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1.
J Clin Densitom ; 22(2): 257-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29661684

RESUMO

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.


Assuntos
Osso Esponjoso/diagnóstico por imagem , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Colo do Fêmur/diagnóstico por imagem , Glucocorticoides/uso terapêutico , Articulação do Quadril/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Absorciometria de Fóton , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Osso Cortical/anatomia & histologia , Osso Cortical/diagnóstico por imagem , Diáfises , Feminino , Fraturas do Fêmur/epidemiologia , Fêmur/anatomia & histologia , Fêmur/diagnóstico por imagem , Colo do Fêmur/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Medição de Risco
2.
J Clin Densitom ; 18(3): 331-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26277850

RESUMO

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.


Assuntos
Absorciometria de Fóton , Algoritmos , Fêmur/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Acetábulo/diagnóstico por imagem , Acetábulo/patologia , Densidade Óssea , Fêmur/patologia , Articulação do Quadril/patologia , Humanos
3.
J Clin Densitom ; 17(1): 170-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23478079

RESUMO

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.


Assuntos
Adaptação Fisiológica/fisiologia , Colo do Fêmur/fisiopatologia , Fraturas por Osteoporose/etiologia , Absorciometria de Fóton , Fatores Etários , Idoso , Densidade Óssea , Canadá , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Estresse Mecânico , Suporte de Carga/fisiologia
4.
Sci Technol Adv Mater ; 15(4): 045005, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27877706

RESUMO

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.

5.
J Xray Sci Technol ; 21(1): 9-24, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23507849

RESUMO

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.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Simulação por Computador , Fêmur/diagnóstico por imagem , Humanos , Perna (Membro)/diagnóstico por imagem
6.
J Clin Densitom ; 15(1): 78-85, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22071026

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiopatologia , Força Muscular/fisiologia , Absorciometria de Fóton , Idade de Início , Análise de Variância , Densidade Óssea , Feminino , Humanos , Masculino , Fatores de Risco
7.
J Clin Densitom ; 15(1): 39-48, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21852170

RESUMO

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.


Assuntos
Absorciometria de Fóton , Artrite Reumatoide/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Idoso , Artrite Reumatoide/patologia , Densidade Óssea , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Articulação do Quadril/patologia , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Osteoporose/patologia
8.
Calcif Tissue Int ; 88(3): 198-208, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21253715

RESUMO

Calcium plus vitamin D (CaD) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women. The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk. We studied 1,970 postmenopausal women enrolled in the Women's Health Initiative randomized controlled trial of CaD at one of three bone mineral density (BMD) clinical centers. Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions: femoral narrow neck, intertrochanter, and shaft. Random effects models were used to test the average differences in hip BMD and geometry between intervention and placebo. There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across 6 years of intervention. CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength, with small increases in cross-sectional area and section modulus and a decrease in buckling ratio with CaD relative to placebo. While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck, no significant intervention effects were evident. There was no significant interaction of CaD and age or baseline calcium levels for hip structural properties. CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck, which may explain some of the benefit of CaD in reducing hip fracture risk.


Assuntos
Cálcio/administração & dosagem , Fêmur/anatomia & histologia , Fêmur/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa/efeitos dos fármacos , Vitamina D/administração & dosagem , Idoso , Constituição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Cálcio/farmacologia , Força Compressiva/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia , Placebos , Vitamina D/farmacologia , Saúde da Mulher
9.
J Bone Miner Metab ; 28(5): 561-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20333418

RESUMO

The purpose of this study was to clarify the effects of 2-year treatment with raloxifene on the proximal femoral geometry among Japanese patients with osteoporosis by hip structure analysis. One hundred ninety-eight community-dwelling postmenopausal women with osteoporosis were enrolled. The structural variables were areal bone mineral density (BMD), cross-sectional area (CSA), section modulus (index of resistance to bending forces), and buckling ratio (index of cortical instability). BMD, CSA, and section modulus at the narrow neck significantly increased by 1.27, 2.67, and 3.90% at 2 years, respectively. BMD, CSA, and section modulus at the intertrochanter significantly increased by 2.55, 4.49, and 6.60% at study termination, respectively. The buckling ratio at the intertrochanter decreased by 2.36% at 1 year, but differences at 2 years became non-significant. Parameters at the shaft were qualitatively similar to those of the narrow neck and intertrochanter. The percent change of the section modulus was significantly higher than that of BMD at 2 years in all three regions. The percent changes of the section modulus is strongly correlated with the percent changes of BMD and CSA, and negative correlated with the percent changes of buckling ratio in all regions. In conclusion, Japanese osteoporotic women on raloxifene therapy have significant improvements of both BMD and geometry in the proximal femur.


Assuntos
Conservadores da Densidade Óssea , Fêmur , Osteoporose , Cloridrato de Raloxifeno , Absorciometria de Fóton , Povo Asiático , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Fêmur/anatomia & histologia , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Quadril/anatomia & histologia , Quadril/diagnóstico por imagem , Humanos , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Pós-Menopausa , Cloridrato de Raloxifeno/farmacologia , Cloridrato de Raloxifeno/uso terapêutico
10.
Bone ; 132: 115187, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31812699

RESUMO

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.


Assuntos
Fraturas do Quadril , Osteoporose , Ossos Pélvicos , Absorciometria de Fóton , Idoso , Densidade Óssea , Estudos Transversais , Colo do Fêmur/diagnóstico por imagem , Fraturas do Quadril/diagnóstico por imagem , Humanos , Masculino
11.
Bone ; 122: 237-245, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30840919

RESUMO

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.


Assuntos
Quadril/anatomia & histologia , Menstruação , Saúde da Mulher , Densidade Óssea , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade
12.
Bone ; 122: 150-155, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798002

RESUMO

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.


Assuntos
Fraturas do Fêmur/epidemiologia , Fêmur/patologia , Estresse Fisiológico , Densidade Óssea , Criança , Feminino , Humanos , Masculino , Fatores de Risco
13.
J Bone Miner Res ; 34(2): 241-251, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30320955

RESUMO

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.


Assuntos
Cabeça do Fêmur , Loci Gênicos , Fraturas do Quadril/genética , Desequilíbrio de Ligação , Fraturas por Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Animais , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Fraturas do Quadril/patologia , Humanos , Estudos Longitudinais , Camundongos , Fraturas por Osteoporose/patologia
14.
J Clin Endocrinol Metab ; 93(5): 1789-95, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18303076

RESUMO

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.


Assuntos
Densidade Óssea , Colo do Fêmur/patologia , Osteoprotegerina/sangue , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligante RANK/sangue
15.
J Clin Densitom ; 11(3): 351-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18495508

RESUMO

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.


Assuntos
Alendronato/farmacologia , Anticorpos Monoclonais/farmacologia , Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Ligante RANK/farmacologia , Absorciometria de Fóton , Alendronato/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Conservadores da Densidade Óssea/administração & dosagem , Denosumab , Feminino , Humanos , Análise dos Mínimos Quadrados , Pessoa de Meia-Idade , Ligante RANK/administração & dosagem , Resultado do Tratamento
16.
J Bone Miner Res ; 22(4): 551-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17243860

RESUMO

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.


Assuntos
Densidade Óssea/efeitos dos fármacos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Fêmur/efeitos dos fármacos , Fêmur/patologia , Glucocorticoides/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença de Crohn/metabolismo , Resistência a Medicamentos , Feminino , Fêmur/metabolismo , Humanos , Masculino , Síndrome Nefrótica/metabolismo , Osteoporose/induzido quimicamente
17.
J Bone Miner Res ; 22(11): 1781-90, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17638578

RESUMO

UNLABELLED: We studied HSA measurements in relation to hip fracture risk in 4,806 individuals (2,740 women). Hip fractures (n = 147) occurred at the same absolute levels of bone instability in both sexes. Cortical instability (propensity of thinner cortices in wide diameters to buckle) explains why hip fracture risk at different BMD levels is the same across sexes. INTRODUCTION: Despite the sexual dimorphism of bone, hip fracture risk is very similar in men and women at the same absolute BMD. We aimed to elucidate the main structural properties of bone that underlie the measured BMD and that ultimately determines the risk of hip fracture in elderly men and women. MATERIALS AND METHODS: This study is part of the Rotterdam Study (a large prospective population-based cohort) and included 147 incident hip fracture cases in 4,806 participants with DXA-derived hip structural analysis (mean follow-up, 8.6 yr). Indices compared in relation to fracture included neck width, cortical thickness, section modulus (an index of bending strength), and buckling ratio (an index of cortical bone instability). We used a mathematical model to calculate the hip fracture distribution by femoral neck BMD, BMC, bone area, and hip structure analysis (HSA) parameters (cortical thickness, section modulus narrow neck width, and buckling ratio) and compared it with prospective data from the Rotterdam Study. RESULTS: In the prospective data, hip fracture cases in both sexes had lower BMD, thinner cortices, greater bone width, lower strength, and higher instability at baseline. In fractured individuals, men had an average BMD that was 0.09 g/cm(2) higher than women (p < 0.00001), whereas no significant difference in buckling ratios was seen. Modeled fracture distribution by BMD and buckling ratio levels were in concordance to the prospective data and showed that hip fractures seem to occur at the same absolute levels of bone instability (buckling ratio) in both men and women. No significant differences were observed between the areas under the ROC curves of BMD (0.8146 in women and 0.8048 in men) and the buckling ratio (0.8161 in women and 0.7759 in men). CONCLUSIONS: The buckling ratio (an index of bone instability) portrays in both sexes the critical balance between cortical thickness and bone width. Our findings suggest that extreme thinning of cortices in expanded bones plays a key role on local susceptibility to fracture. Even though the buckling ratio does not offer additional predictive value, these findings improve our understanding of why low BMD is a good predictor of fragility fractures.


Assuntos
Densidade Óssea , Colo do Fêmur/diagnóstico por imagem , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/epidemiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Países Baixos , Prognóstico , Radiografia , Risco
18.
J Bone Miner Res ; 22(3): 416-24, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17147487

RESUMO

UNLABELLED: A population-based study on 1008 postmenopausal women identified that the 24% of women achieving high levels of PA and CI had 3.4-4.4% higher femoral bone strength in axial compression and 1.7-5.2% in bending than those achieving low levels, indicating that lifestyle factors influence bone strength in the proximal femur. INTRODUCTION: Extensive research has shown that increased physical activity (PA) and calcium intake (CI) decrease the rate of bone loss; however, there is little research on how these lifestyle variables affect bone geometry. This study was designed to investigate the effects of modifiable lifestyle variables, habitual PA and dietary CI, on femoral geometry in older women. MATERIALS AND METHODS: Femoral geometry, habitual PA, and dietary CI were measured in a population-based sample of 1008 women (median age+/-interquartile range, 75+/-4years) enrolled in a randomized controlled trial (RCT) of calcium supplementation. Baseline PA and CI were assessed by validated questionnaires, and 1-year DXA scans (Hologic 4500A) were analyzed using the hip structural analysis technique. Section modulus (Z), an index of bending strength, cross-sectional area (CSA), an index of axial compression strength, subperiosteal width (SPW), and centroid position, the position of the center of mass, were measured at the femoral neck (NN), intertrochanter (IT), and femoral shaft (FS) sites. These data were divided into tertiles of PA and CI, and the results were compared using analysis of covariance (ANCOVA), with corrections for age, height, weight, and treatment (calcium/placebo). RESULTS AND CONCLUSIONS: PA showed a significant dose-response effect on CSA all hip sites (p<0.03) and Z at the narrow neck and intertrochanter sites (p<0.02). For CI, there was a dose-response effect for centroid position at the intertrochanter (p=0.03). These effects were additive, such that the women (n=240) with PA in excess of 65.5 kcal/day and CI in excess of 1039 mg/day had significantly greater CSA (NN, 4.4%; IT, 4.3%; FS, 3.4%) and Z (NN, 3.9%; IT, 5.2%). These data show a favorable association between PA and aspects of bone structural geometry consistent with better bone strength. Association between CI and bone structure was only evident in 1 of 15 variables tested. However, there was evidence that there may be additive effects, whereby women with high levels of PA and CI in excess of 1039 mg/day had significantly greater CSA (NN, 0.4%; FS, 2.1%) and Z (IT, 3.0%) than women with high PA but low CI. These data show that current public health guidelines for PA and dietary CI are not inappropriate where bone structure is the health component of interest.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea , Cálcio da Dieta/administração & dosagem , Colo do Fêmur , Atividade Motora , Pós-Menopausa , Idoso , Força Compressiva , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Bone ; 41(1): 97-102, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17513185

RESUMO

Hip structure analysis (HSA) can be used to measure proximal femur geometry using conventional DXA scans of the hip. This study is the first analysis of HSA data in Japanese women to evaluate apparent age trends in the geometry of cross-sectional regions in the proximal femur. 409 Japanese women aged from 50 to 93 years of age were measured by DXA at three sites (narrow neck, intertrochanter, shaft). Using the mean value those between 50-59 years as a reference value, age trends were evaluated using groupings of 5-year intervals and those over 80 as a single group. BMD at three measured sites and section modulus (index of bending strength) at narrow neck declined in a similar age dependent manner, but section modulus at intertrochanter and shaft showed a different pattern. The decline in section modulus at narrow neck occurs after 50-59 years of age, whereas section modulus at intertrochanter remain 70-74 years, after that began to decrease. Section modulus at shaft, an uncommon fracture location, remains fairly static through life. In conclusion, HSA in Japanese women showed that reduction in geometric strength, as reflected by the section modulus, was not dependent on decline in BMD.


Assuntos
Envelhecimento/patologia , Fêmur/patologia , Absorciometria de Fóton , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Densidade Óssea , Feminino , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Humanos , Japão , Menopausa , Pessoa de Meia-Idade
20.
Bone ; 41(4): 722-32, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17662680

RESUMO

INTRODUCTION: Changes in hip structure and geometry during aging contribute to decreased bone strength. Little is known, however, about these characteristics at advanced age, when fragility fractures are common. We examined hip structural geometry in men and women of old age (72-84 years) and old-old age (85-96 years) to determine (1) gender differences; (2) whether or not these differences are consistent with the increased occurrence of hip fracture in elderly women, compared to men; and (3) whether or not gender-specific changes are consistent with the increased occurrence of fragility fractures after age 80 in both men and women. METHODS: We used Hip Structure Analysis (HSA) software to analyze bone densitometry scans from 916 community-dwelling men and women aged 72-96 years. We examined gender differences in hip geometry by age group (72-74, 75-79, 80-84, and >or=85 years) and between gender-specific age groups using multivariable linear regression. RESULTS: At the femoral narrow neck, there was no gender difference at age 72-74 in bone mineral density (BMD), cortical thickness (CT), and buckling ratio (BR). In contrast, at age 85 or older women had 13% less BMD and CT than men and 8% higher BR. At the intertrochanteric region, women >or=85 years had 25-31% less BMD, cross-sectional bone area (CSA), and CT than men of comparable age, and 38% higher BR. These gender differences were approximately 10-20% greater than those between men and women in their 70s. In gender-specific comparisons, women showed increasing change in structural geometry with increasing age. At both narrow neck and trochanteric regions, women >or=85 years had nearly 35% higher BR, 15% less BMD and CT, and 10% less CSA than women aged 72-74 years. At the narrow neck, they also had 6% greater outer diameter than the youngest women and 8% lower section modulus (Z), an index of bending strength. In contrast, men showed significant age differences only at the narrow neck region, and only at 85 years or older, including 22% higher BR, 10% less BMD and CT, and 5% greater outer diameter, compared to men in their early 70s. Unlike women, men showed no age-associated decline in section modulus. CONCLUSIONS: Gender differences in hip geometry consistent with increased fragility and fracture risk in elderly women, compared to men, continue into old-old age. Both men and women 85 or older show the most unfavorable features, suggesting a structural basis for the increased occurrence of hip fracture in both sexes at advanced age.


Assuntos
Quadril/anatomia & histologia , Ossos Pélvicos/anatomia & histologia , Caracteres Sexuais , Absorciometria de Fóton , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Densidade Óssea , Feminino , Humanos , Masculino
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