TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association.

Abstract

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. 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. 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. 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. Odds ratio of hip fracture by quartile of TNF soluble receptors. 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. 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.