Cauley Jane A, Danielson Michelle E, Boudreau Robert M, Forrest Kimberly Yz, Zmuda Joseph M, Pahor Marco, Tylavsky Frances A, Cummings Steven R, Harris Tamara B, Newman Anne B
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
J Bone Miner Res. 2007 Jul;22(7):1088-95. doi: 10.1359/jbmr.070409.
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.
Cytokines play major roles in regulating bone remodeling in the bone microenvironment, but their relationship to fractures is uncertain.
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), TNFalpha, 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.
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 TNFalpha; 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.
衰老炎症假说认为，衰老是损伤的积累，部分是由炎症过程的慢性激活导致的。我们在参与健康、衰老和身体成分研究（Health ABC study）的2985名男性和女性中，就骨折问题对这一假说进行了验证。结果显示，炎症标志物数量最多的受试者骨折风险最高。
细胞因子在调节骨微环境中的骨重塑过程中起主要作用，但其与骨折的关系尚不确定。
研究人群包括参与健康、衰老和身体成分研究的2985名功能良好的70至79岁白人和黑人男性及女性（42%为黑人；51%为女性）。使用标准化检测方法在冷冻血清中测量炎症标志物。我们检测了白细胞介素（IL-6）、肿瘤坏死因子α（TNFα）、C反应蛋白（CRP）以及可溶性受体（IL-2 sR、IL-6 sR、TNF sR1和TNF sR2）。在一个亚组（n = 1430）中检测了细胞因子可溶性受体。通过双能X线吸收法（DXA）测量全髋骨密度。在95%的完整随访期5.8±1.6年中，268名受试者确诊发生了新发骨折。使用比例风险模型比较了炎症标志物水平最高（四分位数4）与较低水平（四分位数1、2和3）的受试者的骨折风险。
发生骨折的受试者更可能是白人且为女性。随后发生新发骨折的受试者的基线炎症标志物水平更高。在多变量模型中，炎症标志物水平最高（四分位数4）的受试者与炎症标志物水平较低（四分位数1、2和3）的受试者相比，骨折的相对风险（95%置信区间）为：CRP为1.34（0.99，1.82）；IL-6为1.28（0.95 - 1.74）；TNFα为1.28（0.97 - 1.70）；IL-2 sR为1.52（1.04 - 2.21）；IL-6 sR为1.33（0.90 - 1.96）；TNF sR1为1.73（1.18 - 2.55）；TNF sR2为1.48（1.01 - 2.20）。在具有七个炎症标志物中三个或更多高炎症标志物的受试者中，与无升高标志物的受试者相比，骨折的相对风险为2.65（1.44 - 4.89）。（p趋势 = 0.001）。我们得出结论，炎症标志物升高对骨折具有预后意义，将衰老的炎症假说扩展至骨质疏松性骨折。
