Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. ishiis‐
J Bone Miner Res. 2013 Jul;28(7):1688-98. doi: 10.1002/jbmr.1915.
Higher levels of C-reactive protein (CRP), an inflammatory marker, are associated with increased fracture risk, although previous studies on CRP and bone mineral density (BMD) have yielded conflicting results. We aimed to test the hypotheses that composite indices of femoral neck strength relative to load, which are inversely associated with fracture risk, would also be inversely associated with CRP, and would explain part of the association between CRP and fracture risk. We analyzed data from a multisite, multiethnic prospective cohort of 1872 community-dwelling women, premenopausal or early perimenopausal at baseline. Femoral neck composite strength indices in three failure modes were calculated using dual-energy X-ray absorptiometry (DXA)-derived femoral neck width (FNW), femoral neck axis length (FNAL), femoral neck BMD and body size at baseline, as BMDFNW/weight for compression strength, BMD(FNW)(2) /(FNALweight) for bending strength, and BMDFNWFNAL/(heightweight) for impact strength. Incident nondigital, noncraniofacial fractures were ascertained annually over a median follow-up of 9 years. In analyses adjusted for age, race/ethnicity, diabetes, menopause transition stage, body mass index, smoking, alcohol use, physical activity, medications, prior fracture, and study site, CRP was associated inversely with each composite strength index (0.035-0.041 SD decrement per doubling of CRP, all p < 0.001), but not associated with femoral neck or lumbar spine BMD. During the follow-up, 194 women (10.4%) had fractures. In Cox proportional hazards analyses, fracture hazard increased linearly with loge (CRP), only for CRP levels ≥ 3 mg/L. Addition of femoral neck or lumbar spine BMD to the model did not attenuate the CRP-fracture association. However, addition of any of the composite strength indices attenuated the CRP-fracture association and made it statistically nonsignificant. We conclude that fracture risk increases with increasing CRP, only above the threshold of 3 mg/L. Unlike BMD, composite strength indices are inversely related to CRP levels, and partially explain the increased fracture risk associated with inflammation.
较高水平的 C 反应蛋白（CRP），一种炎症标志物，与骨折风险增加相关，尽管先前关于 CRP 和骨密度（BMD）的研究结果存在矛盾。我们旨在检验以下假设：相对于负荷的股骨颈强度复合指数与骨折风险呈反比相关，也与 CRP 呈反比相关，并解释 CRP 与骨折风险之间的部分关联。我们分析了来自一个多地点、多民族的前瞻性队列研究的 1872 名社区居住的女性的数据，这些女性在基线时处于绝经前期或早期围绝经期。使用双能 X 射线吸收法（DXA）衍生的股骨颈宽度（FNW）、股骨颈轴长（FNAL）、股骨颈 BMD 和基线时的身体大小，计算了三种失效模式下的股骨颈复合强度指数，用于压缩强度的 BMDFNW/体重，用于弯曲强度的 BMD（FNW）^2/（FNAL体重），以及用于冲击强度的 BMDFNWFNAL/（身高体重）。在中位数为 9 年的随访期间，每年确定非数字、非颅面骨折的发生情况。在调整年龄、种族/民族、糖尿病、绝经过渡阶段、体重指数、吸烟、饮酒、体力活动、药物、既往骨折和研究地点后，CRP 与每个复合强度指数呈负相关（每增加 CRP 两倍的 0.035-0.041 标准差降低，均 P<0.001），但与股骨颈或腰椎 BMD 无关。在随访期间，194 名女性（10.4%）发生了骨折。在 Cox 比例风险分析中，只有 CRP 水平≥3mg/L 时，骨折风险才会随着 loge（CRP）的线性增加而增加。将股骨颈或腰椎 BMD 添加到模型中并不能减弱 CRP 与骨折的关联。然而，任何复合强度指数的添加都减弱了 CRP 与骨折的关联，并使其在统计学上变得无意义。我们的结论是，只有在 CRP 水平超过 3mg/L 时，骨折风险才会随着 CRP 的增加而增加。与 BMD 不同，复合强度指数与 CRP 水平呈反比关系，并部分解释了与炎症相关的骨折风险增加。
