In this cross-sectional analysis of sexual dimorphism of hip structure in 3914 peripubertal children, important sex differences were seen in hip geometry. For example, boys had wider FNs and thicker cortices, resulting in greater CSA as well as a higher bending strength reflected by CSMI, which was approximately 35% greater compared with girls. Sex differences in FNW and CSMI were greater in late vs.
early pubertal children, but this effect was largely attenuated by adjusting for height, fat mass, and lean mass. Profound changes in fat mass, and lean mass take place during puberty, which differ significantly according to sex, and skeletal development is thought to be closely related to lean mass in particular (14
). Therefore, the increase in sex differences in bone size after puberty that we observed may have arisen from functional adaptation of the skeleton to associated changes in body composition. Consistent with this possibility, Forwood et al.
), who examined DXA-derived indices of hip structure in a longitudinal study of 70 boys and 68 girls, likewise found that observed sex differences in CSA, FNW, and SM were attenuated by adjusting for height and lean mass. A strong association between changes in muscle mass and sex differences in cortical bone size at puberty has also been observed at the femur, tibia, and forearm (9
). Evidence from a prospective study of changes in hip structure of 83 boys and girls that peak accrual of lean mass during puberty precedes that of SM is consistent with the possibility that such bone changes during puberty occur secondary to increased muscle forces (17
). On the other hand, in a recent prospective study of tibial structure across puberty as assessed by pQCT in girls, growth in muscle cross-sectional area peaked 1 yr after that of tibial outer dimensions (18
Our observation that parameters related to FN size and bending strength were greater in early pubertal boys compared with girls in unadjusted analyses is also consistent with findings from Forwood et al.
). In the present study, sex differences before puberty were partly attenuated by adjusting for height fat and lean mass but were still present. These findings suggest that the wider FNs of boys compared with girls cannot be accounted for entirely by puberty and/or functional adaptation to differences in fat or lean mass. However, changes in hormonal milieu, which precede clinical puberty, may explain a proportion of the sex differences observed. Consistent with the present findings, we recently reported that humeral width relative to its length is greater in prepubertal boys compared with girls in this cohort (11
). Similarly, previous radiogrametry studies observed wider bones in boys compared with girls at all stages of development (5
Whereas CSMI was greater in boys, we found that BR was lower in girls. Unlike CSMI, the sex differences in BR was small in early pubertal boys and girls but became more pronounced as puberty progressed. These differences in BR reflect the fact that in boys, puberty leads to a greater increase in bone diameter relative to CT. Interestingly, these differences were more marked in models adjusted for height and lean and fat mass, in which the difference in CT and BR between early and late puberty was approximately twice as great in girls compared with boys. This finding of greater sex differences in adjusted models suggests that maturational status affects bone development independently of growth, possibly reflecting a direct influence of sex steroids on cellular activity of the skeleton.
We are not aware of any previous study reporting sex differences in BR in childhood at the hip or any other skeletal site. Because BR represents a ratio between FNW and CT, the lower BR in girls is at least partly accounted for by sex differences in periosteal growth. In addition, slower endocortical expansion in girls may have contributed to sex differences in BR that we observed, reflecting differences in the rate of endocortical remodeling and/or endosteal apposition. Consistent with this possibility, a previous radiogrametry study of metacarpal bones revealed evidence of endosteal apposition in pubertal girls (5
). However, equivalent changes were not observed in a previous pQCT study of the midtibia (3
), possibly reflecting the fact that endocortical changes during puberty are site specific. As for possible influences of sex steroids on endosteal apposition, our findings are also consistent with evidence that rising estrogen levels in pubertal girls have been found to correlate with endosteal apposition as assessed by tibial pQCT (7
). This effect of rising estrogen levels in late pubertal girls on endocortical surfaces appears to be mirrored by gains in trabecular bone mass, as reflected by equivalent associations observed in ALSPAC between sex, puberty, and size-corrected spinal BMD (20
). Finally, constitutional factors might exist that affect both the age of onset of puberty and hip structure, so associations that we observed between hip structure and pubertal stage are not necessarily a direct result of hormonal differences.
Although we observed that bending strength was clearly higher in late pubertal boys, BR was lower in late pubertal girls implying greater cortical stability, suggesting that greater endocortical apposition in late and postpubertal girls due to increased estrogen exposure can compensate biomechanically for their lower periosteal apposition compared with boys. However, although BR has been found to be superior to measures of bending strength in predicting hip fractures in the elderly, cortical instability may be less important in determining skeletal strength in children, in whom intact internal trabecular structure is expected to make an important contribution to resisting buckling (21
). Nonetheless, in analyses of the relationship between hip geometry and fracture risk in ALSPAC, CSMI and BR showed equivalent albeit weak associations with past history of any fracture (results not shown). Although these results suggest that hip strength around the time of puberty may be equivalent in both sexes, presumably, estrogen depletion after the menopause results in reversal of these gains in endocortical bone during puberty in girls, suggesting that the high fracture risk in elderly women compared with men (23
) has its antecedents in these differences in bone structure, which appear to be established during puberty if not before (24
In the present study, we used secondary sex characteristics as assessed by Tanner stage questionnaire to compare how maturational changes at puberty affect hip structure in boys and girls. This approach is well suited to analyzing sex differences in hip structure related to sex steroid exposure, as exemplified by the greater reduction in endosteal expansion in peripubertal girls that we observed, assumed to be related to rising estrogen levels. However, one limitation of analyzing sex differences according to puberty is that children in distinct Tanner stages may differ in other important ways that we have not been able to adjust for. In addition, when comparing boys and girls of the same age, even after adjusting for Tanner stage, girls are likely to be more advanced in terms of their skeletal maturation, as suggested by observations that girls reach peak height velocity at a slightly earlier Tanner stage as compared with boys (25
A further weakness of this study is our use of DXA- derived measures of bone structure, which has limitations in predicting three-dimensional properties such as CSMI from two-dimensional projected DXA images (13
). Whereas the same assumption for the relative proportion of trabecular to cortical bone at the femoral neck was used as in adults, bone mineralization has previously been found to vary in relation to both sex and maturational status, which we attempted to correct for based on previously published literature. However, the values used were derived from a distinct population that was approximately 2 yr younger than ours (6
) and obtained at the tibia rather than the hip. In addition, because this data analysis is cross-sectional, within-individual changes in hip structure throughout puberty may not be the same as comparing individuals of the same age at different pubertal stages.
In conclusion, on examining hip structure in a large cohort of peripubertal children, we found evidence of sexual dimorphism in hip development, characterized by greater CSMI in boys but lower BR in girls. The former differences appeared to result from more rapid periosteal bone growth in boys established in early childhood and subsequently increased throughout puberty. The lower BR in girls reflected their narrower FNs relative to CT, which we attribute to slower rates of both periosteal and endocortical expansion. Although sex differences in bending differences were mainly accounted for by those in height and fat and lean mass, those in BR were largely independent of these factors, suggesting that other factors such as sex steroids make an important contribution to sexual dimorphism of hip structure around the time of puberty.