Calcified Tissue International

, Volume 88, Issue 4, pp 281–293

Bone Mass and Bone Size in Pre- or Early Pubertal 10-Year-Old Black and White South African Children and Their Parents

Authors

    • MRC Mineral Metabolism Research Unit, Department of Paediatrics, Chris Hani Baragwanath HospitalUniversity of the Witwatersrand
  • S. A. Norris
    • MRC Mineral Metabolism Research Unit, Department of Paediatrics, Chris Hani Baragwanath HospitalUniversity of the Witwatersrand
  • N. Cameron
    • Centre for Global Health and Human DevelopmentLoughborough University
  • J. M. Pettifor
    • MRC Mineral Metabolism Research Unit, Department of Paediatrics, Chris Hani Baragwanath HospitalUniversity of the Witwatersrand
Original Research

DOI: 10.1007/s00223-011-9460-x

Cite this article as:
Vidulich, L., Norris, S.A., Cameron, N. et al. Calcif Tissue Int (2011) 88: 281. doi:10.1007/s00223-011-9460-x

Abstract

Genetic factors are thought to maintain bone mass in socioeconomically disadvantaged black South Africans. We compared bone mass between environmentally disadvantaged black and advantaged white children and their parents, after determining the most appropriate method by which to correct bone mineral content (BMC) for size. We collected data from 419 healthy black and white children of mean age 10.6 years (range 10.0–10.9), 406 biological mothers, and 100 biological fathers. Whole-body, femoral neck, lumbar spine, and mid- and distal one-third of radius bone area (BA) and BMC were measured by dual-energy X-ray absorptiometry. Power coefficients (PCs) were calculated from the linear-regression analyses of ln(BMC) on ln(BA) and used to correct site-specific BMC for bone size differences. Heritability (½h2, %) by maternal and paternal descent was estimated by regressing children’s Z scores on parents’ Z scores. Correcting BMC for height, weight, and BAPC accounted for the greatest variance of BMC at all skeletal sites. In so doing, BMC in blacks was up to 2.6 times greater at the femoral neck and lumbar spine. Maternal and paternal heritability was estimated to be ~30% in both black and white subjects. These results may in part explain the lower prevalence of fragility fractures at the hip in black South African children when compared to whites. Heritability was comparable between environmentally disadvantaged black and advantaged white South African children and similar to that reported for Caucasians in other parts of the world.

Keywords

Bone densitometryPopulation studyAssociationSouth AfricaChildrenEthnicity

Populations subjected to environmental factors known to negatively influence bone mass are expected to have lower bone mass, higher fragility fracture rates, and lower heritability estimates. Black South Africans are subject to poor growth and nutrition [1], low dietary calcium intake [2], and little physical activity [3, 4] yet have higher bone mass at the femoral neck [5, 6] and lower fracture rates [79]. Genetic factors, which account for a major proportion of bone mass variance in adults [10], adolescents [11], and children [12], are thought to maintain bone mass in black South Africans in the face of these adverse environmental factors. Yet, assessment of heritability of bone mass and bone size by way of parent–child associations has not been previously explored in this population.

Dual-energy X-ray absorptiometry (DXA) remains the most widely used technique for the measurement of bone mass in both adult [13] and pediatric [13, 14] populations and was used in this study. DXA measurements, their analyses, and interpretation are dependent on size-related variables such as age, body size (height and weight), and bone volume [15] and on skeletal maturity, ethnicity, and body composition [16, 17].

There is no standard way to correct BMC or areal BMD data for changes in skeletal size; they have been corrected for varying combinations of body size, bone size, bone area, pubertal stage, skeletal maturity, and body composition [16]. The many different methods used make the interpretation of uncorrected and corrected DXA data and the objective comparisons between studies, populations, and age groups very complex, confusing, and potentially erroneous [13].

To address these concerns, Katzman et al. [18] and Carter et al. [19] proposed measurements that are less dependent on size by mathematically converting bone mineral content (BMC) to a three-dimensional estimate of volumetric bone mineral density (BMD) or bone mineral apparent density (BMAD). Bones were assumed to be shaped as cubes, and the following formulae were applied to calculate BMAD at the whole body [BMC/(BA2/height)], femoral neck, mid-forearm (BMC/BA2), and lumbar spine (BMC/BA1.5). Kröger et al. [20] applied a similar concept, assuming bones (vertebral bodies, femoral shaft and neck) to be shaped as cylinders and applying the formula BMAD = (BMC){4/[π(bone width)]}. Similarly, Lu et al. [21] assumed the femoral neck, mid-third of the femoral shaft, and the four lumbar vertebral bodies to be cylinders and used bone width (d) and height (h) to calculate bone volume [π(d/2)2 × h]. All methods, however, calculate coefficients by assuming that bones are shaped as cubes or cylinders, which does not necessarily hold true in groups differing in ethnicity, age, and sex [22].

Prentice et al. [22] proposed a method that calculated population-specific power coefficients (PCs) and then corrected BMC for bone area (BAPC), height, and weight. This method allows BMC to be custom-corrected for size for each ethnic and sex group and each skeletal site.

Therefore, the first aim of this study was to compare BMC corrected for BAPC, height, and weight [22] against BMC corrected for other combinations of height, weight, and/or BA in black and white children and their parents. The second aim of the study was to explore the associations of BMC and bone size between black and white children and their parents in order to obtain an estimate of heritability.

Materials and Methods

Subjects

Subjects were 419 healthy children stratified by ethnicity and gender (135 black girls, 63 white girls, 154 black boys, 67 white boys) of mean age 10.6 years (range 10.0–10.9) who formed part of a longitudinal cohort of children born in Johannesburg during 1990 (the Bone Health subcohort of the Birth to Twenty study) and whose growth and development have been tracked since birth. Subjects with chronic illness (such as juvenile idiopathic arthritis, epilepsy, or asthma) or on medication known to affect growth or bone mass development were excluded from the study (n = 4). Of the parents of the 419 children, we collected maternal data from 406 biological mothers (280 black mothers, 126 white mothers) of median age 37 years and paternal data from 100 biological fathers (53 black fathers, 47 white fathers) of median age 42 years. Many children were no longer living with their fathers, while other fathers were not able to make themselves available for DXA scans for a number of reasons, including work commitments. Both maternal and paternal data were available for 88 children. The study protocol was approved by the Committee for Research on Human Subjects of the University of the Witwatersrand, Johannesburg, and the Ethical Advisory Committee of Loughborough University, UK. Guardians gave written informed consent and the children written assent to be studied.

Anthropometry

Height was measured to the last completed 1 mm using a wall-mounted stadiometer (Holtain, Crosswell, UK) and weight to the nearest completed 0.1 kg using a digital electronic instrument (Dismed), using standardized protocols [23]. Both instruments were regularly calibrated, and subjects wore minimal clothing when being weighed.

Maturity

Sexual maturity was self-assessed as pubic hair development in boys and girls, using the Tanner scaling technique [24, 25]. In addition, skeletal maturity was assessed by scoring bone age from hand radiographs using the Tanner–Whitehouse bone-specific scoring technique (TWII20) [26].

Socioeconomic Questionnaire

Primary caregivers answered questions about their social and economic status. This questionnaire had been modified appropriately for a South African population and previously validated [27]. The socioeconomic score was formulated from the presence or absence of 13 asset indicators: house type, electricity, indoor flushing toilet, indoor running water, refuse removal, television, digital satellite television, motor vehicle, refrigerator, microwave, washing machine, video machine, and telephone.

DXA

Children’s and their parents’ BA and BMC of the whole body including and excluding the head (WB), femoral neck (FN), lumbar spine (LS, L1–L4), mid-radius (MR), and distal one-third of the radius (DR) were scanned using a fan beam densitometer in array mode (model QDR-4500A; Hologic, Bedford, MA). Adult and children’s data were analyzed using adult software supplied by the manufacturer, version 11.2 (Hologic). To determine the densitometer’s measurement precision, a lumbar spine phantom was scanned daily. The coefficients of variations (CV) were 0.47 and 0.78% for BA and BMC, respectively. To determine operator measurement precision, 15 subjects were scanned twice and the resultant CV was <1% for both BA and BMC. Precision of measurement in the children was not assessed because of radiation concerns.

Structural Geometry of the Femoral Neck

A series of standard formulae developed by Beck and colleagues [28, 29] was used to calculate cross-sectional area (CSA, cm2) and section modulus (Z, cm3) of the femoral neck from DXA-measured BMC and BA. Assumptions were made that the fixed length of the femoral neck area was 1.5 cm, the effective density of bone in fully mineralized bone tissue was ~1.05 g/cm3, and the proportion of cortical mass was 0.6. The standard formulae included estimating femoral neck width, cross-sectional moment of inertia, endosteal diameter, cross-sectional area, trabecular porosity, mean cortical thickness, and buckling ratio.

Statistics

Statistica (data analysis software system), version 6 (StatSoft, Tulsa, OK), was used to analyze data sets of children and their parents and the associations between them. Data sets included age, bone age (in children), height, weight, and BA and BMC of the whole body, femoral neck, lumbar spine, mid- and distal one-third of the radius. All data are reported as means and standard errors of the mean. Probability values <0.05 were considered significant for all tests.

PCs were derived from the linear-regression analyses of ln(BMC) on ln(BA). These regression coefficients were used as the PCs to which BA were raised to correct for bone size and determined for each skeletal site for each of the eight groups in this study (black and white boys and girls, mothers and fathers). BMC was then corrected for the size-related predictors of height, weight, and/or BAPC or BA.

To allow for comparisons between size-adjusted BMC of children and those of their parents, BMC was corrected for height, weight, BAPC, and age (the latter in adults only) and then converted to Z scores. Z scores were calculated from the means and standard deviations of each of the eight groups. The associations between children’s and parents’ Z scores were assessed by way of Pearson’s correlation coefficients (r) and the calculation of heritability estimates (½h2, %). Heritability by maternal and paternal descent was estimated by regressing children’s Z scores on mother’s or father’s Z scores. The resulting regression coefficient gives the appropriate heritability estimate [12, 30, 31].

Lastly, the predictors of children’s BA and BMC were assessed by way of multiple regression analyses. Mother’s and father’s BAPC values were included separately as predictors of children’s BA in addition to ethnicity, gender, and child’s height, weight, and BAPC. Mother’s and father’s size-adjusted BMC values (corrected for height, weight, and BAPC) were included separately as predictors of children’s BMC in addition to ethnicity, gender, and child’s height, weight, and BAPC. Residual plots of all regression models showed no outlying or influential points, no deviation from the assumptions of linear relationships, and constant variances.

Results

Descriptive Characteristics of Study Population

Black families lived in households that scored significantly lower on the socioeconomic scale (median = 7, range 0–13) than white families (median = 12, range 6–13) (P < 0.05, Mann–Whitney U test).

Descriptive characteristics of the 10-year-old black and white children and their parents are shown in Table 1. Ethnic differences in anthropometry in this cohort of children have been reported elsewhere [35, 32]. Briefly, when compared to their white peers, black children and their parents were significantly shorter and black boys and their fathers were significantly lighter. At the time of the study, the children had achieved ~80% of their parents’ heights and ~50% of their parents’ weights.
Table 1

Descriptive characteristics (±SE) of 10-year old black and white girls and boys and their parents

 

Girls

P

Boys

P

Black

White

Black

White

Mean ± SE

n

Mean ± SE

n

Mean ± SE

n

Mean ± SE

n

Age (years)

10.53 ± 0.27

135

10.61 ± 0.25

63

<0.05

10.55 ± 0.27

154

10.65 ± 0.24

67

<0.05

Skeletal age (years)

10.26 ± 1.09

135

10.30 ± 1.21

63

ns

10.19 ± 1.15

154

10.36 ± 1.23

67

ns

Height (cm)

139.2 ± 6.40

135

142.7 ± 7.61

63

<0.01

137.3 ± 6.2

154

143.5 ± 7.4

67

<0.0001

Weight (kg)

34.8 ± 8.3

135

35.7 ± 8.0

63

ns

32.7 ± 6.5

154

35.9 ± 6.2

67

<0.001

Lean mass (kg)

23.9 ± 4.0

135

25.1 ± 4.3

63

ns

24.1 ± .31

154

26.9 ±3.6

67

<0.0001

Fat mass (kg)

10.1 ± 5.0

135

9.8 ± 4.4

63

ns

7.5 ± 4.0

154

8.1 ± 3.2

67

ns

Whole body less head BA (cm2)

1,049 ± 173

135

1,081 ± 183

63

ns

1,010 ± 133

154

1,095 ± 151

67

<0.0001

Whole body less head BMC (g)

741 ± 170

135

759 ± 172

63

ns

717 ± 126

154

781 ± 139

67

<0.001

Femoral neck BA (cm2)

4.05 ± 0.32

135

4.20 ± 0.29

63

<0.01

4.13 ± 0.32

153

4.33 ± 0.33

66

<0.0001

Femoral neck BMC (g)

2.78 ± 0.42

135

2.68 ± 0.45

63

ns

3.05 ± 0.39

153

3.03 ± 0.43

66

ns

Lumbar spine BA (cm2)

34.02 ± 3.49

135

34.79 ± 3.33

63

ns

34.11 ± 3.26

154

36.40 ± 4.01

67

<0.0001

Lumbar spine BMC (g)

20.72 ± 4.32

135

20.66 ± 4.17

63

ns

19.09 ± 3.02

154

21.40 ± 3.67

67

<0.0001

Mid-radius BA (cm2)

4.37 ± 0.87

135

4.27 ± 0.85

63

ns

4.49 ± 0.77

152

4.51 ± 0.80

64

ns

Mid-radius BMC (g)

1.69 ± 0.43

135

1.71 ± 0.40

63

ns

1.76 ± 0.34

152

1.87 ± 0.37

64

<0.05

Distal one-third radius BA (cm2)

2.17 ± 0.20

135

2.19 ± 0.21

63

ns

2.32 ± 0.22

152

2.32 ± 0.19

64

ns

Distal one-third radius BMC (g)

1.04 ± 0.16

135

1.06 ± 0.15

63

ns

1.09 ± 0.13

152

1.14 ± 0.12

64

<0.01

Cross-sectional area (cm2)

1.76 ± 0.27

126

1.70 ± 0.29

63

ns

1.94 ± 0.25

143

1.93 ± 0.27

66

ns

Cross-sectional area (cm2)a

1.79 ± 0.02

126

1.66 ± 0.02

63

<0.001

1.99 ± 0.02

143

1.82 ± 0.03

66

<0.0001

Section modulus (cm3)

1.12 ± 0.40

126

1.25 ± 0.44

63

<0.05

1.28 ±0.43

143

1.51 ± 0.50

66

<0.001

Section modulus (cm3)a

1.16 ± 0.03

126

1.16 ± 0.04

63

ns

1.24 ± 0.03

143

1.31 ± 0.04

66

ns

 

Mothers

P

Fathers

P

Black

White

Black

White

Mean ± SE

n

Mean ± SE

n

Mean ± SE

n

Mean ± SE

n

Age (years)

35.6 ± 4.81

280

40.2 ± 6.07

126

<0.0001

42.5 ± 7.8

53

41.9 ± 5.5

47

ns

Height (cm)

157.7 ± 5.7

280

165.2 ± 5.9

126

<0.0001

169.6 ± 6.2

53

179.6 ± 6.2

47

<0.0001

Weight (kg)

71.7 ± 14.9

280

69.4 ± 14.6

126

ns

71.4 ± 13.5

53

81.2 ± 12.0

47

<0.001

Lean mass (kg)

30.5 ± 10.5

280

25.4 ± 10.1

126

<0.0001

49.5 ± 6.4

53

58.3 ± 6.7

47

<0.0001

Fat mass (kg)

37.3 ± 5.3

280

41.3 ± 6.4

126

<0.0001

17.2 ± 7.8

53

19.9 ± 8.0

47

ns

Whole-body BA (cm2)

1,917 ± 147

278

2,003 ± 143

125

<0.0001

2,139 ± 146

53

2,330 ± 131

47

<0.0001

Whole-body BMC (g)

2,096 ± 276

278

2,221 ± 278

125

<0.0001

2,498 ± 261

53

2,716 ± 304

47

<0.001

Femoral neck BA (cm2)

4.83 ± 0.35

280

5.12 ± 0.34

126

<0.0001

5.47 ± 0.36

53

5.91 ± 0.30

47

<0.0001

Femoral neck BMC (g)

4.26 ± 0.65

280

4.09 ± 0.64

126

<0.05

4.81 ± 0.57

53

4.95 ± 0.81

47

ns

Lumbar spine BA (cm2)

42.6 ± 4.3

280

47.5 ± 4.2

125

<0.0001

49.3 ± 4.3

53

55.2 ± 4.7

47

<0.0001

Lumbar spine BMC (g)

44.4 ± 7.8

280

50.5 ± 9.1

125

<0.0001

51.2 ± 6.5

53

56.3 ± 8.5

47

<0.01

Mid-radius BA (cm2)

7.16 ± 0.99

280

7.01 ± 0.99

126

ns

9.31 ± 1.26

53

10.1 ± 1.18

47

<0.01

Mid-radius BMC (g)

4.11 ± 0.68

280

4.12 ± 0.69

126

ns

6.09 ± 1.07

53

6.73 ± 0.96

47

<0.01

Distal one-third radius BA (cm2)

2.63 ± 0.28

280

2.65 ± 0.24

126

ns

3.06 ± 0.44

53

3.12 ± 0.24

47

ns

Distal one-third radius BMC (g)

1.77 ± 0.19

280

1.83 ± 0.20

126

<0.01

2.30 ± 0.28

53

2.46 ± 0.28

47

<0.01

Cross-sectional area (cm2)

2.71 ± 0.41

280

2.60 ± 0.41

126

<0.05

3.05 ± 0.38

43

3.14 ± 0.51

47

ns

Cross-sectional area (cm2)a

2.82 ± 1.01

280

3.52 ± 1.23

126

<0.001

5.28 ± 1.97

43

7.58 ± 2.44

47

<0.0001

Section modulus (cm3)

2.73 ± 0.02

280

2.55 ± 0.04

125

<0.05

3.24 ± 0.08

43

2.97 ± 0.07

47

<0.05

Section modulus (cm3)a

3.01 ± 0.06

280

3.11 ± 0.10

125

<0.001

6.15 ± 0.39

43

6.79 ± 0.37

47

ns

BA and BMC reported in this table are not size-corrected. P values indicate ethnic differences

aFemoral neck geometry results cross-sectional area and section modulus are corrected for height and total lean mass (less head for children)

All children were pre- or early pubertal (Tanner stages 1 or 2) as determined by pubic hair development. There were no ethnic differences in sexual maturity (Fisher’s exact test) or skeletal maturity (independent t-test) within each sex.

BA and BMC

Uncorrected BA

Uncorrected BA data are shown in Table 1. BA was generally smaller in black children and their parents or, at the most, similar but never larger. At 10 years of age, children had achieved ~80% of their parental BA at the femoral neck and distal one-third of the radius, ~75% at the lumbar spine, ~60% at the whole body, and ~55% at the mid-radius.

Uncorrected BMC

Uncorrected BMC data are shown in Table 1. When compared to their white peers, uncorrected BMC was lower in black boys and their fathers at all sites except the femoral neck. Uncorrected BMC was similar in black and white girls but less in black mothers at all sites except the mid-radius. Uncorrected BMC in children had reached ~65% of parental values at the femoral neck, ~50% at the distal one-third of the radius, ~45% at the whole body, ~40% at the lumbar spine, and ~35% at the mid radius.

PCs

The calculated PCs are shown for each of the eight groups (black and white boys and girls, mothers and fathers) at each skeletal site in Table 2. Calculated PCs ranged from 0.87 to 1.83 in children and 0.43 to 1.58 in adults. They differed between blacks and whites in both children and adults at the femoral neck, between black and white adults at the distal one-third of the radius, and only between black and white mothers at the mid-radius. In addition, for the most part, PCs were significantly different from 1, 1.5, and/or 2, which have been used by different authors to adjust for differences in size.
Table 2

Power coefficients (PC ± SE) at each skeletal site in black and white children and their parents

 

Girls

Ethnic differences P

Boys

Ethnic differences P

Gender differences P

Black

n

White

n

Black

n

White

n

Black

White

Whole body less head

1.34 ± 0.02

135

1.32 ± 0.03

63

0.5749

1.28 ± 0.03

154

1.27 ± 0.04

67

0.8490

0.1046

0.3276

Femoral neck

1.18 ± 0.13d

135

1.83 ± 0.212

63

0.0010

0.87 ± 0.11a

153

1.35 ± 0.164

66

0.0160

0.0696

0.0721

Lumbar spine

1.52 ± 0.101

135

1.72 ± 0.151

63

0.1750

1.21 ± 0.094c

154

1.30 ± 0.113

67

0.5689

0.0220

0.0253

Mid-radius

1.16 ± 0.042a

135

1.09 ± 0.051a

63

0.3005

0.96 ± 0.04a

152

1.04 ± 0.05a

64

0.2499

0.0004

0.4825

Distal one-third radius

1.24 ± 0.093c

135

1.17 ± 0.11c

63

0.6214

0.81 ± 0.084a

152

1.07 ± 0.05a

64

0.0439

0.0004

0.5012

 

Mothers

Ethnic differences P

Fathers

Ethnic differences P

Black

n

White

n

Black

n

White

n

Whole body

1.39 ± 0.061

278

1.37 ± 0.102

125

0.8585

1.26 ± 0.124d

53

1.60 ± 0.183

47

0.1107

Femoral neck

0.78 ± 0.114a

280

0.94 ± 0.20c

126

0.4500

0.43 ± 0.251b

53

1.10 ± 0.46

47

0.1898

Lumbar spine

1.33 ± 0.061c

280

1.58 ± 0.111

125

0.0314

0.90 ± 0.16b

53

1.09 ± 0.21b

47

0.4671

Mid-radius

1.00 ± 0.04a

280

1.02 ± 0.06a

126

0.7810

1.07 ± 0.11b

53

1.06 ± 0.10

47

0.0591

Distal one-third radius

0.80 ± 0.052a

280

1.02 ± 0.07a

126

0.0111

0.70 ± 0.113a

53

1.16 ± 0.14d

47

0.0114

PCs were calculated from the linear-regression analyses of ln(BMC) on ln(BA). BAPC was used as a correction for BMC together with height and weight in Figs. 1 and 2. P values indicate ethnic and gender differences

Superscripts indicate whether the PC is different from 1 or 1.5. 1−4 Significantly different from 1: 1 P < 0.0001, 2 P < 0.001, 3 P < 0.01, 4 P < 0.05; a–d significantly different from 1.5: a P < 0.0001, b P < 0.001, c P < 0.01, d P < 0.05

Size-Adjusted BMC

Figures 1 and 2 illustrate how BMC values vary in black and white children and their parents when corrected for different combinations of height, weight, BA and/or BAPC at the different skeletal sites (radial and femoral neck BMC graphs not shown). Correcting BMC for height, weight, and BAPC or BA accounted for the greatest proportion of the variance in BMC at most skeletal sites. However, ethnic differences in BMC were magnified when correcting for BAPC vs. BA. That is, BMC (corrected for BAPC) was greater in black children and their parents than in their white peers at the femoral neck (all P < 0.0001) and lumbar spine (all P < 0.0001) and in black boys and fathers at the whole body (both P < 0.0001). At the femoral neck, black girls had 7% more BMC than whites when corrected for BA, height, and weight, which increased to 69% when corrected for BAPC, height, and weight. Similar increases were observed in black boys (from 8 to 64%), mothers (from 8 to 34%), and fathers (from 6 to 98%) as well as at the lumbar spine (black girls, from 4 to 85%; boys, from 3 to 34%; mothers, from 1 to 166%; fathers, from 2 to 89%). BMC was less in black girls and their mothers at the whole body (both P < 0.0001), mid-radius (girls P < 0.0001, mothers P < 0.001), and distal one-third of the radius (girls only P < 0.0001).
https://static-content.springer.com/image/art%3A10.1007%2Fs00223-011-9460-x/MediaObjects/223_2011_9460_Fig1a-b_HTML.gif
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Fig. 1

Whole-body less head (for girls and boys) and whole-body (for mothers and fathers) BMC (±SE) corrected for ln(height), ln(weight), or combinations of size-related predictors of BA, BAPC, (BAx), height (ht), and/or weight (wt) in black and white girls (a) and boys (b), mothers (c), and fathers (d). Asterisks indicate ethnic differences: * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

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Fig. 2

Lumbar spine BMC (±SE) corrected for ln(height), ln(weight), or combinations of size-related predictors of BA, BAPC, (BAx), height (ht), and/or weight (wt) in black and white girls (a), boys (b), mothers (c), and fathers (d). Asterisks indicate ethnic differences: * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Structural Geometry of the Femoral Neck

There were no ethnic differences between children or parents in uncorrected CSA. Uncorrected section modulus (Z) was significantly greater in black children and their parents (P < 0.05–0.0001). Once corrected for height and total lean mass (less head for children), CSA was significantly greater in blacks (P < 0.05–0.0001) and Z was significantly smaller in black mothers (P < 0.001) (Table 1).

Associations Between Children’s and Parents’ BMC Adjusted for Height, Weight, and BAPC

The associations between children’s and parents’ adjusted BMC Z scores assessed by way of Pearson’s correlation coefficients (r) and heritability estimates (½h2, %) are presented in Table 3. BMC Z scores of black and white children were significantly correlated with those of their mothers at all skeletal sites. Heritability by maternal or paternal descent was estimated to be ~30%. There were no significant ethnic differences in correlation coefficients or heritability estimates.
Table 3

Associations between children’s and parents’ BMC Z scores assessed by Pearson correlation coefficients (r) and heritability estimates (½h2)

 

Children vs. mothers

Girls

Boys

Ethnic differences

Gender differences

Black

White

Black

White

Girls

Boys

Black

White

r

½h2 ± SE

n

r

½h2 ± SE

n

r

½h2 ± SE

n

r

½h2 ± SE

n

P

P

P

P

Whole body

0.38a

0.39 ± 0.08

128

0.51a

0.40 ± 0.13

59

0.46a

0.40 ± 0.07

149

0.46a

0.45 ± 0.11

61

r = 0.313 ½h2 = 0.946

r = 1.000 ½h2 = 0.701

r = 0.426 ½h2 = 0.925

r = 0.728 ½h2 = 0.769

Femoral neck

0.31a

0.32 ± 0.09

128

0.44a

0.43 ± 0.12

60

0.23d

0.23 ± 0.08

151

0.29d

0.32 ± 0.12

62

r = 0.344 ½h2 = 0.479

r = 0.184 ½h2 = 0.540

r = 0.478 ½h2 = 0.454

r = 0.352 ½h2 = 0.518

Lumbar spine

0.20d

0.22 ± 0.10

128

0.27d

0.29 ± 0.14

59

0.42a

0.38 ± 0.07

152

0.29d

0.34 ± 0.13

62

r = 0.645 ½h2 = 0.685

r = 0.333 ½h2 = 0.771

r = 0.543 ½h2 = 0.181

r = 0.908 ½h2 = 0.794

Mid-radius

0.48a

0.52 ± 0.08

128

0.28d

0.28 ± 0.13

60

0.27d

0.25 ± 0.08

150

0.39c

0.40 ± 0.12

60

r = 0.096 ½h2 = 0.103

r = 0.388 ½h2 = 0.311

r = 0.044 ½h2 = 0.018

r = 0.509 ½h2 = 0.499

Distal one-third radius

0.40a

0.46 ± 0.09

128

0.36c

0.35 ± 0.12

59

0.15d

0.14 ± 0.07

149

0.34d

0.38 ± 0.12

58

r = 0.772 ½h2 = 0.483

r = 0.201 ½h2 = 0.077

r = 0.026 ½h2 = 0.048

r = 0.905 ½h2 = 0.860

 

Children vs. fathers

Girls

Boys

Ethnic differences

Gender differences

Black

White

Black

White

Girls

Boys

Black

White

r

½h2 ± SE

n

r

½h2 ± SE

n

r

½h2 ± SE

n

r

½h2 ± SE

n

P

P

P

P

Whole body

0.11

0.12 ± 0.23

25

0.39

0.30 ± 0.15

24

0.28

0.31 ± 0.21

27

0.45d

0.36 ± 0.15

23

r = 0.323 ½h2 = 0.516

r = 0.515 ½h2 = 0.846

r = 0.548 ½h2 = 0.545

r = 0.816 ½h2 = 0.779

Femoral neck

0.49d

0.52 ± 0.29

25

0.38

0.32 ± 0.17

24

0.33

0.39 ± 0.22

27

−0.21

−0.18 ± 0.18

23

r = 0.656 ½h2 = 0.558

r = 0.066 ½h2 = 0.049

r = 0.513 ½h2 = 0.722

r = 0.050 ½h2 = 0.051

Lumbar spine

0.41d

0.46 ± 0.22

25

−0.03

−0.03 ± 0.21

24

0.47d

0.60 ± 0.22

28

0.49d

0.33 ± 0.13

23

r = 0.127 ½h2 = 0.114

r = 0.931 ½h2 = 0.301

r = 0.799 ½h2 = 0.654

r =0.070 ½h2 = 0.154

Mid-radius

0.33

0.32 ± 0.19

25

−0.43

−0.06 ± 0.31

24

0.43d

0.46 ± 0.19

28

0.47d

0.34 ± 0.14

22

r = 0.009 ½h2 = 0.305

r = 0.869 ½h2 = 0.616

r = 0.689 ½h2 = 0.604

r = 0.002 ½h2 = 0.248

Distal one-third radius

0.59d

0.57 ± 0.20

25

−0.17

−0.20 ± 0.24

24

0.36

0.37 ± 0.18

28

0.50d

0.26 ± 0.10

22

r = 0.005 ½h2 = 0.070

r = 0.571 ½h2 = 0.592

r = 0.304 ½h2 = 0.459

r = 0.023 ½h2 = 0.233

Z scores were calculated from the means and standard deviations of BMC adjusted for height, weight, and BAPC (PCs listed in Table 1) and age in adults. Z scores were used so that children and their parents’ data were comparative

a–d Significantly correlated: a P < 0.0001, b P < 0.001, c P < 0.01, d P < 0.05

Discussion

This study illustrates how various combinations of size-related adjustments influence DXA-measured BMC in black and white prepubertal children and their parents. Ethnic differences in BMC were dependent on ethnic differences in size. Correcting BMC for BAPC (or BA), height, and weight proved to be the combination of size-related corrections that accounted for the greatest proportion of the variance in BMC at all skeletal sites. Size-adjusted BMC (adjusted for BA) at the different sites was greater in blacks by 2–8% but by 34–166% when adjusted for BAPC. We previously reported that BMC corrected for height and weight only (excluding BA) in the same black children was ~6% greater at the femoral neck but not different at the lumbar spine [5]. In support of these latter findings, similar lumbar spine BMDs were shown in pre-, peri-, and postmenopausal black and white South African women when corrected for height only [6, 33]. Adjusting BMC for BAPC, height, and weight vs. BA, height, and weight increased ethnic differences in both adults and children at the femoral neck (in girls, from 7 to 69%; boys, 8 to 64%; mothers, 8 to 34%; fathers, 6 to 98%), unmasked ethnic differences at the lumbar spine (girls, 4% vs. 85%; boys, 3% vs. 34%; mothers, 1% vs. 166%; fathers, 2% vs. 89%), and may in part explain the 10-fold lower prevalence of femoral neck fractures in adult black South Africans compared to whites [9, 34].

DXA, histomorphometric, and radiogrammetric evidence has accumulated supporting superior bone quality and strength in black South Africans and African Americans compared to their white counterparts; the macroarchitecture of the proximal femur in blacks is characterized by narrower marrow cavities, thicker cortices, and lower buckling ratios (ratio of outer radius to cortical thickness), despite nonsignificant differences in outer bone diameter [3537]. The microarchitecture of the iliac crest in South African blacks is characterized by thicker cortical bone, less porous cortices, greater endocortical wall thickness, and greater osteoid thickness. Adults in addition have fewer canals in the cortical bone and thicker trabeculae than whites [3840]. Estimates of strength as determined by cross-sectional geometry (CSA and section modulus) at the femoral neck were greater in both South African blacks and African Americans compared to whites [35, 41]. These macro- and microarchitectural features are consistent with greater bone strength and lower fracture rates [37]. Lastly, black South Africans have been shown to have greater bone apposition and formation rates [38, 39]. Smaller bones with thicker cortices and trabeculae have also been found using high-resolution pQCT in Chinese premenopausal women at the distal radius and tibia compared to white women [42]; these findings are similar to those at the femoral neck in the comparison between our black and white South African children.

Structural differences in bone are suggested to originate in the peripubertal period because few ethnic differences in bone size and microarchitecture before puberty have been reported [43]. Our findings demonstrate that differences in various DXA measures are present between children of African and European descent by age 10, suggesting that these differences had developed prior to puberty.

It is possible that the better bone mass in black children and adults might have been due to greater weight-bearing or physical activity in which poorer people might need to engage. In fact, we had previously proposed this to be a mechanism for the greater femoral neck BMD in black South African women [6]. However, given that black 10-year-old children, who are lighter than or of similar weight as white children, also have a greater femoral neck bone mass, other explanations must be sought. Physical activity is actually lower in our black than white children [3, 4], thus excluding physical activity as a possible explanation. Thus, it appears that skeletal loading is unlikely to have contributed to the higher bone mass, and we now postulate that the differences are mainly genetically determined in otherwise unfavorable social and environmental conditions (poor growth and nutrition [1] and low dietary calcium intake [2] of black children). In support of our findings, a study conducted in individuals of African descent in the West Indies, which analyzed genetic and environmental factors influencing BMD measured by both DXA and QCT, found overall heritability of both areal and volumetric BMD to be substantial [44].

Areal BMD remains an important predictor of fracture risk. The calculation of areal BMD or another measure of apparent density, BMAD, assumes PCs to be 1 (when calculating BMD), 1.5 (when calculating BMAD at the femoral neck and mid-radius), or 2 (when calculating BMAD at the whole body). PCs calculated in this study were for the most part significantly different from each of the three values in both children and their parents, confirming that neither BMD nor BMAD reflects true volumetric bone density. It is of interest to note that the calculated PCs were generally similar for the two ethnic groups at each of the different bone sites with the exception of the femoral neck in both boys and girls and at the distal third of the radius in boys. Similar PCs suggest that three-dimensional size changes in bone associated with growth are similar at the whole body, lumbar spine, and mid-radius in the two ethnic groups.

Maternal BA and size-adjusted BMC significantly predicted their children’s BA and adjusted BMC at all skeletal sites. Heritability by maternal descent was estimated to be ~30% and similar for both black and white children. This is not the first study to demonstrate the influence of maternal genetics on the prepubertal acquisition of bone mass [12, 45], but it is the first to show similar genetic influences in BMC in both black and white prepubertal populations, despite their differences in body and bone size and environmental influences. Black South Africans, children in particular, are exposed to a number of environmental factors known to impact negatively on bone mass, such as poor growth and nutrition [1], low calcium intake [2], and little physical activity [3, 4]. Given the important contributions that diet and other environmental factors have on the phenotypic variance in bone mass or BMD, lower bone mass and heritability estimates in blacks would be expected. Lower heritability estimates have been shown before for stature in West African populations compared to European populations, which were explained by the rigors of the traditional way of life in West African surroundings [46].

In general, the possible genetic contribution to the variance of the bone mass phenotype is reported to be 50–80% at any age or in any group [47]. The bone mass phenotype in black South Africans is expressed even in pre-/early pubertal childhood. These heredity estimates in black children are comparable to those from environmentally advantaged white South African children and Caucasians from other parts of the world.

Mother–daughter estimates of heritability of BMC are usually better than mother–son estimates [12]. In the current study, this was true only at the mid- and distal one-third of the radius in black children; at all other sites no differences in heritability between male and female children were seen. It has also been suggested that estimates of maternal heritability are better than paternal estimates in both boys and girls [12]. Due to the small number of fathers, a major limitation in the current study, it was not possible to draw any conclusions from our data.

In conclusion, this study confirms that correcting BMC for height, weight, and BAPC was the combination of size-related adjustments that accounted for the greatest proportion of the variance of BMC at all skeletal sites. This combination increased ethnic differences in BMC 2.6 times at the femoral neck, unmasked ethnic differences at the lumbar spine in both adults and children, and may in part explain the lower prevalence of fragility fractures at the hip in black South Africans compared to whites [34]. Heritability by maternal descent, estimated by regressing children’s Z scores on parents Z scores, was ~30%, comparable between environmentally disadvantaged black and advantaged white South African children, and similar to that found in Caucasians from other parts of the world. It is unclear at this stage whether improvement in the adverse environmental factors in our black children would result in an increase in bone mass, even lower fracture rates, and greater heritability. The intriguing question remains as to how genetic influences maintain bone mass in the face of what are generally considered to be adverse environmental factors. These genetic influences not only have a positive effect on bone mass during childhood but also are maintained through adult life and are associated with a very low incidence of femoral neck fractures in the elderly.

Acknowledgments

We acknowledge the contributions of Saeeda Mohamed and Thabile Sibiya for their DXA measurements. The Wellcome Trust of the United Kingdom and the Medical Research Council of South Africa funded this research.

Copyright information

© Springer Science+Business Media, LLC 2011