Inflammatory Markers and Incident Fracture Risk in Older Men and Women: The Health Aging and Body Composition Study

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Abstract
The inflammation of aging hypothesis purports that aging is the accumulation of damage, which results, in part, from chronic activation of inflammation process. We tested this hypothesis in relationship to fractures in 2985 men and women enrolled in the Health ABC study. Results showed that subjects with the greatest number of inflammatory markers have the highest risk of fracture. Introduction: Cytokines play major roles in regulating bone remodeling in the bone microenvironment, but their relationship to fractures is uncertain. Materials and Methods: The study population includes 2985 well‐functioning white and black women and men (42%, black; 51%, women) 70–79 yr of age enrolled in the Health Aging and Body Composition Study. Inflammatory markers were measured in frozen serum using standardized assays. We measured interleukin (IL‐6), TNFα, C‐reactive protein (CRP), and soluble receptors (IL‐2 sR, IL‐6 sR, TNF sR1and TNF sR2).Cytokine‐soluble receptors were measured in a subset (n = 1430). Total hip BMD was measured by DXA. During 5.8 ± 1.6 yr of 95% complete follow‐up, incident fractures were confirmed in 268 subjects. The risk of fracture was compared among subjects with the highest inflammatory markers (quartile 4) versus lower levels (quartiles 1, 2, and 3) using proportional hazard models. Results and Conclusions: Subjects who fractured were more likely to be white and female. Baseline markers of inflammation were higher among subjects who subsequently experienced an incident fracture. In multivariate models, the relative risk of fracture (95% CIs) for subjects with the highest inflammatory markers (quartile 4) compared with those with lower inflammatory markers (quartiles 1, 2, and 3) was 1.34 (0.99, 1.82) for CRP; 1.28 (0.95–1.74) for IL‐6; 1.28 (0.97–1.70) for TNFα; 1.52 (1.04–2.21) for IL‐2 sR; 1.33 (0.90–1.96) for IL‐6 sR; 1.73 (1.18–2.55) for TNF sR1 and 1.48 (1.01–2.20) for TNF sR2. In subjects with three or more (out of seven) high inflammatory markers, the relative risk of fracture was 2.65 (1.44–4.89) in comparison with subjects with no elevated markers. (p trend = 0.001). We conclude that elevated inflammatory markers are prognostic for fractures, extending the inflammation hypothesis of aging to osteoporotic fractures.