RESUMEN

OBJECTIVES: To determine whether lower extremity sensorimotor peripheral nerve deficits are associated with reduced walking endurance in older adults. DESIGN: Prospective cohort study with 6 years of follow-up. SETTING: Two university research clinics. PARTICIPANTS: Community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from the 2000-2001 annual clinical examination (N=2393; mean age ± SD, 76.5±2.9y; 48.2% men; 38.2% black) and a subset with longitudinal data (n=1178). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants underwent peripheral nerve function examination in 2000-2001, including peroneal motor nerve conduction amplitude and velocity, vibration perception threshold, and monofilament testing. Symptoms of lower extremity peripheral neuropathy included numbness or tingling and sudden stabbing, burning, pain, or aches in the feet or legs. The Long Distance Corridor Walk (LDCW) (400 m) was administered in 2000-2001 and every 2 years afterward for 6 years to assess endurance walking performance over time. RESULTS: In separate, fully adjusted linear mixed models, poor vibration threshold (>130 µm), 10-g and 1.4-g monofilament insensitivity were each associated with a slower 400-m walk completion time (16.0 s, 14.4s, and 6.9 s slower, respectively; P<.05 for each). Poor motor amplitude (<1 mV), poor vibration perception threshold, and 10-g monofilament insensitivity were related to greater slowing per year (4.7, 4.2, and 3.8 additional seconds per year, respectively; P<.05), although poor motor amplitude was not associated with initial completion time. CONCLUSIONS: Poorer sensorimotor peripheral nerve function is related to slower endurance walking and greater slowing longitudinally. Interventions to reduce the burden of sensorimotor peripheral nerve function impairments should be considered to help older adults maintain walking endurance-a critical component for remaining independent in the community.

Asunto(s)

Envejecimiento/fisiología , Nervio Peroneo/fisiopatología , Resistencia Física/fisiología , Umbral Sensorial , Caminata/fisiología , Negro o Afroamericano , Anciano , Composición Corporal , Prueba de Esfuerzo , Femenino , Humanos , Estudios Longitudinales , Masculino , Neuronas Motoras/fisiología , Conducción Nerviosa , Estudios Prospectivos , Células Receptoras Sensoriales/fisiología , Vibración , Población Blanca

RESUMEN

OBJECTIVE: Circadian rest-activity rhythms (CARs) have been cross-sectionally associated with depressive symptoms, although no longitudinal research has examined whether CARs are a risk factor for developing depressive symptoms. METHODS: We examined associations of CARs (measured with actigraphy over a mean of 4.8 days) with depressive symptoms (measured with the Geriatric Depression Scale) among 2,892 community-dwelling older men (mean age: 76.2 ± 5.5 years) from the MrOS Sleep Study who were without cognitive impairment. Among 2,124 men with minimal (0-2) symptoms at baseline, we assessed associations between CAR parameters and increases to mild (3-5) or clinically significant (≥6) symptoms after an average of 1.2 (±0.32) years. RESULTS: Cross-sectional associations between rhythm height parameters were independent of chronic diseases, lifestyle, sleep, and self-reported physical activity covariates. For example, men in the lowest mesor quartile had twice the adjusted odds (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.36-3.04, p = 0.0005) of having prevalent clinically significant symptoms (compared to minimal). Longitudinally, low CAR robustness (being in the lowest quartile of the pseudo-F statistic) was independently associated with increasing odds of developing symptoms (i.e., AOR for having clinically significant depressive symptoms at follow-up = 2.58, 95% CI: 1.11-5.99, p = 0.03). CONCLUSION: CAR disturbances are indicative of depressive symptomology. Low CAR robustness may independently contribute to the risk of worsening depression symptomology.

Asunto(s)

Envejecimiento , Trastornos Cronobiológicos , Depresión , Actigrafía/métodos , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Envejecimiento/psicología , Trastornos Cronobiológicos/complicaciones , Trastornos Cronobiológicos/diagnóstico , Trastornos Cronobiológicos/epidemiología , Trastornos Cronobiológicos/psicología , Comorbilidad , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Depresión/fisiopatología , Estudios de Seguimiento , Evaluación Geriátrica/métodos , Humanos , Vida Independiente/psicología , Estilo de Vida , Masculino , Actividad Motora , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Sueño , Estados Unidos/epidemiología

RESUMEN

PURPOSE: Uric acid inhibits vitamin D activation experimentally and higher serum urate levels are associated with higher parathyroid hormone levels in humans suggesting a link between uric acid and bone health. We hypothesized that hyperuricemia may increase the risk of fractures in older adults. METHODS: 1963 men and 2729 women ≥65 years of age who participated in the Cardiovascular Health Study and had baseline serum urate levels were included in the study. The primary outcome was incident hip fracture, assessed prospectively through June, 2008 by inpatient and outpatient records. The analysis was stratified by sex a priori. RESULTS: There was a U-shaped relationship between serum urate levels and hip fractures in men. Men in the lowest and the highest urate quartiles (<4.88 and ≥6.88 mg/dL respectively) had a significantly higher rate of fractures in unadjusted analysis. However, upon multivariate adjustment, only the HR for hip fracture in highest quartile versus the reference remained significant (HR 1.9; 95% C.I. 1.1, 3.1; p value 0.02). High serum urate levels were not associated with hip fractures in women. CONCLUSION: In this large prospective cohort of community-dwelling older adults, increased serum urate levels were associated with an increased risk of hip fractures in men. Further studies are needed to confirm these findings and to understand the mechanisms that underlie them.

Asunto(s)

Fracturas de Cadera/epidemiología , Ácido Úrico/sangre , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Cohortes , Terapia de Reemplazo de Estrógeno , Femenino , Encuestas Epidemiológicas , Fracturas de Cadera/sangre , Humanos , Estimación de Kaplan-Meier , Masculino , Estudios Prospectivos , Riesgo , Factores Sexuales , Estados Unidos/epidemiología

RESUMEN

OBJECTIVE: This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. METHODS: We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. RESULTS: In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. CONCLUSIONS: The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.

Asunto(s)

Calcinosis/sangre , Enfermedad de la Arteria Coronaria/sangre , Osteoprotegerina/sangre , Posmenopausia/sangre , Ligando RANK/sangre , Receptor Activador del Factor Nuclear kappa-B/sangre , Triglicéridos/sangre , Biomarcadores/sangre , Calcinosis/fisiopatología , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo

RESUMEN

Although fracture rates are lower in individuals of African descent compared to individuals of European ancestry, morbidity and mortality following a fracture may be greater in individuals of African ancestry. However, fracture risk and associated clinical risk factors have not been well-defined among African ancestry populations, especially among men of African ancestry. We used data collected from the Tobago Bone Health Study to examine potential clinical risk factors for incident fractures, including demographic information, anthropometric measurements, medical history, lifestyle factors, bone mineral density (BMD), and hip structural geometry. Among 1933 Afro-Caribbean men aged ≥40 years at study entry (mean age: 57.2 ± 11.0 years), 65 reported at least one new fracture during 10 years of subsequent follow-up. Younger age, mixed Afro-Caribbean ancestry, prior fracture history, BMD, and hip structural geometry were statistically significant risk factors for incident fractures. A 1-SD change in several skeletal parameters (hip BMD, cross-sectional area, outer diameter, cortical thickness, and buckling ratio) were each associated with a 35% to 56% increase in incident fracture risk after adjusting for age. Men with a prior fracture history were three times more likely to experience a new fracture during follow-up, and the association remained strong after adjusting for age, mixed Afro-Caribbean ancestry, and skeletal parameters (hazard ratios ranged from 2.72 to 2.82). Our findings suggest that except for age, risk factors for fracture in men of African ancestry are similar to established risk factors in white populations. Prior fracture history is a powerful and independent risk factor for incident fractures among men of African ancestry and could easily be incorporated into clinical risk evaluation.

Asunto(s)

Población Negra , Fracturas Óseas/etiología , Absorciometría de Fotón , Adulto , Anciano , Anciano de 80 o más Años , Densidad Ósea , Fracturas Óseas/epidemiología , Cadera/diagnóstico por imagen , Fracturas de Cadera/etiología , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Trinidad y Tobago/epidemiología

RESUMEN

OBJECTIVE: To assess whether sensorimotor peripheral nerve function is associated with muscle power in community-dwelling older men. DESIGN: Longitudinal cohort study with 2.3±0.3 years of follow-up. SETTING: One clinical site. PARTICIPANTS: Participants (n=372; mean age ± SD, 77.2±5.1y; 99.5% white; body mass index, 27.9±3.7kg/m(2); power, 1.88±0.6W/kg) at 1 site of the Osteoporotic Fractures in Men Study (N=5994). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A nerve function ancillary study was performed 4.6±0.4 years after baseline. Muscle power was measured using a power rig. Peroneal motor nerve conduction amplitude, distal motor latency, and mean f-wave latency were measured. Sensory nerve function was assessed using 10-g and 1.4-g monofilaments and sural sensory nerve conduction amplitude and distal latency. Peripheral neuropathy symptoms at the leg and feet were assessed by self-report. RESULTS: After adjustments for age, height, and total body lean and fat mass, 1 SD lower motor (ß=-.07, P<.05) and sensory amplitude (ß=-.09, P<.05) and 1.4-g (ß=-.11, P<.05) and 10-g monofilament insensitivity (ß=-.17, P<.05) were associated with lower muscle power/kg. Compared with the effect of age on muscle power (ß per year, -.05; P<.001), this was equivalent to aging 1.4 years for motor amplitude, 1.8 years for sensory amplitude, 2.2 years for 1.4-g monofilament detection, and 3.4 years for 10-g detection. Baseline 1.4-g monofilament detection predicted a greater decline in muscle power/kg. Short-term change in nerve function was not associated with concurrent short-term change in muscle power/kg. CONCLUSIONS: Worse sensory and motor nerve function were associated with lower muscle power/kg and are likely important for impaired muscle function in older men. Monofilament sensitivity was associated with a greater decline in muscle power/kg, and screening may identify an early risk for muscle function decline in late life, which has implications for disability.

Asunto(s)

Extremidad Inferior/fisiología , Fuerza Muscular/fisiología , Conducción Nerviosa/fisiología , Nervio Peroneo/fisiología , Nervio Sural/fisiología , Potenciales de Acción/fisiología , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Estudios de Cohortes , Humanos , Modelos Lineales , Estudios Longitudinales , Extremidad Inferior/inervación , Masculino

RESUMEN

Recent studies indicate that obesity is not protective against fracture in postmenopausal women and increases the risk of fracture at some sites. Risk factors for fracture in obese women may differ from those in the nonobese. We aimed to compare the ability of FRAX with and without bone mineral density (BMD) to predict fractures in obese and nonobese older postmenopausal women who were participants in the Study of Osteoporotic Fractures. Data for FRAX clinical risk factors and femoral neck BMD were available in 6049 women, of whom 18.5% were obese. Hip fractures, major osteoporotic fractures, and any clinical fractures were ascertained during a mean follow-up period of 9.03 years. Receiving operator curve (ROC) analysis, model calibration, and decision curve analysis were used to compare fracture prediction in obese and nonobese women. ROC analysis revealed no significant differences between obese and nonobese women in fracture prediction by FRAX, with or without BMD. Predicted hip fracture risk was lower than observed risk in both groups of women, particularly when FRAX + BMD was used, but there was good calibration for FRAX + BMD in prediction of major osteoporotic fracture in both groups. Decision curve analysis demonstrated that both FRAX models were useful for hip fracture prediction in obese and nonobese women for threshold 10-year fracture probabilities in the range of 4% to 10%, although in obese women FRAX + BMD was superior to FRAX alone. For major osteoporotic fracture, both FRAX models were useful in both groups of women for threshold probabilities in the range of 10% to 30%. For all clinical fractures, the FRAX models were not useful at threshold probabilities below 30%. We conclude that FRAX is of value in predicting hip and major osteoporotic fractures in obese postmenopausal women, particularly when used with BMD.

Asunto(s)

Algoritmos , Obesidad/complicaciones , Obesidad/epidemiología , Fracturas Osteoporóticas/complicaciones , Fracturas Osteoporóticas/epidemiología , Medición de Riesgo/métodos , Anciano , Área Bajo la Curva , Femenino , Humanos , Incidencia , Curva ROC , Estados Unidos/epidemiología

RESUMEN

Vitamin D deficiency is highly prevalent worldwide, and is linked to several major chronic, inflammatory and autoimmune diseases. Vitamin D deficiency has not been evaluated in dark skinned individuals living in areas of high sun exposure utilizing more reliable mass spectrometry assay techniques. We determined the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in Afro-Caribbean men on the tropical island of Tobago, where there is a high level of sunshine year round. Serum 25(OH)D2 and 25(OH)D3 metabolites were measured following extraction and purification using liquid chromatography and tandem mass spectrometry in 424 Afro-Caribbean men aged > 65 years from a larger population-based cohort study. The mean (+/- SD) serum total 25(OH)D concentration was 35.1 +/- 8.9 ng/mL. Deficiency (< 20 ng/mL) was present in only 2.8% and insufficiency (< 30 ng/mL) in 24% of the men. Multiple linear regression analysis identified age, BMI and daily vitamin D supplementation as the independent correlates of 25(OH)D. None of the men who consumed fish more than once per week had vitamin D deficiency, compared to 4% of the men who consumed fish once per week or less (P = .01, adjusted for age, BMI, and daily vitamin D supplementation). In conclusion, vitamin D deficiency is very uncommon in this Afro-Caribbean population. Longitudinal studies are needed to delineate the possible effects of high vitamin D levels in this population on major diseases hypothesized to be associated with vitamin D deficiency.

Asunto(s)

Población Negra , Deficiencia de Vitamina D/etnología , Anciano , Anciano de 80 o más Años , Humanos , Modelos Lineales , Masculino , Análisis Multivariante , Prevalencia , Trinidad y Tobago/epidemiología , Vitamina D/análogos & derivados , Vitamina D/sangre

RESUMEN

Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry; and calf skeletal muscle fat distribution (subcutaneous and intermuscular fat; skeletal muscle density) was measured using quantitative computed tomography in 472 Afro-Caribbean men 65 years and older. Bioactive androgens, testosterone, free testosterone, and dihydrotestosterone were associated with less skeletal muscle fat infiltration (r = -0.14 to -0.18, P < .05) and increased skeletal muscle density (r = 0.10 to 0.14, P < .05), independent of total adiposity. In addition, glucuronidated androgen metabolites were associated with less subcutaneous fat (r = -0.11 to -0.15, P < .05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (odds ratio = 1.38, P < .01) and a decreased level of dihydrotestosterone (odds ratio = 0.66, P < .01) to be significantly associated with T2DM. Our findings suggest that, in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM.

Asunto(s)

Adiposidad/fisiología , Envejecimiento/metabolismo , Andrógenos/metabolismo , Músculo Esquelético/metabolismo , Anciano , Anciano de 80 o más Años , Población Negra , Composición Corporal/fisiología , Índice de Masa Corporal , Humanos , Resistencia a la Insulina/fisiología , Masculino , Sobrepeso/metabolismo , Trinidad y Tobago

RESUMEN

BACKGROUND: Despite considerable racial and geographical differences in human phenotypes and in the incidence of diseases that may be associated with sex steroid action, there are few data concerning variation in sex steroid levels among populations. We designed an international study to determine the degree to which geography and race influence sex steroid levels in older men. METHODS: Using mass spectrometry, concentrations of serum androgens, estrogens, and sex steroid precursors/metabolites were measured in 5003 older men from five countries. SHBG levels were assessed using radioimmunoassay. RESULTS: There was substantial geographical variation in the levels of sex steroids, precursors, and metabolites, as well as SHBG. For instance, Asian men in Hong Kong and Japan, but not in the United States, had levels of total testosterone approximately 20% higher than in other groups. Even greater variation was present in levels of estradiol, SHBG, and dihydrotestosterone. Group differences in body mass index did not explain most geographical differences. In addition, body mass index-independent racial differences were present; Black men had higher levels of estrogens (estradiol, estrone), and Asian men had lower levels of glucuronidated androgen metabolites. CONCLUSIONS: On a global scale, there are important geographical and racial differences in the concentrations of serum sex steroids and SHBG in older men.

Asunto(s)

Hormonas Esteroides Gonadales/sangre , Grupos Raciales , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Envejecimiento/metabolismo , Análisis Químico de la Sangre/métodos , Estudios de Cohortes , Geografía , Hormonas Esteroides Gonadales/análisis , Hormonas Esteroides Gonadales/metabolismo , Hong Kong , Humanos , Japón , Masculino , Espectrometría de Masas , Modelos Biológicos , Grupos Raciales/estadística & datos numéricos , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/metabolismo , Trinidad y Tobago , Estados Unidos

RESUMEN

Although low body weight is a risk factor for osteoporosis-related fractures, conflicting data exist for the association between adiposity and bone mineral density (BMD). Studies examining these relationships have measured body fat and BMD with dual-energy X-ray absorptiometry (DXA), which cannot distinguish subcutaneous adipose tissue area (SAT) from total adiposity or trabecular from cortical bone. To investigate the relationship between adiposity and BMD further, we analyzed body composition and adipose tissue distribution by quantitative computed tomography (QCT) in 1829 Afro-Caribbean men aged 40 years and older from a population-based sample. Cortical volumetric BMD, muscle cross-sectional area, total adipose tissue area (TAT), and percentage SAT were measured at the proximal tibia. Trabecular volumetric BMD was measured at the distal tibia. We used analysis of covariance to test for associations between quartile of the adipose tissue measures and BMD, adjusting for anthropometric, health, and lifestyle factors. Higher TAT was associated with lower cortical BMD in both unadjusted and adjusted models (p < .001). Men with a higher percentage SAT had greater cortical BMD (p < .001). Similar associations were seen between percent SAT and trabecular BMD at the distal tibia. These results indicate that total adiposity is a potentially important correlate of bone mass in older men and that different fat depots may have opposing associations with bone mass. Additional research is needed to better understand the mechanisms underlying the relationship between body fat distribution and bone mass.

Asunto(s)

Tejido Adiposo/diagnóstico por imagen , Población Negra , Densidad Ósea , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Coherencia Óptica , Tomografía Computarizada por Rayos X , Trinidad y Tobago

RESUMEN

QCT provides a measure of volumetric BMD (vBMD) and distinguishes trabecular from cortical bone. Few studies have determined the factors related to vBMD in men, especially among men of African heritage. This study evaluated the relationship of anthropometric, medical, and behavioral factors and vBMD in a population-based cohort of men of African ancestry (n = 1901) >or=40 yr of age who had undergone screening for prostate cancer for the first time. Trabecular and cortical vBMD were measured at the radius and tibia by pQCT. Multiple linear regression analysis identified age, height, body weight, cigarette smoking, history of diabetes, fracture, and prostate cancer as the independent correlates of vBMD. However, associations with several variables differed between cortical and trabecular vBMD and between the radius and tibia. Longitudinal studies are needed to gain a better understanding of the mechanisms underlying these differential associations that may show new insight into the etiology of trabecular and cortical bone loss in men.

Asunto(s)

Población Negra , Densidad Ósea , Adulto , Anciano , Anciano de 80 o más Años , Composición Corporal , Huesos/anatomía & histología , Humanos , Masculino , Persona de Mediana Edad , Indias Occidentales

RESUMEN

Little is known about the magnitude, pattern, and determinants of bone loss with advancing age among men, particularly among those of African descent. We examined the rate of decline in hip BMD and identified factors associated with BMD loss among 1478 Afro-Caribbean men >or=40 yr of age. BMD was measured at baseline and after an average of 4.4 yr by DXA. The rate of decline in femoral neck BMD was 0.29 +/- 0.81%/yr in the total sample (p < 0.0001). However, a U-shaped relationship between advancing age and the rate of decline in BMD was observed. The rate of decline in BMD at the femoral neck was -0.38 +/- 0.77%/yr among men 40-44 yr of age, decelerated to -0.15 +/- 0.81%/yr among men 50-54 yr of age, and then accelerated to -0.52 +/- 0.90%/yr among those 75+ yr of age (all p < 0.003). Men who lost >or=5% of their body weight during follow-up had significantly greater BMD loss than those who remained weight stable or gained weight (p < 0.0001). The relationship between weight loss and BMD loss was more pronounced among men who were older and leaner at study entry (p < 0.03). We also observed a strong impact of advanced prostate cancer and its treatment with androgen deprivation on BMD loss. Men of African ancestry experience substantial BMD loss with advancing age that seems to be comparable to the rate of loss among white men in other studies. Additional studies are needed to better define the natural history and factors underlying bone loss with aging in men of African ancestry.

Asunto(s)

Envejecimiento , Peso Corporal , Densidad Ósea , Cuello Femoral/fisiopatología , Osteoporosis/fisiopatología , Anciano , Población Negra , Cuello Femoral/patología , Estudios de Seguimiento , Cadera , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/epidemiología , Osteoporosis/etnología , Osteoporosis/patología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/fisiopatología , Trinidad y Tobago/epidemiología , Trinidad y Tobago/etnología

RESUMEN

WNT signaling is an important determinant of bone formation. The WNT co-receptor, Frizzled homolog 1 (FZD1), initiates WNT signal transduction. To study the influence of FZD1 genetic variation on measures of bone health, we first sequenced a 6.8-kb region surrounding FZD1 in 48 samples of African ancestry. We genotyped all common polymorphisms and performed association analysis with bone phenotypes in a larger sample. Only 3 of 35 SNPs identified were present in >or=5% of the sample and assayed further in 1084 men of African ancestry. Two of these SNPs were in the FZD1 promoter (rs2232157, rs2232158) and were associated with femoral neck areal BMD (p = 0.041 and 0.009, respectively). The minor alleles of these two SNPs were also associated with larger bone size at the radius (p < 0.05 for both), and rs2232158 was associated with greater strength-strain index, an indicator of bone's ability to withstand torsion. Functional experiments were completed to assess the influence of the rs2232158 promoter polymorphism on transcriptional regulation of FZD1. The minor C allele in rs2232158 creates a binding site for the transcription factor Egr1, has higher Egr1 binding affinity, and has greater FZD1 promoter activity in MG63 and SaOS-2 cells, providing a plausible molecular mechanism for the population associations. This study indicates that a cis-regulatory polymorphism in the FZD1 promoter region may have a functional role in determining bone structural geometry.

Asunto(s)

Huesos/metabolismo , Receptores Frizzled/genética , Variación Genética , Proteínas Relacionadas con Receptor de LDL/genética , Adulto , Alelos , Sitios de Unión , Densidad Ósea , Humanos , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Trinidad y Tobago

RESUMEN

Population dynamics predict a drastic growth in the number of older minority women, and resultant increases in the number of fractures. Low bone mineral density (BMD) is an important risk factor for fracture. Many studies have identified the lifestyle and health-related factors that correlate with BMD in Whites. Few studies have focused on non-Whites. The objective of the current analyses is to examine the lifestyle, anthropometric and health-related factors that are correlated with BMD in a population based cohort of Caribbean women of West African ancestry. We enrolled 340 postmenopausal women residing on the Caribbean Island of Tobago. Participants completed a questionnaire and had anthropometric measures taken. Hip BMD was measured by DXA. We estimated volumetric BMD by calculating bone mineral apparent density (BMAD). BMD was >10% and >25% higher across all age groups in Tobagonian women compared to US non-Hispanic Black and White women, respectively. In multiple linear regression models, 35-36% of the variability in femoral neck and total hip BMD respectively was predicted. Each 16-kg (one standard deviation (SD)) increase in weight was associated with 5% higher BMD; and weight explained over 10% of the variability of BMD. Each 8-year (1 SD) increase in age was associated with 5% lower BMD. Current use of both thiazide diuretics and oral hypoglycemic medication were associated with 4-5% higher BMD. For femoral neck BMAD, 26% of the variability was explained by a multiple linear regression model. Current statin use was associated with 5% higher BMAD and a history of breast feeding or coronary heart disease was associated with 1-1.5% of higher BMAD. In conclusion, African Caribbean women have the highest BMD on a population level reported to date for women. This may reflect low European admixture. Correlates of BMD among Caribbean women of West African ancestry were similar to those reported for U.S. Black and White women.

Asunto(s)

Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Humanos , Femenino , Research Support, Non-U.S. Gov't , Densidad Ósea , Encuestas Epidemiológicas , Estilo de Vida , Posmenopausia , Encuestas y Cuestionarios , Trinidad y Tobago/epidemiología , Salud de la Mujer , Población Negra , Osteoporosis Posmenopáusica

RESUMEN

Population dynamics predict a drastic growth in the number of older minority women, and resultant increases in the number of fractures. Low bone mineral density (BMD) is an important risk factor for fracture. Many studies have identified the lifestyle and health-related factors that correlate with BMD in Whites. Few studies have focused on non-Whites. The objective of the current analyses is to examine the lifestyle, anthropometric and health-related factors that are correlated with BMD in a population based cohort of Caribbean women of West African ancestry. We enrolled 340 postmenopausal women residing on the Caribbean Island of Tobago. Participants completed a questionnaire and had anthropometric measures taken. Hip BMD was measured by DXA. We estimated volumetric BMD by calculating bone mineral apparent density (BMAD). BMD was >10% and >25% higher across all age groups in Tobagonian women compared to US non-Hispanic Black and White women, respectively. In multiple linear regression models, 35-36% of the variability in femoral neck and total hip BMD respectively was predicted. Each 16-kg (one standard deviation (SD)) increase in weight was associated with 5% higher BMD; and weight explained over 10% of the variability of BMD. Each 8-year (1 SD) increase in age was associated with 5% lower BMD. Current use of both thiazide diuretics and oral hypoglycemic medication were associated with 4-5% higher BMD. For femoral neck BMAD, 26% of the variability was explained by a multiple linear regression model. Current statin use was associated with 5% higher BMAD and a history of breast feeding or coronary heart disease was associated with 1-1.5% of higher BMAD. In conclusion, African Caribbean women have the highest BMD on a population level reported to date for women. This may reflect low European admixture. Correlates of BMD among Caribbean women of West African ancestry were similar to those reported for U.S. Black and White women.

Asunto(s)

Densidad Ósea , Posmenopausia , Salud de la Mujer , Anciano , Anciano de 80 o más Años , Femenino , Encuestas Epidemiológicas , Humanos , Estilo de Vida , Persona de Mediana Edad , Análisis de Regresión , Encuestas y Cuestionarios , Trinidad y Tobago/epidemiología

RESUMEN

OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a possible surrogate of lifetime exposure to hormone/growth factor/vitamin D/calcium exposure, is higher in prostate cancer cases than controls. METHODS: Hip BMD was measured by dual X-ray absorptiometry in 222 Afro-Caribbean screening-detected prostate cancer cases and 1,503 screened non-cases, aged 45-79, in the population-based Tobago Prostate Survey. Because possible skeletal metastases may modulate BMD, men with prostate specific antigen >20 ng/ml or highly undifferentiated tumors (Gleason score > or = 8) were excluded. Mean BMD, adjusted for age and body mass index, was compared in cases and non-cases by analysis of variance. Risk across age group-specific BMD quartiles was compared using logistic regression. RESULTS: Overall, adjusted mean hip BMD was higher in cases (1.157 g/cm2) than non-cases (1.134 g/cm2) (p = 0.02). In men aged 60-79, prostate cancer risk was two-fold higher (OR, 2.12; 95% CI: 1.21-3.71) in the highest BMD quartile compared to the lowest. There was no association in younger men (interaction, p = 0.055). CONCLUSIONS: High bone density is associated with prostate cancer among older men, consistent with an etiological role for lifetime exposure to factors which modulate bone density. However, other etiologies may dominate prostate cancer risk among younger men.

Asunto(s)

Envejecimiento/fisiología , Población Negra/estadística & datos numéricos , Densidad Ósea/fisiología , Encuestas Epidemiológicas , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/fisiopatología , Adulto , Distribución por Edad , Anciano , Estudios de Casos y Controles , Cadera/fisiología , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Trinidad y Tobago/epidemiología