Differences in geometric strength at the contralateral hip between men with hip fracture and non-fractured comparators.

Older men sustain excess bone mineral density (BMD) declines after hip fracture; however, BMD provides no information on mechanical structure and strength. The aim was to assess whether changes in hip bone geometry in older men after hip fracture differ than that expected with aging. Two cohorts were used: Baltimore Hip Studies 7th cohort (BHS-7) and Baltimore Men's Osteoporosis Study (MOST). The sample (N = 170) included older Caucasian men with hip fracture that were propensity score matched (1:1) to community-dwelling non-fractured comparators. Hip Structural Analysis (HSA) calculated aerial BMD and metrics of bone structural strength: cross-sectional bone area (CSA), cortical outer diameter (OD), section modulus (SM), and centroid position (CP). Mixed-effect models estimated changes in HSA parameters and adjusted robust regression models evaluated between-cohort differences in annual percent change at the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS). Hip fracture was associated with statistically greater declines in NN CSA (ß = -2.818; 95% CI: -3.300%, -2.336%), SM (ß = -1.896%; 95% CI: -2.711%, -1.080%) and CP (ß = -0.884%; 95% CI: -0.889%, -0.880%) and significantly larger increases in NN OD (ß = 0.187%; 95% CI: 0.185%, 0.190%). Differences in IT HSA parameters were like the NN but larger in magnitude, while there were favorable changes in FS geometry where fragility fractures are rare. Findings indicate there are declines in bone structure and strength at the NN and IT regions of the proximal femur in older men during hip fracture recovery that far exceed what occurs during normal aging.

Longitudinal changes in hip geometry in relation to the final menstrual period: Study of Women's Health Across the Nation (SWAN).

BACKGROUND: In SWAN, we showed that accelerated loss of bone mineral density (BMD) begins 1 year before the final menstrual period (FMP) to 2 years after the FMP and slows thereafter. However, the risk of fracture depends on both BMD and bone geometry. The hip structural analysis (HSA) measures important geometric properties of bone. Changes in HSA parameters across the menopausal transition have not been previously assessed. METHODS: The current analysis uses data from SWAN, 5 years before to 5 years after FMP (N = 900, Age (mean(SD)) = 46.85(2.60), 44% White). HSA parameters at the femoral narrow neck were obtained from 2D DXA scans and normalized to baseline values. FMP was determined from annual interviews. Changes in HSA were assessed over 3 periods, 5 to 2 years before FMP (pre-transmenopausal), 2 years before to 1 years after FMP (transmenopausal), 1 to 5 years after FMP (postmenopausal). Mixed linear models with random slopes were used to estimate the rate of change in HSA parameters relative to FMP. RESULTS: Loss of BMD, cross-sectional area (CSA), and section modulus (SM) and increases in outer diameter (OD) were greatest in the transmenopausal period (p for all<0.05). Changes continued in the postmenopausal period but were not statistically significant. The cumulative percentage changes over 10 years in BMD (-10.67%), CSA (-9.01), SM (-7.03) and OD (+1.95) were statistically significant. CONCLUSION: Changes in hip geometry across the menopause transition parallel changes in BMD and provide insight into mechanisms that may increase risk of fragility fracture.

Femoral stress is prominently associated with fracture risk in children: The Generation R Study.

Bone modeling is an important process in the growing skeleton. An inadequate bone modeling in response to mechanical loads would lead some children to develop weaker bones than others. The resulting higher stresses in the bones would render them more susceptible to fracture. We aimed to examine the association between femoral stress (FS) derived from structural parameters and BMD in relation to incident fractures in children. Bone stress was evaluated at the medial femoral neck, a skeletal site subject to large forces during normal locomotion. This study comprises 1840 children from the Generation R Study, with whole body and hip DXA scans at a mean age of 6.01 years. Hip structural analysis (HSA) was used to measure femur geometry for the FS calculation. Data on fractures occurring over the following 4 years after the DXA assessment were obtained by questionnaire. Incident fracture was observed in 7.6% of the participating children. Cox-multivariate regression analysis, described as hazard ratios (HR), showed that after adjustment for sex, ethnicity, age, weight and lean mass fraction, there was a significant increase in the risk of incident fracture for every standard deviation (SD) decrease in total body BMD (HR: 1.35, 95% CI 1.05-1.74, p-value = 0.021), femoral neck BMD (HR: 1.31, 95% CI 1.09-1.58, p-value = 0.005) and narrow neck BMD (HR: 1.39, 95% CI 1.14-1.68, p-value = 0.001). Whereas, every increment of one SD in femoral stress resulted in 1.33 increased risk of incident fractures (HR: 1.33, 95% CI 1.13-1.57, p-value = 0.001). This association remained (borderline) significant after the adjustment for DXA derived BMD measurements. Our results show that increased bone stress may underlie greater susceptibility to traumatic fractures in children (partially independent of BMD) and underscore the utility of hip DXA scans for the assessment of paediatric bone health and specifically fracture risk.

Trabecular Bone Score and Hip Structural Analysis in Patients With Atypical Femur Fractures.

Bisphosphonate use has declined dramatically in recent years, partly because of fear of rare side effects like atypical femur fractures (AFFs). It is therefore desirable to have a diagnostic method to identify those at risk of AFF to prevent this serious complication. We compared trabecular microarchitecture and hip geometry between 30 patients with AFF and 141 controls of similar age and sex, using bisphosphonates. Trabecular bone score (TBS) and hip structural analysis (HSA) were used to assess trabecular microarchitecture and macroscopic hip geometry from dual-energy X-ray absorptiometry images of the lumbar spine and hip, respectively. General characteristics, TBS, and HSA were compared between patients with AFF and controls using Student's t tests and chi-square statistics. Associations between AFF and TBS and femur geometric characteristics by HSA were adjusted for sex, age, height, weight, ethnicity, duration of bisphosphonate use, and glucocorticoid use. Additionally, the analysis of TBS was adjusted for lumbar spine bone mineral density and the time difference between dual-energy X-ray absorptiometry scanning and the diagnosis of AFF. Patients with AFF had significantly higher body mass index than controls, had used bisphosphonates longer, and glucocorticoids and proton pump inhibitors more frequently. Sex-specific T-score was significantly higher in patients with AFF at the lumbar spine (p = 0.004), but not at the femoral neck (p = 0.190) after adjustment for age, height, and weight. TBS did not differ significantly between patients with AFF and controls. Neither neck shaft angle nor any geometric variables at the femoral shaft measured by HSA differed between patients with AFF and controls. At the narrow neck, patients with AFF had lower buckling ratio and higher centroid position, consistent with a lower risk of classical fragility hip fractures. The findings at narrow neck and higher bone mineral density might be explained by the fact that the majority of patients with AFF used bisphosphonates to prevent glucocorticoid-induced osteoporosis. Based on our results, TBS and HSA do not appear to have value in detecting patients at risk of AFF.

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.

Difference in the trajectory of change in bone geometry as measured by hip structural analysis in the narrow neck, intertrochanteric region, and femoral shaft between men and women following hip fracture.

Prior studies have shown that women have declines in bone structure and strength after hip fracture, but it is unclear whether men sustain similar changes. Therefore, the objective was to examine sex differences in proximal femur geometry following hip fracture. Hip structural analysis was used to derive metrics of bone structure and strength: aerial bone mineral density, cross-sectional bone area (CSA), cortical outer diameter, section modulus (SM), and buckling ratio (BR) from dual-energy x-ray absorptiometry scans performed at baseline (within 22days of hospital admission), two, six, or twelve months after hip fracture in men and women (n=282) enrolled in the Baltimore Hip Studies 7th cohort. Weighted estimating equations were used to evaluate sex differences at the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS). Men had significantly different one year NN changes compared to women in CSA: -6.33% (-12.47, -0.20) vs. 1.37% (-3.31, 6.43), P=0.049; SM: -4.98% (-11.08, 1.10) vs. 3.94% (-2.51, 10.42), P=0.042; and BR: 7.50% (0.65, 14.36) vs. -1.20% (-6.41, 4.00), P=0.044. One year IT changes displayed similar patterns, but the sex differences were not statistically significant for CSA: -4.07% (-10.83, 2.67) vs. 0.41% (-3.41, 4.24), P=0.252; SM: -4.78% (-12.10, 5.53) vs. -0.31 (-4.74, 4.11), P=0.287; and BR: 4.59% (-0.65, 9.84) vs. 1.52% (-4.23, 7.28), P=0.425. Differences in FS geometric parameters were even smaller in magnitude and not significantly different by sex. Women generally experienced non-significant increases in bone tissue and strength following hip fracture, while men had structural declines that were statistically greater at the NN region. Reductions in the mechanical strength of the proximal femur after hip fracture could put men at higher risk for subsequent fractures of the contralateral hip.

Bone Mass and Strength in School-Age Children Exhibit Sexual Dimorphism Related to Differences in Lean Mass: The Generation R Study.

Bone strength, a key determinant of fracture risk, has been shown to display clear sexual dimorphism after puberty. We sought to determine whether sex differences in bone mass and hip bone geometry as an index of strength exist in school-age prepubertal children and the degree to which the differences are independent of body size and lean mass. We studied 3514 children whose whole-body and hip scans were measured using the same densitometer (GE-Lunar iDXA) at a mean age of 6.2 years. Hip dual-energy X-ray absorptiometry (DXA) scans underwent hip structural analyses (HSA) with derivation of bone strength indices. Sex differences in these parameters were assessed by regression models adjusted for age, height, ethnicity, weight, and lean mass fraction (LMF). Whole-body bone mineral density (BMD) and bone mineral content (BMC) levels were 1.3% and 4.3% higher in girls after adjustment by LMF. Independent of LMF, boys had 1.5% shorter femurs, 1.9% and 2.2% narrower shaft and femoral neck with 1.6% to 3.4% thicker cortices than girls. Consequent with this geometry configuration, girls observed 6.6% higher stresses in the medial femoral neck than boys. When considering LMF, the sexual differences on the derived bone strength indices were attenuated, suggesting that differences in muscle loads may reflect an innate disadvantage in bone strength in girls, as consequence of their lower muscular acquisition. In summary, we show that bone sexual dimorphism is already present at 6 years of age, with boys having stronger bones than girls, the relation of which is influenced by body composition and likely attributable to differential adaptation to mechanical loading. Our results support the view that early life interventions (ie, increased physical activity) targeted during the pre- and peripubertal stages may be of high importance, particularly in girls, because before puberty onset, muscle mass is strongly associated with bone density and geometry in children. © 2015 American Society for Bone and Mineral Research.

Measurement of Hip Geometry-Technical Background.

Conventional dual-energy X-ray absorptiometry images display a digital projection of the inorganic mineral mass in a scanned region. Bone mineral density software generates an average of the pixels within one or more regions. Although not used in the conventional analysis, the images also contain dimensional information limited to the plane of the image. The hip structure analysis method and that of the similar GE, Madison, WI, algorithm Advanced Hip Analysis use both the dimensional information and the mineral mass data to compute the types of dimensional properties (i.e., geometry) that are used to evaluate mechanical strength in engineering analyses. This article describes the hip structure analysis method and a somewhat cruder geometry approximation that does not require a reanalysis of the image. Limitations of the methods are discussed.

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.

Adolescent physical activity and bone strength at the proximal femur in adulthood.

INTRODUCTION: Physical activity (PA) enhances bone structural strength at the proximal femur in adolescence, but whether these benefits are maintained into early adulthood remains unknown. The purpose of this study was to investigate whether males and females, described as active, average, and inactive during adolescence, display differences in structural strength at the proximal femur in early adulthood (20-30 yr). METHODS: One hundred four participants (55 males and 49 females) from the Pediatric Bone Mineral Accrual Study (PBMAS) were categorized into adolescent PA groupings (inactive, average, and active) using the Physical Activity Questionnaire for Adolescents. Cross-sectional area and section modulus (Z) at the narrow neck, intertrochanter, and femoral shaft (S) sites of the proximal femur were assessed using hip structural analysis in young adulthood from femoral neck dual-energy x-ray absorptiometry scans. Group differences were assessed using ANCOVA, controlling for adult height (Ht), adult weight (Wt), adolescent bone geometry, sex, percentage adult total body lean tissue (LTM%), and adult PA levels. RESULTS: Active adolescents had significantly greater adjusted bone geometric measures at all sites than their inactive classified peers during adolescence (P < 0.05). In adulthood, when adjusted for Ht, Wt, adolescent bone geometry, sex, LTM%, and adult PA levels, adolescent participants categorized as active had significantly greater adjusted adult bone geometric measures at the proximal femur than adult participants who were classified as inactive during adolescence (P < 0.05). CONCLUSIONS: Skeletal advantages associated with adolescence activity appear to confer greater geometric bone structural strength at the proximal femur in young adulthood.

Heterogeneity in skeletal load adaptation points to a role for modeling in the pathogenesis of osteoporotic fracture.

Genetic, environmental, or hormonal factors may cause heterogeneity in skeletal load response. Individuals with reduced sensitivity to load should require higher strains to generate an adaptive response, consequently have weaker bones and fracture more frequently. The purpose of our study was to determine if stresses (proportional to strains) at the femoral neck under equivalent loads were higher in women with a history of fractures compared with women without fractures. We studied postmenopausal women participating in the Canadian Multicentre Osteoporosis Study who had available hip structure analysis data from dual-energy X-ray absorptiometry scans (n = 2168). Women were categorized into 2 groups based on their number of self-reported fractures. We computed stress (megapascals) at the inferomedial margin of the femoral neck in a one-legged stance mode using a 2-dimensional engineering beam analysis. We used linear regression (SAS 9.3) to determine associations between stress, geometry parameters, and number of fractures. Postmenopausal women with 1 or more fractures had higher stress (2.6%), lower narrow neck bone mineral density (4.2%), cross-sectional area (3.9%), and section modulus (9.6%) than postmenopausal women without fractures (all p < 0.05). These findings provide evidence of heterogeneity in load response and suggest an important role for modeling in the pathogenesis of osteoporotic fracture.

Does hormone replacement normalize bone geometry in adolescents with anorexia nervosa?

Young women with anorexia nervosa (AN) have reduced secretion of dehydroepiandrosterone (DHEA) and estrogen contributing to skeletal deficits. In this randomized, placebo-controlled trial, we investigated the effects of oral DHEA + combined oral contraceptive (COC) versus placebo on changes in bone geometry in young women with AN. Eighty women with AN, aged 13 to 27 years, received a random, double-blinded assignment to micronized DHEA (50 mg/day) + COC (20 µg ethinyl estradiol/0.1 mg levonorgestrel) or placebo for 18 months. Measurements of areal bone mineral density (aBMD) at the total hip were obtained by dual-energy X-ray absorptiometry at 0, 6, 12, and 18 months. We used the Hip Structural Analysis (HSA) program to determine BMD, cross-sectional area (CSA), and section modulus at the femoral neck and shaft. Each measurement was expressed as a percentage of the age-, height-, and lean mass-specific mean from an independent sample of healthy adolescent females. Over the 18 months, DHEA + COC led to stabilization in femoral shaft BMD (0.0 ± 0.5% of normal mean for age, height, and lean mass/year) compared with decreases in the placebo group (-1.1 ± 0.5% per year, p = 0.03). Similarly, CSA, section modulus, and cortical thickness improved with treatment. In young women with AN, adrenal and gonadal hormone replacement improved bone health and increased cross-sectional geometry. Our results indicate that this combination treatment has a beneficial impact on surrogate measures of bone strength, and not only bone density, in young women with AN.

Ratchet effect study in Si/SiGe heterostructures in the presence of asymmetrical antidots for different polarizations of microwaves.

In this work, we studied the photovoltage response of an antidot lattice to microwave radiation for different antidot parameters. The study was carried out in a Si/SiGe heterostructure by illuminating the antidot lattice with linearly polarized microwaves and recording the polarity of induced photovoltage for different angles of incidence. Our study revealed that with increased antidot density and etching depth, the polarity of induced photovoltage changed when the angle of incidence was rotated 90 degrees. In samples with large antidot density and/or a deeply etched antidot lattice, scattering was dominated by electron interaction with the asymmetrical potential created by semicircular antidots. The strong electron-electron interaction prevailed in other cases. Our study provides insight into the mechanism of interaction between microwaves and electrons in an antidot lattice, which is the key for developing an innovative ratchet-based device. Moreover, we present an original and fundamental example of antidot lattice etching through the use of a two-dimensional electron gas. This system deals with a hole lattice instead of an electron depletion in the antidot lattice region.

Effect of vitamin D replacement on hip structural geometry in adolescents: a randomized controlled trial.

BACKGROUND: We have shown in a randomized controlled trial that vitamin D increases bone mass, lean mass and bone area in adolescent girls, but not boys. These increments may translate into improvements in bone geometry and therefore bone strength. This study investigated the impact of vitamin D on hip geometric dimensions from DXA-derived hip structural analyses in adolescents who participated in the trial. METHODS: 167 girls (mean age 13.1 years) and 171 boys (mean age 12.7 years) were randomly assigned to receive weekly placebo oil or vitamin D3, at doses of 1400 IU or 14,000 IU, in a double blind placebo-controlled 1-year trial. DXA images were obtained at baseline and one year, and hip images were analyzed using the hip structural analysis (HSA) software to derive parameters of bone geometry. These include outer diameter (OD), cross sectional area (CSA), section modulus (Z), and buckling ratio (BR) at the narrow neck (NN), intertrochanteric (IT), and shaft (S) regions. Analysis of Covariance (ANCOVA) was used to examine group differences for changes of bone structural parameters. RESULTS: In the overall group of girls, vitamin D supplementation increased aBMD (7.9% and 6.8% in low and high doses, versus 4.2% in placebo) and reduced the BR of NN (6.1% and 2.4% in low and high doses, versus 1.9% in placebo). It also improved aBMD (7.9% and 5.2% versus 3.6%) and CSA (7.5% and 5.1% versus 4.1%) of the IT and OD of the S (2.4% and 2.5% versus 0.8% respectively). Significant changes in the OD and BR of the NN, in the overall group of girls remained, after adjusting for lean mass, and were unaffected with further adjustments for lifestyle, pubertal status, and height measures. Conversely, boys did not exhibit any significant changes in any parameters of interest. A dose effect was not detected and subgroup analyses revealed no beneficial effect of vitamin D by pubertal stage. CONCLUSIONS: Vitamin D supplementation improved bone mass and several DXA-derived structural bone parameters, in adolescent girls, but not boys. This occurred at a critical site, the femoral neck, and if maintained through adulthood could improve bone strength and lower the risk of hip fractures.

Evidence for impaired skeletal load adaptation among Canadian women with type 2 diabetes mellitus: insight into the BMD and bone fragility paradox.

OBJECTIVE: Recent data suggest that women with type 2 diabetes mellitus (T2DM) might be more susceptible to fractures due to an impaired adaptive response to mechanical load, despite reportedly higher bone mineral density (BMD). The purpose of this study was to use an engineering beam analysis to calculate and compare the load stresses on the femurs of healthy women and women with T2DM and compare these levels to conventional measures of femoral neck BMD. MATERIALS/METHODS: We studied 3658 women who participated in the Canadian Multicentre Osteoporosis Study (CaMos), and who had available Hip Structure Analysis (HSA) data from baseline dual energy x-ray absorptiometry (DXA) scans. Women were categorized into two groups based on the presence or absence of self-reported T2DM. We computed stress in megapascals (MPa) at the infero-medial margin of the femoral neck in a one-legged stance using an engineering beam analysis incorporating dimensions and geometry from DXA scans using the HSA method. We used linear regression (SAS 9.3) to determine the association between T2DM status and stress. We also determined the association between T2DM status and femoral neck BMD. RESULTS: Stresses were 4.5% higher in T2DM women than in non-diabetics (11.03±0.18 vs. 10.56±0.04 MPa; p=0.0093). Femoral neck BMD was 4.2% greater in women with T2DM than in non-diabetics (0.74±0.002 vs. 0.71±0.01 g/cm(2); p=0.0008). CONCLUSIONS: Despite higher femoral neck BMD, higher stress indicates weaker skeletal geometry for a given load, and suggests an impaired skeletal adaptive response to load may be present in women with T2DM.

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.

Ethnic variability in bone geometry as assessed by hip structure analysis: findings from the hip strength across the menopausal transition study.

Racial/ethnic origin plays an important role in fracture risk. Racial/ethnic differences in fracture rates cannot be fully explained by bone mineral density (BMD). Studies examining the influence of bone geometry and strength on fracture risk have focused primarily on older adults and have not included people from diverse racial/ethnic backgrounds. Our goal was to explore racial/ethnic differences in hip geometry and strength in a large sample of midlife women. We performed hip structure analysis (HSA) on hip dual-energy X-ray absorptiometry (DXA) scans from 1942 premenopausal and early perimenopausal women. The sample included white (50%), African American (27%), Chinese (11%), and Japanese (12%) women aged 42 to 52 years. HSA was performed using software developed at Johns Hopkins University. African American women had higher conventional (8.4% to 9.7%) and HSA BMD (5.4% to 19.8%) than other groups with the exception being Japanese women, who had the highest HSA BMD (9.7% to 31.4%). HSA indices associated with more favorable geometry and greater strength and resistance to fracture were more prevalent in African American and Japanese women. Femurs of African American women had a smaller outer diameter, a larger cross-sectional area and section modulus, and a lower buckling ratio. Japanese women presented a different pattern with a higher section modulus and lower buckling ratio, similar to African American women, but a wider outer diameter; this was offset by a greater cross-sectional area and a more centrally located centroid. Chinese women had similar conventional BMD as white women but a smaller neck region area and HSA BMD at both regions. They also had a smaller cross-sectional area and section modulus, a more medially located centroid, and a higher buckling ratio than white women. The observed biomechanical differences may help explain racial/ethnic variability in fracture rates. Future research should explore the contribution of hip geometry to fracture risk across all race/ethnicities.

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.

Rheumatoid arthritis is associated with less optimal hip structural geometry.

The overall goal of this study was to assess the longitudinal changes in bone strength in women reporting rheumatoid arthritis (RA; n=78) compared with nonarthritic control participants (n=4779) of the Women's Health Initiative bone mineral density (WHI-BMD) subcohort. Hip structural analysis program was applied to archived dual-energy X-ray absorptiometry scans (baseline, years 3, 6, and 9) to estimate bone mineral density (BMD) and hip structural geometry parameters in 3 femoral regions: narrow neck (NN), intertrochanteric (IT), and shaft (S). The association between RA and hip structural geometry was tested using linear regression and random coefficient models. Compared with the nonarthritic control, the RA group had a lower BMD (p=0.061) and significantly lower outer diameter (p=0.017), cross-sectional area (p=0.004), and section modulus (p=0.035) at the NN region in the longitudinal models. No significant associations were seen at the IT regions or S regions, and the association was not modified by age, ethnicity, glucocorticoid use, or time. Within the WHI-BMD, women with RA group had reduced BMD and structural geometry at baseline, and this reduction was seen at a fixed rate throughout the 9 yr of study.

Hip strength in adults with type 1 diabetes is associated with age at onset of diabetes.

We investigated the association of age at onset of type 1 diabetes with areal bone mineral density (aBMD), estimates of bone strength, and outer diameter. Using dual-energy X-ray absorptiometry (DXA), aBMD, axial strength (cross-sectional area [CSA]), bending strength (section modulus [SM]), and outer diameter at the narrow neck, intertrochanter, and shaft of the proximal femur were determined for 60 adults. Analysis of covariance (ANCOVA) was used to determine if the DXA-based measures of bone were related to age at onset and if this relationship differed by gender. Age at onset, gender, and the interaction of age at onset by gender were included in the ANCOVA models along with current age, duration, height, lean soft tissue mass, and hemoglobin A1c as covariates. In the adjusted models with CSA, SM, or outer diameter as the dependent variable, age at onset (p<0.01) and gender (p<0.0001) were significant with no interaction. For shaft aBMD, there was a significant age at onset by gender interaction (p=0.0285), where an earlier onset was associated with lower aBMD in the femoral shaft of females but not males. The findings suggest that an earlier onset of type 1 diabetes is associated with lower measures of bone strength and outer diameter.