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

Ing SW1, Orchard TS1, Lu B2, LaMonte MJ3, Barbour KE4, Cauley JA5, Jackson RD1.

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Abstract

CONTEXT:

Chronic inflammation may increase risk of fracture and omega-3 polyunsaturated fatty acids (PUFA) 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, tumor necrosis factor α 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 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). 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 (OR) of hip fracture by quartile of TNF soluble receptors Results: OR of hip fracture comparing the highest to lowest quartile was 2.24 (95% confidence interval [CI], 1.05-4.79; p for linear trend 0.048) for TNFα-sR1 and 2.83 (95% CI, 1.34-5.99; p for linear trend 0.011) 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 greater than two-fold increased hip fracture risk, independent of other fracture risk factors. These associations did not differ by high versus low PUFA intake.