolescents aged from 5 to 19-years were recruited from southern China. Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were measured for the total body (TB) and total body less head (TBLH). The height-for-age, height-for-BA, and BMC-for-BA percentile curves were developed using the least mean square method. TB BMD and TBLH BMD were highly correlated. After 18 years, TB BMD was significantly higher in boys than girls. For TB BMC and TBLH BMC, gender differences were found in age groups 12 years and 16–19 years; however, the TBLH BMD was significantly different between genders [16 years. The head region accounted for 13–52 and 16–49 % of the TB BMC in boys and girls, respectively. Furthermore, the percentages were negatively correlated with age and height. This study describes a gender-specific reference database for Chinese children and adolescents aged 5–19 years. These normative values could be used for clinical assessment in this population. B. Guo  J. Gong  Y. Tang  H. Xu (&) Department of Nuclear Medicine, First Affiliated Hospital, Jinan University, No. 613 West Huangpu Road, Guangzhou 510630, China e-mail: [email protected] Y. Xu Department of Clinical Medicine, Medical College, Jinan University, Guangzhou 510630, China

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Keywords Bone mineral density  Children  DXA  Normal reference Introduction Osteoporosis is increasingly recognized as a common health problem worldwide. It is generally accepted that proper development of bone mineral during childhood and adolescence is a key for skeletal health. Failure to achieve optimal peak bone mass (PBM) is associated with an increased risk of osteoporosis and fractures in adulthood [1]. Pediatric patients with skeletal disorders, such as cystic fibrosis, inflammatory bowel disease, and type 1 diabetes mellitus, are associated with low bone mass and increased risk of fracture [2]. Due to its speed, high precision, accuracy, safety, low cost, low radiation exposure and widespread availability, dual-energy X-ray absorptiometry (DXA) has become the gold standard for measuring bone mineral density (BMD) and bone mineral content (BMC) in children and adolescents throughout the world [3]. To evaluate skeletal status in children, the most accurate and reproducible skeletal sites for performing BMC and areal BMD measurements in this population are posteroanterior (PA) spine and total body less head (TBLH) as recommended by the International Society of Clinical Densitometry (ISCD) [4]. For BMD reporting, Z scores, rather than T scores should be used for this population. However, Z scores are based on a sample of the general healthy population sufficiently large enough to characterize the normal variability in bone measurements that takes into consideration gender, age, race/ethnicity and other factors [5] as suggested by the ISCD [6]. Several pediatric normative databases from different geographies have been published [7]. To date, there has been no complete study covering children and adolescents in the Chinese

J Bone Miner Metab (2013) 31:304–314

population. We have previously reported DXA normative data for children aged 5–13 years based on data from 505 boys and 372 girls [8]; however, a broader range of subjects are needed. In this study, we report age- and sex-specific means and standard deviations (SDs) for BMC and BMD of the total body (TB) and the TBLH in Chinese children and adolescents aged 5–19 years using the Lunar Prodigy DXA system (GE Healthcare, Madison, WI, USA). This data could provide researchers and clinicians with appropriate information to evaluate the bone status in Chinese children and adolescents.

Materials and methods Healthy subjects A total of 1,541 healthy school children (777 boys, 764 girls) were recruited from 4 local schools in Guangzhou district and 1 school in Jiaxing district in southern China. The age range was 5.0–19.9 years for both boys and girls. All participating children were of Chinese ethnicity. Participants included in the study were between 3rd and 97th percentile for height and weight on current growth reference curves [9, 10]. Children were excluded from the study if they had (1) a history of metabolic disease or other medical disorders affecting bone growth and metabolism; (2) a history of use of medications affecting bone growth and metabolism; and (3) a history of fracture. Informed consent was obtained from all participants and their parents. This study was approved by the Ethics Committee of the First Affiliated Hospital, Jinan University. Anthropometric and DXA measurements Anthropometric and DXA measurements were obtained for the children and adolescents during the same visit. Weight was measured using platform digital scales with a precision of 0.1 kg, and height was recorded with a stadiometer to the nearest 0.1 cm. TB composition including BMC, lean mass (LM) and fat mass (FM) was measured with a Lunar Prodigy DXA bone densitometer (GE Healthcare), and data were analyzed using enCORE software (ver. 10.0, standard-array mode). DXA measured parameters included BMD, BMC, and BA. The TBLH variables were determined with the head region of interest removed from analysis. The precision for TB BMD was 0.5 % (expressed as the root-mean-square percent coefficient of variation), determined by duplicate scans with repositioning between each measurement in 30 volunteer subjects. Daily quality assurance scan was conducted by scanning an aluminum

305

spine phantom according to the manufacturer’s instructions. All DXA measurements were performed by a welltrained technologist throughout the study. Statistical analysis Descriptive statistics were used to analyze baseline characteristics and measurements. Paired-sample t tests were performed to compare the BMD of the TB and the TBLH for each gender and age group. Two sample t tests were used to find possible differences in various parameters between boys and girls of the same age group. Pearson’s correlation coefficients (r) were calculated to assess correlations among different variables. The heightfor-age, height-for-BA, and BMC-for-BA percentile curves (3rd, 25th, 50th, 75th, and 97th) were developed by using the least mean square (LMS) method as described by Cole and Green [11]. The LMS method summarizes the changing distribution by 3 curves representing the median (M), coefficient of variation (S), and the skewness (L) expressed as a Box-Cox power. These 3 values were estimated, and the curves were calculated using the formula: Measurement percentile ¼ Mð1 þ LSZÞ1=L where Z is the Z score corresponding to a given percentile. The percentile curves were constructed using the lmsChartMaker program (ver. 2.3; Medical Research Council, UK). All the tests were 2-tailed, and a p value of\0.05 was considered statistically significant.

Results Table 1 summarizes the baseline characteristics of the participating subjects. Bone measurements (i.e., BMD, BMC, and BA) of the subjects are shown in Tables 2 and 3. TB BMD and TBLH BMD were highly correlated (r = 0.762–0.981 in boys, r = 0.758–0.968 in girls, p \ 0.001) for each age group in Table 4. After 18 years, TB BMD was significantly higher in boys than girls. For TB BMC, significant gender differences were found in age groups 12 years and 16–19 years; the gender differences in these age groups were also observed for TBLH BMC. However, the TBLH BMD was significantly different between genders from age 16 onwards. Tables 5 and 6 present the percentile distribution of BMD of the TB and subcranial skeleton. The percentile distribution of TB and subcranial skeleton BMC is shown in Tables 7 and 8. The head region accounted for 13–52 and 16–49 % of the TB BMC in boys and girls for each age group, respectively. Furthermore, the percentages were negatively correlated with age (r = -0.895 in boys, r = -0.819 in

123

123

66 85

36

66

68

91

70

55

28

41

34

41

39

38

19

5 6

7

8

9

10

11

12

13

14

15

16

17

18

19

19.4 (0.3)

18.2 (0.2)

17.5 (0.3)

16.6 (0.3)

15.4 (0.2)

14.5 (0.3)

13.4 (0.3)

12.4 (0.3)

11.3 (0.3)

10.5 (0.3)

9.4 (0.3)

8.6 (0.3)

7.3 (0.3)

5.4 (0.3) 6.3 (0.3)

Age (years)

Boys

57.0 (6.3)c c

169.5 (4.2)c c

60.1 (8.8)

56.2 (7.0)c

168.4 (5.0)c

172.1 (6.1)

55.4 (6.3)c

168.3 (5.4)c

49.4 (7.6) 52.1 (6.4)a

c

39.5 (4.2)

a

166.4 (6.7)c

165.7 (8.1)

153.5 (9.1)

33.7 (7.3) 35.3 (8.2)

30.8 (6.3)

27.3 (6.3)

145.6 (8.2)a

a

16.3 (2.5)

20.2 (2.3)

19.8 (2.3)

19.8 (2.1)

19.6 (1.9)

18.8 (2.1)

17.9 (1.9)

16.7 (2.3)

16.5 (2.6)

25.8 (3.8)

a

p \ 0.05,

b

c

46.9 (4.0)

9.6 (5.4)

b

6.6 (4.5)c

7.0 (3.0)c

6.2 (3.2)c

6.8 (3.3)c

5.3 (2.8)

41

55

72

38

31

43

26

c

5.6 (3.7)b

61 41

6.5 (4.7)

5.9 (4.0)

71

51

62

41

63 68

n

p \ 0.01, c p \ 0.001 compared with girls of the same age group (unpaired-sample t tests)

c

46.5 (4.3)c

45.5 (5.3)c

45.3 (4.8)c

42.7 (4.9)c

41.2 (6.6)

32.4 (6.1)

27.6 (4.7)

5.5 (3.6)

4.6 (4.3)

21.7 (2.4)

15.6 (2.8)a 23.7 (3.1)b

3.1 (1.9)b

16.1 (2.1)c

3.1 (2.0)

2.4 (1.5) 2.5 (1.6)a

20.5 (1.9)b

15.6 (1.6)c 16.9 (2.1)c

FM (kg)

15.5 (1.7)

15.6 (1.4)a

23.5 (3.8)a 25.5 (3.7)

14.6 (1.9) 14.8 (1.7)a

19.0 (2.9)a 20.6 (3.5)a

LM (kg)

18.4 (2.1)c

BMI (kg/m )

Weight (kg)

143.0 (6.9)

137.8 (7.6)

131.9 (5.2)

127.9 (0.6)

122.3 (6.3)

113.8 (4.9) 117.5 (5.5)

Height (cm)

2

BMI body mass index, SD standard deviation, LM lean mass, FM fat mass

n

Age

Table 1 Baseline characteristics of the participating subjects by gender and age group [mean (SD)]

19.6 (0.3)

18.3 (0.3)

17.5 (0.3)

16.6 (0.3)

15.3 (0.3)

14.4 (0.3)

13.5 (0.3)

12.4 (0.3)

11.4 (0.3)

10.4 (0.3)

9.5 (0.3)

8.5 (0.3)

7.4 (0.2)

5.4 (0.3) 6.4 (0.3)

Age (years)

Girls

159.5 (7.2)

157.5 (5.3)

157.1 (6.2)

157.1 (5.8)

159.4 (5.8)

158.7 (6.0)

155.8 (7.5)

149.5 (6.2)

145.7 (7.6)

138.6 (6.9)

131.4 (6.0)

128.5 (6.6)

121.1 (7.5)

112.9 (5.6) 117.1 (4.5)

Height (cm)

50.2 (7.7)

48.4 (6.6)

48.5 (7.2)

49.4 (6.6)

47.7 (7.5)

47.0 (7.6)

41.7 (7.1)

36.2 (6.2)

34.4 (6.9)

28.9 (4.7)

25.9 (3.7)

25.4 (5.6)

21.6 (3.0)

17.9 (2.7) 19.9 (3.1)

Weight (kg)

19.7 (2.3)

19.5 (2.0)

19.6 (2.4)

20.0 (2.4)

18.7 (2.3)

18.6 (2.3)

17.1 (1.9)

16.1 (2.0)

16.1 (2.3)

14.9 (1.9)

15.0 (1.4)

15.3 (2.4)

14.8 (1.7)

14.0 (1.7) 14.5 (1.6)

BMI (kg/m2)

32.9 (3.8)

32.2 (4.9)

32.0 (3.5)

32.1 (3.4)

32.5 (4.2)

32.7 (4.3)

31.4 (3.9)

27.6 (3.5)

25.5 (3.6)

22.2 (3.0)

19.8 (2.3)

19.2 (2.2)

16.7 (1.6)

14.3 (1.7) 15.5 (1.6)

LM (kg)

14.2 (5.5)

12.9 (3.4)

13.4 (3.8)

14.0 (4.5)

13.2 (5.4)

11.4 (4.7)

8.7 (3.9)

7.3 (3.4)

6.6 (3.2)

4.9 (2.1)

4.4 (1.8)

3.3 (1.6)

3.3 (1.7)

2.5 (1.1) 3.1 (1.6)

FM (kg)

306 J Bone Miner Metab (2013) 31:304–314

J Bone Miner Metab (2013) 31:304–314

307

Table 2 BMD, BMC, and BA of total body by gender and age group [mean (SD)] Age

n

Boys

n 2

BMD (g/cm )

2

BMC (g)

Girls BMD (g/cm2)

BA (cm )

BMC (g)

BA (cm2)

5

66

0.767 (0.048)

631.05 (96.83)

819.43 (92.42)a

63

0.761 (0.040)

599.45 (86.92)

785.98 (89.65)

6

85

0.786 (0.045)

698.41 (121.12)

884.37 (116.36)

68

0.778 (0.040)

664.06 (107.28)

850.77 (103.94)

7

36

0.796 (0.049)

770.48 (138.39)

964.04 (137.13)

41

0.797 (0.041)

745.02 (122.66)

930.83 (116.79)

8

66

0.815 (0.041)

869.55 (120.84)

1064.58 (117.64)

62

0.810 (0.049)

862.83 (160.70)

1059.63 (149.57)

9

68

0.817 (0.047)

932.71 (155.85)

1136.91 (145.94)

51

0.817 (0.053)

909.36 (157.38)

1107.50 (134.76)

10

91

0.841 (0.046)

1061.12 (174.92)

1255.84 (156.22)

71

0.830 (0.049)

1013.65 (179.80)

1215.26 (161.47)

11 12

70 55

0.869 (0.057) 0.864 (0.053)

1199.16 (215.10) 1224.16 (244.02)a

1373.00 (181.18) 1409.07 (211.92)

61 41

0.872 (0.056) 0.889 (0.070)

1215.02 (219.09) 1333.02 (250.38)

1387.19 (188.15) 1490.35 (185.55)

13

28

0.896 (0.058)

1415.66 (257.94)

1571.98 (211.91)

14

41

0.975 (0.098)

1921.20 (437.81)

15

34

1.004 (0.084)

2032.87 (367.44)

26

0.925 (0.077)

1538.22 (282.12)

1653.78 (206.47)

1948.6 (277.59)a

43

1.008 (0.087)

1862.99 (354.58)

1835.50 (216.77)

2011.48 (216.24)a

31

1.025 (0.072)

1943.84 (312.03)

1888.67 (202.24)

c

2146.10 (185.26)c

38

1.048 (0.080)

1964.39 (295.05)

1867.08 (177.74)

16

41

1.070 (0.074)

2307.24 (327.72)

17

39

1.070 (0.077)

2338.91 (315.51)c

2178.78 (173.76)c

72

1.047 (0.078)

1970.83 (299.99)

1875.64 (188.99)

c

c

55

1.059 (0.083)

2010.35 (320.38)

1888.98 (176.19)

2264.10 (219.77)c

41

1.055 (0.082)

2042.86 (354.43)

1927.26 (233.91)

b

18

38

1.114 (0.112)

19

19

1.122 (0.048)b

2473.95 (418.15)

2546.93 (327.44)c

2207.39 (167.34)

BMD bone mineral density, BMC bone mineral content, BA bone area, SD standard deviation a

p \ 0.05,

b

p \ 0.01,

c

p \ 0.001 compared with girls of the same age group (unpaired-sample t tests)

Table 3 BMD, BMC, and BA of TBLH by gender and age group [mean (SD)] Age

n

Boys

n 2

BMD (g/cm )

BMC (g)

2

Girls BMD (g/cm2)

BA (cm )

BMC (g)

BA (cm2)

5

66

0.598 (0.039)

366.10 (72.63)

607.66 (86.91)

63

0.594 (0.037)

349.40 (68.40)

584.01 (83.04)

6

85

0.621 (0.046)

420.00 (96.93)

669.51 (109.30)

68

0.617 (0.039)

400.87 (84.66)

644.98 (97.02)

7

36

0.637 (0.044)

478.95 (112.39)

744.89 (127.57)

41

0.642 (0.035)

466.65 (92.92)

722.44 (108.05)

8

66

0.663 (0.037)

561.52 (100.34)

842.24 (114.06)

62

0.672 (0.047)

573.51 (135.51)

845.28 (144.20)

9

68

0.682 (0.046)

629.69 (136.59)

915.29 (141.64)

51

0.685 (0.054)

618.30 (129.85)

894.69 (126.98)

10

91

0.720 (0.052)

745.76 (158.85)

1026.43 (152.48)

71

0.713 (0.053)

717.54 (158.45)

997.26 (153.66)

11 12

70 55

0.750 (0.058) 0.760 (0.063)

864.05 (193.87) 907.18 (232.59)a

1141.11 (175.07) 1180.36 (208.68)a

61 41

0.769 (0.058) 0.786 (0.069)

904.99 (202.66) 1006.07 (222.30)

1166.57 (182.80) 1267.71 (182.36)

13

28

0.804 (0.061)

1083.43 (243.66)

1333.85 (203.14)

26

0.824 (0.073)

1187.68 (251.82)

1427.35 (202.10)

14

41

0.904 (0.103)

1566.25 (395.87)

1706.73 (268.63)

43

0.901 (0.076)

1459.74 (297.34)

1607.01 (207.33)

a

15

34

0.933 (0.081)

1661.59 (324.31)

1766.77 (209.97)

31

0.907 (0.069)

1513.70 (281.56)

1658.73 (197.53)

16

41

0.984 (0.077)c

1885.63 (301.93)c

1904.63 (182.54)c

38

0.918 (0.074)

1514.13 (253.86)

1640.47 (169.40)

17

39

0.983 (0.075)c

1909.12 (287.31)c

1932.33 (168.37)c

72

0.914 (0.070)

1514.68 (256.09)

1648.97 (180.87)

18

38

1.025 (0.100)c

2026.97 (353.29)c

1964.63 (162.91)c

55

0.921 (0.080)

1542.57 (282.67)

1663.11 (172.47)

19

19

1.024 (0.050)c

2069.96 (292.01)c

2016.05 (212.39)c

41

0.923 (0.076)

1582.83 (316.62)

1704.40 (229.35)

BMD bone mineral density, BMC bone mineral content, BA bone area, TBLH total body less head, SD standard deviation a

p \ 0.05,

b

p \ 0.01,

c

p \ 0.001 compared with girls of the same age group (unpaired-sample t tests)

girls, p \ 0.001) and height (r = -0.875 in boys, r = -0.929 in girls, p \ 0.001). The gender-specific height-for-age and height-for-BA percentile curves are displayed in Fig. 1. In general, the

percentile curves for the 2 genders were similar in shape. The BA-dependent percentile curves for BMC (Fig. 2) showed that BMC was closely associated with BA for both TB and TBLH.

123

308

J Bone Miner Metab (2013) 31:304–314

Discussion In this study, we presented gender-specific reference data for Chinese children and adolescents aged 5–19 years. The percentile curves generated using the LMS method can be used to determine a child’s percentile rank for whole body BMC and BMD, similar to evaluating a child’s growth Table 4 Pearson’s r values for the correlations between total body BMD and TBLH BMD by age group Age

Boys

Girls

n

r

p

n

r

p

5

66

0.762

\0.001

63

0.758

\0.001

6

85

0.824

\0.001

68

0.828

\0.001

7

36

0.772

\0.001

41

0.818

\0.001

8

66

0.823

\0.001

62

0.841

\0.001

9

68

0.833

\0.001

51

0.914

\0.001

10 11

91 70

0.867 0.860

\0.001 \0.001

71 61

0.869 0.858

\0.001 \0.001

12

55

0.886

\0.001

41

0.942

\0.001

13

28

0.877

\0.001

26

0.958

\0.001

14

41

0.981

\0.001

43

0.968

\0.001

15

34

0.974

\0.001

31

0.958

\0.001

16

41

0.970

\0.001

38

0.962

\0.001

17

39

0.937

\0.001

72

0.937

\0.001

18

38

0.978

\0.001

55

0.930

\0.001

19

19

0.934

\0.001

41

0.933

\0.001

n number of subjects

using height and weight growth charts. In addition, Z score could be reported based on the normal reference database established. China is a large country of high population migration, so it is difficult to distinguish differences between southern and northern Chinese children and adolescents. The subjects were enrolled only from the southern part of China. No previous reports have shown BMD and BMC differences between southern and northern Chinese children and adolescents. A wider range of subjects covering broader geographic regions may be required. In this study, participants were between 3rd and 97th percentile for height and weight on current standardized growth charts, roughly consistent with the mean values for Chinese children and adolescents. Therefore, we believe the data presented can reflect BMD and BMC reference values for a healthy population but do not necessarily represent optimal values. Various studies have reported that ethnic factors are significant determinants of bone mineral accrual [12–17] during childhood. Wang et al. [15] reported significant ethnic differences in bone mass in a cross-sectional study of 423 Asian, Black, Hispanic, and non-Hispanic White American youths aged 9–25 years. Boot et al. [12] found ethnicity had a significant influence on TB BMD in girls, but not in boys, after studying 500 children and adolescents aged 4–20 years from various ethnic backgrounds, including Caucasian, Black and Asian. At most age groups in our study, boys and girls had significantly lower TB BMD and BMC compared with children from Poland and the Netherlands [17, 18], but higher TB BMD and BMC as

Table 5 Percentile distribution of BMD (g/cm2) for total body and subcranial skeleton by age group in boys Age

n

Subcranial skeletona

Total body Min

3rd

25th

50th

75th

97th

Max

Min

3rd

25th

50th

75th

97th

Max

5

66

0.683

0.686

0.739

0.767

0.798

0.878

0.882

0.519

0.520

0.570

0.595

0.632

0.671

0.689

6

85

0.704

0.710

0.751

0.785

0.816

0.871

0.937

0.505

0.547

0.583

0.616

0.654

0.711

0.740

7

36

0.722

0.722

0.759

0.788

0.831

0.904

0.905

0.560

0.560

0.613

0.630

0.660

0.732

0.732

8

66

0.709

0.729

0.791

0.822

0.841

0.901

0.910

0.580

0.586

0.641

0.669

0.686

0.732

0.766

9

68

0.707

0.716

0.785

0.813

0.850

0.902

0.915

0.599

0.601

0.645

0.684

0.709

0.773

0.793

10

71

0.719

0.739

0.812

0.845

0.875

0.930

0.958

0.593

0.624

0.684

0.716

0.749

0.829

0.838

11

70

0.760

0.764

0.830

0.865

0.913

0.996

1.001

0.636

0.652

0.704

0.742

0.792

0.881

0.895

12

55

0.754

0.774

0.818

0.860

0.900

0.976

0.997

0.647

0.663

0.711

0.743

0.793

0.885

0.896

13

28

0.782

0.782

0.842

0.896

0.945

0.997

0.997

0.715

0.715

0.762

0.789

0.847

0.941

0.941

14

41

0.770

0.778

0.914

0.975

1.044

1.204

1.219

0.689

0.689

0.852

0.907

0.969

1.114

1.121

15

34

0.865

0.865

0.927

1.024

1.072

1.203

1.206

0.778

0.779

0.862

0.939

0.992

1.133

1.137

16

41

0.862

0.871

1.045

1.073

1.108

1.215

1.216

0.768

0.774

0.946

0.986

1.038

1.139

1.142

17

39

0.926

0.93

1.009

1.071

1.138

1.221

1.231

0.841

0.841

0.925

0.986

1.031

1.153

1.158

18

38

0.859

0.868

1.059

1.093

1.206

1.316

1.319

0.836

0.838

0.970

1.006

1.103

1.204

1.205

19

19

1.021

1.021

1.096

1.189

1.164

1.200

1.200

0.935

0.935

0.981

1.029

1.071

1.101

1.101

BMD bone mineral density, ROI region of interest a

Total body with the head ROI removed from analysis

123

63

68

41

62

51

91

61

41

26

43

31 38

72

55

41

5

6

7

8

9

10

11

12

13

14

15 16

17

18

19

0.862

0.909

0.895

0.887 0.895

0.810

0.747

0.765

0.753

0.719

0.705

0.713

0.711

0.672

0.651

Min

Total body

0.877

0.921

0.918

0.887 0.902

0.828

0.747

0.768

0.774

0.743

0.705

0.726

0.718

0.692

0.695

3rd

0.981

1.004

0.992

0.968 0.993

0.956

0.890

0.833

0.832

0.793

0.783

0.770

0.766

0.750

0.730

25th

a

Total body with the head ROI removed from analysis

BMD bone mineral density, ROI region of interest

n

Age

1.073

1.049

1.045

1.009 1.035

1.007

0.920

0.891

0.870

0.823

0.824

0.819

0.793

0.779

0.756

50th

1.105

1.110

1.086

1.064 1.111

1.081

0.979

0.952

0.914

0.868

0.850

0.844

0.823

0.799

0.788

75th

1.228

1.265

1.220

1.194 1.235

1.152

1.087

1.042

0.999

0.937

0.944

0.894

0.899

0.862

0.849

97th

1.237

1.286

1.267

1.194 1.243

1.155

1.087

1.044

1.033

0.955

0.961

0.916

0.909

0.876

0.855

Max

0.754

0.736

0.796

0.768 0.799

0.736

0.681

0.648

0.661

0.578

0.562

0.587

0.578

0.560

0.514

Min

0.764

0.753

1.157

0.768 0.804

0.747

0.681

0.655

0.664

0.612

0.573

0.592

0.581

0.560

0.524

3rd

Subcranial skeletona

Table 6 Percentile distribution of BMD (g/cm2) for total body and subcranial skeleton by age group in girls

0.865

0.863

0.797

0.861 0.862

0.852

0.787

0.731

0.730

0.673

0.650

0.632

0.612

0.587

0.567

25th

0.925

0.919

0.870

0.902 0.904

0.892

0.832

0.783

0.765

0.711

0.685

0.670

0.637

0.607

0.590

50th

0.967

0.968

0.911

0.941 0.975

0.966

0.862

0.839

0.806

0.744

0.719

0.708

0.664

0.643

0.624

75th

1.085

1.136

0.959

1.108 1.117

1.025

1.001

0.942

0.929

0.822

0.791

0.762

0.725

0.707

0.672

97th

1.092

1.200

1.064

1.108 1.134

1.027

1.001

0.951

0.943

0.862

0.792

0.766

0.734

0.737

0.675

Max

J Bone Miner Metab (2013) 31:304–314 309

123

123

66 85

36

66

68

71

70

55

35

41

34

41

39

38

19

5 6

7

8

9

10

11

12

13

14

15

16

17

18

19

2033.21

1631.19

1647.22

1378.28

1443.55

1000.62

1072.00

819.42

752.52

641.63

624.38

596.03

556.77

390.49 443.32

2033.21

1653.64

1670.42

1468.85

1443.97

1022.47

1073.49

881.09

819.93

740.67

694.97

637.91

557.39

455.07 522.83

2276.61

2239.40

2096.24

2108.64

1751.77

1672.58

1190.37

1056.06

1052.59

925.84

801.28

800.57

657.47

559.74 600.91

a

Total body with the head ROI removed from analysis

2547.49

2388.02

2402.46

2290.92

1997.66

1865.65

1403.07

1169.97

1147.11

1059.79

924.81

863.07

748.80

617.47 684.15

50th

2856.23

2774.76

2573.19

2566.13

2342.07

2191.50

1744.58

1388.73

1303.74

1186.60

1060.47

943.87

831.65

711.22 782.90

75th

3003.69

3279.74

2957.00

2895.22

2794.42

2896.75

2139.07

1829.54

1676.17

1429.05

1226.10

1137.69

1137.59

812.33 9334.56

97th

3003.69

3301.48

2700.00

2903.18

2801.06

2928.52

2152.99

1887.11

1725.72

1494.27

1237.82

1282.26

1143.33

830.61 1076.47

Max

1598.53

1395.81

1263.62

1051.31

1128.27

739.94

708.12

533.59

513.84

395.70

378.64

372.64

301.18

194.66 222.64

1598.53

1398.16

1290.05

1122.31

1128.42

741.38

713.65

602.92

541.67

470.32

432.94

382.77

303.78

243.22 270.42

3rd

Min

25th

Min

3rd

Subcranial skeletona

Total body

BMC bone mineral content, ROI region of interest

n

Age

Table 7 Percentile distribution of BMC (g) for total body and subcranial skeleton by age group in boys

1821.30

1813.57

1728.11

1674.43

1432.90

1354.14

915.13

742.99

712.70

630.80

530.36

485.39

401.58

312.12 340.09

25th

2080.37

1920.39

1923.02

1857.67

1638.48

1556.06

1083.23

839.80

808.35

736.41

624.02

558.20

453.68

366.71 406.74

50th

2325.11

2270.07

2070.15

2080.34

1915.92

1800.62

1367.49

1035.52

944.49

834.15

712.10

624.87

535.70

416.90 475.90

75th

2488.60

2690.80

2500.53

2425.85

2380.50

2445.37

1804.77

1475.46

1318.42

1092.91

905.17

798.68

791.75

504.88 629.05

97th

2488.60

2691.36

2502.00

2449.46

2387.56

2493.67

1819.59

1541.80

1352.17

1187.05

949.64

904.15

796.68

529.93 675.03

Max

310 J Bone Miner Metab (2013) 31:304–314

63 68

41

62

51

91

61

49

39

43

31

38

72

55

41

5 6

7

8

9

10

11

12

13

14

15

16

17

18

19

1345.41

1457.1

1342.27

1389.60

1489.48

1302.65

960.21

844.99

716.74

606.38

525.98

591.67

552.59

378.14 480.36

1384.74

1523.75

1510.5

1420.00

1489.48

1323.16

1020.8

904.35

772.7

712.59

620.09

600.44

558.52

428.64 488.98

1789.13

1779.48

1781.31

1707.65

1717.81

1610.53

1453.62

1169.7

1092.11

867.82

802.98

747.46

656.45

538.41 588.89

a

Total body with the head ROI removed from analysis

2024.54

1929.71

1913.47

1953.01

1977.66

1784.41

1623.02

1320.06

1192.46

992.73

905.97

847.97

715.11

587.28 643.94

50th

2446.10

2164.15

2121.09

2183.58

2110.77

2115.07

1912.13

1533.49

1338.70

1132.22

1003.43

957.77

813.25

678.30 732.39

75th

2859.37

2936.21

2721.95

2639.2

3004.67

2613.13

2338.67

2060.16

1872.90

1416.06

1263.25

1229.49

1091.78

774.79 901.33

97th

2897.73

2960.63

2778.32

2664.90

3004.67

2655.66

2347.25

2118.49

2003.92

1559.05

1296.00

1303.57

1119.02

782.37 1048.19

Max

954.77

1008.49

1060.97

1053.53

1107.92

1013.02

728.57

570.51

480.81

380.22

328.53

370.04

324.61

204.80 247.30

993.79

1063.28

1117.79

1068.37

1107.92

1031.23

770.60

620.13

546.74

470.45

380.83

383.48

330.11

221.13 263.06

3rd

Min

25th

Min

3rd

Subcranial skeletona

Total body

BMC bone mineral content, ROI region of interest

n

Age

Table 8 Percentile distribution of BMC (g) for total body and subcranial skeleton by age group in girls

1360.21

1349.45

1356.98

1304.67

1316.53

1261.97

1104.53

857.77

757.87

584.49

529.70

479.77

402.72

300.45 343.41

25th

1540.62

1519.65

1462.61

1486.24

1504.26

1369.17

1289.97

997.01

907.98

705.24

609.60

542.69

444.82

343.7 384.01

50th

1745.73

1678.03

1624.84

1688.10

1674.59

1664.67

1432.61

1225.78

1007.35

806.81

708.04

642.70

531.55

404.54 457.65

75th

2324.81

2425.76

2212.90

2135.52

2520.31

2135.4

1870.92

1659.96

1534.7

1086.55

895.92

867.85

716.65

508.95 626.96

97th

2363.14

2463.78

2260.74

2161.79

2520.31

2169.57

1874.82

1691.83

1592.18

1219.38

902.90

986.04

740.45

528.19 705.38

Max

J Bone Miner Metab (2013) 31:304–314 311

123

312

J Bone Miner Metab (2013) 31:304–314

Fig. 1 Height percentile curves adjusted for age and bone area (BA) percentile curves adjusted for height. Solid lines from the upper one represent the 97th, 75th, 50th, 25th, and 3rd percentiles

compared to children from India [19]. It is generally accepted that different normal reference curves for different ethnic background are necessary for the accurate representation of specific ethnic group. A significant increase in BMC/BMD for TB and TBLH was found during growth. Our findings are similar to those in other studies [8, 20–27]. Reports of gender difference in BMD and BMC during childhood and adolescents are largely inconsistent [22, 24, 28]. In our study, we found significant gender differences starting at 18 years of age in TB BMD, and 16 years of age in TBLH BMD. Girls have higher BMC in TB and TBLH than boys in the 12-15 age group, and boys have higher BMC in TB and TBLH from 16 years of age onwards. These results may reflect a difference in age of onset of puberty in males and females, and the later increased height in males. In a cross-sectional study, Zanchetta et al. [22] found gender difference concerning TB BMC maximum mean value in Argentinian children (2–20 years) starting at age 16, and becoming significant at age 17. In a study of Canadian children aged 8–17 years, Faulkner et al. [24] found no gender differences until age 16 for TB BMD and age 14 for BMC. Maynard et al. [28] reported that significant sex difference

123

were found at 15–18 years in TB BMC and 16–18 years in TB BMD in White children. In general, the normal reference database for pediatric DXA should be gender-specific. The influence of head in TB BMD and BMC needs to be taken into consideration when assessing bone density in growing children. There is growing evidence that TBLH measurements should be the standard when assessing TB bone. Various studies have already published a pediatric BMC and BMD normative database excluding the head region [23, 27, 29, 30]. Willing et al. [29] revealed that the BMC of the head comprised a greater percentage of whole body BMC in small children compared to taller children. Taylor et al. [30] showed that in normal children aged 2–9 years, TBLH BMD was better predicted by age than TB BMD and that head BMD accounted for most of the variance in TB BMD and age accounted for \50 % of the variance in the head BMD. The results of our study further verified the contribution of the head region in TB BMD and BMC. TBLH BMD may be a better parameter than TB BMD in terms of explaining the real skeletal status for children and adolescents. DXA measurements are 2-dimensional and BMD is an areal (g/cm2) rather than a volumetric bone density. BMD

J Bone Miner Metab (2013) 31:304–314

313

Fig. 2 Bone mineral content (BMC) percentile curves adjusted for bone area (BA). Solid lines from the upper one represent the 97th, 75th, 50th, 25th, and 3rd percentiles

is affected by the subject’s size, and tends to underestimate bone density in small subjects and overestimate in larger subjects [31]. Various approaches could correct the size effects. Molgaard recommended a 3-step method to adjust height-for-age, bone area (BA)-for-height, and BMC-forBA, to discriminate 3 possible clinical situations in which a low bone mass may occur as ‘short’ bones, ‘narrow’ bones, and ‘light’ bones [32]. In our study, we adopted the method of Molgaard et al. to develop percentile curves for bone size and BMC for use in addition to normative DXA data. Our study might have some limitations related to study design. First of all, it was a cross-sectional study and longitudinal data need to be obtained. Secondly, other limitations should be pointed out concerning DXA. DXA devices from different manufacturers might not give identical results, due to differences in scan modes, software version [33], and the calibration methods adopted by different DXA manufacturers [34, 35]. Our reference data is limited only to results derived from the Lunar Prodigy DXA densitometer. In addition, attention should be paid when using provided normative values due to the potential differences in genetic, nutrition, and physical activities between the population being assessed and the population used to establish such normative values.

This study describes complete DXA TB normal reference data for Chinese children and adolescents aged 5–19 years. The results of this study may be used to establish a normal reference database and can be used in assessment of children and adolescents with bone disorders in China. Acknowledgments The authors would like to express their gratitude to all participating children and their parents. We are grateful to Dr Qi Zhou, GE Healthcare Shanghai and Dr Jing Xiang, First Hospital of Jiaxing for their useful comments and suggestions. We also thank the staff members of the Department of Nuclear Medicine, First Affiliated Hospital of Jinan University for excellent technical support. Conflict of interest None of the authors have any personal or financial conflicts of interest.

References 1. Bogunovic L, Doyle SM, Vogiatzi MG (2009) Measurement of bone density in the pediatric population. Curr Opin Pediatr 21:77–82 2. Gordon CM (2005) Evaluation of bone density in children. Curr Opin Endocrinol Diabetes 12:444–451

123

314 3. Bachrach LK (2005) Osteoporosis and measurement of bone mass in children and adolescents. Endocrinol Metab Clin North Am 34:521–535 4. Khan AA, Bachrach L, Brown JP, Hanley DA, Josse RG, Kendler DL, Leib ES, Lentle BC, Leslie WD, Lewiecki EM, Miller PD, Nicholson RL, O’Brien C, Olszynski WP, Theriault MY, Watts NB, Canadian Panel of the International Society of Clinical Densitometry (2004) Standards and guidelines for performing central dual-energy x-ray absorptiometry in premenopausal women, men, and children. J Clin Densitom 7:51–64 5. Ekbote VH, Khadilkar AV, Chiplonkar SA, Khadilkar VV (2011) Determinants of bone mineral content and bone area in Indian preschool children. J Bone Miner Metab 29:334–341 6. Baim S, Leonard MB, Bianchi ML, Hans DB, Kalkwarf HJ, Langman CB, Rauch F (2008) Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom 11:6–21 7. Gordon CM, Bachrach LK, Carpenter TO, Crabtree N, El-Hajj Fuleihan G, Kutilek S, Lorenc RS, Tosi LL, Ward KA, Ward LM, Kalkwarf HJ (2008) Dual energy X-ray absorptiometry interpretation and reporting in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom 11:43–58 8. Xu H, Chen JX, Gong J, Zhang TM, Wu QL, Yuan ZM, Wang JP (2008) Normal reference for bone density in healthy Chinese children. J Clin Densitom 10:266–275 9. Li H, Ji CY, Zong XN, Zhang YQ (2009) Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years. Zhonghua Er Ke Za Zhi 47:487–492 10. Ministry of Education of the People’s Republic of China (2007) Report on the physical fitness and health surveillance of Chinese school students. Higher Education Press, Beijing 11. Cole TJ, Green PJ (1992) Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 11:1305–1319 12. Boot AM, de Ridder MA, Pols HA, Krenning EP, de Muinck Keizer-Schrama SM (1997) Bone mineral density in children and adolescents: relation to puberty, calcium intake, and physical activity. J Clin Endocrinol Metab 82:57–62 13. Nelson DA, Simpson PM, Johnson CC, Barondess DA, Kleerekoper M (1997) The accumulation of whole body skeletal mass in third- and fourth-grade children: effects of age, gender, ethnicity, and body composition. Bone 20:73–78 14. Crabtree NJ, Oldroyd B, Truscott JG, Fordham JN, Kibirige M, Fewtrell M, Gordon I, Shaw NJ (2005) UK paediatric DXA reference data (GE Lunar Prodigy): effects of ethnicity, gender, and pubertal status. Bone 36:S42 15. Wang MC, Aguirre M, Bhudhikanok GS, Kendall CG, Kirsch S, Marcus R, Bachrach LK (1997) Bone mass and hip axis length in healthy Asian, black, Hispanic, and white American youths. J Bone Miner Res 12:1922–1935 16. Bachrach LK, Hastie T, Wang MC, Narasimhan B, Marcus R (1999) Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab 84:4702–4712 17. Kalkwarf HJ, Zemel BS, Gilsanz V, Lappe JM, Horlick M, Oberfield S, Mahboubi S, Fan B, Frederick MM, Winer K, Shepherd JA (2007) The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab 92:2087–2099 18. Pludowski P, Matusik H, Olszaniecka M, Lebiedowski M, Lorenc RS (2005) Reference values for the indicators of skeletal and

123

J Bone Miner Metab (2013) 31:304–314

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

muscular status of healthy Polish children. J Clin Densitom 8:164–177 Khadilkar AV, Sanwalka NJ, Chiplonkar SA, Khadilkar VV, Mughal MZ (2011) Normative data and percentile curves for Dual Energy X-ray Absorptiometry in healthy Indian girls and boys aged 5–17 years. Bone 4:810–819 Ward KA, Ashby RL, Roberts SA, Adams JE, Zulf Mughal M (1997) UK reference data for the Hologic QDR Discovery dualenergy x ray absorptiometry scanner in healthy children and young adults aged 6–17 years. Arch Dis Child 92:53–59 Molgaard C, Thomsen BL, Michaelsen KF (1999) Whole body bone mineral accretion in healthy children and adolescents. Arch Dis Child 81:10–15 Zanchetta JR, Plotkin H, Alvarez FML (1995) Bone mass in children: normative values for the 2–20-year-old population. Bone 16:S393–S399 Arabi A, Nabulsi M, Maalouf J, Choucair M, Khalife´ H, Vieth R, El-Hajj Fuleihan G (2004) Bone mineral density by age, gender, pubertal stages, and socioeconomic status in healthy Lebanese children and adolescents. Bone 35:1169–1179 Faulkner RA, Bailey DA, Drinkwater DT, McKay HA, Arnold C, Wilkinson AA (1996) Bone densitometry in Canadian children 8–17 years of age. Calcif Tissue Int 59:344–351 Goksen D, Darcan S, Coker M, Kose T (2006) Bone mineral density of healthy Turkish children and adolescents. J Clin Densitom 9:84–90 Binkley TL, Specker BL, Wittig TA (2002) Centile curves for bone densitometry measurements in healthy males and females ages 5–22 yr. J Clin Densitom 5:343–353 Lazcano-Ponce E, Tamayo J, Cruz-Valdez A, Dı´az R, Herna´ndez B, Del Cueto R, Herna´ndez-Avila M (2003) Peak bone mineral area density and determinants among females aged 9 to 24 years in Mexico. Osteoporos Int 14:539–547 Maynard LM, Guo SS, Chumlea WC, Roche AF, Wisemandle WA, Zeller CM, Towne B, Siervogel RM (1998) Total-body and regional bone mineral content and areal bone mineral density in children aged 8–18 y: the Fels Longitudinal Study. Am J Clin Nutr 68:1111–1117 Willing MC, Torner JC, Burns TL, Janz KF, Marshall TA, Gilmore J, Warren JJ, Levy SM (2005) Percentile distributions of bone measurements in Iowa children: the Iowa Bone Development Study. J Clin Densitom 8:39–47 Taylor A, Konrad PT, Norman ME, Harcke HT (1997) Total body bone mineral density in young children: influence of head bone mineral density. J Bone Miner Res 12:652–655 Fewtrell MS, British Paediatric & Adolescent Bone Group (2003) Bone densitometry in children assessed by dual x ray absorptiometry: uses and pitfalls. Arch Dis Child 88:795–798 Mølgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF (1997) Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 76:9–15 Laskey MA, Prentice A (1999) Comparison of adult and paediatric spine and whole body software for the Lunar dual energy X-ray absorptiometer. Br J Radiol 72:967–976 Tothill P, Hannan WJ (2002) Bone mineral and soft tissue measurements by dual-energy X-ray absorptiometry during growth. Bone 31:492–496 Tothill P, Avenell A, Love J, Reid DM (1994) Comparisons between Hologic, Lunar and Norland dual-energy X-ray absorptiometers and other techniques used for whole-body soft tissue measurements. Eur J Clin Nutr 48:781–794