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Now showing items 1 - 16 of 1964

  • Disentangling the genetics of lean mass.

    Karasik, David   Zillikens, M Carola   Hsu, Yi-Hsiang   Aghdassi, Ali   Akesson, Kristina   Amin, Najaf   Barroso, Ines   Bennett, David A   Bertram, Lars   Bochud, Murielle   Borecki, Ingrid B   Broer, Linda   Buchman, Aron S   Byberg, Liisa   Campbell, Harry   Campos-Obando, Natalia   Cauley, Jane A   Cawthon, Peggy M   Chambers, John C   Chen, Zhao   Cho, Nam H   Choi, Hyung Jin   Chou, Wen-Chi   Cummings, Steven R   de Groot, Lisette C P G M   De Jager, Phillip L   Demuth, Ilja   Diatchenko, Luda   Econs, Michael J   Eiriksdottir, Gudny   Enneman, Anke W   Eriksson, Joel   Eriksson, Johan G   Estrada, Karol   Evans, Daniel S   Feitosa, Mary F   Fu, Mao   Gieger, Christian   Grallert, Harald   Gudnason, Vilmundur   Lenore, Launer J   Hayward, Caroline   Hofman, Albert   Homuth, Georg   Huffman, Kim M   Husted, Lise B   Illig, Thomas   Ingelsson, Erik   Ittermann, Till   Jansson, John-Olov   Johnson, Toby   Biffar, Reiner   Jordan, Joanne M   Jula, Antti   Karlsson, Magnus   Khaw, Kay-Tee   Kilpelainen, Tuomas O   Klopp, Norman   Kloth, Jacqueline S L   Koller, Daniel L   Kooner, Jaspal S   Kraus, William E   Kritchevsky, Stephen   Kutalik, Zoltan   Kuulasmaa, Teemu   Kuusisto, Johanna   Laakso, Markku   Lahti, Jari   Lang, Thomas   Langdahl, Bente L   Lerch, Markus M   Lewis, Joshua R   Lill, Christina   Lind, Lars   Lindgren, Cecilia   Liu, Yongmei   Livshits, Gregory   Ljunggren, Osten   Loos, Ruth J F   Lorentzon, Mattias   Luan, Jian'an   Luben, Robert N   Malkin, Ida   McGuigan, Fiona E   Medina-Gomez, Carolina   Meitinger, Thomas   Melhus, Hakan   Mellstrom, Dan   Michaelsson, Karl   Mitchell, Braxton D   Morris, Andrew P   Mosekilde, Leif   Nethander, Maria   Newman, Anne B   O'Connell, Jeffery R   Oostra, Ben A   Orwoll, Eric S   Palotie, Aarno   Peacock, Munro   Perola, Markus   Peters, Annette   Prince, Richard L   Psaty, Bruce M   Raikkonen, Katri   Ralston, Stuart H   Ripatti, Samuli   Rivadeneira, Fernando   Robbins, John A   Rotter, Jerome I   Rudan, Igor   Salomaa, Veikko   Satterfield, Suzanne   Schipf, Sabine   Shin, Chan Soo   Smith, Albert V   Smith, Shad B   Soranzo, Nicole   Spector, Timothy D   Stancakova, Alena   Stefansson, Kari   Steinhagen-Thiessen, Elisabeth   Stolk, Lisette   Streeten, Elizabeth A   Styrkarsdottir, Unnur   Swart, Karin M A   Thompson, Patricia   Thomson, Cynthia A   Thorleifsson, Gudmar   Thorsteinsdottir, Unnur   Tikkanen, Emmi   Tranah, Gregory J   Uitterlinden, Andre G   van Duijn, Cornelia M   van Schoor, Natasja M   Vandenput, Liesbeth   Vollenweider, Peter   Volzke, Henry   Wactawski-Wende, Jean   Walker, Mark   J Wareham, Nicholas   Waterworth, Dawn   Weedon, Michael N   Wichmann, H-Erich   Widen, Elisabeth   Williams, Frances M K   Wilson, James F   Wright, Nicole C   Yerges-Armstrong, Laura M   Yu, Lei   Zhang, Weihua   Zhao, Jing Hua   Zhou, Yanhua   Nielson, Carrie M   Harris, Tamara B   Demissie, Serkalem   Kiel, Douglas P   Ohlsson, Claes  

    Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.; Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.; Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n=3D38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).; Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.; Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.=20
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  • Response to Dr. Lamy and Dr. Gonzalez-Rodriguez

    Cummings, Steven R   Ferrari, Serge   Brown, Jacques P   Wang, Andrea T  

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  • Fracture risk in diabetic elderly men: the MrOS study.

    Napoli, Nicola   Strotmeyer, Elsa S   Ensrud, Kristine E   Sellmeyer, Deborah E   Bauer, Douglas C   Hoffman, Andrew R   Dam, Thuy-Tien L   Barrett-Connor, Elizabeth   Palermo, Lisa   Orwoll, Eric S   Cummings, Steven R   Black, Dennis M   Schwartz, Ann V  

    AIMS/HYPOTHESIS: Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.; METHODS: The MrOS enrolled 5,994 men (aged =E2=89=A565 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.; RESULTS: In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).; CONCLUSIONS/INTERPRETATION: Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.=20
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  • High hip fracture risk in men with severe aortic calcification: MrOS study.

    Szulc, Pawel   Blackwell, Terri   Schousboe, John T   Bauer, Douglas C   Cawthon, Peggy   Lane, Nancy E   Cummings, Steven R   Orwoll, Eric S   Black, Dennis M   Ensrud, Kristine E  

    A significant link between cardiovascular disease and osteoporosis is established in postmenopausal women, but data for men are scarce. We tested the hypothesis that greater severity of abdominal aortic calcification (AAC) was associated with an increased risk of nonspine fracture in 5994 men aged =E2=89=A5 65 years. AAC was assessed on 5400 baseline lateral thoracolumbar radiographs using a validated visual semiquantitative score. Total hip bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Incident nonspine fractures were centrally adjudicated. After adjustment for age, body mass index (BMI), total hip BMD, fall history, prior fracture, smoking status, comorbidities, race, and clinical center, the risk of nonspine fracture (n=3D805) was increased among men with higher AAC (hazard ratio [HR] quartile 4 [Q4] [AAC score =E2=89=A5 9] versus quartile 1 [Q1] [0-1], 1.36; 96% confidence interval [CI], 1.10-1.68). This association was due to an increased risk of hip fracture (n=3D178) among men with higher AAC (HR Q4 versus Q1, 2.33; 95% CI, 1.41-3.87). By contrast, the association between AAC and the risk of nonspine, nonhip fracture was weaker and not significant (HR Q4 versus Q1, 1.22; 95% CI, 0.96-1.55). The findings regarding higher AAC and increased risk of fracture were not altered in additional analyses accounting for degree of trauma, estimated glomerular filtration rate, presence of lumbar vertebral fractures (which may bias AAC assessment), preexisting cardiovascular disease, ankle brachial index, or competing risk of death. Thus, in this large cohort of elderly men, greater AAC was independently associated with an increased risk of hip fracture, but not with other nonspine fractures. These findings suggest that AAC assessment may be a useful method for identification of older men at high risk of hip fracture. =C2=A9 2014 American Society for Bone and Mineral Research.
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  • Goal-directed treatment of osteoporosis

    Cummings, Steven R   Cosman, Felicia   Eastell, Richard   Reid, Ian R   Mehta, Mona   Lewiecki, E Michael  

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  • Diabetes and risk of hospitalized fall injury among older adults.

    Yau, Rebecca K   Strotmeyer, Elsa S   Resnick, Helaine E   Sellmeyer, Deborah E   Feingold, Kenneth R   Cauley, Jane A   Vittinghoff, Eric   De Rekeneire, Nathalie   Harris, Tamara B   Nevitt, Michael C   Cummings, Steven R   Shorr, Ronald I   Schwartz, Ann V  

    OBJECTIVE To determine whether older adults with diabetes are at increased risk of an injurious fall requiring hospitalization. RESEARCH DESIGN AND METHODS The longitudinal Health, Aging, and Body Composition Study included 3,075 adults aged 70-79 years at baseline. Hospitalizations that included ICD-9-Clinical Modification codes for a fall and an injury were identified. The effect of diabetes with and without insulin use on the rate of first fall-related injury hospitalization was assessed using proportional hazards models. RESULTS At baseline, 719 participants had diabetes, and 117 of them were using insulin. Of the 293 participants who were hospitalized for a fall-related injury, 71 had diabetes, and 16 were using insulin. Diabetes was associated with a higher rate of injurious fall requiring hospitalization (hazard ratio [HR] 1.48 [95% CI 1.12-1.95]) in models adjusted for age, race, sex, BMI, and education. In those participants using insulin, compared with participants without diabetes, the HR was 3.00 (1.78-5.07). Additional adjustment for potential intermediaries, such as fainting in the past year, standing balance score, cystatin C level, and number of prescription medications, accounted for some of the increased risk associated with diabetes (1.41 [1.05-1.88]) and insulin-treated diabetes (2.24 [1.24-4.03]). Among participants with diabetes, a history of falling, poor standing balance score, and A1C level ≥8% were risk factors for an injurious fall requiring hospitalization. CONCLUSIONS Older adults with diabetes, in particular those using insulin, are at greater risk of an injurious fall requiring hospitalization than those without diabetes. Among those with diabetes, poor glycemic control may increase the risk of an injurious fall.
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  • Genome-wide Meta-analysis on the Sense of Smell Among US Older Adults.

    Dong, Jing   Yang, Jingyun   Tranah, Greg   Franceschini, Nora   Parimi, Neeta   Alkorta-Aranburu, Gorka   Xu, Zongli   Alonso, Alvaro   Cummings, Steven R   Fornage, Myriam   Huang, Xuemei   Kritchevsky, Stephen   Liu, Yongmei   London, Stephanie   Niu, Liang   Wilson, Robert S   De Jager, Philip L   Yu, Lei   Singleton, Andrew B   Harris, Tamara   Mosley, Thomas H Jr   Pinto, Jayant M   Bennett, David A   Chen, Honglei  

    Olfactory dysfunction is common among older adults and affects their safety, nutrition, quality of life, and mortality. More importantly, the decreased sense of smell is an early symptom of neurodegenerative diseases such as Parkinson disease (PD) and Alzheimer disease. However, the genetic determinants for the sense of smell have been poorly investigated. We here performed the first genome-wide meta-analysis on the sense of smell among 6252 US older adults of European descent from the Atherosclerosis Risk in Communities (ARIC) study, the Health, Aging, and Body Composition (Health ABC) study, and the Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). Genome-wide association study analysis was performed first by individual cohorts and then meta-analyzed using fixed-effect models with inverse variance weights. Although no SNPs reached genome-wide statistical significance, we identified 13 loci with suggestive evidence for an association with the sense of smell (Pmeta < 1 * 10). Of these, 2 SNPs at chromosome 17q21.31 (rs199443 in NSF, P =3D 3.02 * 10; and rs2732614 in KIAA1267-LRRC37A, P =3D 6.65 * 10) exhibited cis effects on the expression of microtubule-associated protein tau (MAPT, 17q21.31) in 447 frontal-cortex samples obtained postmortem and profiled by RNA-seq (P < 1 * 10). Gene-based and pathway-enrichment analyses further implicated MAPT in regulating the sense of smell in older adults. Similar results were obtained after excluding participants who reported a physician-diagnosed PD or use of PD medications. In conclusion, we provide preliminary evidence that the MAPT locus may play a role in regulating the sense of smell in older adults and therefore offer a potential genetic link between poor sense of smell and major neurodegenerative diseases.=20
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  • Prediction models of prevalent radiographic vertebral fractures among older men.

    Schousboe, John T   Rosen, Harold R   Vokes, Tamara J   Cauley, Jane A   Cummings, Steven R   Nevitt, Michael C   Black, Dennis M   Orwoll, Eric S   Kado, Deborah M   Ensrud, Kristine E  

    No studies have compared how well different prediction models discriminate older men who have a radiographic prevalent vertebral fracture (PVFx) from those who do not. We used area under receiver operating characteristic curves and a net reclassification index to compare how well regression-derived prediction models and nonregression prediction tools identify PVFx among men age =E2=89=A565 yr with femoral neck T-score of -1.0 or less enrolled in the Osteoporotic Fractures in Men Study. The area under receiver operating characteristic for a model with age, bone mineral density, and historical height loss (HHL) was 0.682 compared with 0.692 for a complex model with age, bone mineral density, HHL, prior non-spine fracture, body mass index, back pain, grip strength, smoking, and glucocorticoid use (p values for difference in 5 bootstrapped samples 0.14-0.92). This complex model, using a cutpoint prevalence of 5%, correctly reclassified only a net 5.7% (p =3D 0.13) of men as having or not having a PVFx compared with a simple criteria list (age =E2=89=A5 80 yr, HHL >4 cm, or glucocorticoid use). In conclusion, simple criteria identify older men with PVFx and regression-based models. Future research to identify additional risk factors that more accurately identify older men with PVFx is needed. Copyright =C2=A9 2014 The International Society for Clinical Densitometry. All rights reserved.
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  • A History of Pivotal Advances in Clinical Research into Bone and Mineral Diseases

    Cummings, Steven R   Eastell, Richard  

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  • Physical performance and radiographic and clinical vertebral fractures in older men.

    Cawthon, Peggy M   Blackwell, Terri L   Marshall, Lynn M   Fink, Howard A   Kado, Deborah M   Ensrud, Kristine E   Cauley, Jane A   Black, Dennis   Orwoll, Eric S   Cummings, Steven R   Schousboe, John T  

    In men, the association between poor physical performance and likelihood of incident vertebral fractures is unknown. Using data from the MrOS study (N=3D5958), we describe the association between baseline physical performance (walking speed, grip strength, leg power, repeat chair stands, narrow walk [dynamic balance]) and incidence of radiographic and clinical vertebral fractures. At baseline and follow-up an average of 4.6 years later, radiographic vertebral fractures were assessed using semiquantitative (SQ) scoring on lateral thoracic and lumbar radiographs. Logistic regression modeled the association between physical performance and incident radiographic vertebral fractures (change in SQ grade =E2=89=A51 from baseline to follow-up). Every 4 months after baseline, participants self-reported fractures; clinical vertebral fractures were confirmed by centralized radiologist review of the baseline study radiograph and community-acquired spine images. Proportional hazards regression modeled the association between physical performance with incident clinical vertebral fractures. Multivariate models were adjusted for age, bone mineral density (BMD, by dual-energy X-ray absorptiometry [DXA]), clinical center, race, smoking, height, weight, history of falls, activity level, and comorbid medical conditions; physical performance was analyzed as quartiles. Of 4332 men with baseline and repeat radiographs, 192 (4.4%) had an incident radiographic vertebral fracture. With the exception of walking speed, poorer performance on repeat chair stands, leg power, narrow walk, and grip strength were each associated in a graded manner with an increased risk of incident radiographic vertebral fracture (p for trend across quartiles <0.001). In addition, men with performance in the worst quartile on three or more exams had an increased risk of radiographic fracture (odds ratio [OR]=3D1.81, 95% confidence interval [CI] 1.33-2.45) compared with men with better performance on all exams. Clinical vertebral fracture (n =3D149 of 5813, 2.6%) was not consistently associated with physical performance. We conclude that poorer physical performance is associated with an increased risk of incident radiographic (but not clinical) vertebral fracture in older men. =C2=A9 2014 American Society for Bone and Mineral Research.
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  • Adipose tissue density, a novel biomarker predicting mortality risk in older adults.

    Murphy, Rachel A   Register, Thomas C   Shively, Carol A   Carr, J Jeffrey   Ge, Yaorong   Heilbrun, Marta E   Cummings, Steven R   Koster, Annemarie   Nevitt, Michael C   Satterfield, Suzanne   Tylvasky, Frances A   Strotmeyer, Elsa S   Newman, Anne B   Simonsick, Eleanor M   Scherzinger, Ann   Goodpaster, Bret H   Launer, Lenore J   Eiriksdottir, Gudny   Sigurdsson, Sigurdur   Sigurdsson, Gunnar   Gudnason, Vilmundur   Lang, Thomas F   Kritchevsky, Stephen B   Harris, Tamara B  

    BACKGROUND: Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics.; METHODS: VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n =3D 2,735) and AGES-Reykjavik (n =3D 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics.; RESULTS: Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36-2.80; Health ABC) and 1.88 (1.31-2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35-2.28; Health ABC) and 1.56 (1.15-2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12-2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21-2.07), and AGES-Reykjavik, 1.43 (1.07-1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs.; CONCLUSION: VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.=20
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  • Alcohol use, physical performance, and functional limitations in older men.

    Cawthon, Peggy M   Fink, Howard A   Barrett-Connor, Elizabeth   Cauley, Jane A   Dam, Thuy-Tien   Lewis, Cora E   Marshall, Lynn M   Orwoll, Eric S   Cummings, Steven R  

    OBJECTIVES: To describe associations between recent alcohol intake, physical performance, and functional limitations in older men.DESIGN: Cross-sectional study.SETTING: Six U.S. clinical centers.PARTICIPANTS: Five thousand nine hundred sixty-two men aged 65 and older.MEASUREMENTS: Self-reported functional limitations; problem drinking history (>or=2 positive responses on the CAGE questionnaire); history of sustained excessive drinking (history of consumption of >or=5 drinks/day on most days); and alcohol intake categorized by drinks/week (0=abstainers, n=2,116; < 1=intermittent, n=739); 1 to <7= light, n=1,563; 7 to <14=low-moderate, n=848; 14 to <21 =high-moderate, n=459; and >or=21=heavy, n=237). Grip strength, leg power, chair stand, and walking tests were completed during a standard examination.RESULTS: After age adjustment, men with low-moderate or high-moderate intake generally performed 3% to 5% better on physical performance tests than abstainers; heavy drinkers performed similarly to abstainers. These associations lessened yet tended to remain significant after multivariate adjustment. Men with low-moderate alcohol intake had the lowest odds of reporting a limitation in instrumental activities of daily living (multivariate-adjusted odds ratio (OR)=0.52, 95% confidence interval (CI)=0.39-0.69) compared to abstainers; similar odds were seen for high-moderate and heavy use. The association between alcohol intake and self-reported physical limitation was U-shaped, with the highest odds of physical limitation in abstainers (OR=1.0, referent) and heavy users (OR=0.88, 95% CI=0.58-1.36) and the lowest odds in low-moderate users (OR=0.62, 95% CI=0.46-0.95).CONCLUSION: Moderate alcohol intake was associated with modestly better physical performance and lower odds of reporting a functional limitation in older men.
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  • Meta‐Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry

    Hsu, Yi‐Hsiang   Estrada, Karol   Evangelou, Evangelos   Ackert‐Bicknell, Cheryl   Akesson, Kristina   Beck, Thomas   Brown, Suzanne J   Capellini, Terence   Carbone, Laura   Cauley, Jane   Cheung, Ching‐Lung   Cummings, Steven R   Czerwinski, Stefan   Demissie, Serkalem   Econs, Michael   Evans, Daniel   Farber, Charles   Gautvik, Kaare   Harris, Tamara   Kammerer, Candace   Kemp, John   Koller, Daniel L   Kung, Annie   Lawlor, Debbie   Lee, Miryoung   Lorentzon, Mattias   McGuigan, Fiona   Medina‐Gomez, Carolina   Mitchell, Braxton   Newman, Anne   Nielson, Carrie   Ohlsson, Claes   Peacock, Munro   Reppe, Sjur   Richards, J Brent   Robbins, John   Sigurdsson, Gunnar   Spector, Timothy D   Stefansson, Kari   Streeten, Elizabeth   Styrkarsdottir, Unnur   Tobias, Jonathan   Trajanoska, Katerina   Uitterlinden, André   Vandenput, Liesbeth   Wilson, Scott G   Yerges‐Armstrong, Laura   Young, Mariel   Zillikens, Carola   Rivadeneira, Fernando   Kiel, Douglas P   Karasik, David  

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  • Cystatin-C, renal function, and incidence of hip fracture in postmenopausal women.

    LaCroix, Andrea Z   Lee, Jennifer S   Wu, LieLing   Cauley, Jane A   Shlipak, Michael G   Ott, Susan M   Robbins, John   Curb, J David   Leboff, Meryl   Bauer, Douglas C   Jackson, Rebecca D   Kooperberg, Charles L   Cummings, Steven R  

    OBJECTIVES: To evaluate the association between chronic kidney disease and incident hip fracture using serum cystatin-C as a biomarker of renal function calculated without reference to muscle mass.DESIGN: Case-control study nested within a prospective study.SETTING: The Women's Health Initiative Observational Study conducted at 40 U.S. clinical centers.PARTICIPANTS: From 93,676 women aged 50 to 79 followed for an average of 7 years, 397 incident hip fracture cases and 397 matched controls were studied.MEASUREMENTS: Cystatin-C levels were measured on baseline serum using a particle-enhanced immunonepholometric assay. Estimated glomerular filtration rates (eGFR(cys-c)) were calculated using a validated equation and categorized into three groups (>or=90.0 mL/min per 1.73 m(2), 60.0-89.9 mL/min per 1.73 m(2), and <60.0 mL/min per 1.73 m(2) indicating chronic kidney disease Stages 3 to 4).RESULTS: The odds ratio (OR) for hip fracture was 2.50 (95% confidence interval (CI)=1.32-4.72) for eGFR(cys-c) less than 60 mL/min per 1.73 m(2) compared with Stages 0 to 1, after adjustment for body mass, parental hip fracture, smoking, alcohol consumption, and physical function. No association was observed for eGFR(cys-c) of 60 to 90 mL/min per 1.73 m(2) (OR=1.04, 95% CI=0.66-1.64). Additional adjustment for poor health status, hemoglobin, serum 25-hydroxy vitamin D, and bone metabolism markers did not affect these associations. Adjustment for plasma homocysteine reduced the OR for eGFR(cys-c) less than 60 mL/min per 1.73 m(2) to 1.83 (95% CI=0.93-3.61).CONCLUSION: Women with eGFR(cys-c) levels less than 60 mL/min per 1.73 m(2) have a substantially greater risk of hip fracture. Effects of renal function on homocysteine levels may partially mediate, or accompany, this association.
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  • Finite element analysis of the proximal femur and hip fracture risk in older men.

    Orwoll, Eric S   Marshall, Lynn M   Nielson, Carrie M   Cummings, Steven R   Lapidus, Jodi   Cauley, Jane A   Ensrud, Kristine   Lane, Nancy   Hoffmann, Paul R   Kopperdahl, David L   Keaveny, Tony M  

    Low areal BMD (aBMD) is associated with increased risk of hip fracture, but many hip fractures occur in persons without low aBMD. Finite element (FE) analysis of QCT scans provides a measure of hip strength. We studied the association of FE measures with risk of hip fracture in older men. A prospective case-cohort study of all first hip fractures (n = 40) and a random sample (n = 210) of nonfracture cases from 3549 community-dwelling men > or =65 yr of age used baseline QCT scans of the hip (mean follow-up, 5.6 yr). Analyses included FE measures of strength and load-to-strength ratio and BMD by DXA. Hazard ratios (HRs) for hip fracture were estimated with proportional hazards regression. Both femoral strength (HR per SD change = 13.1; 95% CI: 3.9-43.5) and the load-to-strength ratio (HR = 4.0; 95% CI: 2.7-6.0) were strongly associated with hip fracture risk, as was aBMD as measured by DXA (HR = 5.1; 95% CI: 2.8-9.2). After adjusting for age, BMI, and study site, the associations remained significant (femoral strength HR = 6.5, 95% CI: 2.3-18.3; load-to-strength ratio HR = 4.3, 95% CI: 2.5-7.4; aBMD HR = 4.4, 95% CI: 2.1-9.1). When adjusted additionally for aBMD, the load-to-strength ratio remained significantly associated with fracture (HR = 3.1, 95% CI: 1.6-6.1). These results provide insight into hip fracture etiology and demonstrate the ability of FE-based biomechanical analysis of QCT scans to prospectively predict hip fractures in men.
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  • Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women.

    Wang, Jun   Higuchi, Russell   Modugno, Francesmary   Li, Jia   Umblas, Nanette   Lee, Jocelyn   Lui, Li-Yung   Ziv, Elad   Tice, Jeffery A   Cummings, Steven R   Rhees, Brian  

    Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent. In this study, we investigated breast cancer risk associated with genotypes and haplotypes resulting from four ESR1 single nucleotide polymorphisms (SNPs), rs746432, rs2234693, rs9340799, and rs1801132. Genotyping has been performed on 393 breast cancer cases and 790 randomly selected controls in 1,183 Caucasian women over age 65 from the Study of Osteoporotic Fractures (SOF). We observed an allelic protective effect for SNP rs9340799 with an estimated odds ratio (OR) of 0.82 (95% CI = 0.68-1.00; P = 0.04) after adjustment for age, BMI and hip BMD. A protective effect of this SNP has been reported before in several different studies. We did not replicate the previously reported C-C-A-G haplotype association to breast cancer-the C-C-A-G haplotype from these SNPs was rare in this study (estimated frequency below 0.001% in cases and controls). No other statistically significant associations were observed between ESR1 haplotypes from the same four SNPs and the risk of breast cancer in older Caucasian women.
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