1. Chapter 41 Chapter 41 Bone Mineral Acquisition in Utero and During Infancy and Childhood Copyright © 2013 Elsevier Inc. All rights reserved.

2. FIGURE 41.1 Linear regression comparing PedWB and InfWB estimates of whole body bone mineral content (BMC) obtained by dual energy x-ray absorptiometry (DXA) with total carcass ash in small piglets. Source: from Brunton et al. (1997) [9]. 2

3. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.2 The whole body software (Hologic, version 12.1) results in significantly lower estimates of whole body bone mineral density (BMD) compared with version 11.2 among subjects with a body weight less than 40 kg. (A) The BMD results from the two software versions fall on the line of identify in subjects with a body weight greater than 40 kg, and the BMD results from version 12.1 are lower than the results from version 11.1 in subjects with a body weight less than 40 kg. (B) The percentage decreases in BMD estimates with the newer software (compared with the original software) are progressively larger in children of smaller body weight. Source: from Shypailo and Ellis (2005) [18]. 3

4. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.3 Ionized calcium (A) and maternal–fetal calcium gradient (B) in parathyroid hormone-related protein (PTHrP) knockout fetuses. WT: wild-type fetus; HET: heterozygote; HOM: homozygote. *p < 0.001 in HOM versus WT or HET. Source: from Kovacs et al. (1996) [124]. 4

5. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.4 Relation between vitamin D receptor genotype (BB, Bb, and bb) and lumbar spine bone mineral density (BMD), according to tertile of birth weight (low, average, or high) among 126 women ages 60–75 years. Source: from Dennison et al. (2001) [135]. 5

6. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.5 GH1 genotype, 24-hour growth hormone concentration, weight in infancy, and rates of adult bone loss. BMD: bone mineral density. GH: growth hormone. Source: data from Dennison et al. (2004) [134]. Figure from Sayer and Cooper (2005) [155]. 6

7. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.6 Relationships between neonatal birth length, birth weight, gestational age, and neonatal whole body bone mineral content (BMC) in 119 infants. Volumetric bone mineral density (BMD) was generated as BMC corrected for bone area, infant length, birth weight, and age. Source: from Javaid et al. (2004) [159]. 7

8. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.7 Illustration of potential mechanisms of how maternal caloric restriction and maternal high-fat diets may both lead to lower bone mass in offspring. MSC: mesenchymal stem cells; SNS: sympathetic nervous system; VMH: ventromedial hypothalamus. Source: from Devlin and Bouxstein (2012) [171]. 8

9. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.8 Whole body bone mineral density (BMD) (means and standard error of the mean (SE) values) in children according to the mother’s frequency of intake of milk, milk products, and calcium-rich foods at 28 weeks of gestation. Source: from Ganpule et al. (2006) [149]. 9

10. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.9 Whole body bone mineral content (BMC) in infants in the calcium-supplemented and placebo groups, stratified by quintile of maternal calcium intake. For women in the lowest quintile of calcium intake (quintile I, <600 mg/day), whole body BMC (mean ± standard error of the mean (SE)) was significantly greater in infants born to calcium-supplemented mothers. I: Calcium 64.1 ± 3.2, Placebo 55.7 ± 2.7. II: Calcium 64.3 ± 3.8, Placebo 63.1 ± 2.8; III: Calcium 62.5 ± 2.7, Placebo 62.9 ± 3.9; IV: Calcium 67.3 ± 2.4, Placebo 64.6 ± 2.7; V: Calcium 66.3 ± 3.3, Placebo 62.6 ± 2.6. Source: figure generated from data reported in Koo et al. (1999) [126]. 10

11. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.10 Total body bone mineral content (TBBMC) of Korean newborn infants in winter and summer in a population without routine vitamin D supplementation. Source: from Namgung et al. (1998) [191]. 11

12. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.11 The three levels of volumetric bone mineral density (BMD). The mineral mass (gray), which determines the material BMD and compartment BMD in trabecular (A and B) and cortical (C and D) bone, is identical (mass 1 = mass 2), but the volumes differ. The compartment volumes include marrow space (B) and osteonal canals, lacunae, and canaliculi (D); therefore, the material BMD is greater than the compartment BMD. The total BMD (E) can be applied to the entire bone, a portion of the bone (e.g., the distal end), or a section through the bone. Source: from Rauch and Schoenau (2001) [28]. 12

13. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.12 Side-to-side differences (%) in structural and density parameters in the shaft of the humerus of elite female racket sports players. CoA: cross-sectional area of the cortical bone; CoD: cortical compartment BMD; BSIt, torsional bone strength index; aBMD, areal body mineral density. Source: from Kontulainen et al. (2003) [251]. 13

14. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.13 Effect of calcium supplementation on bone mineral density (BMD) of the upper limb (defined as the distal radius or the upper limb site closest to that point) at the end of the trials and at the longest point after supplementation stopped. CI: confidence interval; SD: standard deviation; SMD: standardized mean difference. Source: from Winzenberg et al. (2006) [284]. 14

15. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.14 Relationship between serum 25(OH)D and parathyroid hormone (PTH) in healthy children and adolescents after adjustment of PTH for site demonstrating lack of inflection point in PTH values for a given value of 25(OH)D. The linear function is: serum PTH = 51.60–0.22D, where D is serum 25(OH)D. The solid line is the fitted linear function and the surrounding dashed lines represent the 95% CI around the linear function. Source: from Hill et al. (2010) [296]. 15

16. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.15 Mean changes in serum 25(OH)2D concentrations and parathyroid hormone (PTH) concentrations following 25(OH)D supplementation, according to the baseline 25(OH)D concentrations. Source: from Docio et al. (1998) [298]. * p < 0.05., ** p < 0.001. 16

17. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.16 Mean (± standard deviation (SD)) cortical compartment volumetric bone mineral density (vBMD) of the radius and tibia according to 25(OH)D concentration groups. *,** Significantly different from the vitamin D-deficient [25(OH)D < 25 nmol/L] group: *p < 0.001, **p = 0.002. Source: from Cheng et al. (2003) [297]. 17

18. Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 41.17 The relationship between femoral shaft section modulus and whole body lean mass (A) or fat mass (B) for healthy weight and overweight children and adolescents. Source: from Petit et al. (2005) [312]. 18