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

Authors

  • Todd R. Sponholtz,

    1. Boston University School of Public Health, Boston, Massachusetts
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  • Xiaochun Zhang,

    1. Hebrew SeniorLife, Boston, Massachusetts
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  • Joao D. T. Fontes,

    1. Framingham Heart Study, Framingham, and Boston University School of Medicine, Boston, Massachusetts
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  • James B. Meigs,

    1. Massachusetts General Hospital and Harvard Medical School, Boston
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  • L. Adrienne Cupples,

    1. Boston University School of Public Health, Boston, Massachusetts
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  • Douglas P. Kiel,

    1. Hebrew SeniorLife, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts
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    • Dr. Kiel has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Merck, Amgen, Lilly, and Novartis; was an author/editor on books published by Springer and UpToDate with Wolters Kluwer, for which he received royalties; and has served as a paid consultant with investment analysts on behalf of Guidepoint for osteoporosis market developments.

  • Marian T. Hannan,

    1. Hebrew SeniorLife, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts
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    • Dr. Hannan has received honoraria (more than $10,000) for her role as Editor of Arthritis Care & Research.

  • Robert R. McLean

    Corresponding author
    1. Hebrew SeniorLife, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts
    • Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA 02131. E-mail: rmclean@hsl.harvard.edu

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  • Because Dr. Hannan is Editor of Arthritis Care & Research, review of this article was handled by the Editor of Arthritis & Rheumatology.

  • The content herein is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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 (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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