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1.
J Matern Fetal Neonatal Med ; : 1-6, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31039650

RESUMO

BACKGROUND: In the USA, 12-14% have type 2 diabetes mellitus and the incidence is rising. Adolescent birth has been shown to be associated with significant gestational weight gain and obesity in adulthood. OBJECTIVE: We sought to evaluate the association between the history of adolescent birth and diabetes in adulthood. STUDY DESIGN: We conducted a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) data, examining 2-year cycles from 2005 to 2014. In a population of adult women who had experienced at least one live birth and who were not currently pregnant, we examined the prevalence of type 2 diabetes mellitus by the history of adolescent birth (live birth prior to 20 years of age). Sample characteristics were compared using survey-weighted chi-square tests. Multivariate logistic regression was used to examine the association between diabetes mellitus and adolescent birth history, with progressive adjustments for birth cohort, race/ethnicity, education level, and body mass index (BMI). RESULTS: In a survey sample of 6507 individuals, we found that 38% of the women had experienced adolescent birth. Significant differences were found between those who had experienced adolescent birth and those who had not by birth cohort, race/ethnicity, federal poverty level, education attainment, parity, and BMI (p < .001 for all). The prevalence of type 2 diabetes was higher in women with a history of adolescent birth in adulthood than in women without a history of adolescent birth (17.2 versus 12.1%, p < .001; BMI-adjusted odds ratio = 1.27; 95% confidence interval, 1.03-1.58, p = .03). CONCLUSION: American women with a history of adolescent birth are at a significantly higher risk of type 2 diabetes mellitus in adulthood. Greater attention must be paid to preventing metabolic disease in women who experience early parity.

2.
Bone ; 126: 18-26, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30954730

RESUMO

Proteins are an essential part of essentially all biological processes, and there is enormous variation in protein forms and concentrations that is not reflected in DNA or RNA. Recently there have been rapid advances in the ability to measure protein sequence, modification and concentration, particularly with methods based in mass spectrometry. Global measures of proteins in tissues or in the circulation provide a broad assessment of the proteome that can be extremely useful for discovery, and targeted proteomic measures can yield specific and sensitive assessments of specific peptides and proteins. While most proteomic measures are directed at the detection of consensus peptide sequences, mass spectrometry based proteomic methods also allow a detailed examination of the peptide sequence differences that result from genetic variants and that may have important effects on protein function. In evaluating proteomic data, a number of analytical considerations are important, including an understanding of missing data, the challenge of multiple testing and replication, and the use of rapidly evolving methods in systems biology. While proteomics has not yet had a major impact in skeletal research, interesting recent research has used these approaches in the study of bone cell biology and the discovery of biomarkers of skeletal disorders. Proteomics can be expected to have an increasing influence in the study of bone biology and pathophysiology.

3.
J Gen Intern Med ; 34(6): 978-985, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30684199

RESUMO

BACKGROUND: Colorectal cancer screening by fecal immunochemical test (FIT) reduces the burden of colorectal cancer. However, effectiveness relies on annual adherence, which presents challenges for clinic staff and patients. OBJECTIVE: Describe FIT return rates and identify factors associated with FIT adherence over 2 years in a mailed FIT outreach program in federally qualified health centers. DESIGN: Observational study nested in the Strategies and Opportunities to Stop Colon Cancer in Priority Populations (STOP CRC) trial. Five thousand one hundred ninety-five patients had an initial FIT order and were followed for ≥ 2 years (3574 also had a FIT order in the second year). MAIN MEASURES: FIT return percent in each year and patient- and neighborhood-level characteristics associated with FIT adherence. KEY RESULTS: Overall, the proportion of FIT orders that were completed was 46% in the patients' first year and 41% in the patients' second year. Of the 5195 patients with a FIT order in year 1, 3574 (69%) also had a FIT order in year 2 (71% of year 1 adherers and 67% of year 1 non-adherers, p = 0.009). Among those with a FIT order in the second year, the FIT return rate was about twice as high among those who were adherent in the first year (952/1674, or 57%) as among those who were not (531/1900, or 28%, p < 0.0001). Patient-level characteristics associated with higher odds of FIT return were a history of FIT screening at baseline, age over 65 (vs 50-65), no current tobacco use, recent receipt of a mammogram or flu vaccine, Asian ancestry (compared to non-Hispanic white), and non-English preference. The only neighborhood factor associated with lower FIT return rate was patient's larger residential city size. CONCLUSION: Our findings can inform the customization of programs to promote FIT return among patients who receive care at federally qualified health centers. TRIAL REGISTRATION: http://www.clinicaltrials.gov.

4.
Prev Med Rep ; 12: 210-213, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30364785

RESUMO

The effectiveness of annual mailed fecal immunochemical testing (FIT) outreach is highest when return rates are optimized, which is aided by patient reminders. In a pilot patient-randomized controlled trial in two western Washington clinics of the Sea Mar Community Health Centers, we compared the effectiveness of two phone-based approaches to mailed FIT outreach reminders. In fall 2016, patients ages 50-75, due for colorectal cancer screening, and with a visit in the previous year at either of two clinics, were mailed an introductory letter and FIT. Those who did not return the FIT within 3 weeks (N = 427) were randomized to receive either: a) a series of up to 6 automated phone reminders; or b) the combination of automated and live phone reminders (up to 6 in total). The sole outcome was FIT return within 6 months after the FIT mailing. FIT completion rates were similar in the groups assigned to receive automated calls vs automated plus live calls (40% vs 39%; p = 0.89). The effectiveness of FIT reminder mode differed by language preference (p for interaction = 0.03): among Spanish-preferring patients (n = 106), FIT return rates were higher in the automated-only group than to the auto- plus live-call group (62% vs 39%, p = 0.02). Among English-preferring patients, no difference in modes was observed (n = 279, 32% vs 34%, p = 0.74). We observed no added benefit of live reminder calls in a mailed FIT plus automated call reminder program; our findings may inform efforts to efficiently optimize mailed-FIT outreach programs. ClinicalTrials.gov identifier NCT01742065.

5.
PLoS Genet ; 14(9): e1007601, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30261039

RESUMO

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10-8. Suggestive (p<5×10-7) and genome-wide significant (p<5×10-8) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2×10-10). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10-11), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10-19). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4×10-13), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10-10). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

6.
Cancer Med ; 7(9): 4781-4790, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30101513

RESUMO

Annual fecal immunochemical testing (FIT) is cost-effective for colorectal cancer (CRC) screening. However, FIT positivity rates and positive predictive value (PPV) can vary substantially, with false-positive (FP) results adding to colonoscopy burden without improving cancer detection. Our objective was to describe FIT PPV and the factors associated with FP results among patients undergoing CRC screening. In an ongoing pragmatic clinical trial of mailed-FIT outreach, clinics delivered one of three FIT brands (InSure, OC-Micro, and Hemosure). Patients who had a positive FIT result and a follow-up colonoscopy were included in this analysis (N = 1130). Patients' demographic and medical histories were abstracted from electronic health records (EHR). Associations with a FP result (ie, a positive FIT result with no evidence of advanced neoplasia during follow-up colonoscopy) were evaluated for FIT brand and patient factors using mixed-effects multivariable logistic regression. The mean proportion of FIT-positive results ranged from 8% in centers using the OC-Micro test to 21% for Hemosure. PPVs for advanced neoplasia were 0.30 to 0.17, respectively (P for χ2  = 0.08). In multivariable-adjusted models, use of Hemosure was associated with greater odds of a FP result than OC-Micro (OR = 2.00, 95% CI: 0.47-8.56) or InSure (OR = 1.72, 95% CI: 0.44-6.68). However, only female sex (OR = 1.58, 95% CI: 1.19-2.10) and history of a colorectal condition (OR = 2.17, 95% CI: 1.13-4.15) were significantly associated with FP. In conclusion, FIT positivity varied by brand, and FP results differed by patient factors available through the EHR. These results can be used to minimize the frequency of FP results, reducing patient distress and colonoscopy burden.

7.
Aging Cell ; 17(2)2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29399943

RESUMO

The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri-annual questionnaire. Rigorous statistical methods were utilized to identify 56 peptides (31 proteins) that were associated with 5-year mortality. In an independent replication phase, selected reaction monitoring was used to examine 21 of those peptides in baseline serum from 750 additional men; 81% of those peptides remained significantly associated with mortality. Mortality-associated proteins included a variety involved in inflammation or complement activation; several have been previously linked to mortality (e.g., C-reactive protein, alpha 1-antichymotrypsin) and others are not previously known to be associated with mortality. Other novel proteins of interest included pregnancy-associated plasma protein, VE-cadherin, leucine-rich α-2 glycoprotein 1, vinculin, vitronectin, mast/stem cell growth factor receptor, and Saa4. A panel of peptides improved the predictive value of a commonly used clinical predictor of mortality. Overall, these results suggest that complex inflammatory pathways, and proteins in other pathways, are linked to 5-year mortality risk. This work may serve to identify novel biomarkers for near-term mortality.

8.
J Clin Endocrinol Metab ; 103(3): 991-1004, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325096

RESUMO

Context: Serum estradiol (E2) and estrone (E1) levels exhibit substantial heritability. Objective: To investigate the genetic regulation of serum E2 and E1 in men. Design, Setting, and Participants: Genome-wide association study in 11,097 men of European origin from nine epidemiological cohorts. Main Outcome Measures: Genetic determinants of serum E2 and E1 levels. Results: Variants in/near CYP19A1 demonstrated the strongest evidence for association with E2, resolving to three independent signals. Two additional independent signals were found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B), rs5934505 (P = 3.4 × 10-8) and Xq27.3, rs5951794 (P = 3.1 × 10-10). E1 signals were found in CYP19A1 (rs2899472, P = 5.5 × 10-23), in Tripartite motif containing 4 (TRIM4; rs17277546, P = 5.8 × 10-14), and CYP11B1/B2 (rs10093796, P = 1.2 × 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral density (BMD). Mendelian randomization analysis suggested a causal effect of serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a 0.048 standard deviation increase in lumbar spine BMD (P = 2.8 × 10-12). In men and women combined, CYP19A1 alleles associated with higher E2 levels were associated with lower degrees of insulin resistance. Conclusions: Our findings confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and strengthen the causal importance of E2 for bone health in men. We also report two independent loci on the X-chromosome for E2, and one locus each in TRIM4 and CYP11B1/B2, for E1.


Assuntos
Aromatase/genética , Densidade Óssea/genética , Estradiol/sangue , Densidade Óssea/fisiologia , Cromossomos Humanos X , Estudos de Coortes , Estradiol/genética , Estradiol/fisiologia , Estrona/sangue , Estrona/genética , Feminino , Regulação da Expressão Gênica/fisiologia , Estudo de Associação Genômica Ampla , Genótipo , Hormônios Esteroides Gonadais/sangue , Humanos , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Vértebras Lombares/fisiologia , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Testosterona/sangue
9.
Ann Rheum Dis ; 77(3): 378-385, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29170203

RESUMO

OBJECTIVES: To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. METHODS: Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. RESULTS: A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. CONCLUSION: We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism.

10.
J Am Soc Nephrol ; 28(8): 2311-2321, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28360221

RESUMO

Disorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P<5.0 × 10-6 Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 × 10-5), with combined stages 1 and 2 genome-wide significance of P=5.6 × 10-10 Transethnic meta-analysis further supported the association at rs9980 (P=5.9 × 10-12). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 × 10-8). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous system and relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance.


Assuntos
Loci Gênicos , Plasma/química , Simportadores de Sódio-Bicarbonato/genética , Sódio/análise , Fatores de Transcrição/genética , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/genética , Idoso , Grupos de Populações Continentais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar
11.
Arch Osteoporos ; 12(1): 29, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28286929

RESUMO

Cannabis use is rising in the USA. Its relationship to cannabinoid signaling in bone cells implies its use could affect bone mineral density (BMD) in the population. In a national survey of people ages 20-59, we found no association between self-reported cannabis use and BMD of the hip or spine. INTRODUCTION: Cannabis is the most widely used illegal drug in the USA, and its recreational use has recently been approved in several US states. Cannabinoids play a role in bone homeostasis. We aimed to determine the association between cannabis use and BMD in US adults. METHODS: In the National Health and Nutrition Examination Survey 2007-2010, 4743 participants between 20 and 59 years old, history of cannabis use was categorized into never, former (previous use, but not in last 30 days), light (1-4 days of use in last 30 days), and heavy (≥5 days of use in last 30 days). Multivariable linear regression was used to test the association between cannabis use and DXA BMD of the proximal femur and lumbar spine with adjustment for age, sex, BMI, and race/ethnicity among other BMD determinants. RESULTS: Sixty percent of the population reported ever using cannabis; 47% were former users, 5% were light users, and 7% were heavy users. Heavy cannabis users were more likely to be male, have a lower BMI, increased daily alcohol intake, increased tobacco pack-years, and were more likely to have used other illegal drugs (cocaine, heroin, or methamphetamines). No association between cannabis and BMD was observed for any level of use (p ≥ 0.28). CONCLUSIONS: A history of cannabis use, although highly prevalent and related to other risk factors for low BMD, was not independently associated with BMD in this cross-sectional study of American men and women.


Assuntos
Densidade Óssea/efeitos dos fármacos , Cannabis/efeitos adversos , Fumar Maconha/efeitos adversos , Absorciometria de Fóton/métodos , Adulto , Estudos Transversais , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/efeitos dos fármacos , Humanos , Modelos Lineares , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Masculino , Fumar Maconha/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
12.
J Bone Miner Res ; 32(7): 1559-1567, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28316103

RESUMO

Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men (MrOS) study comprises men ≥65 years old in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multidimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥0 g/cm2 , n = 453); expected loss (estimated change 0 to 1 SD below the estimated mean change, -0.034 g/cm2 for femoral neck, n = 1184); and accelerated loss (estimated change ≥1 SD below mean change, n = 237). Differential abundance values of 3946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss versus maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥1.1 or ≤0.9 (p < 0.10), 20 proteins were associated with accelerated BMD loss. Associations of those 20 proteins with incident hip fracture were tested using Cox proportional hazards models with age and BMI adjustment in 2473 men. Five proteins were associated with incident hip fracture (HR between 1.29 and 1.41 per SD increase in estimated protein abundance). Some proteins have been previously associated with fracture risk (eg, CD14 and SHBG), whereas others have roles in cellular senescence and aging (B2MG and TIMP1) and complement activation and innate immunity (CO7, CO9, CFAD). These findings may inform development of biomarkers for future research in bone biology and fracture prediction. © 2017 American Society for Bone and Mineral Research.


Assuntos
Densidade Óssea , Fraturas do Quadril/sangue , Quadril , Osteoporose/sangue , Peptídeos/sangue , Proteoma/metabolismo , Proteômica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Humanos , Masculino , Osteoporose/patologia
13.
J Bone Miner Res ; 32(6): 1182-1193, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28177140

RESUMO

Extreme phosphate levels (P) have been associated with mineralization defects and increased fracture risk. Whether P within normal range is related to bone health in the general population is not well understood. To investigate the association of P with bone mineral density (BMD) and fracture risk, we assessed two population-based cohorts: the Dutch Rotterdam Study (RS-I, RS-II, RS-III; n = 6791) and the US Osteoporotic Fractures in Men (MrOS; n = 5425) study. The relationship of P with lumbar spine (LS) and femoral neck (FN) BMD was tested in all cohorts via linear models; fracture risk was tested in RS-I, RS-II, and MrOS through Cox models, after follow-up of 8.6, 6.6, and 10.9 years, respectively. Adjustments were made for age, body mass index, smoking, serum levels of calcium, potassium, 25-hydroxyvitamin D, estimated glomerular filtration rate (eGFR), FN-BMD, prevalent diabetes, and cardiovascular disease. Additional adjustments were made for phosphate intake, parathyroid hormone, and fibroblast growth factor 23 levels in MrOS. We further stratified by eGFR. Results were pooled through study-level meta-analyses. Hazard ratios (HR) and betas (ß) (from meta-analyses) are expressed per 1 mg/dL P increase. P was positively associated with fracture risk in men and women from RS, and findings were replicated in MrOS (pooled HR all [95% CI]: 1.47 [1.31-1.65]). P was associated with fracture risk in subjects without chronic kidney disease (CKD): all (1.44 [1.26-1.63]) and in men with CKD (1.93 [1.42-2.62]). P was inversely related to LS-BMD in men (ß: -0.06 [-0.11 to -0.02]) and not to FN-BMD in either sex. In summary, serum P was positively related to fracture risk independently from BMD and phosphate intake after adjustments for potential confounders. P and LS-BMD were negatively related in men. Our findings suggest that increased P levels even within normal range might be deleterious for bone health in the normal population. © 2017 American Society for Bone and Mineral Research.


Assuntos
Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Fosfatos/sangue , Idoso , Densidade Óssea , Jejum/sangue , Feminino , Colo do Fêmur/fisiopatologia , Fraturas Ósseas/fisiopatologia , Humanos , Incidência , Masculino , Países Baixos , Fraturas por Osteoporose/fisiopatologia , Fatores de Risco
14.
J Aging Health ; 29(7): 1235-1250, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27469600

RESUMO

OBJECTIVE: The aim of this study is to evaluate fall rates across body mass index (BMI) categories by age group, considering physical performance and comorbidities. METHOD: In the Osteoporotic Fractures in Men (MrOS) study, 5,834 men aged ≥65 reported falls every 4 months over 4.8 (±0.8) years. Adjusted associations between BMI and an incident fall were tested using mixed-effects models. RESULTS: The fall rate (0.66/man-year overall, 95% confidence interval [CI] = [0.65, 0.67]) was lowest in the youngest, normal weight men (0.44/man-year, 95% CI = [0.41, 0.47]) and greatest in the oldest, highest BMI men (1.47 falls/man-year, 95% CI = [1.22, 1.76]). Obesity was associated with a 24% to 92% increased fall risk in men below 80 ( ptrend ≤ .0001, p for interaction by age = .03). Only adjustment for dynamic balance test altered the BMI-falls association substantially. DISCUSSION: Obesity was independently associated with higher fall rates in men 65 to 80 years old. Narrow walk time, a measure of gait stability, may mediate the association.

15.
J Am Soc Nephrol ; 28(5): 1553-1565, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27927781

RESUMO

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10-17), rs219779 adjacent to CLDN14 (P=3.5 × 10-16), rs4443100 near RTDR1 (P=8.7 × 10-9), and rs73186030 near CASR (P=4.8 × 10-8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.


Assuntos
Variação Genética , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Europa (Continente) , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade
16.
Prev Chronic Dis ; 13: E151, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27809419

RESUMO

INTRODUCTION: The development of functional limitations among adults aged 65 or older has profound effects on individual and population resources. Improved understanding of the relationship between functional limitations and co-occurring chronic diseases (multimorbidity) is an emerging area of interest. The objective of this study was to investigate the association between multimorbidity and functional limitations among community-dwelling adults 65 or older in the United States and explore factors that modify this association. METHODS: We conducted a cross-sectional analysis of adults aged 65 or older using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 through 2012. We used negative binomial regression to estimate the association between multimorbidity (≥2 concurrent diseases) and functional limitations and to determine whether the association differed by sex or age. RESULTS: The prevalence of multimorbidity in this population was 67% (95% confidence interval [CI], 65%-68%). Each additional chronic condition was associated with an increase in the number of functional limitations, and the association was stronger among those aged 75 or older than among those aged 65 to 74. For those aged 65 to 74, each additional chronic condition was associated with 1.35 (95% CI, 1.27-1.43) times the number of functional limitations for men and 1.62 times (95% CI, 1.31-2.02) the number of functional limitations for women. For those 75 or older, the associations increased to 1.71 (95% CI, 1.35-2.16) for men and 2.06 (95% CI, 1.51-2.81) for women for each additional chronic condition. CONCLUSION: Multimorbidity was associated with increases in functional limitations, and the associations were stronger among women than among men and among adults aged 75 or older than among those aged 65 to 74. These findings underscore the importance of addressing age and sex differences when formulating prevention strategies.


Assuntos
Envelhecimento , Doença Crônica/classificação , Doença Crônica/epidemiologia , Comorbidade/tendências , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Análise de Regressão , Estados Unidos
17.
J Bone Miner Res ; 31(12): 2085-2097, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27476799

RESUMO

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (ß = 0.22, p = 1.9 × 10-8 ) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (ß = 0.09, p = 1.2 × 10-10 ) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10-4 ). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (ß = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (ß = 0.12, FDR p = 1.7 × 10-3 , functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.


Assuntos
Densidade Óssea/genética , Transportador 1 de Aminoácido Excitatório/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptor EphB2/genética , Fraturas da Coluna Vertebral/genética , Coluna Vertebral/patologia , Animais , Biópsia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/patologia , Osso Esponjoso/fisiopatologia , Transportador 1 de Aminoácido Excitatório/metabolismo , Regulação da Expressão Gênica , Humanos , Desequilíbrio de Ligação/genética , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , Camundongos , Anotação de Sequência Molecular , Tamanho do Órgão , Osteoblastos/metabolismo , Locos de Características Quantitativas/genética , Receptor EphB2/metabolismo , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/patologia , Fraturas da Coluna Vertebral/fisiopatologia , Coluna Vertebral/diagnóstico por imagem
19.
J Clin Endocrinol Metab ; 101(5): 2226-34, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27007693

RESUMO

CONTEXT: Total 25-hydroxyvitamin D (25OHD) is a marker of vitamin D status and is lower in African Americans than in whites. Whether this difference holds for free 25OHOD (f25OHD) is unclear, considering reported genetic-racial differences in vitamin D binding protein (DBP) used to calculate f25OHD. OBJECTIVES: Our objective was to assess racial-geographic differences in f25OHD and to understand inconsistencies in racial associations with DBP and calculated f25OHD. DESIGN: This study used a cross-sectional design. SETTING: The general community in the United States, United Kingdom, and The Gambia were included in this study. PARTICIPANTS: Men in Osteoporotic Fractures in Men and Medical Research Council studies (N = 1057) were included. EXPOSURES: Total 25OHD concentration, race, and DBP (GC) genotype exposures were included. OUTCOME MEASURES: Directly measured f25OHD, DBP assessed by proteomics, monoclonal and polyclonal immunoassays, and calculated f25OHD were the outcome measures. RESULTS: Total 25OHD correlated strongly with directly measured f25OHD (Spearman r = 0.84). Measured by monoclonal assay, mean DBP in African-ancestry subjects was approximately 50% lower than in whites, whereas DBP measured by polyclonal DBP antibodies or proteomic methods was not lower in African-ancestry. Calculated f25OHD (using polyclonal DBP assays) correlated strongly with directly measured f25OHD (r = 0.80-0.83). Free 25OHD, measured or calculated from polyclonal DBP assays, reflected total 25OHD concentration irrespective of race and was lower in African Americans than in US whites. CONCLUSIONS: Previously reported racial differences in DBP concentration are likely from monoclonal assay bias, as there was no racial difference in DBP concentration by other methods. This confirms the poor vitamin D status of many African-Americans and the utility of total 25OHD in assessing vitamin D in the general population.


Assuntos
Proteína de Ligação a Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , Humanos , Masculino , Vitamina D/sangue
20.
Am J Prev Med ; 50(6): 727-736, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26821835

RESUMO

INTRODUCTION: For older men who undergo bone mineral density (BMD) testing, the optimal osteoporosis screening schedule is unknown. Time-to-disease estimates are necessary to inform screening intervals. METHODS: A prospective cohort study of 5,415 community-dwelling men aged ≥65 years without hip or clinical vertebral fracture or antifracture treatment at baseline was conducted. Participants had concurrent BMD and fracture follow-up between 2000 and 2009, and additional fracture follow-up through 2014. Data were analyzed in 2015. Time to incident osteoporosis (lowest T-score ≤ -2.50) for men without baseline osteoporosis, and time to hip or clinical vertebral fracture or major osteoporotic fracture for men without or with baseline osteoporosis, were estimated. RESULTS: Nine men (0.2%) with BMD T-scores >-1.50 at baseline developed osteoporosis during follow-up. The adjusted estimated time for 10% to develop osteoporosis was 8.5 (95% CI=6.7, 10.9) years for those with moderate osteopenia (lowest T-score, -1.50 to -1.99) and 2.7 (95% CI=2.1, 3.4) years for those with advanced osteopenia (lowest T-score, -2.00 to -2.49) at baseline. The adjusted times for 3% to develop a first hip or clinical vertebral fracture ranged from 7.1 (95% CI=6.0, 8.3) years in men with baseline T-scores > -1.50 to 1.7 (95% CI=1.0, 3.1) years in men with baseline osteoporosis. CONCLUSIONS: Men aged 65 years and older with femoral neck, total hip, and lumbar spine BMD T-scores >-1.50 on a first BMD test were very unlikely to develop osteoporosis during follow-up. Additional BMD testing may be most informative in older men with T-scores ≤-1.50.


Assuntos
Modelos Estatísticos , Osteoporose/complicações , Fraturas por Osteoporose/fisiopatologia , Idoso , Densidade Óssea/fisiologia , Humanos , Masculino , Osteoporose/diagnóstico , Fraturas por Osteoporose/etiologia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
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