Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents

Abstract

More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p < 0.001) and boys (∼0.43 years, p < 0.001). Boys and girls of all ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research.

Keywords: BONE AGE; GROWTH; PEDIATRIC ENDOCRINOLOGY; POPULATION ANCESTRY; SKELETAL MATURATION.

Fig. 1

Genetic population ancestry and self-reported population ancestry, by sex. Population ancestry can be estimated using genetic analyses. The distribution of the proportion of genetic African admixture is reported for the entire BMDCS/ancillary cohort with available DNA for genetic analyses, according to self-reported population ancestry and sex. AA = African-American; Non-AA = Non-African-American.

Fig. 2

Self-reported population ancestry and relative skeletal maturation, by sex and chronologic age. Box plots showing the distribution of relative skeletal maturation (bone age minus chronologic age) by chronologic age (rounded to the nearest year) and self-reported population ancestry are shown for girls (on the left) and boys (on the right); the distributions for non-AA children are shown in blue, and the distributions for AA children in red. The dotted black horizontal line indicates a relative skeletal maturation of zero; ie, where the mean relative skeletal maturation would be if the observed values were similar to the reference values.

Fig. 3

Genetic population ancestry and relative skeletal maturation, adjusted for clinical covariates. Mixed effects regression analyses of relative skeletal maturation (defined by the difference between bone age and chronologic age), here illustrating the effect of genetically defined ancestry, after accounting for other important clinical covariates. To provide a visual demonstration of the “dose effect” of African ancestry, ancestry is modeled as a factor in this figure (but as a continuous variable in the tables). Only skeletally immature (<13 years for girls, <15 years for boys) films are included. Clinical covariates included in mixed effects regression analyses were: age, body composition (lean mass, fat mass), height, and pubertal stage.