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Costal cartilage plays an important functional role in the rib cage, but its mechanical properties have not been well characterized. The objective of this study is to characterize the properties of human costal cartilage and examine the effects of age, sex, rib level, and degree of calcification. We obtained cadaveric costal cartilage samples of ribs 3-6 with intact perichondrium from 24 donors (12 females and 12 males) evenly distributed by age (range 47-94 yr). Peripheral QCT scans were used to quantify geometric properties (area moments) and tissue calcification (as volume, length, and classified as central, peripheral, and mixed). Four-point bending tests were performed on each sample, and bending stiffness and modulus outcomes were evaluated by fitting data from mechanical testing with non-linear pseudo-elastic models (composed of linear and cubic components, separated into loading and unloading regimes). Effects of sex, age, rib level, and cartilage calcification on bending stiffness and modulus outcomes were assessed with mixed-effects regression models. Cartilage size (area moment) was larger in males than females and positively associated with age, while there was more calcification volume in cartilage of females than males. During loading, stiffness (linear and cubic) was larger in males, while modulus (linear and cubic) was larger in females. Linear stiffness and modulus were both negatively associated with age, positively associated with calcification, and varied between rib levels. Cubic (nonlinear) components of stiffness and modulus were positively associated with calcification and varied by rib, while modulus (but not stiffness) was negatively associated with age. During unloading, the linear stiffness and modulus values were much lower, though some similar associations were found. Overall, this study adds to our understanding of the behavior of costal cartilage as a nonlinear visco-elastic material, and the effects of sex, aging, and calcification on mechanical behavior., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Quantifying precision error for DXA, peripheral QCT (pQCT), and HR-pQCT is crucial for monitoring longitudinal changes in body composition and musculoskeletal outcomes. Agreement and associations between bone variables assessed using pQCT and second-generation HR-pQCT are unclear. This study aimed to determine the precision of, and agreement and associations between, bone variables assessed via DXA, pQCT, and second-generation HR-pQCT. Thirty older adults (mean age: 64.2  ±  8.0 yr; women: 67%) were recruited. DXA scans were performed at the total hip, lumbar spine, and whole body. Distal (4%) and proximal (30%/33%/66%) skeletal sites at the radius and tibia were scanned with pQCT and/or HR-pQCT. Root-mean-squared coefficients of variation (%CV RMS ) were calculated to define precision errors, and Bland-Altman plots assessed agreement between densitometric estimates. Pearson correlations and linear regression explored relationships between bone variables at different skeletal sites and proportional bias, respectively. Precision errors ranged between 0.55% and 1.6% for DXA, 0.40% and 4.8% for pQCT, and 0.13% and 30.7% for HR-pQCT. Systematic bias was identified between pQCT- and HR-pQCT-determined radius and tibia volumetric BMD (vBMD) estimates (all p <.001). Proportional bias was not observed between vBMD measures at any skeletal site (all p >.05). pQCT- and HR-pQCT-determined total, trabecular, and cortical vBMD and estimates of bone strength at the radius and tibia were strongly correlated (all p <.05). Precision error was low for most bone variables and within the expected range for all imaging modalities. We observed significant systematic bias, but no proportional bias, between pQCT- and second-generation HR-pQCT-determined vBMD estimates at the radius and tibia. Nevertheless, measures of bone density and strength were strongly correlated at all skeletal sites. These findings suggest that although bone density and strength estimates from both imaging modalities are not interchangeable, they are strongly related and likely have similar fracture prediction capabilities., Competing Interests: All authors declare no conflicts of interest related to this body of work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

ABSTRACT We investigated the predictive performance of peripheral quantitative computed tomography (pQCT) measures of both calf muscle density (an established surrogate for muscle adiposity, with higher values indicating lower muscle adiposity and higher muscle quality) and size (cross‐sectional area [CSA]) for incident fracture. pQCT (Stratec XCT2000/3000) measurements at the tibia were undertaken in Osteoporotic Fractures in Men (MrOS) United States (US), Hong Kong (HK), and Swedish (SW) cohorts. Analyses were by cohort and synthesized by meta‐analysis. The predictive value for incident fracture outcomes, illustrated here for hip fracture (HF), using an extension of Poisson regression adjusted for age and follow‐up time, was expressed as hazard ratio (HR) per standard deviation (SD) increase in exposure (HR/SD). Further analyses adjusted for femoral neck (fn) bone mineral density (BMD) T‐score, Fracture Risk Assessment Tool (FRAX) 10‐year fracture probability (major osteoporotic fracture) and prior falls. We studied 991 (US), 1662 (HK), and 1521 (SW) men, mean ± SD age 77.0 ± 5.1, 73.9 ± 4.9, 80 ± 3.4 years, followed for a mean ± SD 7.8 ± 2.2, 8.1 ± 2.3, 5.3 ± 2.0 years, with 31, 47, and 78 incident HFs, respectively. Both greater muscle CSA and greater muscle density were associated with a lower risk of incident HF [HR/SD: 0.84; 95% confidence interval [CI], 0.72–1.0 and 0.78; 95% CI, 0.66–0.91, respectively]. The pattern of associations was not materially changed by adjustment for prior falls or FRAX probability. In contrast, after inclusion of fn BMD T‐score, the association for muscle CSA was no longer apparent (1.04; 95% CI, 0.88–1.24), whereas that for muscle density was not materially changed (0.69; 95% CI, 0.59–0.82). Findings were similar for osteoporotic fractures. pQCT measures of greater calf muscle density and CSA were both associated with lower incidence of fractures in older men, but only muscle density remained an independent risk factor for fracture after accounting for fn BMD. These findings demonstrate a complex interplay between measures of bone, muscle size, and quality, in determining fracture risk. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Understanding bone accrual in adolescents may inform approaches to improve skeletal health and reduce adult fracture risk. We investigated the effect of HIV on bone mineral accrual assessed by peripheral quantitative computed tomography (pQCT). Children with HIV (CWH) on ART for ≥2 years, and children without HIV (CWOH), aged 8-16 years (n = 609), had tibial pQCT scans at 0 and 12 months. Linear regression estimated sex-stratified differences in change (∆) and mean pQCT bone density (trabecular and cortical), size (total cross-sectional area [CSA]), and strength (SSI) between CWH and CWOH, adjusting for socio-economic status (SES) and orphanhood and incorporating an interaction term for baseline pubertal status (Tanner 1-2[pre/early] vs 3-5[mid/late]). Structural equation modeling tested whether baseline height-for-age-Z-scores (HAZ) mediate the effect of HIV on ∆bone outcomes. CWH were more likely than CWOH to be orphans (44% vs 7%), of lower SES (43% vs 27%), and be stunted (30% vs 8%); but similar in age. At baseline and follow-up, CWH had lower trabecular density, CSA, and SSI than CWOH. After adjustment, bone density and strength increased similarly in CWH and CWOH. CWH in mid/late puberty at baseline had greater 12 months increases in CSA than CWOH, particularly males (mean difference [31.3(95%CI:-3.1, 65.6) mm2 in mid/late puberty vs -2.04(-23.8, 19.7) mm2 in pre/early puberty; interaction p-value = 0.013]). HAZ mediated the effect of HIV on ∆bone outcomes only in females. as follows: indirect pathways from HIV to ∆trabecular density [-2.47 (-4.4, -0.5) mg/cm3], ∆cortical density [-3.26 (-5.5, -0.9) mg/cm3], and ∆SSI [-15.76 (-27.3, -4.2) mm3]. In conclusion, CWH show bone deficits at follow-up. Investigations of bone mineral accrual earlier in life and post-puberty to peak bone mass are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Dietary interventions designed to examine the role of nutrition on childhood bone accrual have often focused on the role of individual micronutrients (eg, calcium, vitamin D, and zinc) and macronutrients (eg, protein). The osteogenic benefits of whole foods, such as eggs, are not well understood despite eggs being a source of high-quality nutrients and bioactive compounds known to positively influence bone. A significant positive cross-sectional association between whole egg consumption and tibia cortical bone mass has recently been shown in young children; however, randomized controlled trials (RCTs) have not been conducted. This study is a double-blind RCT in male and female children ages 9-13 years of different ancestries, designed to determine if consuming food products with whole eggs (equivalent to 8-10 eggs/wk) versus foods with milk or gelatin (placebo) over a 9-month period will improve measures of bone strength. Total body less head (TBLH) and lumbar spine bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed using dual-energy X-ray absorptiometry (DXA). DXA Z-scores were computed using published pediatric growth charts and were adjusted for height-for-age Z-score (HAZ). Mid-tibia cortical volumetric BMD, BMC, cortical area, total bone area, cortical thickness, and strength strain index were measured using peripheral quantitative computed tomography. Overall, there were no significant intervention effects for any bone outcomes. The increase in spine BMC HAZ Z-score in the egg group versus the gelatin group approached significance (p = 0.07). Significant time effects in TBLH aBMD HAZ Z-score occurred as all groups decreased over 9 months (p < 0.03). Most tibia cortical bone outcomes increased over time (all p < 0.02), but changes did not differ across intervention groups. Whole eggs provide important nutritional benefits for children, but the bone responses to consumption of 8-10 eggs/wk over a period of 9 months in children entering the early stages of puberty were small. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous heritable connective tissue disorder mainly characterized by bone fragility and increased fracture risk. This study investigated bone parameters in adults with OI type I and their relationship with physical activity and muscle function parameters in comparison with controls. A total of 27 (15 women, 12 men) adults with OI type I and 27 healthy age- and sex-matched controls, with mean age 45 years (range 18-72 years), were included. Peripheral quantitative computed tomography was performed at the lower leg and forearm to assess muscle density, muscle and fat cross-sectional area (CSA) (66% site), and trabecular (4% site) and cortical bone parameters (66% site) at radius and tibia. Physical activity (step count and moderate-to-vigorous physical activity [MVPA]) was assessed by accelerometry, muscle function parameters by Leonardo mechanography (single two-legged jump - peak power), and hand grip dynamometry (maximal hand grip strength). Overall, the OI type I group had significantly lower muscle CSA at the lower leg and forearm, lower trabecular and cortical bone mineral content, lower polar stress-strain index (SSIp), and smaller cortices but higher cortical bone mineral density and lower step count and MVPA in comparison with controls. Maximal hand grip strength was positively associated with SSIp at radius (p = 0.012) in the control group but not in the OI type I group (p = 0.338) (difference in associations: p = 0.012). No other significantly different associations between bone and muscle function parameters or physical activity (step count or MVPA) were found in the OI type I versus control group. We conclude that adults with OI type I have smaller bones, lower trabecular bone mass, lower estimates of bone strength, and higher cortical density in comparison with controls and that there are some indications of a disturbed biomechanical muscle-bone relationship in adults with OI type I. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

Bone and muscle have shown to interact, but little is known about fat within bone and muscle. Clinical studies have isolated fat within bone and muscle using MRI. In this cross-sectional study, we hypothesized that bone marrow adiposity and muscle adiposity are related and that this relationship is associated with osteoporosis. Postmenopausal women aged 60 to 85 years were recruited as part of the Appendicular Muscle and Bone Extension Research Study (AMBERS). Participants completed dual-energy X-ray absorptiometry (DXA) of the hip and spine to diagnose osteoporosis. Muscle adiposity was measured with MRI at the 66% site of the leg. Fat segmentation was achieved using a semi-automated iterative threshold-optimizing algorithm (error < 5%). Peripheral quantitative computed tomography measured marrow density of the 4% distal tibia (surrogate for marrow fat) by threshold-based, edge-detection segmentations and by examining residuals from trabecular bone density regressed on trabecular tissue mineral density. Muscle adiposity from MRI was regressed on marrow density using linear regression. Models were further examined with an interaction with osteoporosis status. Among 312 women (aged 75.4 ± 5.9 years, body mass index [BMI] 29.5 ± 5.7 kg/m 2 ), a larger amount of muscle fat was associated with lower marrow density at the 66% mid-tibia (B = 84.08 [27.56], p = 0.002) and at the 4% distal tibia (B = 129.17 [55.96], p = 0.022) after accounting for age, height, weight, average daily energy expenditure, hypertension, and diabetes. Interactions of this relationship with osteoporosis status were also significant. Upon probing these interactions, the relationships were significant only in women with osteoporosis but not in those without osteoporosis. Fat from bone marrow and muscle may be related to one another through the same phenomenon, which is likely also responsible for osteoporosis, but independent of hypertension and diabetes. More research should focus on the potential abnormalities in muscle and bone fat metabolism and mesenchymal cell commitment to fat within patients with osteoporosis. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Observations that insulin and adiponectin levels are related to cortical bone size in adolescents, independently of body composition, suggest factors related to fat metabolism directly influence skeletal development. To explore this question, we examined associations between a metabolic screen focusing on fat metabolism, and peripheral quantitative computed tomography (pQCT) measures of the mid-tibia, in 15-year-olds from the Avon Longitudinal Study of Parents and Children. Metabolic profiles were generated by proton nuclear magnetic resonance spectroscopy, from blood samples obtained at the same time as pQCT scans. Ordinary least squares linear regression was used to investigate relationships between metabolic measures and periosteal circumference (PC), cortical thickness (CT), and cortical bone mineral density (BMD C ). Metabolic profiles yielded 22 independent components following principal component analysis (PCA), giving a Bonferroni-adjusted threshold for statistical significance of p = 0.002. Data were available in 1121 subjects (487 males), mean age 15 years. Several metabolites related to lipid and cholesterol metabolism were associated with PC, CT, and BMD C after adjustment for age, sex, and Tanner stage. After additional adjustment for height, fat, and lean mass, only the association between citrate and BMD C remained below the Bonferroni-significant threshold (β = -0.14 [-0.18, -0.09]) (β represents a standardized coefficient). Citrate also showed evidence of association with PC (β = 0.06 [0.03, 0.10]) and strength strain index (SSI; β = 0.04 [0.01, 0.08]). Subsequently, we investigated whether these relationships were explained by increased bone resorption. Citrate was strongly related to serum β-C-telopeptides of type I collagen (β-CTX) (β = 0.20 [0.16, 0.23]). After additional adjustment for β-CTX the above associations between citrate and BMD C (β = -0.04 [-0.08, 0.01]), PC (β = 0.03 [-0.01, 0.07]) and SSI (β = 0.03 [-0.01, 0.07]) were no longer observed. We conclude that in adolescents, circulating levels of citrate are inversely related to BMD C and positively related to PC, reflecting associations with higher bone turnover. Further studies are justified to elucidate possible contributions of citrate, a constituent of bone matrix, to bone resorption and cortical density. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Obese adolescents have increased fracture risk, but effects of alterations in adiposity on bone accrual and strength in obese adolescents are not understood. We evaluated 12-month changes in trabecular and cortical volumetric bone mineral density (vBMD) and cortical geometry in obese adolescents undergoing a randomized weight management program, and investigated the effect of body composition changes on bone outcomes. Peripheral quantitative computed tomography (pQCT) of the radius and tibia, and whole-body dual-energy X-ray absorptiometry (DXA) scans were obtained at baseline, 6 months, and 12 months in 91 obese adolescents randomized to standard care versus behavioral intervention for weight loss. Longitudinal models assessed effects of body composition changes on bone outcomes, adjusted for age, bone length, and African-American ancestry, and stratified by sex. Secondary analyses included adjustment for physical activity, maturation, vitamin D, and inflammatory biomarkers. Baseline body mass index (BMI) was similar between intervention groups. Twelve-month change in BMI in the standard care group was 1.0 kg/m 2 versus -0.4 kg/m 2 in the behavioral intervention group (p < 0.01). Intervention groups were similar in bone outcomes, so they were combined for subsequent analyses. For the tibia, BMI change was not associated with change in vBMD or structure. Greater baseline lean body mass index (LBMI) associated with higher cortical vBMD in males, trabecular vBMD in females, and polar section modulus (pZ) and periosteal circumference (Peri-C) in both sexes. In females, change in LBMI positively associated with gains in pZ and Peri-C. Baseline visceral adipose tissue (VFAT) was inversely associated with pZ in males and cortical vBMD in females. Change in VFAT did not affect bone outcomes. For the radius, BMI and LBMI changes positively associated with pZ in males. Thus, in obese adolescents, weight loss intervention with modest changes in BMI was not detrimental to radius or tibia bone strength, and changes in lean, but not adiposity, measures were beneficial to bone development. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (p Interaction  < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (β Indirect Effect  = 0.321, p < 0.001). However, this relationship was moderated in the children with high (β Indirect Effect  = 0.200, p < 0.001) versus normal (β Indirect Effect  = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

We investigated relationships between placental size and offspring adolescent bone indices using a population-based, mother-offspring cohort. The Avon Longitudinal Study of Parents and Children (ALSPAC) recruited pregnant women from the southwest of England between 1991 and 1993. There were 12,942 singleton babies born at term who survived at least the first 12 months. From these, 8933 placentas were preserved in formaldehyde, with maternal permission for their use in research studies. At the approximate age of 15.5 years, the children underwent a dual-energy X-ray absorptiometry (DXA) scan (measurements taken of the whole body minus head bone area [BA], bone mineral content [BMC], and areal bone mineral density [aBMD]). A peripheral quantitative computed tomography (pQCT) scan (Stratec XCT2000L; Stratec, Pforzheim, Germany) at the 50% tibial site was performed at this visit and at approximately age 17.7 years. In 2010 a sample of 1680 placentas were measured and photographed. To enable comparison of effect size across different variables, predictor and outcome variables were standardized to Z-scores and therefore results may be interpreted as partial correlation coefficients. Complete placental, DXA, and pQCT data were available for 518 children at age 15.5 years. After adjustment for gender, gestational age at birth, and age at time of pQCT, the placental area was positively associated with endosteal circumference (β [95% CI]: 0.21 [0.13, 0.30], p < 0.001), periosteal circumference (β [95% CI]: 0.19 [0.10, 0.27], p < 0.001), and cortical area (β [95% CI]: 0.10 [0.01, 0.18], p = 0.03), and was negatively associated with cortical density (β [95% CI]: -0.11 [-0.20, -0.03], p = 0.01) at age 15.5 years. Similar relationships were observed for placental volume, and after adjustment for additional maternal and offspring covariates. These results suggest that previously observed associations between placental size and offspring bone development persist into older childhood, even during puberty, and that placental size is differentially related to bone size and volumetric density. © 2016 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)., Competing Interests: All authors report no conflict of interest, (© 2016 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).)

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.)

We revisit Stanley Garn's theory related to sex differences in endocortical and periosteal apposition during adolescence using a 12-year mixed longitudinal study design. We used peripheral quantitative computed tomography to examine bone parameters in 230 participants (110 boys, 120 girls; aged 11.0 years at baseline). We assessed total (Tt.Ar, mm(2)), cortical (Ct.Ar, mm(2)), and medullary canal area (Me.Ar, mm(2)), Ct.Ar/Tt.Ar, cortical bone mineral density (Ct.BMD, mg/cm(3)), and polar strength-strain index (SSIp , mm(3)) at the tibial midshaft (50% site). We used annual measures of height and chronological age to identify age at peak height velocity (APHV) for each participant. We compared annual accrual rates of bone parameters between boys and girls, aligned on APHV using a linear mixed effects model. At APHV, boys demonstrated greater Tt.Ar (ratio = 1.27; 95% confidence interval [CI] 1.21, 1.32), Ct.Ar (1.24 [1.18, 1.30]), Me.Ar (1.31 [1.22, 1.40]), and SSIp (1.36 [1.28, 1.45]) and less Ct.Ar/Tt.Ar (0.98 [0.96, 1.00]) and Ct.BMD (0.97 [0.96, 0.97]) compared with girls. Boys and girls demonstrated periosteal bone formation and net bone loss at the endocortical surface. Compared with girls, boys demonstrated greater annual accrual rates pre-APHV for Tt.Ar (1.18 [1.02, 1.34]) and Me.Ar (1.34 [1.11, 1.57]), lower annual accrual rates pre-APHV for Ct.Ar/Tt.Ar (0.56 [0.29, 0.83]) and Ct.BMD (-0.07 [-0.17, 0.04]), and similar annual accrual rates pre-APHV for Ct.Ar (1.10 [0.94, 1.26]) and SSIp (1.14 [0.98, 1.30]). Post-APHV, boys demonstrated similar annual accrual rates for Ct.Ar/Tt.Ar (1.01 [0.71, 1.31]) and greater annual accrual rates for all other bone parameters compared with girls (ratio = 1.23 to 2.63; 95% CI 1.11 to 3.45). Our findings support those of Garn and others of accelerated periosteal apposition during adolescence, more evident in boys than girls. However, our findings challenge the notion of greater endocortical apposition in girls, suggesting instead that girls experience diminished endocortical resorption compared with boys., Competing Interests: All authors state that they have no conflicts of interest., (© 2015 American Society for Bone and Mineral Research.)

Previous studies suggest that dairy intake may be associated with reduced bone and muscle loss with aging, but there are limited data in the very old. We evaluated the association between intake of dairy foods and peripheral bone structure and muscle mass in 564 elderly women aged 80 to 92 (mean 84.7) years, who were participants of the Calcium Intake Fracture Outcome Study/CAIFOS Aged Extension Study (CAIFOS/CARES) cohort and attended the 10-year follow-up. Assessments included dairy consumption (milk, yogurt, and cheese) by a validated food frequency questionnaire, 15% tibia bone mass, area and volumetric bone mineral density (vBMD) by peripheral quantitative computed tomography (pQCT), and appendicular bone and skeletal muscle mass by dual-energy X-ray absorptiometry (DXA). Women were categorized according to tertiles of dairy intake: first tertile (≤ 1.5 servings/d), second tertile (1.5 to 2.2 servings/d) and third tertile (≥ 2.2 servings/d). Controlling for confounding factors, pQCT assessment at the 15% tibia showed that compared with those in the first tertile of dairy intake, women in the third tertile had 5.7% greater total bone mass (p = 0.005), principally because of an increase in cortical and subcortical bone mass (5.9%, p = 0.050), resulting in a 6.2% increase in total vBMD (p = 0.013). Trabecular but not cortical and subcortical vBMD was also higher (7.8%, p = 0.044). DXA assessment showed that women in the third tertile of dairy intake had greater appendicular bone mass (7.1%, p = 0.007) and skeletal muscle mass (3.3%, p = 0.014) compared with tertile 1. The associations with bone measures were dependent on dairy protein and calcium intakes, whereas the association with appendicular muscle mass was not totally dependent on dairy protein intake. Our results suggest a positive association of dairy intake with appendicular bone mineralization and muscle mass in elderly women. Because many fractures in this age group are of the appendicular skeleton often associated with falls, dairy intake may be a modifiable lifestyle factor contributing to healthy aging., (© 2014 American Society for Bone and Mineral Research.)

Most pediatric exercise intervention studies that evaluate the effect on skeletal traits include volunteers and follow bone mass for less than 3 years. We present a population-based 6-year controlled exercise intervention study in children with bone structure and incident fractures as endpoints. Fractures were registered in 417 girls and 500 boys in the intervention group (3969 person-years) and 835 girls and 869 boys in the control group (8245 person-years), all aged 6 to 9 years at study start, during the 6-year study period. Children in the intervention group had 40 minutes daily school physical education (PE) and the control group 60 minutes per week. In a subcohort with 78 girls and 111 boys in the intervention group and 52 girls and 54 boys in the control group, bone mineral density (BMD; g/cm(2) ) and bone area (mm(2) ) were measured repeatedly by dual-energy X-ray absorptiometry (DXA). Peripheral quantitative computed tomography (pQCT) measured bone mass and bone structure at follow-up. There were 21.7 low and moderate energy-related fractures per 1000 person-years in the intervention group and 19.3 fractures in the control group, leading to a rate ratio (RR) of 1.12 (0.85, 1.46). Girls in the intervention group, compared with girls in the control group, had 0.009 g/cm(2) (0.003, 0.015) larger gain annually in spine BMD, 0.07 g (0.014, 0.123) larger gain in femoral neck bone mineral content (BMC), and 4.1 mm(2) (0.5, 7.8) larger gain in femoral neck area, and at follow-up 24.1 g (7.6, 40.6) higher tibial cortical BMC (g) and 23.9 mm(2) (5.27, 42.6) larger tibial cross-sectional area. Boys with daily PE had 0.006 g/cm(2) (0.002, 0.010) larger gain annually in spine BMD than control boys but at follow-up no higher pQCT values than boys in the control group. Daily PE for 6 years in at study start 6- to 9-year-olds improves bone mass and bone size in girls and bone mass in boys, without affecting the fracture risk., (© 2014 American Society for Bone and Mineral Research.)

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC ). CTX and mid-tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β=0.19 [0.13, 0.24]) (coefficient=SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (β=-0.46 [-0.52,-0.40]) and cortical thickness [β=-0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) (β=0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single-nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p<0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n=938), and the Young Finns Study (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p<0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion., (© 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.)

The long-term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSIp ) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSIc ) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z-scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSIp , p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSIp in males, and greater CoA, CoC, and TrC in females., (© 2014 American Society for Bone and Mineral Research.)