Sexual dimorphism of the femoral neck during the adolescent growth spurt: a structural analysis

Before puberty, there are only small sex differences in body shape and composition. During adolescence, sexual dimorphism in bone, lean, and fat mass increases, giving rise to the greater size and strength of the male skeleton. The question remains as to whether there are sex differences in bone strength or simply differences in anthropometric dimensions. To test this, we applied hip structural analysis (HSA) to derive strength and geometric indices of the femoral neck using bone densitometry scans (DXA) from a 6-year longitudinal study in Canadian children. Seventy boys and sixty-eight girls were assessed annually for 6 consecutive years. At the femoral neck, cross-sectional area (CSA, an index of axial strength), subperiosteal width (SPW), and section modulus (Z, an index of bending strength) were determined, and data were analyzed using a hierarchical (random effects) modeling approach. Biological age (BA) was defined as years from age at peak height velocity (PHV). When BA, stature, and total-body lean mass (TB lean) were controlled, boys had significantly higher Z than girls at all maturity levels (P < 0.05). Controlling height and TB lean for CSA demonstrated a significant independent sex by BA interaction effect (P < 0.05). That is, CSA was greater in boys before PHV but higher in girls after PHV. The coefficients contributing the greatest proportion to the prediction of CSA, SPW, and Z were height and lean mass. Because the significant sex difference in Z was relatively small and close to the error of measurement, we questioned its biological significance. The sex difference in bending strength was therefore explained by anthropometric differences. In contrast to recent hypotheses, we conclude that the CSA-lean ratio does not imply altered mechanosensitivity in girls because bending dominates loading at the neck, and the Z -lean ratio remained similar between the sexes throughout adolescence. That is, despite the greater CSA in girls, the bone is strategically placed to resist bending; hence, the bones of girls and boys adapt to mechanical challenges in a similar way.     

The Relationship Between Greater Prepubertal Adiposity,Subsequent Age of Maturation,and Bone Strength During Adolescence

This longitudinal study investigated whether greater prepubertal adiposity was associated with subsequent timing of maturation and bone strength during adolescence in 135 girls and 123 boys participating in the Iowa Bone Development Study. Greater adiposity was defined using body mass index (BMI) data at age 8 years to classify participants as overweight (OW, ≥85th percentile for age and sex) or healthy weight (HW). Maturation was defined as the estimated age of peak height velocity (PHV) based on a series of cross‐sectional estimates. Measurements were taken at ages 11, 13, 15, and 17 years for estimates of body composition by dual‐energy X‐ray absorptiometry (DXA), bone compression (bone strength index), and torsion strength (polar strength‐strain index) at the radius and tibia by pQCT, and femoral neck bending strength (section modulus) by hip structural analysis. Bone strength in OW versus HW were evaluated by fitting sex‐specific linear mixed models that included centered age (visit age – grand mean age of cohort) as the time variable and adjusted for change in fat mass, and limb length in model 1. Analyses were repeated using biological age (visit age – age PHV) as the time variable for model 1 with additional adjustment for lean mass in model 2. BMI was negatively associated with age of maturation (p < 0.05). OW versus HW girls had significantly greater bone strength (p < 0.001) in model 1, whereas OW versus HW boys had significantly greater bone strength (p < 0.001) at the tibia and femoral neck but not radius (p > 0.05). Analyses were repeated using biological age, which yielded reduced parameter estimates for girls but similar results for boys (model 1.) Differences were no longer present after adjustment for lean mass (model 2) in girls (p > 0.05) whereas differences at the tibia were sustained in boys (p < 0.05). These findings demonstrate sex‐ and site‐specific differences in the associations between adiposity, maturation, and bone strength. © 2016 American Society for Bone and Mineral Research.     

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

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.     

Bone mineral density by age, gender, pubertal stages, and socioeconomic status in healthy Lebanese children and adolescents

Gender, ethnicity, and lifestyle factors affect bone mass acquisition during childhood, thus the need for age- and sex-adjusted Z scores using ethnic-specific data for bone mineral density (BMD) measurement. This study aimed at establishing normative data for BMD in healthy Lebanese children and adolescents. Three hundred sixty-three healthy children aged 10 to 17 years (mean+/-SD: 13.1+/-2.0) were studied. BMD, bone mineral content (BMC), and lean mass were measured by dual-energy X-ray absorptiometry (DXA) using a Hologic 4500A device, and apparent volumetric BMD (BMAD) of the lumbar spine and the femoral neck were calculated. BMD, BMC, and BMAD were expressed by age groups and Tanner stages for boys and girls separately. There was a significant effect of age and puberty on all bone parameters, except at the femoral neck BMAD in boys. BMC and BMD were higher at cortical sites in boys, including subtotal body and hip; whereas, in girls, it was higher at a site more enriched in trabecular bone, namely the lumbar spine. At several skeletal sites, girls had significantly higher BMD adjusted for lean mass than boys. By the end of puberty, adolescents had a mean BMD that was 43-66% higher at the lumbar spine and 25-41% higher at cortical sites than pre-pubertal children, depending on the gender. Mean BMD values in the study group were significantly lower (P<0.01) than Western normative values, with Z scores ranging between -0.2 and -1.1. In both genders, children of lower socioeconomic status tended to have lower BMD than those from a higher socioeconomic background. This study allows additional insight into gender dimorphism in mineral accretion during puberty. It also provides a valuable reference database for the assessment of BMD in children with pubertal or growth disorders who are of Middle Eastern origin.     

Later Age at Onset of Independent Walking Is Associated With Lower Bone Strength at Fracture‐Prone Sites in Older Men

Later age at onset of independent walking is associated with lower leg bone strength in childhood and adolescence. However, it is unknown whether these associations persist into older age or whether they are evident at axial (central) or upper limb sites. Therefore, we examined walking age obtained at age 2 years and bone outcomes obtained by dual‐energy X‐ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) scans at ages 60 to 64 years in a nationally representative cohort study of British people, the MRC National Survey of Health and Development. It was hypothesized that later walking age would be associated with lower bone strength at all sites. Later independent walking age was associated with lower height‐adjusted hip (standardized regression coefficients with 95% confidence interval [CI] –0.179 [–0.251 to –0.107]), spine (–0.157 [–0.232 to –0.082]), and distal radius (–0.159 [–0.245 to –0.073]) bone mineral content (BMC, indicating bone compressive strength) in men (all p < 0.001). Adjustment for covariates partially attenuated these associations, primarily because of lower lean mass and adolescent sporting ability in later walkers. These associations were also evident for a number of hip geometric parameters (including cross‐sectional moment of inertia [CSMI], indicating bone bending/torsional strength) assessed by hip structural analysis (HSA) from DXA scans. Similar height‐adjusted associations were also observed in women for several hip, spine, and upper limb outcomes, although adjustment for fat or lean mass led to complete attenuation for most outcomes, with the exception of femoral shaft CSMI and spine bone area (BA). In conclusion, later independent walking age appears to have a lifelong association with bone strength across multiple skeletal sites in men. These effects may result from direct effects of early life loading on bone growth and mediation by adult body composition. Results suggest that late walking age may represent a novel risk factor for subsequent low bone strength. Existing interventions effective in hastening walking age may have positive effects on bone across life. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

Physical activity and femoral neck bone strength during childhood: the Iowa Bone Development Study

Structural adaptations of bone to changing mechanical loads have recently been documented during adolescence. However, little is known about how bone adapts structurally during the earlier years. Using a longitudinal observational design spanning 6 years of growth (age range 4 to 12 years), we investigated associations between everyday physical activity and hip geometry in a cohort of healthy Midwestern children (n=468). Femoral neck (FN) cross sectional area (CSA, cm(2)) and FN section modulus (Z, cm(3)) were used to describe hip geometry. CSA and Z, indices of axial and bending strength, were assessed using dual-energy X-ray absorptiometry (DXA) scans and the hip structure analysis (HSA) program. Moderate and vigorous physical activity (MVPA) was assessed using accelerometry-based activity monitors and calculated as the number of minutes > or =3000 accelerometry movement counts. Data were analyzed using multilevel (random- and fixed-effects) regression models with adjustment for age (year), height (cm), and weight (kg) or lean mass (kg). For boys and girls, MVPA was a positive independent predictor of CSA and Z (p<0.05). On average, children who participated in 40 min of MVPA per day would be expected to have 3% to 5% greater CSA and Z than peers participating in 10 min of MVPA per day. Ten-minute increases in daily MVPA had similar effects on CSA in girls and Z in boys as did each additional 1 kg of body weight. When lean mass was substituted for weight, MVPA continued to be a positive independent predictor of CSA and Z for boys, but not girls. This study demonstrates that everyday amounts of physical activity in children are associated with indices of FN bone strength during childhood. Differences in lean mass mediate associations between physical activity and hip geometry in girls, but only somewhat in boys. These results suggest that physical activity is an important contributor to bone strength prior to adolescence and that increasing levels of physical activity during childhood are likely to enhance optimal bone strength.     

Effects of Repetitive Loading on Bone Mass and Geometry in Young Male Tennis Players: A Quantitative Study Using MRI

Pre‐ and early puberty seem to be the most opportune times for exercise to improve bone strength in girls, but few studies have addressed this issue in boys. This study investigated the site‐, surface‐, and maturity‐specific exercise‐induced changes in bone mass and geometry in young boys. The osteogenic effects of loading were analyzed by comparing the playing and nonplaying humeri of 43 male pre‐, peri‐, and postpubertal competitive tennis players 10–19 yr of age. Total bone area, medullary area, and cortical area were determined at the mid (40–50%) and distal humerus (60–70%) of both arms using MRI. Humeral bone mass (BMC) was derived from a whole body DXA scan. In prepubertal boys, BMC was 17% greater in the playing compared with nonplaying arm (p < 0.001), which was accompanied by a 12–21% greater cortical area, because of greater periosteal expansion than medullary expansion at the midhumerus and periosteal expansion associated with medullary contraction at the distal humerus. Compared with prepuberty, the side‐to‐side differences in BMC (27%) and cortical area (20–33%) were greater in peripuberty (p < 0.01). No differences were found between peri‐ and postpuberty despite longer playing history in the postpubertal players. The osteogenic response to loading was greater in peri‐ compared with prepubertal boys, which is in contrast with our previous findings in girls and may be caused by differences in training history. This suggests that the window of opportunity to improve bone mass and size through exercise may be longer in boys than in girls.     

The Association Between Trabecular Bone Score and Lumbar Spine Volumetric BMD Is Attenuated Among Older Men With High Body Mass Index

Trabecular bone score (TBS) has been proposed as a dual‐energy X‐ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m². Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS‐VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS‐VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI <37 kg/m². TBS was categorized as normal (n = 925), partially degraded (n = 1747), and degraded (n = 807). TBS was inversely related to BMI, trunk fat mass, and trunk lean mass (all p < 0.001). The relationship between TBS and LS‐VBMD was nonlinear with magnitude of effect (slope of regression line using standardized variables) ranging from 0.07 (95% CI, –0.02 to 0.15) among those with degraded TBS up to 0.71 (95% CI, 0.54 to 0.89) among those with normal TBS. The relationship was still nonlinear after adjusting for age, clinical site, and either BMI, trunk lean mass, or trunk fat mass. The magnitude of effect relating TBS and LS‐VBMD also decreased with increasing BMI (interaction, p = 0.090) and increasing trunk lean mass (interaction, p = 0.001), but not with increasing trunk fat mass (interaction, p = 0.224). In summary, the strength of the association between TBS and LS‐VBMD among older men was variable and dependent on BMI and body composition, particularly trunk lean mass. The clinical utility of TBS among older men may be somewhat limited among men with high BMI or high trunk lean mass. © 2016 American Society for Bone and Mineral Research.     

Effects of a Specialist‐Led,School Physical Education Program on Bone Mass,Structure, and Strength in Primary School Children: A 4‐Year Cluster Randomized Controlled Trial

This 4‐year cluster randomized controlled trial of 365 boys and 362 girls (mean age 8.1 ± 0.3 years) from grade 2 in 29 primary schools investigated the effects of a specialist‐taught physical education (PE) program on bone strength and body composition. All children received 150 min/week of common practice (CP) PE from general classroom teachers but in 13 schools 100 min/week of CP PE was replaced by specialized‐led PE (SPE) by teachers who emphasized more vigorous exercise/games combined with static and dynamic postural activities involving muscle strength. Outcome measures assessed in grades 2, 4, and 6 included: total body bone mineral content (BMC), lean mass (LM), and fat mass (FM) by DXA, and radius and tibia (4% and 66% sites) bone structure, volumetric density and strength, and muscle cross‐sectional area (CSA) by pQCT. After 4‐years, gains in total body BMC, FM, and muscle CSA were similar between the groups in both sexes, but girls in the SPE group experienced a greater gain in total body LM (mean 1.0 kg; 95% CI, 0.2 to 1.9 kg). Compared to CP, girls in the SPE group also had greater gains in cortical area (CoA) and cortical thickness (CoTh) at the mid‐tibia (CoA, 5.0% [95% CI, 0.2% to 1.9%]; CoTh, 7.5% [95% CI, 2.4% to 12.6%]) and mid‐radius (CoA, 9.3% [95% CI, 3.5% to 15.1%]; CoTh, 14.4% [95% CI, 6.1% to 22.7%]), whereas SPE boys had a 5.2% (95% CI, 0.4% to 10.0%) greater gain in mid‐tibia CoTh. These benefits were due to reduced endocortical expansion. There were no significant benefits of SPE on total bone area, cortical density or bone strength at the mid‐shaft sites, nor any appreciable effects at the distal skeletal sites. This study indicates that a specialist‐led school‐based PE program improves cortical bone structure, due to reduced endocortical expansion. This finding challenges the notion that periosteal apposition is the predominant response of bone to loading during the prepubertal and early‐pubertal period. © 2015 American Society for Bone and Mineral Research.     

Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study

The aim of this study was to determine the sex- and maturity-related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high-resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years (n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri- and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (-118% and -56%, respectively) compared with peri- and postpubertal boys (all p < 0.001). Peri- and postpubertal boys had higher trabecular bone volume ratios (p < 0.001) and larger cortical cross-sectional areas (p < 0.05, p < 0.001) when compared with girls. Based upon the load-to-strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po (p < 0.01) and failure load (p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri-, and postpubertal groups and boys in peri- and postpubertal groups had higher estimates of bone strength compared with their same-sex prepubertal peers (p < 0.001). These results provide insight into the sex- and maturity-related differences in bone microstructure and estimated bone strength.     

Adiponectin and its association with bone mass accrual in childhood

Circulating adiponectin levels are inversely related to bone mineral density (BMD) in humans and animal models. Previous studies in humans have been confined largely to adult populations, and whether adiponectin influences bone mass accrual in childhood is unclear. We examined this question using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort by investigating relationships between circulating adiponectin levels at a mean age of 9.9 years, indices of bone mass as measured by total‐body dual‐energy X‐ray absorptiometry (DXA) at ages 9.9 and 15.5 years, and cortical bone parameters as measured by peripheral quantitative computed tomography (pQCT) of the midtibia at age 15.5 years. A total of 4927 children were included at age 9.9 years, of whom 97% and 90% of boys and girls, respectively, were in prepuberty or early puberty, as defined by Tanner stage 1–2. A total of 2754 children were included at age 15.5 years, of whom 95% and 97% of boys and girls, respectively, were in late puberty, as defined by Tanner stage 4–5. Circulating adiponectin was found to be related to fat mass, lean mass, and, to a lesser extent, height, so analyses were adjusted for these three variables to identify possible independent effects of adiponectin on bone development. Adiponectin was inversely related to total‐body‐less‐head bone mineral content (BMC; ?3.0%), bone area (BA; ?1.8%), BMC divided by BA (BMD; ?4.8%), and BMC adjusted for BA by linear regression (aBMC; ?5.6%), as measured at age 9.9 years (coefficients show change per doubling in adiponectin concentration, p < .001). Consistent with these results, inverse associations also were seen between adiponectin and cortical BMC (?4.8%) and cortical bone area (?4.7%), as measured by tibial pQCT at age 15.5 years (p < .001). Further pQCT results suggested that this inverse association of adiponectin with skeletal development predominantly involved a negative association with endosteal relative to periosteal expansion, as reflected by cortical thickness (?6.0%, p < .001). We conclude that, independent of fat mass, lean mass, and height, adiponectin is associated with lower bone mass in childhood predominantly owing to an influence on relative endosteal expansion. Since these associations were observed before and after puberty, this suggests that setting of adiponectin levels in midchildhood has the potential to exert long‐term effects on bone strength and fracture risk. © 2010 American Society for Bone and Mineral Research.     

Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents

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.     

Ward's area location,physical activity,and body composition in 8‐ and 9‐year‐old boys and girls

Bone strength is the result of its material composition and structural design, particularly bone mass distribution. The purpose of this study was to analyze femoral neck bone mass distribution by Ward's area location and its relationship with physical activity (PA) and body composition in children 8 and 9 years of age. The proximal femur shape was defined by geometric morphometric analysis in 88 participants (48 boys and 40 girls). Using dual‐energy X‐ray absorptiometry (DXA) images, 18 landmarks were digitized to define the proximal femur shape and to identify Ward's area position. Body weight, lean and fat mass, and bone mineral were assessed by DXA, PA by accelerometry, and bone age by the Tanner‐Whitehouse III method. Warps analysis with Thin‐Plate Spline software showed that the first axis explained 63% of proximal femur shape variation in boys and 58% in girls. Most of this variation was associated with differences in Ward's area location, from the central zone to the superior aspect of the femoral neck in both genders. Regression analysis demonstrated that body composition explained 4% to 7% of the proximal femur shape variation in girls. In boys, body composition variables explained a similar amount of variance, but moderate plus vigorous PA (MVPA) also accounted for 6% of proximal femur shape variation. In conclusion, proximal femur shape variation in children ages 8 and 9 was due mainly to differences in Ward's area position determined, in part, by body composition in both genders and by MVPA in boys. These variables were positively associated with a central Ward's area and thus with a more balanced femoral neck bone mass distribution. © 2010 American Society for Bone and Mineral Research.     

Association Between Components of Body Composition and Scoliosis: A Prospective Cohort Study Reporting Differences Identifiable Before the Onset of Scoliosis

There is an increasing body of research suggesting that low body weight is associated with scoliosis, but this is based on case‐control studies, which are prone to bias. No studies have investigated the components of body weight: fat and lean mass. We have therefore carried out the first population‐based prospective study of the association between fat and lean mass at age 10 years assessed by dual‐energy X‐ray absorptiometry (DXA), with presence of scoliosis at age 15 years using the Avon Longitudinal Study of Parents and Children (ALSPAC). All children with scoliosis at age 10 years were excluded. Of 5299 children at age 15 years, 312 (5.9%) had scoliosis. Our results show a negative association between body mass index (BMI)/body weight at age 10 years and scoliosis at age 15 years, with a 20% reduced risk of scoliosis per SD increase in BMI (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.70–0.92; p = 0.001). This association with BMI/body weight reflects associations with both fat mass and lean mass. After adjustment for age, gender, leg length, and fat mass per SD increase in lean mass, there was a 20% reduced risk of scoliosis (OR, 0.80; 95% CI, 0.65–0.97) and per SD increase in fat mass there was a 13% reduced risk of scoliosis (OR, 0.87; 95% CI, 0.74–1.03). In terms of adipocyte function, an inverse association was seen between leptin at age 10 years and scoliosis (OR for scoliosis per SD increase in leptin of 0.78; 95% CI, 0.63–0.99), and a positive association between adiponectin at age 10 years and scoliosis (OR for scoliosis per SD increase in adiponectin of 1.44; 95% CI, 0.99–2.10). This is the first study to address the association between the individual components of body weight and scoliosis in a prospective cohort study, and shows altered body composition that is present before the onset of clinically detected scoliosis. © 2014 American Society for Bone and Mineral Research.     

Lean Mass and Not Fat Mass Is Associated With Male Proximal Femur Strength

Obesity is suspected to confer protection against fracture, but evidence is mixed. We examined proximal femur geometry and body composition measures in a diverse group of 1171 men (30–79 yr of age). Analyses showed that nonbone lean mass, but not fat mass, is independently associated with measures of proximal femur density, axial and bending strength, and resistance to buckling. Introduction: Obesity is often said to confer protection against fracture, but the mechanisms driving such an association remain poorly understood. We hypothesized that the effect of increased body mass on bone structure would be accounted for by total and/or appendicular nonbone lean mass, and that once these trends were removed, fat mass would show no protective influence. To test this hypothesis, we examined body composition and geometric indices of proximal femur strength in an ethnically diverse (black, Hispanic, and white) sample of randomly selected men, 30–79 yr of age. Materials and Methods: Data were obtained from N = 1171 community‐dwelling subjects enrolled in the cross‐sectional Boston Area Community Health/Bone study. Body composition was obtained by DXA. Hip geometry parameters at the narrow neck, intertrochanter, and shaft were obtained using Hip Structural Analysis of DXA images. These measures included BMD, bone material in cross‐sections (cross‐sectional area), bending strength (section modulus), and propensity to buckle under compression (average buckling ratio). Analyses controlled for age, race/ethnicity, height, and physical activity. Results: In exploratory analyses, lean mass, fat mass, and BMI were each positively associated with hip strength. However, controlling for lean mass was sufficient to remove the positive, and induce a negative, association for fat mass or BMI. Associations between lean mass and hip strength were strongest and resistant to control for other measures. Lean mass alone was sufficient to account for a substantial proportion of racial/ethnic difference in hip strength measures, whereas fat mass exhibited no comparable explanatory power. Conclusions: The positive association between relative weight and proximal femur strength is accounted for by lean mass, suggesting that, in men, the protective effect of BMI in preventing fracture is mediated not by adipose tissue but by the influence of increased muscle mass accompanying elevated BMI.     

Determinants of bone size and strength in 13-year-old South African children: the influence of ethnicity, sex and pubertal maturation

We have previously shown ethnic differences in bone mass between pre-pubertal black and white children using DXA. To investigate these ethnic differences further, using pQCT, and to determine the influence of sex and pubertal development, we measured appendicular bone variables in 13-year-old children using pQCT. We collected pQCT data on a cohort of 471 black and white children at age 13years. Black boys and girls were shorter and had less lean mass than their white peers, and black boys were lighter than white boys at an earlier stage of pubertal development. Metaphyseal (4%) radial trabecular density was greater in the black girls than their white peers (239.5±49.5 vs. 222.7±34.2 mg/cm(3); p<0.05). Bone strength index was not different between the ethnic groups. All metaphyseal measures were 3-41% greater in boys than girls, after adjusting for height where appropriate. Diaphyseal (38%) tibial values, including total area, endosteal diameter, tibial diameter, periosteal circumference and polar strength-strain index were 4-22% greater in the black than white children and in boys than in girls. Cortical density was greater in black than white boys (1079.0±39.4 vs. 1058.7±34.5 mg/mm(3); p<0.001) and greater in the girls than boys (black: 1129.3±33.7 vs. 1079.0±39.4 mg/mm(3); p<0.001; white: 1126.8±28.3 vs. 1058.7±34.5mg/mm(3); p<0.001). Cortical thickness was less in the black groups. Lower leg muscle cross-sectional area (MCSA) was higher in white than black children, and forearm MCSA was higher in white than black boys. There was no difference in fat cross-sectional area between the ethnic groups. In conclusion, ethnic and sex differences in both metaphyseal and diaphyseal bone parameters exist during puberty, which are not accounted for by differences in body size or skeletal maturity. South African black children have wider diaphyseal regions of appendicular bones with greater measures of bone strength.     

Influence of a 3‐year exercise intervention program on fracture risk,bone mass,and bone size in prepubertal children

Published prospective pediatric exercise intervention studies are short term and use skeletal traits as surrogate endpoints for fractures, whereas other reports infer exercise to be associated with more trauma and fractures. This prospective, controlled exercise intervention study therefore followed both skeletal traits and fracture risk for 36 months. Fractures were registered in children aged 7 to 9 years; there were 446 boys and 362 girls in the intervention group (2129 person‐years) and 807 boys and 780 girls in the control group (4430 person‐years). The intervention included school physical education of 40 minutes per day for 3 years. The control children achieved the Swedish standard of 60 minutes per week. In a subsample of 76 boys and 48 girls in the intervention group and 55 boys and 44 girls in the control group, bone mineral content (BMC, g) and bone width (cm) were followed in the lumbar spine and hip by dual‐energy X‐ray absorptiometry (DXA). The rate ratio (RR) for fractures was 1.08 (0.71, 1.62) [mean (95% confidence interval)]. In the DXA‐measured children, there were no group differences at baseline in age, anthropometrics, or bone traits. The mean annual gain in the intervention group in lumbar spine BMC was 0.9 SD higher in girls and 0.8 SD higher in boys (both p < .001) and in third lumbar vertebra width 0.4 SD higher in girls and 0.3 SD higher in boys (both p < .05) than in control children. It is concluded that a moderately intense 3‐year exercise program in 7‐ to 9‐year‐old children increases bone mass and possibly also bone size without increasing fracture risk. © 2011 American Society for Bone and Mineral Research     

Low Lean Mass Predicts Incident Fractures Independently From FRAX: a Prospective Cohort Study of Recent Retirees

Whether low muscle mass predisposes to fracture is still poorly understood. In the diagnosis of sarcopenia, different thresholds for low lean mass have been proposed but comparative data for these criteria against hard outcomes such as fractures are lacking. This study aimed to investigate the prevalence of low lean mass according to different thresholds used in operational definitions of sarcopenia and their association with 3‐year fracture incidence in a cohort of healthy 63‐ to 67‐year‐old community dwellers. In a longitudinal analysis of 913 participants (mean age 65.0 ± 1.4 years) enrolled in the Geneva Retirees Cohort (GERICO) study, lean mass was assessed by dual‐energy X‐ray absorptiometry (DXA), and low trauma clinical fracture incidence was recorded over a 3‐year period. Prevalence of low lean mass ranged from 3.5% to 20.2% according to the threshold applied. During a follow‐up of 3.4 ± 0.9 years, 40 (4.4%) participants sustained at least one low trauma fracture. After multivariate adjustment including Fracture Risk Assessment Tool (FRAX) probability with femoral neck bone mineral density (BMD), low lean mass, as defined by Baumgartner thresholds, was associated with higher fracture risk (odds ratio [OR], 2.32; 95% CI, 1.04 to 5.18; p = 0.040). It also added significant predictive value beyond FRAX (likelihood ratio test for nested models, 4.28; p < 0.039). No significant association was found for other definition thresholds. The coexistence of sarcopenia and a T‐score <–2.5 at spine or hip was associated with a 3.39‐fold (95% CI, 1.54 to 7.46; p = 0.002) increase in low trauma fracture risk. In conclusion, low lean mass, as defined by the Baumgartner thresholds, is a predictor of incident fractures in a large cohort of healthy 65‐year‐old community dwellers, independently of FRAX probability. The increased risk is related to the threshold for low lean mass selected. These findings suggest that identification of sarcopenia should be considered in fracture risk assessment beyond usual risk factors. © 2016 American Society for Bone and Mineral Research.     

Differences in bone size and bone mass between black and white 10-year-old South African children

Introduction Black and white South Africans hail from vastly disparate cultural and socio-economic backgrounds the result of which exposes black children to numerous factors known to impact negatively on bone mass. Thus, we studied ethnic differences in bone size and bone mass between 476 10-year-old black and white South African girls and boys (black boys n=182, white boys n=72, black girls n=158, white girls n=64) who formed part of a longitudinal cohort of children born in Johannesburg, South Africa, during 1990. Methods Bone area (BA) and bone mineral content (BMC) were measured at the whole body, total hip, femoral neck, lumbar spine (L1–L4) and mid- and distal radii by dual energy X-ray absorptiometry (DXA). Vertebral heights and metacarpal indices were measured. Anthropometry, skeletal maturity and pubertal development were also assessed. Results After correction for height, weight, gender and puberty, black children had greater BMC at the femoral neck (P<0.0001), total hip (P<0.05) and mid-radius (P<0.001) than white children.. At the whole body, lumbar spine, and distal one-third of the radius, there were no differences in BMC between black and white children after correction for differences in body size. After correction for height and puberty, vertebral heights were less in black children than white children, and cortical areas at the second metacarpal were greater in black children. Conclusion These findings suggest that, at the femoral neck, total hip and mid-radius, these differences are not a result of differences in anthropometry, bone age or pubertal stage, or environmental factors but are most likely to result from genetic differences.     

The Role of Bone Shape in Determining Gender Differences in Vertebral Bone Mass

Dual-energy X-ray absorptiometry (DXA) measures of bone mineral density (BMD) in children fail to account for growth because bone depth is unmeasured. While multiple adjustment methods have been proposed using body or bone size, the effect of vertebral shape is relatively unknown. Our study aimed to determine gender differences in vertebral shape and their impact on areal BMD (aBMD).We recruited 189 children, including 107 boys, aged 4–17 years, who attended the emergency department due to trauma. None had fractured. Height, weight, Tanner stage, and DXA measurements of the lumbar spine (LS) and total body were obtained. Cylindrical models were used to predict relationships between vertebral width (VW) and areal density for a given vertebral area assuming uniform volumetric density. The actual relationships between VW, bone area, and aBMD for the LS in the children were then determined.The theoretical models predicted a positive relationship between width and areal density for a constant vertebral area. Actual vertebral measurements demonstrated that boys had greater VW for a given vertebral area but lower aBMD for a given VW than girls at any age.The most likely explanation for the apparent paradox was that vertebral cortical thickness relative to width was greater in girls. This difference remained after adjusting for lean mass, suggesting that bone’s response to mechanical stimulation may vary between the sexes during growth with consequent evolutionary advantage for girls approaching reproductive age.