Association Between Inflammatory Biomarkers and Bone Mineral Density in a Community‐Based Cohort of Men and Women

Abstract

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 (TNF-α), and the inflammatory marker C-reactive protein (CRP) would be inversely associated with BMD in a community-based cohort of men and women, with the strongest associations among post-menopausal women not using menopausal hormone therapy (MHT). METHODS We ascertained fasting serum concentrations of IL-6, TNF-α, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual energy X-ray absorptiometry in 2,915 members of the Framingham Offspring cohort (1996 to 2001). We used multivariable linear regression to estimate the difference (β) in BMD at each bone site associated with a one-unit increase in log-transformed serum concentrations of IL-6, TNF-α, and CRP separately for men (n=1,293), pre-menopausal women (n=231), post-menopausal women using MHT (n=498), and post-menopausal women not using 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). TNF-α, was positively associated with spine BMD (β=0.043, p=0.01). In post-menopausal MHT users, CRP was positively associated with femoral neck BMD (β=0.011, p=0.04). There were no associations among post-menopausal women not using MHT. CONCLUSIONS The lack of consistency in our results suggests that elevated circulating concentration of inflammatory biomarkers may not be a risk factor for low BMD.

The effect of body composition and serum inflammatory markers on the functional muscle–bone unit in premenopausal women

“…Our result that CRP plasma concentration was negatively correlated with relative bone mass and strength values is in contrast to a previous report 28 but is supported by the outcomes of a multitude of studies. 17,[29][30][31] Hence, negative correlations between CRP and relative bone variables, as found in this study, may represent an early indicator for the negative effect of chronic inflammation, which after prolonged exposure might result in decreased absolute bone mass and strength, as reported in other studies. 17,[29][30][31] In summary, we conclude that high body fat percentage was associated with lower relative bone mass and strength despite normal habitual muscle force in premenopausal women, indicating that high body fat percentage compromised the functional muscle-bone unit in these individuals.…”

C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort

“…Furthermore, Sponholtz et al, found that CRP was positively and significantly associated with femoral neck BMD in women shortly after menopause among hormone therapy users (mean age 59y) [30]. In terms of fracture risk, several studies have also reported no association between elevated CRP and low BMD, despite a higher fracture risk [21,22,24,31].…”

Visceral Adipose Tissue Is Associated With Bone Microarchitecture in the Framingham Osteoporosis Study

“…(28)(29)(30) Mechanisms that have been proposed to explain the effects of visceral adiposity on end-organ disease include the portal free fatty acid theory in which VAT might alter lipoprotein metabolism by inducing an overproduction of large triglyceriderich very low density lipoproteins, (31) and secretion of proinflammatory adipocyte-derived cytokines (10) that may have deleterious effects on the skeleton. (32,33) There are several strengths of our study. First we are the first study using state-of-the-art imaging to measure VAT and stateof-the-art measures of bone microarchitecture in the cortical and trabecular compartments.…”