Ahn S H, Lee S H, Kim B-J, Lim K-H, Bae S J, Kim E H, Kim H-K, Choe J W, Koh J-M, Kim G S
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Songpa-Gu, Seoul, 138-736, Republic of Korea.
Osteoporos Int. 2013 Dec;24(12):2961-70. doi: 10.1007/s00198-013-2377-7. Epub 2013 May 4.
Higher serum uric acid (UA) was associated with higher bone mass, lower bone turnover, and lower prevalence of vertebral fracture in postmenopausal women. Furthermore, UA suppressed osteoclastogenesis and decreased production of reactive oxygen species in osteoclast precursors, indicating UA may have beneficial effects on bone metabolism as an antioxidant.
UA is known to play a physiological role as an antioxidant, and oxidative stress has detrimental effects on bone metabolism. In the present study, we investigated the association of serum UA level with the osteoporosis-related phenotypes and its direct effect on bone-resorbing osteoclasts using in vitro systems.
This is a large cross-sectional study, including 7,502 healthy postmenopausal women. Bone mineral density (BMD) and serum UA concentrations were obtained from all subjects. Data on bone turnover markers and lateral thoracolumbar radiographs were available for 1,023 and 6,918 subjects, respectively. An in vitro study investigated osteoclastogenesis and reactive oxygen species (ROS) levels according to UA treatment.
After adjusting for multiple confounders, serum UA levels were positively associated with BMD at all sites (all p < 0.001). Compared with the participants in the highest UA quartile, the odds for osteoporosis were 40 % higher in those in the lowest quartile. The serum UA levels were inversely related to both serum C-terminal telopeptide of type I collagen and osteocalcin levels (p < 0.001 and p = 0.004, respectively). Consistently, subjects with vertebral fracture had lower serum UA levels, compared with those without it (p = 0.009). An in vitro study showed that UA decreased osteoclastogenesis in a dose-dependent manner and reduced the production of ROS in osteoclast precursors.
These results provide epidemiological and experimental evidence that serum UA may have a beneficial effect on bone metabolism as an antioxidant in postmenopausal women.
绝经后女性血清尿酸(UA)水平升高与骨量增加、骨转换降低及椎体骨折患病率降低相关。此外,UA可抑制破骨细胞生成,并减少破骨细胞前体细胞中活性氧的产生,提示UA作为抗氧化剂可能对骨代谢具有有益作用。
已知UA作为抗氧化剂发挥生理作用,且氧化应激对骨代谢有不利影响。在本研究中,我们使用体外系统研究了血清UA水平与骨质疏松相关表型的关联及其对骨吸收破骨细胞的直接作用。
这是一项大型横断面研究,纳入7502名健康绝经后女性。获取所有受试者的骨密度(BMD)和血清UA浓度。分别有1023名和6918名受试者可获得骨转换标志物及胸腰椎侧位X线片数据。一项体外研究根据UA处理情况研究破骨细胞生成及活性氧(ROS)水平。
在调整多个混杂因素后,血清UA水平与所有部位的BMD均呈正相关(所有p<0.001)。与UA四分位数最高组的参与者相比,四分位数最低组患骨质疏松症的几率高40%。血清UA水平与血清I型胶原C末端肽及骨钙素水平均呈负相关(分别为p<0.001和p=0.004)。同样,与无椎体骨折的受试者相比,椎体骨折受试者的血清UA水平较低(p=0.009)。体外研究表明,UA以剂量依赖方式减少破骨细胞生成,并降低破骨细胞前体细胞中ROS的产生。
这些结果提供了流行病学和实验证据,表明血清UA作为抗氧化剂可能对绝经后女性的骨代谢具有有益作用。