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TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association
Steven W Ing1, Tonya S Orchard1, Bo Lu1
1Division 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.
Context:
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.
Design And Setting:
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.
Participants:
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.
Main Outcome Measures:
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.
