Sponholtz Todd R, Zhang Xiaochun, Fontes Joao D T, Meigs James B, Cupples L Adrienne, Kiel Douglas P, Hannan Marian T, McLean Robert R
Boston University School of Public Health, Boston, Massachusetts.
Arthritis Care Res (Hoboken). 2014 Aug;66(8):1233-40. doi: 10.1002/acr.22270.
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).
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).
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.
The lack of consistency in our results suggests that elevated circulating concentrations of inflammatory biomarkers may not be a risk factor for low BMD.
基于动物和体外研究的证据,我们检验了这样一个假设,即在一个以社区为基础的男性和女性队列中,细胞因子白细胞介素-6(IL-6)和肿瘤坏死因子α(TNFα)的血清浓度升高以及炎症标志物C反应蛋白(CRP)与骨密度(BMD)呈负相关,在未接受绝经激素治疗(MHT)的绝经后女性中这种关联最为强烈。
我们测定了弗雷明汉后代研究(1996 - 2001年)的2915名成员空腹血清中IL-6、TNFα和CRP的浓度,并使用双能X线吸收法测量了股骨颈、大转子、全股骨和脊柱(L2 - L4)的骨密度。我们使用多变量线性回归分别估计男性(n = 1293)、绝经前女性(n = 231)、接受MHT的绝经后女性(n = 498)和未接受MHT的绝经后女性(n = 893)中,IL-6、TNFα和CRP的对数转换血清浓度每增加1个单位时,各骨部位骨密度的差异(β)。
炎症生物标志物与男性的骨密度无关。在绝经前女性中,IL-6与大转子骨密度之间存在统计学上显著的适度负相关(β = -0.030,P < 0.01),CRP与股骨颈(β = -0.015,P = 0.05)和大转子骨密度之间存在负相关(β = -0.014,P = 0.04)。TNFα与脊柱骨密度呈正相关(β = 0.043,P = 0.01)。在接受MHT的绝经后女性中,CRP与股骨颈骨密度呈正相关(β = 0.011,P = 0.04)。在未接受MHT的绝经后女性中未发现关联。
我们结果缺乏一致性表明,循环中炎症生物标志物浓度升高可能不是低骨密度的危险因素。