Objective Based upon evidence in animal and in vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) and the inflammatory marker C-reactive protein (CRP) would be inversely associated with bone mineral density (BMD) in a community-based cohort of men and women, with the strongest associations among postmenopausal women not receiving menopause hormonal therapy (MHT). Methods We ascertained fasting serum concentrations of IL-6, TNFα, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual x-ray absorptiometry in 2,915 members of the Framingham Offspring Study (1996-2001). We used multivariable linear regression to estimate the difference (β) in BMD at each bone site associated with a 1-unit increase in log-transformed serum concentrations of IL-6, TNFα, and CRP separately for men (n = 1,293), premenopausal women (n = 231), postmenopausal women receiving MHT (n = 498), and postmenopausal women not receiving MHT (n = 893). Results Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (β = -0.030, P < 0.01) and between CRP and femoral neck (β = -0.015, P = 0.05) and trochanter BMD (β = -0.014, P = 0.04). TNFα was positively associated with spine BMD (β = 0.043, P = 0.01). In postmenopausal women receiving MHT, CRP was positively associated with femoral neck BMD (β = 0.011, P = 0.04). There were no associations among postmenopausal women not receiving MHT. Conclusion The lack of consistency in our results suggests that elevated circulating concentrations of inflammatory biomarkers may not be a risk factor for low BMD.
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