RESUMEN
UNLABELLED: We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. INTRODUCTION: Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. METHODS: The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. RESULTS: After adjusting for age, body height, and weight, we found lower cross-sectional area (p = 0.005) and section modulus (p = 0.005), thinner cortex (p = 0.012), and higher buckling ratio (p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. CONCLUSION: Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis.
Asunto(s)
Enfermedades Óseas Metabólicas/etiología , Cuello Femoral/fisiopatología , Cirrosis Hepática Alcohólica/complicaciones , Absorciometría de Fotón/métodos , Adulto , Anciano , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/patología , Enfermedades Óseas Metabólicas/fisiopatología , Estudios de Casos y Controles , Colágeno Tipo I/sangre , Cuello Femoral/patología , Humanos , Cirrosis Hepática Alcohólica/sangre , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Alcohólica/fisiopatología , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Péptidos/sangreRESUMEN
DXA-derived bone structural geometry has been reported extensively but lacks an accuracy standard. In this study, we describe a novel anthropometric structural geometry phantom that simulates the proximal femur for use in assessing accuracy of geometry measurements by DXA or other X-ray methods. The phantom consists of seven different interchangeable neck modules with geometries that span the range of dimensions in an adult human proximal femur, including those representing osteoporosis. Ten repeated hip scans of each neck module using two current DXA scanner models were performed without repositioning. After scanner specific calibration, hip structure analysis was used to derive structural geometry. Scanner performance was similar for the two manufacturers. DXA-derived HSA geometric measurements were highly correlated with values derived directly from phantom geometry and position; R² between DXA and phantom measures were greater than 94% for all parameters, while precision error ranged between 0.3 and 3.9%. Despite high R² there were some systematic geometry errors for both scanners that were small for outer diameter, but increasing with complexity of geometrical parameter; e.g. buckling ratio. In summary, the anthropometric phantom and its fabrication concept were shown to be appropriate for evaluating proximal femoral structural geometry in two different DXA systems.
Asunto(s)
Absorciometría de Fotón/instrumentación , Absorciometría de Fotón/métodos , Fémur/anatomía & histología , Fémur/diagnóstico por imagen , Fantasmas de Imagen , Interpretación de Imagen Radiográfica Asistida por Computador/instrumentación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: The study goal was to compare simple two-dimensional (2D) analyses of bone strength using dual energy x-ray absorptiometry (DXA) data to more sophisticated three-dimensional (3D) finite element analyses using quantitative computed tomography (QCT) data. DXA- and QCT-derived femoral neck geometry, simple strength indices, and strength estimates were well correlated. INTRODUCTION: Simple 2D analyses of bone strength can be done with DXA data and applied to large data sets. We compared 2D analyses to 3D finite element analyses (FEA) based on QCT data. METHODS: Two hundred thirteen women participating in the Study of Women's Health Across the Nation (SWAN) received hip DXA and QCT scans. DXA BMD and femoral neck diameter and axis length were used to estimate geometry for composite bending (BSI) and compressive strength (CSI) indices. These and comparable indices computed by Hip Structure Analysis (HSA) on the same DXA data were compared to indices using QCT geometry. Simple 2D engineering simulations of a fall impacting on the greater trochanter were generated using HSA and QCT femoral neck geometry; these estimates were benchmarked to a 3D FEA of fall impact. RESULTS: DXA-derived CSI and BSI computed from BMD and by HSA correlated well with each other (R=0.92 and 0.70) and with QCT-derived indices (R=0.83-0.85 and 0.65-0.72). The 2D strength estimate using HSA geometry correlated well with that from QCT (R=0.76) and with the 3D FEA estimate (R=0.56). CONCLUSIONS: Femoral neck geometry computed by HSA from DXA data corresponds well enough to that from QCT for an analysis of load stress in the larger SWAN data set. Geometry derived from BMD data performed nearly as well. Proximal femur breaking strength estimated from 2D DXA data is not as well correlated with that derived by a 3D FEA using QCT data.
Asunto(s)
Cuello Femoral/fisiología , Posmenopausia/fisiología , Absorciometría de Fotón/métodos , Adulto , Densidad Ósea/fisiología , Fuerza Compresiva/fisiología , Femenino , Cuello Femoral/anatomía & histología , Cuello Femoral/diagnóstico por imagen , Humanos , Imagenología Tridimensional/métodos , Estudios Longitudinales , Persona de Mediana Edad , Estrés Mecánico , Tomografía Computarizada por Rayos X/métodos , Soporte de Peso/fisiologíaRESUMEN
UNLABELLED: People with both HIV and hepatitis C are more likely than those with HIV alone to have wrist, hip, and spine fractures. We compared hip strength between HIV/HCV-co-infected men and healthy men and found that HIV/HCV-co-infected men had decreased hip strength due to lower lean body mass. INTRODUCTION: Hepatitis C co-infection is a risk factor for fragility fracture among HIV-infected populations. Whether bone strength is compromised in HIV/HCV-co-infected patients is unknown. METHODS: We compared dual-energy x-ray absorptiometry (DXA)-derived hip geometry, a measure of bone strength, in 88 HIV/HCV-co-infected men from the Johns Hopkins HIV Clinic to 289 men of similar age and race and without HIV or HCV from the Boston Area Community Health Survey/Bone Survey. Hip geometry was assessed at the narrow neck, intertrochanter, and shaft using hip structural analysis. Lean body mass (LBM), total fat mass (FM), and fat mass ratio (FMR) were measured by whole-body DXA. Linear regression was used to identify body composition parameters that accounted for differences in bone strength between cohorts. RESULTS: HIV/HCV-co-infected men had lower BMI, LBM, and FM and higher FMR compared to controls (all p < 0.05). At the narrow neck, significant differences were observed between HIV/HCV-co-infected men and controls in bone mineral density, cross-sectional area, section modulus, buckling ratio, and centroid position. After adjustment for race, age, smoking status, height, and weight, only buckling ratio and centroid position remained significantly different between cohorts (all p < 0.05). Substituting LBM, FM, and FMR for weight in the multivariate model revealed that differences in LBM, but not FM or FMR, accounted for differences in all narrow neck parameters between cohorts, except buckling ratio and centroid position. CONCLUSION: HIV/HCV-co-infected men have compromised hip strength at the narrow neck compared to uninfected controls, which is attributable in large part to lower lean body mass.
Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Articulación de la Cadera/patología , Absorciometría de Fotón , Adulto , Anciano , Composición Corporal , Densidad Ósea , Estudios de Casos y Controles , Estudios Transversales , Articulación de la Cadera/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Ratchet based microwave current generators and detectors were developed in Si/SiGe heterostructures for wireless communication with the possibility of extending the detection limit to the terahertz range. A microwave induced ratchet current was generated in the two-dimensional electron gas by patterning an array of semicircular antidots in hexagonal geometry. The spatial asymmetry created by the semicircular antidots forces the electrons under the influence of the microwave electric field to move preferentially towards the direction of the semidisc axis. A photovoltage of the order of few millivolts was observed. Such a photovoltage was completely absent in a symmetric system consisting of circular antidots. The induced photovoltage increased monotonically with microwave power and was found to be independent of the microwave polarization. This device opens the possibility of employing silicon based heterostructures for nanogenerators and other wireless communication devices using microwaves.
RESUMEN
SUMMARY: Participants in the observational study of the Women's Health Initiative (WHI) were studied to determine if ethnic differences in femur geometry can help to explain differences in hip fracture rates. Structural differences in femurs of African and Mexican-American women appear to be consistent with lower rates of hip fractures vs. whites. INTRODUCTION: Ethnic origin has a major influence on hip fractures, but the underlying etiology is unknown. We evaluated ethnic differences in hip fracture rates among 159,579 postmenopausal participants in the WHI then compared femur bone mineral density (BMD) and geometry among a subset with dual X-ray absorptiometry (DXA) scans of the hip and total body. METHODS: The subset included 8,206 non-Hispanic whites, 1,476 African-American (AA), 704 Mexican-American (MA), and 130 Native Americans (NA). Femur geometry derived from hip DXA using hip-structure analysis (HSA) in whites was compared to minority groups after adjustment for age, height, weight, percent lean mass, neck-shaft angle and neck length, hormone use, chronic disease (e.g., diabetes, rheumatoid arthritis, cancer), bone active medications (e.g., corticosteroids, osteoporosis therapies), and clinical center. RESULTS: Both AA and MA women suffered hip fractures at half the rate of whites while NA appeared to be similar to whites. The structural advantage among AA appears to be due to a slightly narrower femur that requires more bone tissue to achieve similar or lower section moduli (SM) vs. whites. This also underlies their higher BMD (reduces region area) and lower buckling ratios (buckling susceptibility). Both MA and NA women had similar advantages vs. whites at the intertrochanter region where cross-sectional area and SM were higher but with no differences at the neck. NA and MA had smaller bending moments vs. whites acting in a fall on the hip (not significant in small NA sample). Buckling ratios of MA did not differ from whites at any region although NA had 4% lower values at the IT region. CONCLUSION: Differences in the geometry at the proximal femur are consistent with the lower hip fracture rates among AA and MA women compared to whites.
Asunto(s)
Fémur/patología , Osteoporosis Posmenopáusica/etnología , Fracturas Osteoporóticas/etnología , Absorciometría de Fotón/métodos , Negro o Afroamericano/estadística & datos numéricos , Anciano , Densidad Ósea/fisiología , Femenino , Fémur/fisiopatología , Cuello Femoral/patología , Cuello Femoral/fisiopatología , Humanos , Indígenas Norteamericanos/estadística & datos numéricos , Americanos Mexicanos/estadística & datos numéricos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/patología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/patología , Fracturas Osteoporóticas/fisiopatología , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
UNLABELLED: This study examined femur geometry underlying previously observed decline in BMD of the contralateral hip in older women the year following hip fracture compared to non-fractured controls. Compared to controls, these women experienced a greater decline in indices of bone structural strength, potentially increasing the risk of a second fracture. INTRODUCTION: This study examined the femur geometry underlying previously observed decline in BMD of the contralateral hip in the year following hip fracture compared to non-fractured controls. METHODS: Geometry was derived from dual-energy X-ray absorptiometry scan images using hip structural analysis from women in the third cohort of the Baltimore Hip Studies and from women in the Study of Osteoporotic Fractures. Change in BMD, section modulus (SM), cross-sectional area (CSA), outer diameter, and buckling ratio (BR) at the narrow neck (NN), intertrochanteric (IT), and shaft (S) regions of the hip were compared. RESULTS: Wider bones and reduced CSA underlie the significantly lower BMD observed in women who fractured their hip resulting in more fragile bones expressed by a lower SM and higher BR. Compared to controls, these women experienced a significantly greater decline in CSA (-2.3% vs. -0.2%NN, -3.2% vs. -0.5%IT), SM (-2.1% vs. -0.2%NN, -3.9% vs. -0.6%IT), and BMD (-3.0% vs. -0.8%NN, -3.3% vs. -0.6%IT, -2.3% vs. -0.2%S) and a greater increase in BR (5.0% vs. 2.1%NN, 6.0% vs. 1.3%IT, 4.4% vs. 1.0%S) and shaft outer diameter (0.9% vs. 0.1%). CONCLUSION: The contralateral femur continued to weaken during the year following fracture, potentially increasing the risk of a second fracture.
Asunto(s)
Fémur/fisiopatología , Fracturas de Cadera/fisiopatología , Fracturas Osteoporóticas/fisiopatología , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Densidad Ósea/fisiología , Métodos Epidemiológicos , Femenino , Fémur/patología , Cuello Femoral/patología , Cuello Femoral/fisiopatología , Fracturas de Cadera/patología , Humanos , Fracturas Osteoporóticas/patologíaRESUMEN
SUMMARY: Hip geometry measurements of outer diameter and buckling ratio at the intertrochanter and shaft of the hip dual energy X-ray absorptiometry (DXA) scan predicted incident hip fracture in postmenopausal women. These associations, independent of age, body size, clinical risk factors, and conventional areal bone mineral density, suggest hip geometry plays a role in fracture etiology and may aid in improving identification of older women at high fracture risk. INTRODUCTION: This study examined whether hip geometry parameters predicted hip fracture independent of body size, clinical risk factors, and conventional femoral neck bone mineral density (aBMD) and whether summary factors could be identified to predict hip fracture. METHODS: We studied 10,290 postmenopausal women from the Women's Health Initiative. Eight thousand eight hundred forty-three remained fracture free during follow-up to 11 years of follow-up, while 147 fractured their hip, and 1,300 had other clinical fractures. Hip structural analysis software measured bone cross-sectional area, outer diameter, section modulus, average cortical thickness, and buckling ratio on archived DXA scans in three hip regions: narrow neck, intertrochanter, and shaft. Hazard ratios were estimated using Cox proportional hazards models for individual parameters and for composite factors extracted from principal components analysis from all 15 parameters. RESULTS: After adjustment for age, body size, clinical risk factors, and aBMD, intertrochanter and shaft outer diameter measurements remained independent predictors of hip fracture with hazard ratios for a one standard deviation increase of 1.61 (95% confidence interval (CI), 1.25-2.08) for the intertrochanter and 1.36 (95% CI, 1.06-1.76) for the shaft. Average buckling ratios also independently predicted incident hip fracture with hazard ratios of 1.43 (95% CI, 1.10-1.87) at the intertrochanter and 1.24 (95% CI, 1.00-1.55) at the shaft. Although two composite factors were extracted from principal components analysis, neither was superior to these individual measurements at predicting incident hip fracture. CONCLUSIONS: Two hip geometry parameters, intertrochanter outer diameter and buckling ratio, predict incident hip fracture after accounting for clinical risk factors and aBMD.
Asunto(s)
Densidad Ósea/fisiología , Fracturas de Cadera/patología , Articulación de la Cadera/patología , Fracturas Osteoporóticas/patología , Absorciometría de Fotón , Anciano , Métodos Epidemiológicos , Femenino , Fémur/patología , Fémur/fisiopatología , Cuello Femoral/fisiopatología , Fracturas de Cadera/epidemiología , Fracturas de Cadera/fisiopatología , Articulación de la Cadera/fisiopatología , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Osteoporosis Posmenopáusica/patología , Osteoporosis Posmenopáusica/fisiopatología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/fisiopatología , Estados Unidos/epidemiologíaRESUMEN
UNLABELLED: The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. INTRODUCTION: It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. METHODS: We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. RESULTS: At age 17, subjects with the highest E2 levels in year 1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. CONCLUSIONS: This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.
Asunto(s)
Estradiol/orina , Cuello Femoral/fisiología , Actividad Motora/fisiología , Pubertad/fisiología , Adolescente , Calcio/orina , Estradiol/fisiología , Femenino , Cuello Femoral/crecimiento & desarrollo , Humanos , Estudios Longitudinales , Menarquia/fisiología , Vitamina D/administración & dosificación , Vitaminas/administración & dosificaciónRESUMEN
OBJECTIVE: Radiographic hip osteoarthritis (RHOA) is associated with increased hip areal bone mineral density (aBMD). This study was undertaken to examine whether femoral geometry is associated with RHOA independent of aBMD. METHODS: Participants in the Study of Osteoporotic Fractures in whom pelvic radiographs had been obtained at visits 1 and 5 (mean 8.3 years apart) and hip dual x-ray absorptiometry (DXA) had been performed (2 years after baseline) were included. Prevalent and incident RHOA phenotypes were defined as composite (osteophytes and joint space narrowing [JSN]), atrophic (JSN without osteophytes), or osteophytic (femoral osteophytes without JSN). Analogous definitions of progression were based on minimum joint space and total osteophyte score. Hip DXA scans were assessed using the Hip Structural Analysis program to derive geometric measures, including femoral neck length, width, and centroid position. Relative risks and 95% confidence intervals for prevalent, incident, and progressive RHOA per SD increase in geometric measure were estimated in a hip-based analysis using multinomial logistic regression with adjustment for age, body mass index, knee height, and total hip aBMD. RESULTS: In 5,245 women (mean age 72.6 years), a wider femoral neck with a more medial centroid position was associated with prevalent and incident osteophytic and composite RHOA phenotypes (P < 0.05). Increased neck width and centroid position were associated with osteophyte progression (both P < 0.05). No significant geometric associations with atrophic RHOA were found. CONCLUSION: Differences in proximal femoral bone geometry and spatial distribution of bone mass occur early in hip OA and predict prevalent, incident, and progressive osteophytic and composite phenotypes, but not the atrophic phenotype. These bone differences may reflect responses to loading occurring early in the natural history of RHOA.
Asunto(s)
Densidad Ósea/fisiología , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/fisiopatología , Fracturas de Cadera/epidemiología , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/fisiopatología , Osteoporosis/complicaciones , Absorciometría de Fotón , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Fracturas de Cadera/fisiopatología , Humanos , Modelos Logísticos , Osteoartritis de la Cadera/epidemiología , Osteofito/diagnóstico por imagen , Osteofito/fisiopatología , Osteoporosis/fisiopatología , Fenotipo , Prevalencia , Factores de RiesgoRESUMEN
SUMMARY: DXA-based hip structural analysis from 947 individuals completing two large osteoporosis clinical trials was pooled and analyzed. Treatment with once-weekly (OW) ALN or OW RIS resulted in significant improvements from baseline in geometric parameters at all three HSA ROIs. Improvements were generally greater with OW ALN than OW RIS. INTRODUCTION: BMD can be altered by changes in distribution and quantity of bone and changes in mineralization. These effects cannot be distinguished with conventional measurements of BMD. Currently, tissue composition is evaluated only by invasive means. Structural geometry of the proximal femur, however, can be measured in vivo by several methods, including dual energy X-ray absorptiometry (DXA) using specialized hip structure analysis (HSA) software. METHODS: DXA-based HSA was obtained and analyzed in a subset of 947 subjects participating in the Fosamax Actonel Comparison Trials. Data were pooled to evaluate treatment effects on the structural geometry of the proximal femur by once-weekly alendronate (ALN) 70 mg and risedronate (RIS) 35 mg in postmenopausal women with low bone mass. RESULTS: Both ALN and RIS treatment over 2 years resulted in improvements in HSA-derived geometry at all three HSA regions of interest (ROI). The largest treatment effects were seen at the intertrochanteric ROI. Consistently greater treatment effects were seen with ALN compared with RIS at all three HSA-ROIs. CONCLUSIONS: HSA offers insight into the potential mechanisms of fracture risk reduction from pharmacologic intervention. In the current study, treatment with once-weekly bisphosphonates resulted in significant improvements in hip geometric parameters.
Asunto(s)
Absorciometría de Fotón/métodos , Densidad Ósea/efectos de los fármacos , Fémur/diagnóstico por imagen , Fracturas Óseas/diagnóstico por imagen , Cadera/diagnóstico por imagen , Osteoporosis Posmenopáusica/diagnóstico por imagen , Alendronato/farmacología , Difosfonatos/farmacología , Ácido Etidrónico/análogos & derivados , Ácido Etidrónico/farmacología , Femenino , Fémur/efectos de los fármacos , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/tratamiento farmacológico , Ácido Risedrónico , Medición de RiesgoRESUMEN
The authors develop a unique CT simulation tool based on the 4D extended cardiac-torso (XCAT) phantom, a whole-body computer model of the human anatomy and physiology based on NURBS surfaces. Unlike current phantoms in CT based on simple mathematical primitives, the 4D XCAT provides an accurate representation of the complex human anatomy and has the advantage, due to its design, that its organ shapes can be changed to realistically model anatomical variations and patient motion. A disadvantage to the NURBS basis of the XCAT, however, is that the mathematical complexity of the surfaces makes the calculation of line integrals through the phantom difficult. They have to be calculated using iterative procedures; therefore, the calculation of CT projections is much slower than for simpler mathematical phantoms. To overcome this limitation, the authors used efficient ray tracing techniques from computer graphics, to develop a fast analytic projection algorithm to accurately calculate CT projections directly from the surface definition of the XCAT phantom given parameters defining the CT scanner and geometry. Using this tool, realistic high-resolution 3D and 4D projection images can be simulated and reconstructed from the XCAT within a reasonable amount of time. In comparison with other simulators with geometrically defined organs, the XCAT-based algorithm was found to be only three times slower in generating a projection data set of the same anatomical structures using a single 3.2 GHz processor. To overcome this decrease in speed would, therefore, only require running the projection algorithm in parallel over three processors. With the ever decreasing cost of computers and the rise of faster processors and multi-processor systems and clusters, this slowdown is basically inconsequential, especially given the vast improvement the XCAT offers in terms of realism and the ability to generate 3D and 4D data from anatomically diverse patients. As such, the authors conclude that the efficient XCAT-based CT simulator developed in this work will have applications in a broad range of CT imaging research.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Miocardio/patología , Fantasmas de Imagen , Mecánica Respiratoria , Tomografía Computarizada por Rayos X/métodos , Algoritmos , Simulación por Computador , Femenino , Humanos , Masculino , Modelos Biológicos , Factores de Tiempo , Irradiación Corporal TotalRESUMEN
INTRODUCTION: Fracture risk is associated with bone mineral density (BMD) and with other indices of bone strength, including hip geometry. While the heritability and associated fracture risk of BMD are well described, less is known about genetic influences of bone geometry. We derived hip structural phenotypes using the Hip Structural Analysis program (HSA) and performed autosome-wide linkage analysis of hip geometric structural phenotypes. MATERIALS AND METHODS: The Amish Family Osteoporosis Study was designed to identify genes affecting bone health. BMD was measured at the hip using dual X-ray absorptiometry (DXA) in 879 participants (mean age+/-SD=49.8+/-16.1 years, range 18-91 years) from large multigenerational families. From DXA scans, we computed structural measures of hip geometry at the femoral neck (NN) and shaft (S) by HSA, including cross-sectional area (CSA), endocortical or inner diameter (ID), outer diameter (OD) buckling ratio (BR) and section modulus (Z). Genotyping of 731 highly polymorphic microsatellite markers (average spacing of 5.4 cM) and autosome-wide multipoint linkage analysis was performed. RESULTS: The heritability of HSA-derived hip phenotypes ranged from 40 to 84%. In the group as a whole, autosome-wide linkage analysis suggested evidence of linkage for QTLs related to NN_Z on chromosome 1p36 (LOD=2.36). In subgroup analysis, ten additional suggestive regions of linkage were found on chromosomes 1, 2, 5, 6, 11, 12, 14, 15 and 17, all with LOD>2.3 except for our linkage at 17q11.2-13 for men and women age 50 and under for NN_CSA, which had a lower LOD of 2.16, but confirmed a previous linkage report. CONCLUSIONS: We found HSA-derived measures of hip structure to be highly heritable independent of BMD. No strong evidence of linkage was found for any phenotype. Confirmatory evidence of linkage was found on chromosome 17q11.2-12 for NN_CSA. Modest evidence was found for genes affecting hip structural phenotypes at ten other chromosomal locations.
Asunto(s)
Curación de Fractura , Ligamiento Genético , Cadera/patología , Osteoporosis/diagnóstico , Osteoporosis/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Densidad Ósea , Mapeo Cromosómico , Femenino , Humanos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
UNLABELLED: The effects of physical activity on bone strength acquisition during growth are not well understood. In our cluster randomized trial, we found that participation in a novel school-based physical activity program enhanced bone strength acquisition and bone mass accrual by 2-5% at the femoral neck in girls; however, these benefits depended on teacher compliance with intervention delivery. Our intervention also enhanced bone mass accrual by 2-4% at the lumbar spine and total body in boys. INTRODUCTION: We investigated the effects of a novel school-based physical activity program on femoral neck (FN) bone strength and mass in children aged 9-11 yrs. METHODS: We used hip structure analysis to compare 16-month changes in FN bone strength, geometry and bone mineral content (BMC) between 293 children who participated in Action Schools! BC (AS! BC) and 117 controls. We assessed proximal femur (PF), lumbar spine (LS) and total body (TB) BMC using DXA. We compared change in bone outcomes between groups using linear regression accounting for the random school effect and select covariates. RESULTS: Change in FN strength (section modulus, Z), cross-sectional area (CSA), subperiosteal width and BMC was similar between control and intervention boys, but intervention boys had greater gains in BMC at the LS (+2.7%, p = 0.05) and TB (+1.7%, p = 0.03) than controls. For girls, change in FN-Z tended to be greater (+3.5%, p = 0.1) for intervention girls than controls. The difference in change increased to 5.4% (p = 0.05) in a per-protocol analysis that included girls whose teachers reported 80% compliance. CONCLUSION: AS! BC benefits bone strength and mass in school-aged children; however, our findings highlight the importance of accounting for teacher compliance in classroom-based physical activity interventions.
Asunto(s)
Cuello Femoral/fisiología , Modelos Biológicos , Actividad Motora/fisiología , Pubertad/fisiología , Absorciometría de Fotón , Antropometría/métodos , Densidad Ósea/fisiología , Niño , Ejercicio Físico/fisiología , Femenino , Humanos , Vértebras Lumbares/fisiología , Masculino , Instituciones Académicas , Factores SexualesRESUMEN
Nitric oxide (NO), produced by endothelial cells, is a signaling molecule synthesized from l-arginine by nitric oxide synthases (NOS). NO is known to reduce the ratio of receptor activator of nuclear factor KappaB (RANKL)/osteoprotegerin (OPG), leading to decreased osteoclastogenesis and a reduction in bone resorption. Endothelial nitric oxide synthase (eNOS or NOS3) is the predominant constitutive isoform of nitric NOS within bone. Recently, a NOS3 polymorphism, Glu298Asp, previously implicated in osteoporosis, failed to demonstrate an association with bone mineral density (BMD), although there was some indication of an association with selected geometry indices. Since a single polymorphism does not capture all of the potential variants in a given gene, we investigated a broader coverage of the NOS3 gene with bone density/ultrasound and geometry indices in a sample of unrelated individuals from the Framingham Offspring Study. Our results indicated that the Glu298Asp polymorphism was not associated with BMD but suggested some haplotype-based associations in the linkage disequilibrium (LD) region that included the Glu298Asp polymorphism with several geometry indices. Although our findings exhibited several associations with selected bone density/ultrasound and geometry indices, the nominally significant associations are regarded as primarily hypothesis generating and suggest that replication in other samples is needed. Thus, NOS3 genetic variation does not appear to be a major contributor to adult bone density/ultrasound and geometry in our sample.
Asunto(s)
Densidad Ósea/genética , Huesos/anatomía & histología , Huesos/diagnóstico por imagen , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Polimorfismo de Nucleótido Simple/genética , Adulto , Haplotipos , Humanos , Desequilibrio de Ligamiento , Persona de Mediana Edad , UltrasonografíaRESUMEN
UNLABELLED: Data on bone architecture in diverse male populations are limited. We examined proximal femur geometry in 1,190 black, Hispanic, and white men. Cross-sectional analyses indicate greatest bone strength among black men, and greater age-related differences in bone strength among Hispanic men than other subjects at the narrow neck and intertrochanter regions of the proximal femur. INTRODUCTION: Although race/ethnic differences in bone mass are well-documented, less is known about differences in bone architecture. We examined proximal femur geometry in a diverse, randomly-sampled population of 1,190 community-dwelling men (age 30-79 y). METHODS: Dual X-ray absorptiometry scans were obtained for 355 black, 394 Hispanic, and 441 white subjects. Measures were obtained for the narrow neck (NN), intertrochanter (IT) and shaft regions of the proximal femur via hip structural analysis. Analyses considered bone mineral density (BMD, g/cm2), outer diameter (cm), cross-sectional area (CSA, cm2), section modulus (Z, cm3), and buckling ratio (BR). Results were adjusted for height, weight and physical activity level. RESULTS: Black subjects exhibited greater age-specific BMD, CSA and Z, than their white counterparts. For instance, at age 50 y, NN BMD was approximately 11% higher among black men (p < 0.001). Hispanic men exhibited sharper age-related differences in NN and IT BMD than did others. IT BMD, for instance, decreased by 2.4% with 10 y age among Hispanic subjects, but had virtually no age trend in others (p < 0.001). CONCLUSIONS: These results imply greater bone strength among black American men than among their white counterparts, and may indicate elevated fracture risk among older Hispanic American subpopulations.
Asunto(s)
Envejecimiento/etnología , Envejecimiento/fisiología , Densidad Ósea/fisiología , Fémur/fisiología , Absorciometría de Fotón , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Envejecimiento/patología , Estatura/fisiología , Peso Corporal/fisiología , Estudios Transversales , Fémur/anatomía & histología , Cuello Femoral/anatomía & histología , Cuello Femoral/fisiología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Población Blanca/estadística & datos numéricosRESUMEN
Areal bone mineral density (aBMD), derived from dual-energy X-ray absorptiometry (DXA) scanners is used routinely to infer bone strength. With DXA hip scans there is growing acceptance of the advantages of also measuring bone structural geometric variables, that complement conventional aBMD to improve understanding of bone modelling, remodelling and processes of metabolic bone disease. However, phantoms for assessing structural geometric variables from DXA scans are not widely available, unlike those for aBMD. This study describes the development of such a phantom, simulating the cortical shell of the human femoral neck, using dental plaster as a material radiologically similar to cortical bone. The mass attenuation coefficient of the dental plaster differed by < 1% from cortical bone, over the relevant energy range. Performance testing was carried out with DXA, to determine accuracy and precision of the phantom structural geometry, using its dimensions and composition as 'gold standards'. Accuracy and precision of cortical structural geometry were poor when measured in a simulated 1 mm-thick osteoporotic cortex (5.5% precision and 50% accuracy errors), but improved with increasing cortical thickness. This study demonstrates the limitations of DXA-based Hip Structure Analysis when applied to femora with thin cortices, and indicates improvements in the design of a phantom to better simulate such cortical structures.
Asunto(s)
Absorciometría de Fotón/métodos , Materiales Biomiméticos/química , Densidad Ósea/fisiología , Revestimiento para Colado Dental/química , Fémur/diagnóstico por imagen , Fémur/fisiología , Fantasmas de Imagen , Humanos , Ensayo de MaterialesRESUMEN
Femoral geometry and body size are both characterized by substantial heritability. The purpose of this study was to discern whether hip geometry and body size (height and body mass index, BMI) share quantitative trait loci (QTL). Dual-energy X-ray absorptiometric scans of the proximal femur from 1,473 members in 323 pedigrees (ages 31-96 years) from the Framingham Osteoporosis Study were studied. We measured femoral neck length, neck-shaft angle, subperiosteal width (outer diameter), cross-sectional bone area, and section modulus, at the narrowest section of the femoral neck (NN), intertrochanteric (IT), and femoral shaft (S) regions. In variance component analyses, genetic correlations (rho ( G )) between hip geometry traits and height ranged 0.30-0.59 and between hip geometry and BMI ranged 0.11-0.47. In a genomewide linkage scan with 636 markers, we obtained nominally suggestive linkages (bivariate LOD scores > or =1.9) for geometric traits and either height or BMI at several chromosomes (4, 6, 9, 15, and 21). Two loci, on chr. 2 (80 cM, BMI/shaft section modulus) and chr. X (height/shaft outer diameter), yielded bivariate LOD scores > or =3.0; although these loci were linked in univariate analyses with a geometric trait, neither was linked with either height or BMI. In conclusion, substantial genetic correlations were found between the femoral geometric traits, height and BMI. Linkage signals from bivariate linkage analyses of bone geometric indices and body size were similar to those obtained in univariate linkage analyses of femoral geometric traits, suggesting that most of the detected QTL primarily influence geometry of the hip.
Asunto(s)
Tamaño Corporal/genética , Fémur/anatomía & histología , Ligamiento Genético , Sitios de Carácter Cuantitativo , Absorciometría de Fotón , Anciano , Anciano de 80 o más Años , Femenino , Articulación de la Cadera/anatomía & histología , Humanos , Masculino , Persona de Mediana Edad , LinajeRESUMEN
INTRODUCTION: Better characterization of bone geometry in adolescents with anorexia nervosa (AN) may improve understanding of skeletal deficits in this population. Our objective was to determine whether hip cross-sectional geometry and bone strength were altered in adolescents with AN. METHODS: Measurements of the left total proximal femur and body composition were obtained in 85 adolescents with AN and 61 healthy controls by dual X-ray absorptiometry. The Hip Structural Analysis (HSA) program was used to determine aBMD, cross-sectional area (CSA), and section modulus (Z) at the femoral neck and shaft. Strength indices were calculated and corrected for lean mass. RESULTS: Femoral neck and shaft aBMD were lower in AN patients than healthy controls (-36% and -29%, p < 0.001). In both regions, bone CSA and Z were lower in AN sufferers (-11 to -35%, p < 0.001). While lean body mass correlated with HSA variables (r = 0.48 to 0.58, p < 0.001), body fat did not. AN sufferers had lower indices of both whole bone strength (-40%, p < 0.001) and relative bone strength (-36%, p < 0.001) than controls. CONCLUSIONS: Anorexia nervosa sufferers had decreased resistance to axial (CSA) and bending loads (Z) compared with healthy controls. Differences in strength properties were significant even when adjusted for lean mass, suggesting that not only decreased mechanical loading, but also known metabolic differences are likely responsible for deficits in bone strength in these patients.
Asunto(s)
Anorexia Nerviosa/patología , Fémur/patología , Absorciometría de Fotón , Adolescente , Adulto , Anorexia Nerviosa/fisiopatología , Antropometría/métodos , Fenómenos Biomecánicos , Composición Corporal , Densidad Ósea , Femenino , Fémur/fisiopatología , Cuello Femoral/patología , Cuello Femoral/fisiopatología , Humanos , Soporte de PesoRESUMEN
CONTEXT: Little is known of associations between hip geometry and skeletal regulators. This is important because geometry is a determinant of both hip function and resistance to fracture. OBJECTIVE: We aimed to determine the effects of sex hormone status and other candidate regulators on hip geometry and strength. SUBJECTS AND METHODS: A random sample of 351 women aged 67-79 had two to four hip dual-energy x-ray absorptiometry scans performed over 8 yr of follow-up. Hip structural analysis software was used to measure subperiosteal diameter (PD) and the distance from the center of mass to the lateral cortical margin (d-lat) on three 5-mm-thick cross-sectional regions: narrow neck, intertrochanter, and shaft. Section modulus (Z), bone mineral density (grams per centimeter squared), and an index of bone mineral content (cross-sectional area) were calculated as estimators of bone strength. Serum analytes measured at baseline included SHBG, estradiol, PTH, creatinine, albumin, vitamin D metabolites, and glutamate- and gamma-carboxyglutamate-osteocalcin (OC). A linear mixed model was used to model associations with predictor variables, including testing whether the predictors significantly modified the effect of aging. RESULTS: Aging was associated with increasing PD and d-lat, and higher baseline SHBG significantly modified this effect, in the case of PD, increasing the rates of change at the narrow neck region by 19% for SHBG level 2 sd higher than population mean (P = 0.026). Higher baseline creatinine was independently associated with faster increases in PD and d-lat with aging (P < 0.041). Z declined faster with aging if baseline PTH was higher, and higher albumin had a contrary effect. Z was positively associated with free estradiol and inversely associated with SHBG and glutamate-OC. CONCLUSION: These results show large effects of SHBG on the regulation of proximal femur expansion and bending resistance, probably acting as a surrogate for low bioavailable estrogen. Potentially important effects for fracture resistance in old age were also revealed for PTH, markers related to renal function and the nutritional markers albumin and undercarboxylated OC.