title: TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association.
abstract: BACKGROUND
  Chronic inflammation may increase the risk of fracture, and omega-3 polyunsaturated fatty acids (PUFAs) may reduce fracture risk via down-regulation of inflammatory cytokine gene expression and other mechanisms.
  
  
  OBJECTIVE
  We investigated associations between baseline samples of inflammatory markers, TNFα soluble receptors 1 and 2 (TNFα-sR1 and -sR2), and incident hip fracture. These associations were then tested for effect modification by dietary PUFA intake estimated by a baseline food frequency questionnaire.
  
  
  METHODS
  A nested case-control study was conducted among participants of the Women's Health Initiative Observational Study (ages, 50-79 y). Multivariable conditional logistic regression models were constructed to account for the paired design.
  
  
  METHODS
  This study sampled 400 pairs of hip fracture cases and controls without incident hip fracture, matched on age, year of enrollment, and menopausal hormone use.
  
  
  METHODS
  Odds ratio of hip fracture by quartile of TNF soluble receptors.
  
  
  RESULTS
  The odds ratio of hip fracture comparing the highest to lowest quartiles was 2.24 (95% confidence interval, 1.05-4.79; P for linear trend, .048) for TNFα-sR1 and 2.83 (95% confidence interval, 1.34-5.99; P for linear trend, .011) for TNFα-sR2, adjusted for FRAX hip fracture score, nutritional variables, and selected factors impacting inflammation; there was a gradient of risk by increasing quartile in TNFα-sR1. PUFA intake did not modify these associations.
  
  
  CONCLUSIONS
  Women with the highest levels of TNFα-sR1 and TNFα-sR2 had a greater than 2-fold increased hip fracture risk, independent of other fracture risk factors. These associations did not differ by high vs low PUFA intake.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Ing
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Tonya S
authors.initials: TS
authors.lastname: Orchard
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: LaMonte
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Kamil E
authors.initials: KE
authors.lastname: Barbour
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism (S.W.I., R.D.J.), Department of Human Sciences, Human Nutrition Program (T.S.O.), and Division of Biostatistics (B.L.), The Ohio State University, Columbus, Ohio 43210; Department of Epidemiology and Environmental Health (M.J.L.), University at Buffalo-State University of New York, Buffalo, New York 14260; Division of Population Health (K.E.B.), Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30431; and Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
mesh_terms: D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D004032:Diet; D015525:Fatty Acids, Omega-3; D005260:Female; D006306:Health Surveys; D006620:Hip Fractures / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*
chemical_list: D015415:Biomarkers; D015525:Fatty Acids, Omega-3; D018124:Receptors, Tumor Necrosis Factor