Identification of Novel Loci Associated With Hip Shape: A Meta-Analysis of Genomewide Association Studies.

We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

The effects of bazedoxifene on bone structural strength evaluated by hip structure analysis.

Bazedoxifene (BZA) is a selective estrogen receptor modulator that has been shown to prevent and treat postmenopausal osteoporosis. Hip structure analysis (HSA) can be used to extract bone structural properties related to strength from hip bone mineral density (BMD) scans. This exploratory analysis used HSA to evaluate changes in hip structural geometry in postmenopausal women enrolled in a phase 3 osteoporosis treatment study who were treated with BZA 20mg or placebo for 2 years. This analysis cohort included women at increased fracture risk based on known skeletal risk factors (n = 521); 1 or more moderate or severe fractures or 2 or more mild vertebral fractures and/or femoral neck BMD T-score ≤ -3.0 at baseline combined with additional women from the overall study population (n = 475); a subgroup analysis included just those women at increased fracture risk. HSA was applied to duplicate hip dual-energy X-ray absorptiometry (DXA) scans acquired at screening and 24 months. Percent change from baseline was evaluated using an analysis of covariance for BMD and geometric parameters including section modulus (SM), cross-sectional area (CSA), outer diameter (OD), and buckling ratio (BR). In all regions, BZA was associated with increased BMD and improvements in hip structural geometry. In the narrow neck, BZA 20mg significantly increased SM, CSA, OD, and BMD compared with placebo (P < 0.05 for all). In the intertrochanter region, BZA 20mg significantly increased CSA and BMD and decreased BR compared with placebo (P < 0.05 for all). Other than BMD (P < 0.05), effects of BZA 20mg at the shaft did not reach statistical significance. Similar trends toward improvement in structural geometry with BZA 20mg were observed in all three regions of the hip for the subgroup of women at increased fracture risk. Overall, BZA was associated with geometry-related improvements in bone strength with regard to resistance to bending and compressive forces and to local buckling. These improvements were evident at common fracture locations such as the femoral neck and intertrochanter regions, and are consistent with the significant treatment effect reported for BZA on nonvertebral fractures in higher-risk postmenopausal women with osteoporosis.

Successive binary algebraic reconstruction technique: an algorithm for reconstruction from limited angle and limited number of projections decomposed into individual components.

Relatively high radiation CT techniques are being widely used in diagnostic imaging raising the concerns about cancer risk especially for routine screening of asymptomatic populations. An important strategy for dose reduction is to reduce the number of projections, although doing so with high image quality is technically difficult. We developed an algorithm to reconstruct discrete (limited gray scale) images decomposed into individual tissue types from a small number of projections acquired over a limited view angle. The algorithm was tested using projection simulations from segmented CT scans of different cross sections including mid femur, distal femur and lower leg. It can provide high quality images from as low as 5-7 projections if the skin boundary of the cross section is used as prior information in the reconstruction process, and from 11-13 projections if the skin boundary is unknown.

Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial.

We determined the effects of 2 years of exercise training and soy isoflavone supplementation on bone mass and lipids in postmenopausal women provided with calcium and vitamin D. Women were randomized to four groups: exercise training (Ex); isoflavone supplementation (Iso: 165 mg/d [105 mg/d aglycone equivalent]); combined Ex and Iso (ExIso); and placebo (control). Exercise included resistance training (2 days/week) and walking (4 days/week). Our primary outcomes were lumbar spine and hip bone mineral density (BMD). Secondary outcomes included hip geometry, tibia and radius speed of sound (SOS), dynamic balance (6 m backward tandem walking), blood lipids, mammography, and endometrial thickness. A total of 351 women (Ex = 86, Iso = 90, ExIso = 87, control = 88) were randomized, with 298 analyzed at 2 years (Ex = 77, Iso = 76, ExIso = 72, control = 73). There was a significant interaction for total hip BMD (p < 0.001) such that ExIso had a greater rate of decrease (absolute change [95% confidence interval] = -0.018 [-0.024, -0.012] g/cm(2) ) than either the Ex or Iso groups alone (-0.005 [-0.01, 0.001] and -0.005 [-0.011, 0.001] g/cm(2) , respectively). There were no differences between groups for changes in lumbar spine BMD and minimal significant changes in hip geometric properties and bone SOS. Exercise groups improved dynamic balance as measured by a decrease in backward tandem walking time over 6 m (p = 0.017). Isoflavone groups decreased low density lipoproteins (Iso: -0.20 [-0.37, -0.02] mmol/L; ExIso: -0.23 [-0.40, -0.06] mmol/L; p = 0.003) compared to non-isoflavone groups (Ex: 0.01 [-0.16, 0.18] mmol/L; control: -0.09 [-0.27, 0.08] mmol/L) and had lower adverse reports of menopausal symptoms (14% versus 33%; p = 0.01) compared to non-isoflavone groups. Isoflavone supplementation did not increase endometrial thickness or abnormal mammograms. We conclude exercise training and isoflavone supplementation maintain hip BMD compared to control, but these two interventions interfere with each other when combined. Isoflavone supplementation decreased LDL and adverse events related to menopausal symptoms.

Relation between serum testosterone, serum estradiol, sex hormone-binding globulin, and geometrical measures of adult male proximal femur strength.

CONTEXT: Although previous studies have indicated associations between circulating testosterone (T) or estradiol (E2) concentrations and bone mineral density, the relationship between gonadal steroids and skeletal geometry is not well defined. OBJECTIVE: Our objective was to uncover the relation between circulating T or E2 and proximal femur geometry in a diverse sample of men. DESIGN: We used data on 808 men enrolled in the Boston Area Community Health/Bone Study. Serum concentrations of total and calculated free T and E2 were obtained via early-morning blood sampling. The geometry of the proximal femur at three sites (the narrow neck, intertrochanter, and shaft) was obtained using the Hip Structural Analysis technology. Analyses adjusted for subjects' age, height, total body lean mass and fat mass, and level of physical activity were performed. SETTING: In-home interviews accompanied by subject visits to the General Clinical Research Center at Boston University School of Medicine were performed. STUDY PARTICIPANTS: A randomly selected cohort of men living in Boston, MA (ages 30-79 yr) was included in the study. INTERVENTIONS: These were not applicable. MAIN OUTCOME MEASURES: Bone mineral density and bone outer diameter, cross-sectional area (measuring bone material), and section modulus (an index of bending strength) were calculated. RESULTS: In age-adjusted models, E2 was positively associated with hip strength parameters, whereas T was not. Adjustment for age and other parameters resulted in substantial reductions in, but not complete elimination of, associations between E2 and hip strength parameters. CONCLUSION: Circulating E2 is strongly associated with proximal femur strength, an association that is partially mediated by body composition.

Hormone therapy improves femur geometry among ethnically diverse postmenopausal participants in the Women's Health Initiative hormone intervention trials.

Loss of bone strength underlies osteoporotic fragility fractures. We hypothesized that hormone interventions significantly improve the structural geometry of proximal femur cross-sections. Study participants were from the Women's Health Initiative hormone intervention trials: either the conjugated equine estrogen (CEE) only (N(placebo) = 447, N(CEE) = 422) trial or the estrogen (E) plus progestin (P) (N(placebo) = 441, N(E+P) = 503) trial, who were 50-79 yr old at baseline and were followed up to 6 yr. BMD scans by DXA were conducted at baseline, year 1, year 3, and year 6. Femur geometry was derived from hip DXA scans using the hip structural analysis (HSA) method. Mixed effects models with the intent-to-treat analysis approach were used. There were no significant differences in treatment effects between the E-alone and the E + P trial, so the analyses were conducted with participants combined from both trials. Treatment benefits (p < 0.05) on femur geometry were observed as early as 1 yr after the intervention. From baseline to year 6, section modulus (a measure of maximum bending stress) was preserved, and buckling ratio (an index of cortical instability under compression) was reduced by hormone interventions (p < 0.05); the differences in the percent changes from baseline to year 6 between women on hormone intervention versus women on placebo were 2.3-3.6% for section modulus and -5.3% to - 4.3% for buckling ratio. Hormone interventions led to favorable changes in femur geometry, which may help explain the reduced fracture risk observed in hormone interventions.

Effects of denosumab on the geometry of the proximal femur in postmenopausal women in comparison with alendronate.

Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, an essential mediator of osteoclast activity and survival. In postmenopausal women with low bone mineral density (BMD), subcutaneous denosumab decreases bone resorption and increases BMD. This post hoc analysis reports on subjects treated for up to 24 months with denosumab 60mg 6 monthly (N=39), placebo (N=39), or open-label alendronate 70mg once weekly (N=38) in a phase 2 study. Hip scans were done by dual-energy X-ray absorptiometry at baseline, 12, and 24 months; these were analyzed with hip structural analysis software to evaluate BMD and cross-sectional geometry parameters at the narrowest segment of the femoral neck, the intertrochanter, and the proximal shaft. Geometric parameters and derived strength indices included bone cross-sectional area, section modulus, and buckling ratio. At 12 and 24 months denosumab and alendronate improved these parameters compared with placebo. Denosumab effects were greater than alendronate at the intertrochanteric and shaft sites. The magnitude and direction of the changes in structural geometry parameters observed in this study suggest that denosumab treatment may lead to improved bone mechanical properties. Ongoing phase 3 studies will determine whether denosumab reduces fracture risk.

Influence of calcium intake and physical activity on proximal femur bone mass and structure among pre- and postmenopausal women. A 10-year prospective study.

This 10-year follow-up evaluated the effect of physical activity and calcium intake on proximal femur bone mass (BMC) and structural indices (CSA and Z) and physical performance. A cohort of 133 premenopausal and 134 postmenopausal women with contrasting levels of physical activity (high [PA+]) and low [PA-]) and calcium intake (high [Ca+] and low [Ca-]) was measured with DXA at baseline and 5 and 10 years thereafter. Among premenopausal women, the mean (95% CI) femoral neck BMC was 3.8% (-0.1 to 7.8%) and the trochanter BMC 6.7% (2.4 to 11.3%) greater in the PA+ group than the PA- group. There was no difference between the Ca-intake groups. Among postmenopausal women, the mean femoral neck BMC was 4.2% (-0.2 to 8.8%) greater in the Ca+ group than in the Ca- group and 6.9% (2.2 to11.8%) greater in the PA+ group than in the PA- group. For trochanter BMC, the corresponding differences were 2.7% (-1.6 to 7.2%) and 5.5% (0.9 to 10.3%). The mean differences in CSA and Z were 3.8% (-0.9 to 8.7%) and 4.4% (-2.1 to 11.4%) in favor of the Ca+ group and 6.8% (1.9 to 12.0%) and 9.6% (2.5 to 17.1%) in favor of the PA+ group, respectively. Proximal femur BMC declined generally, but the initial differences between the physical activity and the calcium intake groups were maintained. High calcium intake seemed to slow the decline in trochanter BMC in premenopausal women, while high physical activity was beneficial for proximal femur, particularly among older women.

Increased plasma osteoprotegerin concentrations are associated with indices of bone strength of the hip.

OBJECTIVE: Osteoprotegerin (OPG) is an important regulator of bone turnover through its effects on osteoclastogenesis, yet findings from previous studies of circulating OPG and commonly measured bone indices in humans have been conflicting. We conducted a cross-sectional study to evaluate the association between plasma OPG and femoral neck (FN) bone density (BMD) and geometry in a large cohort of women and men. DESIGN: Participants included 1379 postmenopausal women and 1165 men, aged 50-89 yr (mean, 64 yr), in the Framingham Offspring Study. Dual x-ray absorptiometry was used to evaluate FN BMD and geometry (bone width, section modulus, and cross-sectional area at the narrow neck region). Plasma OPG concentrations were measured by ELISA. Sex-specific analysis of covariance was used to calculate means and assess linear trend in BMD and geometry values across OPG quartiles, adjusted for confounders. RESULTS: OPG concentrations were greater in women than men, increased with age, and were greater in smokers and those with diabetes and heart disease. Multivariable-adjusted mean FN BMD in women increased from the lowest to the highest OPG quartile (trend, P < 0.01). However, no linear trend between FN BMD and OPG was observed in men (trend, P = 0.34). Section modulus and bone width increased with OPG in men (trend, P < 0.01), whereas no association between hip geometry indices and OPG was observed in women. CONCLUSION: Higher OPG concentration may indicate greater skeletal strength in women and men, possibly through reducing bone loss in women and increasing periosteal apposition in men.

Torsional strength estimates of femoral diaphyses with endosteal lytic lesions: dual-energy X-ray absorptiometry study.

Pathologic fracture is a significant problem for individuals with metastatic bone disease. Current guidelines for prophylactic internal fixation are neither reliable nor easily applied. The purpose of this study was to validate dual-energy X-ray absorptiometry (DXA) as an accurate method for estimating torsional bone strength of diaphyseal bone with endosteal lytic lesions. Endosteal lesions of varying sizes were simulated in the diaphyses of 12 adult cadaveric femurs. Unaltered contralateral femurs served as matched controls. Machined lesions ranged from 3 to 6.5 cm in length, 1 to 3 cm in width, 15 to 48 cm(2) in elliptical area, with 10% to 100% removal of the cortical thickness. Morphology and density data obtained from DXA images were used to estimate torsional strength. All femora were mechanically tested to failure in torsion. Physically measured torsional strength was not significantly correlated to lesion elliptical area (r = 0.542, p > 0.05) or percentage cortical thickness removed (r = 0.257, p > 0.05). Measured torsional strength was significantly correlated to DXA-based torsional strength estimates (r = 0.855, p < 0.01). Lesion size alone did not correlate with the strength of bones with simulated endosteal lytic lesions. In contrast, calculations based on DXA (morphology, density) did correlate with torsional strength. This is the first step in the development of a DXA-based tool for objectively estimating bone strength in the presence of endosteal lytic lesions.

Alterations in proximal femur geometry in children treated with glucocorticoids for Crohn disease or nephrotic syndrome: impact of the underlying disease.

UNLABELLED: Proximal femur geometry was assessed in children and young adults treated with chronic GCs for CD or SSNS. Subperiosteal width and section modulus were significantly lower in CD and greater in SSNS compared with controls, highlighting the importance of the underlying disease, persistent inflammation, and alterations in lean mass. INTRODUCTION: The impact of glucocorticoid (GC) therapy on bone structure during growth is unknown. Our objective was to characterize proximal femur geometry in children and young adults with Crohn disease (CD) or steroid-sensitive nephrotic syndrome (SSNS) compared with controls and to evaluate the influence of lean mass and GC therapy on bone parameters. MATERIALS AND METHODS: DXA scans of the hip and whole body were obtained in 88 subjects with CD, 65 subjects with SSNS, and 128 controls (4-26 years of age). Hip structural analysis parameters (subperiosteal width, cross-sectional area [CSA], and section modulus in the narrow neck [NN], intertrochanteric region [IT], and femoral shaft [FS]), areal BMD, and whole body lean mass were expressed as Z scores compared with controls. Multivariable linear regression was used to adjust outcomes for group differences in age, sex, race, and height. RESULTS: Mean lean mass Z scores were lower in CD (-0.63, p < 0.001) and greater in SSNS (0.36, p = 0.03) compared with controls. Hip areal BMD Z scores were lower in CD (-0.73, p < 0.001) but not SSNS (-0.02, p > 0.2) compared with controls. In CD, Z scores for subperiosteal width (NN: -1.66, p < 0.001; FS: -0.86, p < 0.001) and section modulus (NN: -0.60, p = 0.003; FS: -0.36, p = 0.03) were significantly lower than controls. In contrast, in SSNS, Z scores were greater for IT subperiosteal width (0.39, p = 0.02), FS CSA (0.47, p = 0.005), and FS section modulus (0.49, p = 0.004). Alterations in section modulus in CD and SSNS were eliminated after adjustment for lean mass. Cumulative GC dose was inversely associated with FS subperiosteal width and section modulus only in CD. CONCLUSIONS: These data show that the effects of GC on proximal femur geometry during growth are influenced by the underlying disease, persistent inflammation, and alterations in lean mass. These data also provide insight into the structural basis of hip fragility in CD.

Estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor alpha (ESR1) and insulin-like growth factor I (IGF1) variants influence the risk of fracture in postmenopausal women.

UNLABELLED: In this large population-based cohort study, variants in ESR2 were associated with increased risk of vertebral and incident fragility fracture in postmenopausal women. Interaction of ESR2 with ESR1 and IGF1 was determined and revealed a deleterious genetic combination that enhances the risk of osteoporotic fracture. INTRODUCTION: Osteoporosis is a complex disease with strong genetic influence, but the genes involved are ill-defined. We examined estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor alpha (ESR1) and insulin-like growth factor I (IGF1) variants in relation to the risk of osteoporotic fracture, BMD, and bone geometry. MATERIALS AND METHODS: In the Rotterdam study, a prospective population-based cohort of elderly white individuals, we studied six single nucleotide polymorphisms (SNPs) in ESR2 (n = 6343, 60% women). We analyzed the genetic variants in the form of haplotypes reconstructed by a statistical method. Results refer to the most frequent ESR2 haplotype 1 estimated from two SNPs in intron 2 and the 3'-untranslated region (UTR). Outcomes included vertebral and incident nonvertebral fractures, BMD, and hip structural analysis (HSA). We also studied the interaction with (the most frequent) ESR1 haplotype 1 estimated from the PvuII and XbaI polymorphisms and an IGF1 promoter CA-repeat. RESULTS: Compared with ESR2 haplotype 1 noncarriers, female homozygous carriers had a 1.8- and 1.4-fold increased risk of vertebral and fragility fractures. HSA showed that ESR2 haplotype 1 homozygote women had 2.6% thinner cortices, 1.0% increased neck width, and 4.3% higher bone instability (buckling ratios). For testing the gene interaction, we assumed a recessive model of ESR2 haplotype 1. Female homozygous carriers of ESR2 haplotype 1 and noncarriers of ESR1 haplotype 1 had a 3.5- and 1.8-fold increased risk of vertebral and fragility fractures (p(interaction) = 0.10). Such effects and interactions were stronger in women homozygous for the IGF1 192-bp allele, with 9.3-fold increased risk (p(interaction) = 0.002) for vertebral and 4.0-fold increased risk (p(interaction) = 0.01) for fragility fractures. Multilocus interaction analyses of fracture endured correction for multiple testing using Monte-Carlo simulations (p(interaction) = 0.02 for vertebral and p(interaction) = 0.03 for fragility fractures). Similar patterns of interaction were observed for BMD, cortical thickness, bone strength (section modulus), and instability (buckling ratio). In men, no such effects were observed. CONCLUSIONS: Variants of ESR2 alone and in interaction with ESR1 and IGF1 influence the risk of fracture in postmenopausal women. These findings reinforce the polygenic and complex character of osteoporosis.

Effect of hormone replacement, alendronate, or combination therapy on hip structural geometry: a 3-year, double-blind, placebo-controlled clinical trial.

UNLABELLED: This study examined the effect of hormone replacement, alendronate, or combination therapy on hip structural geometry in 373 postmenopausal women over 3 years. We found that antiresorptive agents alone or in combination result in improvement in parameters of hip structural geometry and BMD. These data provide additional information regarding potential mechanisms for fracture reduction with antiresorptive therapy. INTRODUCTION: Fracture reduction is only partially explained by increased BMD. The aim of this study was to examine changes in structural geometry of the hip, derived from DXA in postmenopausal women after treatment with antiresorptive agents. MATERIALS AND METHODS: This was a double-blind, placebo-controlled, randomized clinical trial of 373 women over the age of 65 years, who were randomized to hormone replacement therapy, alendronate, combination therapy, or placebo for 3 years. The outcomes included the DXA-derived hip structure analysis program by Beck, which is an engineering interpretation of the DXA data. The indices included cross-sectional area, section modulus (a measure of bending strength), outer diameter, cortical thickness, and buckling ratio (an index of cortical bone stability). Properties were measured in cross-sectional regions traversing the femur at the narrowest point on the femoral neck, the intertrochanteric region, and the proximal shaft. RESULTS: In the femoral neck, improvement in the hip structure analysis indices were generally significantly greater with combination therapy than either monotherapy; increases were also greater at the intertrochanter compared with hormone replacement therapy. For example, the section modulus at the intertrochanter and narrow neck increased 10.6% and 10.3%, respectively, with combination therapy, 9.1% and 7.3% with alendronate, 5.8% and 6.9% with hormone replacement therapy, and 3.4% and 3.2% with placebo (p < 0.01 across the four groups). Buckling ratio increased, suggesting decreased stability in the placebo group, whereas there was either no change or significant improvements (p < 0.05) in each active treatment group. CONCLUSIONS: We conclude that changes in the distribution of bone mass underlying the improvements in density with antiresorptive agents in combination or alone have positive effects on structural strength and stability at the proximal femur. This study provides additional information on the potential mechanisms for fracture reduction with antiresorptive agents.

Femoral bone structural geometry adapts to mechanical loading and is influenced by sex steroids: the Penn State Young Women's Health Study.

We used 10 years of longitudinal data from Penn State Young Women's Health Study to explore predictors of adult bone structural geometry and strength. One hundred twelve participants were enrolled in the study at age 12. We report findings on the 76 participants who remained in the study for 10 years. Measurements were recorded biannually for the first 4 years and annually thereafter. Proximal femur DXA scans (Hologic QDR 2000) were taken from 17-22 years and analyzed using a hip structure analysis program to assess areal bone mineral density (BMD, g/cm2), subperiosteal width, cortical thickness, bone cross-sectional area (CSA), and section modulus (Z) at the narrow neck and femoral shaft. Total body lean mass (g) was measured with DXA total body scans. Nutrition, anthropometry, and sex steroids [testosterone (T) and estradiol (E2)] were measured from ages 12-22 years. Multiple regression models were used to assess predictors of change in bone variables (17-22 years) and absolute bone values (average of age 21 and 22 years, n = 79). Neck Z (+3.1%) and width (+1.3%), but not BMD (-0.8%), increased significantly from age 17 to 22 years. At the shaft, all variables increased (+1.0-4.0%, P < 0.01). After controlling for baseline (age 17) height, weight and bone measurement, weight change (neck) or lean mass (shaft), and age of menarche were the primary predictors of change in bone strength. After controlling for height and weight, only lean mass predicted absolute young adult Z at both the neck (r2 = 0.48, P < 0.01) and the shaft (r2 = 0.67, P < 0.01). When lean mass was removed from the model, sports exercise score replaced lean mass as a predictor of Z at both neck (r2 = 0.40, P < 0.01) and shaft (r2 = 0.60, P < 0.01) sites. For neck and shaft cortical thickness and BMD, both estradiol and sports score/lean mass were positive predictors (r2 = 0.15-0.40, P < 0.01). For neck bone width, testosterone levels (negative) and lean mass (positive) were significant (r2 = 0.48). Results were similar for each geometric variable at the shaft site. These data suggest that bone adapts its bending strength primarily to mechanical loading (represented by lean mass and sports exercise score) and that sex steroids are associated with bone geometric structure.

Lifestyle factors and the development of bone mass and bone strength in young women.

OBJECTIVE: To evaluate the contributions of adolescent calcium intake, oral contraceptive use, and exercise on bone mass and bone strength.Study design Eighty white women participated in 10 years of the Penn State Young Women's Health Study, a longitudinal study of community participants. We measured bone mineral mass (g), density (BMD, g/cm(2)), and body composition from dual energy x-ray absorptiometry and estimated proximal femur section modulus (bone bending strength). Calcium intake was determined from 45 days of prospective food records at regular intervals between the ages of 12 and 22 years. Exercise history and oral contraceptive use were assessed by questionnaire. RESULTS: Daily calcium intakes between the ages of 12 and 22 years ranged from 500 to 1900 mg/d and were not significantly associated with bone gain or bone strength. Oral contraceptive use during adolescence was not correlated with bone or body composition measurements. Femoral neck BMD did not change from 17 to 22 years of age, but section modulus increased 3% (P <.05). Only exercise during adolescence was significantly associated with increased BMD and bone bending strength. CONCLUSIONS: Adolescent lifestyle patterns can influence young adult bone strength. Our data suggest that exercise is the predominant lifestyle determinant of bone strength for this cohort.

Effects of gender, anthropometric variables, and aging on the evolution of hip strength in men and women aged over 65.

Although gender differences in fall rates may partly explain the higher prevalence of fractures in elderly women than men, male bones may also be intrinsically stronger or suffer less structural degradation with age than those of women. We used hip structural analysis (HSA) to study gender differences in hip geometry and bone mineral density (BMD) as they evolved over time in elderly white men and women with the aim of identifying candidate biological pathways leading to heightened risk of hip fracture. We recruited 443 women and 439 men aged 67-79 years from a diet and cancer prospective population-based cohort study to a study of hip bone loss. Hip BMD was measured on two occasions 2-5 years apart by dual-energy X-ray absorptiometry and HSA software used to derive BMD and structural parameters at the narrow neck (NN), the intertrochanter (IT), and the shaft (S) regions. Structural indices calculated in each region were cross-sectional area (CSA)-amount of bone surface area in the cross section after excluding soft tissue space; section modulus (Z)-an index of bending resistance, subperiosteal width, endocortical width, cortical thickness; and cortical buckling ratio (CBR)-a measure of cortical instability. Compared to men, women had lower values of BMD, CSA, Z, subperiosteal width, endocortical width, and cortical thickness in all regions, except S endocortical width, after adjusting for weight, height, and age (P < 0.0001). CBR was higher in women than in men (P < 0.0001) in all regions. Longitudinal analysis of rates of change revealed faster rates of BMD decline in women than in men at the Hologic total hip, Hologic femoral neck, and IT regions (P < 0.029). Women had faster rates of subperiosteal and endosteal expansion than men at the NN (P < 0.011) and IT (P < 0.049) and faster increase in Z at the NN (P = 0.029). At the IT region, cortical thinning was faster in women than in men (P = 0.037) and CBR increased at a faster rate in women (P = 0.011). In conclusion, Z is lower in women than in men and expansion of the proximal femur occurs in both sexes, being faster in women than in men. Z does not decline at the same rate as BMD, implying that part of the effect of aging on BMD is due to expansion of the bony envelope without loss of bone mineral content. Faster expansion in the female femoral neck may in turn lead to greater fragility if wider diameter and thinner cortices become locally unstable.