The Saskatchewan Pediatric Bone Mineral Accrual Study: Bone mineral acquisition during the growing years

To investigate bone mineral accretion in growing children, the Saskatchewan Pediatric Bone Mineral Accrual Study was initiated in 1991. The study involves the collection of dietary and physical activity information along with anthropometric growth and maturity measurements every 6 months and dual-energy X-ray absorptiometer (DXA) bone scans of the whole body, AP lumbar spine and proximal femur taken annually, The study has now finished its 6th year and 68 males and 72 females from an original sample of 228 elementary schoolchildren are still involved, To investigate how bone mineral at clinically important sites proceeds in relation to maturation we developed distance and velocity growth curves for height and bone mineral content (BMC) for the AP lumbar spine, the femoral neck and the whole body, In both boys and girls, over 35% of total body and AP spine bone mineral and over 27% of the bone mineral at the femoral neck was laid down during the 4-year adolescent period surrounding peak linear growth velocity. The clinical significance of these values can be appreciated by consideration of the fact that as much bone mineral will be laid down during these 4 adolescent growing years as most people will lose during all of adult life.

Secular trend in the development of fatness during childhood and adolescence

This study examined the development of fatness, as indexed by skinfold thickness, in healthy Caucasian children and adolescents residing in the same location in Canada in the 1960s and the 1990s. The data comes from two longitudinal studies, conducted approximately 30 years apart, of children aged 8-16 years. The first study (1964-1973) annually measured 207 males and 140 females. The second investigation (1991-1997) repeatedly measured 113 males and 115 females. Identical measurement tools and protocols were used for height, body mass, and skinfolds. Maturational age was estimated as a measure in years from age of peak height velocity. Males from the second investigation matured significantly (P < 0.05) earlier. Multilevel regression modeling was utilized to determine developmental curves for the individuals within the two populations. When differences in height, body mass, and maturity were controlled, skinfold thicknesses of the males and females in the second study were significantly greater (P < 0.05) than age- and sex-matched peers in the first study. This was not seen in models of the BMI. The results suggest that when maturity and size were controlled, the fatness of children and adolescents increased over 30 years. (C) 2002 Wiley-Liss, Inc.

Growth hormone binding protein correlates strongly with leptin and percentage body fat in GH-deficient adults, is increased by GH replacement but does not predict IGF-I response

GH-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor (GHR) and has been shown to be closely related to body fat. This study aimed to examine the inter-relationship between GHBP, leptin and body fat, and to test the hypothesis that GHBP is modified by GH replacement in GH-deficient adults and predicts IGF-I response. Twenty adults, mean age 47 years (range 20-69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross-over to the opposite treatment. Plasma GHBP and leptin were measured at baseline and 2, 4, 8 and 12 weeks after each treatment. Whole body composition was measured at baseline by dual-energy X-ray absorptiometry (DEXA). There was a strong correlation between baseline leptin and GHBP (r = 0.88, P < 0.0001) and between baseline GHBP and percentage body fat, (r = 0.83, P < 0.0001). Mean GHBP levels were higher on GH compared with placebo, 1.53 +/- 0.28 vs 1.41 +/- 0.25 nM, P = 0.049. There was no correlation between baseline IGF-I and GHBP (r = -0.049, P = 0.84), and GHBP did not predict IGF-I response to GH replacement. The close inter-relationship between GHBP, leptin and body fat suggests a possible role for GHBP in the regulation of body composition. GHBP is increased by GH replacement in GH-deficient adults, but does not predict biochemical response to GH replacement. (C) 1999 Churchill Livingstone.

Analysis of proximal femur DXA scans in growing children: Comparisons of different protocols for cross-sectional 8-month and 7-year longitudinal data

Dual-energy X-ray absorptiometry (DXA) is a widely used method for measuring bone mineral in the growing skeleton. Because scan analysis in children offers a number of challenges, we compared DXA results using six analysis methods at the total proximal femur (PF) and five methods at the femoral neck (FN), In total we assessed 50 scans (25 boys, 25 girls) from two separate studies for cross-sectional differences in bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) and for percentage change over the short term (8 months) and long term (7 years). At the proximal femur for the short-term longitudinal analysis, there was an approximate 3.5% greater change in bone area and BMC when the global region of interest (ROI) was allowed to increase in size between years as compared with when the global ROI was held constant. Trend analysis showed a significant (p < 0.05) difference between scan analysis methods for bone area and BMC across 7 years. At the femoral neck, cross-sectional analysis using a narrower (from default) ROI, without change in location, resulted in a 12.9 and 12.6% smaller bone area and BMC, respectively (both p < 0.001), Changes in FN area and BMC over 8 months were significantly greater (2.3 %, p < 0.05) using a narrower FN rather than the default ROI, Similarly, the 7-year longitudinal data revealed that differences between scan analysis methods were greatest when the narrower FN ROI was maintained across all years (p < 0.001), For aBMD there were no significant differences in group means between analysis methods at either the PF or FN, Our findings show the need to standardize the analysis of proximal femur DXA scans in growing children.

Gender differences in bone geometry during the adolescent growth spurt

To investigate whether there are gender differences in the bone geometry of the proximal femur during the adolescent years we used an interactive computer program ?Hip Strength Analysis? developed by Beck and associates (Beck et al., Invest Radiol. 1990,25:6-18.) to derive femoral neck geometry parameters from DXA bone scans (Hologic 2000, array mode). We analyzed a longitudinal data-set collected on 70 boys and 68 girls over a seven year period. Distance and velocity curves for height were fitted for each child utilizing a cubic spline procedure and the age of peak height velocity (PHV) was determined. To control for maturational differences between children of the same chronological age and between boys and girls, section modulus (Z) an index of bending strength, cross sectional area of bone (CSA), sub-periosteal width (SPW), and BMD values at the neck and shaft of the proximal femur were determined for points on each individual?s curve at the age of PHV and one and two years on either side of peak. To control for size differences, height and weight were introduced as co-variates in the two-way analyses of variance looking at gender over time measured at the maturational age points (-2, -1, age of PHV, +1, +2). The following figure presents the results of the analyses on two variables, BMD and Z at neck and shaft regions:After the age of peak linear growth (PHV), independent of body size, there was a gender difference in BMD at the shaft but not at the neck. Section modulus at both sites indicated that male bones became significantly stronger after PHV. Underlying these maturational changes, male bones became wider (SPW) after PHV in both the neck and shaft and enclosed more material (CSA) at all maturational age points at both regions. These results call into question the emphasis on using BMD as a measure of skeletal integrity in growing children

Children and economic development: Family size, gender preferences and human capital formation - theory and Indian cases

In the light of Gary Becker's economic theory of the family, considers how economic cost and benefit factors can influence the size of families that parents decide to have. Some support for the importance of such factors is found from results of structured interviews with wives in Kondh-dominated villages in western Orissa. These results are at variance with the hypothesis of Malthus about population growth. Factors that may alter the optimal family size as development proceeds are discussed. It is found in our sampling that, on the whole, there is a preference for daughters rather than sons although this is not as strong in the Kondh-dominated villages as in poor villages in the Santal tribal belt of West Bengal. While in the Kondh-dominated villages some discrimination in access to education in favour of boys compared to girls is present, little such or no such discrimination occurs in relation to access to food and medical attention. In the villages surveyed in the West Bengal Santal tribal belt, discrimination in favour of boys is more pronounced than in the Kondh-dominated area in Orissa. While economic considerations help to explain gender discrimination between boys and girls, we find that social and cultural factors also play a major role. Parents in a similar economic situation seem to display substantially different patterns of gender discrimination between children depending on their social and cultural content. It seems that the extent to which economic theories of the family explain family preferences and behaviour depend significantly on the social and cultural context in which they are to be applied.

Growth hormone therapy in Prader-Willi Syndrome

Prader-Willi syndrome (PWS) was originally described less than 50 y ago,1 although reference to children with characteristics of the syndrome are to be found in other literature previous to this.2 Until relatively recently the diagnosis was made upon the clinical features as outlined by Holm,3 which include severe muscular hypotonia in the neonatal period leading to feeding difficulties and undernutrition, hypogonadism and later hyperphagia and obesity. Latterly the syndrome has been identified as being associated with an interstitial deletion of the q11-13 region on chromosome 15.4 In the majority of cases the deletion is in the paternally derived chromosome. In the remainder of cases there seems to be a failure to inherit the entire paternal chromosome and as a consequence both the chromosomes inherited are maternal, thus leading to maternal disomy.

Factors that affect bone mineral accrual in the adolescent growth spurt

The development of bone mass during the growing years is an important determinant for risk of osteoporosis in later life. Adequate dietary intake during the growth period may be critical in reaching bone growth potential. The Saskatchewan Bone Mineral Accrual Study (BMAS) is a longitudinal study of bone growth in Caucasian children. We have calculated the times of maximal peak bone mineral content (BMC) velocity to be 14.0 +/- 1.0 y in boys and 12.5 +/- 0.9 y in girls; bone growth is maximal similar to6 mo after peak height velocity. In the 2 y of peak skeletal growth, adolescents accumulate over 25% of adult bone. BMAS data may provide biological data on calcium requirements through application of calcium accrual values to factorial calculations of requirement. As well, our data are beginning to reveal how dietary patterns may influence attainment of bone mass during the adolescent growth spurt. Replacing milk intake by soft drinks appears to be detrimental to bone gain by girls, but not boys. Fruit and vegetable intake, providing alkalinity to bones and/or acting as a marker of a healthy diet, appears to influence BMC in adolescent girls, but not boys. The reason why these dietary factors appear to be more influential in girls than in boys may be that BMAS girls are consuming less than their requirement for calcium, while boys are above their threshold. Specific dietary and nutrient recommendations for adolescents are needed in order to ensure optimal bone growth and consolidation during this important life stage.

The 'muscle-bone unit' during the pubertal growth spurt

Mechanostat theory postulates that developmental changes in bone strength are secondary to the increasing loads imposed by larger muscle forces. Therefore, the increase in muscle strength should precede the increase in bone strength. We tested this prediction using densitometric surrogate measures of muscle force (lean body mass, LBM) and bone strength (bone mineral content, BMC) in a study on 70 boys and 68 girls who were longitudinally examined during pubertal development. On the level of the total body, the peak in LBM accrual preceded the peak in BMC accretion by an average of 0.51 years in girls and by 0.36 years in boys. In the arms, the maximal increase in LBM was followed by arm peak BMC accrual after an interval of 0.71 years in girls and 0.63 years in boys. In the lower extremities, the maximal increase in LBM was followed by peak BMC accrual after an interval of 0.22 years in girls and 0.48 years in boys. A multiple regression model revealed that total body peak LBM velocity, but not peak height velocity and sex, was independently associated with total body peak BMC velocity (r(2) = 0.50; P < 0.001). Similarly, arm and leg peak LBM velocity, but not peak height velocity and sex, were independently associated with arm and leg peak BMC velocity, respectively (r(2) = 0.61 for arms, r(2) = 0.41 for legs; P < 0.001 in both cases). These results are compatible with the view that bone development is driven by muscle development, although the data do not exclude the hypothesis that the two processes are independently determined by genetic mechanisms. (C) 2004 Elsevier Inc. All rights reserved.

Sexual dimorphism of the femoral neck during the adolescent growth spurt: a structural analysis

Before puberty, there are only small sex differences in body shape and composition. During adolescence, sexual dimorphism in bone, lean, and fat mass increases, giving rise to the greater size and strength of the male skeleton. The question remains as to whether there are sex differences in bone strength or simply differences in anthropometric dimensions. To test this, we applied hip structural analysis (HSA) to derive strength and geometric indices of the femoral neck using bone densitometry scans (DXA) from a 6-year longitudinal study in Canadian children. Seventy boys and sixty-eight girls were assessed annually for 6 consecutive years. At the femoral neck, cross-sectional area (CSA, an index of axial strength), subperiosteal width (SPW), and section modulus (Z, an index of bending strength) were determined, and data were analyzed using a hierarchical (random effects) modeling approach. Biological age (BA) was defined as years from age at peak height velocity (PHV). When BA, stature, and total-body lean mass (TB lean) were controlled, boys had significantly higher Z than girls at all maturity levels (P < 0.05). Controlling height and TB lean for CSA demonstrated a significant independent sex by BA interaction effect (P < 0.05). That is, CSA was greater in boys before PHV but higher in girls after PHV The coefficients contributing the greatest proportion to the prediction of CSA, SPW, and Z were height and lean mass. Because the significant sex difference in Z was relatively small and close to the error of measurement, we questioned its biological significance. The sex difference in bending strength was therefore explained by anthropometric differences. In contrast to recent hypotheses, we conclude that the CSA-lean ratio does not imply altered mechanosensitivity in girls because bending dominates loading at the neck, and the Z-lean ratio remained similar between the sexes throughout adolescence. That is, despite the greater CSA in girls, the bone is strategically placed to resist bending; hence, the bones of girls and boys adapt to mechanical challenges in a similar way. (C) 2004 Elsevier Inc. All rights reserved.