Sex Differences and Growth-Related Adaptations in Bone Microarchitecture, Geometry, Density, and Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR-pQCT Study

Abstract

Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls' values were 2% greater than boys'. Boys showed 13% to 48% greater cortical and total bone area across growth. Load-to-strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys' superior bone size and strength compared with girls may confer them a protective advantage. However, boys' consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.

Keywords: BONE ACCRUAL; BONE ARCHITECTURE; BONE STRENGTH; GROWTH; HR-PQCT.

Figure 1

Representative HR-pQCT images at the distal tibia from a single participant across 4 years acquired at 11 (far left), 12, 13 and 14 (far right) years of age.

Figure 2

Distal tibia individual growth curves for boys (thin, black lines) and girls (thin, light grey lines) and the polynomial mixed model growth curves for boys (thick, black solid line) and girls (thick, black dashed line) for trabecular bone volume fraction (BV/TV), separation (Tb.Sp), thickness (Tb.Th) and number (Tb.N), cortical BMD (Ct.BMD), area (Ct.Ar), thickness (Ct.Th) and porosity (Ct.Po), and total BMD (Tt.BMD), area (Tt.Ar), failure load (F.Load), and ultimate stress (U.Stress). The vertical line indicates maturity offset (years from age at peak height velocity) of 0.

Figure 3

Distal radius individual growth curves for boys (thin, black lines) and girls (thin, light grey lines) and the polynomial mixed model growth curves for boys (thick, black solid line) and girls (thick, black dashed line) for trabecular bone volume fraction (BV/TV), separation (Tb.Sp), thickness (Tb.Th) and number (Tb.N), cortical BMD (Ct.BMD), area (Ct.Ar), thickness (Ct.Th) and porosity (Ct.Po), and total BMD (Tt.BMD), area (Tt.Ar), failure load (F.Load), and ultimate stress (U.Stress). The vertical line indicates maturity offset (years from age at peak height velocity) of 0.

Figure 4

Sex differences in distal tibia trabecular bone volume fraction (BV/TV), separation (Tb.Sp), thickness (Tb.Th) and number (Tb.N), cortical BMD (Ct.BMD), area (Ct.Ar), thickness (Ct.Th) and porosity (Ct.Po), and total BMD (Tt.BMD), area (Tt.Ar), failure load (F.Load), and ultimate stress (U.Stress) across maturity. The solid black line represents the mean predicted sex difference (boys - girls) accompanied by a shaded 95% confidence interval, correcting for multiple comparisons using a Bonferroni adjustment. Estimates above 0 indicate significantly greater values in boys, while estimates below zero indicate significantly greater values in girls. Confidence intervals that cross 0 indicate non-significant sex differences. The vertical line indicates maturity offset (years from age at peak height velocity) of 0.

Figure 5

Sex differences in distal radius trabecular bone volume fraction (BV/TV), separation (Tb.Sp), thickness (Tb.Th) and number (Tb.N), cortical BMD (Ct.BMD), area (Ct.Ar), thickness (Ct.Th) and porosity (Ct.Po), and total BMD (Tt.BMD), area (Tt.Ar), failure load (F.Load), and ultimate stress (U.Stress) across maturity. The solid black line represents the mean predicted sex difference (boys - girls) accompanied by a shaded 95% confidence interval, correcting for multiple comparisons using a Bonferroni adjustment. Estimates above 0 indicate significantly greater values in boys, while estimates below zero indicate significantly greater values in girls. Confidence intervals that cross 0 indicate non significant sex differences. The vertical line indicates maturity offset (years from age at peak height velocity) of 0.

Figure 6

Load to strength ratio at the distal radius. (A) displays individual data and predicted growth curves for boys (thin black lines and thick black line) and girls (thin grey lines and thick dashed line). (B) displays predicted sex differences (boys-girls) across maturity with 95% confidence intervals, correcting for multiple comparisons using a Bonferroni adjustment. Estimates above 0 indicate significantly greater values in boys, while estimates below zero indicate significantly greater values in girls. Confidence intervals that cross 0 indicate non significant sex differences.