We recruited healthy volunteers through poster advertisements, e-mail to hospital and university staff, and mailing from Sheffield general practices. We studied 30 men and 30 women in two age groups: 16—18 yr to represent late adolescence, and 30—32 yr to represent young adults. Volunteers were excluded if they had any disease or were taking any medication known to affect bone metabolism, if they did not have at least two evaluable vertebrae on dual-energy x-ray absorptiometry DXA , if they had previously fractured both radii or tibiae, if they were pregnant or trying to conceive, or if they were unable to give informed consent.
The study was approved by the Sheffield Research Ethics Committee, and all participants gave written informed consent. All women had a urinary pregnancy test before imaging. In subjects aged 16—18 yr who had visible growth plates on the scout image, the image stack was obtained from 1 mm proximal to the proximal limit of the growth plate 2. This software identifies the periosteal and endosteal boundaries, enabling assessment of cortical microstructural bone properties, including apparent cortical thickness in millimeters, cortical tissue mineral density TMD in grams per cubic centimeter, cortical porosity in percentage, and mean cortical pore diameter in millimeters.
The micro-finite element analysis program developed by Scanco Medical AG version 1.
The model parameters were set as: material properties isotropic and elastic, cortical bone Young's modulus 20 GPa, trabecular bone Young's modulus 17 GPa, Poisson's ratio 0. This finite element analysis software version 1. Women taking oral contraceptives were excluded from analysis of estradiol and testosterone eight women ages 16—18, and four women ages 30— ANOVA with age and gender as fixed factors was used to compare groups.
Data that were not normally distributed were log-transformed for analysis. P values less than 0.
To allow for multiple comparisons, we used Bonferroni-Holm post hoc correction to adjust significance thresholds for the key comparisons of age differences in bone strength and cortical properties. Forward model linear regression analysis with age group and gender as fixed factors was used to determine which measured bone variables were predictors of ultimate failure load, and then to determine which hormones were predictors of the significant bone variables.
Subject characteristics and spine and proximal femur bone mineral density BMD are shown in Table 1. Men were taller than women and had higher body mass index BMI. BMI was higher in young adults than in adolescents. Lumbar spine BMD was greater in young adults than in adolescents, but there was no significant gender difference.
Femoral neck BMD was greater in men than in women in both age groups but did not differ between age groups. Results are given as mean sd. In general, results for the radius and tibia were similar, so only the radius results are presented graphically. Differences between the two sites are specified in the text below.
Univariate analysis including both age groups with age and gender as fixed factors found that cross-sectional size measures cortical perimeter, cortical thickness, and trabecular area were greater in men than in women, except that cortical thickness at the radius did not differ between men and women Fig. Cortical TMD was lower, and cortical porosity was higher in men than in women Fig. Ultimate failure load was higher in men than in women Fig. Radius geometry: cortical perimeter A , cortical thickness B , trabecular area C. Boxes indicate the 25th and 75th centiles, central lines indicate the median, whiskers indicate the minimum and maximum values that are not outliers, and circles represent outliers.
P values for general linear model univariate analysis with age and gender as fixed factors. Radius strength: ultimate failure load. Cortical perimeter did not differ between age groups in women at the radius or the tibia. Young adult men had greater cortical perimeter at the radius but not at the tibia than teenage men.
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Cortical thickness was greater in young adults than adolescents of both genders and at both sites. Trabecular area was lower in young adults than adolescents of both genders at the tibia, but not at the radius Fig. Cortical TMD was greater in young adults than in adolescents, and cortical porosity was lower in young adults than in adolescents at the radius, but not the tibia Fig. Ultimate failure load at the radius was greater in young adult men than in teenage men but did not differ with age in women Fig.
After application of post hoc correction for age differences in cortical measures and ultimate failure load, differences in TMD, porosity, and ultimate failure load remained statistically significant. PTH did not vary with gender or age group. Estradiol was higher in women than in men but did not differ between age groups. Testosterone was higher in men than in women but did not differ between age groups.
IGF-I was lower in young adults than in adolescents and was higher in teenage women than in teenage men Table 2.
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The only differences in the measured variables between women using combined oral contraceptives and nonusers were that teenage users had lower CTX than nonusers 0. The predictors of radius ultimate failure load were cortical perimeter, cortical thickness, trabecular area, cortical TMD, and trabecular separation Table 3.
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Age, gender, cortical porosity, and trabecular thickness were not significant predictors of failure load. The predictors of cortical perimeter were gender, IGF-I, and estradiol. The predictors of cortical thickness were age and IGF-I. Cortical TMD, trabecular area, and trabecular density had no significant endocrine predictors. There were no significant endocrine predictors of any of these variables.
This study has identified geometric and microstructural differences between late adolescence and young adulthood in men and women at the radius and tibia and evaluated these differences in relation to bone turnover and hormones known to affect bone metabolism. The DXA results suggest that peak BMD at the proximal femur may be attained by the end of adolescence but that lumbar spine bone mineral accrual may continue further into young adulthood. Some previous DXA-based studies have found that peak values at the proximal femur and lumbar spine are attained in late adolescence 10 — 12 , but some have found ongoing increases at the lumbar spine into young adulthood 4 , 13 , Gender differences in bone size and trabecular and cortical architecture at the tibia were present in late adolescence and in young adulthood.
All of the gender differences were advantageous to bone strength in men, except that cortical TMD and porosity were more favorable to strength in women.
MDRS 2" Radius Axial Tool "RAT"
Cortical thickness, cortical density, and trabecular number measured by HR-pQCT have been shown to be principal contributors to bone strength and to differ between fracture and nonfracture cases 8 , 9 , Bone strength estimated by stiffness and ultimate failure load was greater in men than in women at both ages, so the net effect of the gender differences is greater bone strength in men.
Similar gender differences of greater bone size, cortical thickness, trabecular number and density in men and greater cortical density in women have been reported in young adults ages 15—20 and 20—29 1 , 16 , Correlated input reveals coexisting coding schemes in a sensory cortex. Hubel, D. Receptive fields, binocular interaction and functional architecture in cats visual cortex. Merzenich, M. Auditory cortex in the grey squirrel: tonotopic organization and architectonic fields. Andermann, M. A somatotopic map of vibrissa motion direction within a barrel column.
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Kremer, Y. Late emergence of the vibrissa direction selectivity map in the rat barrel cortex. Ramirez, A. Spatiotemporal receptive fields of barrel cortex revealed by reverse correlation of synaptic input. Sato, T. The functional microarchitecture of the mouse barrel cortex.
PLoS Biol. Ego-Stengel, V. Coding of apparent motion in the thalamic nucleus of the rat vibrissal somatosensory system. Furuta, T. Septal neurons in barrel cortex derive their receptive field input from the lemniscal pathway.