Introduction 1 2 3 4 5 In the present study, we aimed to characterise the influence of gender and puberty on the ratio between longitudinal and periosteal growth, by exploiting this novel technique of humeral geometric analysis. In particular, we wished to determine whether, in analyses combining fracture and non-fracture controls from the study described above, gender differences exist in the ratio between width and length of the humerus, and if so whether these differences are established prior to puberty. Methods Study population http://www.alspac.bris.ac.uk 6 Measure of size at birth In the immediate post-partum stage, whilst mother and child were still in hospital, trained ALSPAC staff measured crown-heel length with the Harpenden Neonatometer (Holtain Ltd., Crosswell, UK). Alternatively, this measure was collected from clinical records for babies who were not captured by the ALSPAC staff. Measures of size at age 9.8 years 2 2 Measures of humeral dimensions 5 2 1 Fig. 1 a b The precision of measurements of humeral geometry was calculated as the coefficient of variation (CV), based on ten scans with the measures repeated five times. The CV was 2.9% [95% confidence interval (CI): 2.1–3.7] for width, 1.5% (95% CI: 1.2–1.7) for length, and 3.2% (95% CI: 2.4–4.0) for humeral AR. Other measures 7 8 Statistical analyses t Results 1 P P P Table 1 a   Boys Girls   N N P N N P P P Mean SD Mean SD Mean SD Mean SD b 50.9 1.5 50.9 1.5 0.995 50.6 1.5 50.7 1.5 0.658 <0.001 0.316 Age at DXA (years) 9.8 0.3 9.9 0.3 0.615 9.8 0.3 9.8 0.3 0.946 0.631 0.602 Height (cm) 139.4 6.1 140.7 6.1 0.041 138.7 6.0 143.1 6.0 <0.001 0.081 0.011 Weight (kg) 34.1 7.1 34.9 7.1 0.303 34.2 7.3 39.2 7.3 <0.001 0.795 <0.001 TB fat mass (kg) 7.3 4.9 7.7 4.9 0.471 9.3 4.9 12.1 5.0 <0.001 <0.001 <0.001 TB lean mass (kg) 25.3 3.0 25.6 3.0 0.314 23.3 2.8 25.2 2.8 <0.001 <0.001 0.332 2 1,141 154 1,161 155 0.261 1,113 157 1,217 158 <0.001 0.002 0.002 a P t b P P 2 Table 2 a   Boys Girls   N N P N N P P P Mean SD Mean SD Mean SD Mean SD Length (cm) 24.7 1.4 25.0 1.4 0.159 24.9 1.4 25.9 1.5 <0.001 0.026 <0.001 Width (cm) 1.92 0.2 1.93 0.2 0.609 1.88 0.2 1.93 0.2 0.002 <0.001 0.985 AR (%) 7.78 0.7 7.76 0.7 0.699 7.53 0.6 7.47 0.6 0.390 <0.001 0.006 2 47.7 6.0 48.4 6.1 0.297 46.9 65.9 50.2 65.9 <0.001 0.023 0.052 a P t 2 P 2 2 2 Fig. 2 a b c P Discussion 7 Our observation that Tanner stage was found to affect humeral geometry in girls but not boys presumably reflects the fact that boys and girls in Tanner stage 2 are not equivalent in terms of skeletal development. The finding that height and weight differences between Tanner stages 1 and 2 were considerably greater in girls compared to boys is consistent with this view. Therefore, analyses of differences in humeral geometry between Tanner stage 2 boys and girls may have limited validity, since these may not have fully accounted for gender differences in skeletal maturity that are likely to have been present. Nevertheless, since humeral AR was unaffected by Tanner stage in the age of children studied, these reservations are unlikely to affect the main conclusion from this study, namely that humeral AR is greater in boys compared to girls as assessed at age 9.9 years. 2 1 8 9 10 11 12 13 3 14 15 16 17 3 11 13 17 15 16 18 19 20 21 22 5 23 1 In conclusion, we have found that long bone shape, as reflected by humeral AR which we derived using a novel technique from total body DXA scans, is unaffected by age, height and puberty, as evaluated in a child cohort of relatively narrow age range and range of Tanner stages. This finding suggests that the ratio between longitudinal and periosteal growth is controlled to ensure it remains constant during rapid growth. However, humeral AR was related to gender, suggesting that the greater periosteal diameter of boys compared to girls, which is well recognised, is a consequence of gender differences in the balance between longitudinal and periosteal bone growth. Interestingly, these gender differences in humeral AR were present in prepubertal children, possibly resulting from prepubertal differences in sex hormone levels. Further studies are justified to determine whether humeral AR is an important determinant of biomechanical strength and fracture risk, particularly in adult populations.