Kulcsar-Jakab Eva, Petho Zsofia, Pap Zoltan, Kalina Edit, Foldesi Roza, Balogh Adam, Antal-Szalmas Peter, Bhattoa Harjit Pal
Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
BMC Musculoskelet Disord. 2015 Aug 28;16:227. doi: 10.1186/s12891-015-0684-1.
The aim of the present study is to evaluate serum osteoprotegerin (OPG) and soluble receptor activator of nuclear factor κB ligand (sRANKL) levels in a randomly selected male cohort over 50 years of age and its association with cystatin C, a cysteine proteinase inhibitor that decreases formation of osteoclasts by interfering at a late stage of pre-osteoclast differentiation, apart from being a marker of renal function independent of gender, muscle mass and age; in addition to known predictors such as age, sex hormones, vitamin D, bone mineral density (BMD) and biochemical markers of bone turnover.
We determined serum OPG and sRANKL levels and examined its relationship with cystatin C, age, osteocalcin, C-terminal telopeptides of type-I collagen, procollagen type 1 amino-terminal propeptide, 25-hydroxyvitamin D, parathyroid hormone, total 17β-estradiol (E2), total testosterone and L1-L4 (LS) and femur neck (FN) BMD data available from 194 (age, range: 51-81 years) randomly selected ambulatory men belonging to the HunMen cohort.
OPG correlated significantly with age (Spearman's rho (r) = 0.359, p < 0.001), cystatin C (r = 0.298, p < 0.001), E2 (r = 0.160, p = 0.028) and free testosterone index (FTI) (r = -0.230, p = 0.001). Compared to the middle-aged (age: ≤ 59 years, n = 98), older men (age > 59 years, n = 96) had significantly higher serum OPG (4.6 pmol/L vs. 5.4 pmol/L; p < 0.001), and lower sRANKL (0.226 pmol/L vs. 0.167 pmol/L; p = 0.048) levels. The older men showed a significant correlation between serum OPG levels and cystatin C (Spearman's rho = 0.322, p = 0.002), and E2 (Spearman's rho = 0.211, p = 0.043). Including cystatin C and E2 in a regression model showed that cystatin C (standard regression coefficient (β) = 0.345; p = 0.002) was the only significant predictor of serum OPG levels in the older men.
The results of this study demonstrated that in addition to age (which was the stronger predictor), other modifiable factors such as cystatin C, FTI and E2 were also significant predictors of OPG, and that the association between cystatin C and OPG was more evident with increased age (older age group). As such, cystatin C is a significant predictor of OPG independently of age, FTI and E2.
本研究旨在评估随机选取的50岁以上男性队列中的血清骨保护素（OPG）和可溶性核因子κB受体活化因子配体（sRANKL）水平，及其与胱抑素C的关联。胱抑素C是一种半胱氨酸蛋白酶抑制剂，除了作为独立于性别、肌肉量和年龄的肾功能标志物外，还通过在破骨细胞前体细胞分化的后期进行干扰来减少破骨细胞的形成；此外还涉及年龄、性激素、维生素D、骨密度（BMD）和骨转换生化标志物等已知预测因素。
我们测定了194名（年龄范围：51 - 81岁）随机选取的属于HunMen队列的门诊男性的血清OPG和sRANKL水平，并检查了它们与胱抑素C、年龄、骨钙素、I型胶原C末端肽、I型前胶原氨基端前肽、25 - 羟基维生素D、甲状旁腺激素、总17β - 雌二醇（E2）、总睾酮以及L1 - L4（LS）和股骨颈（FN）骨密度数据之间的关系。
OPG与年龄（斯皮尔曼等级相关系数（r） = 0.359，p < 0.001）、胱抑素C（r = 0.298，p < 0.001）、E2（r = 0.160，p = 0.028）和游离睾酮指数（FTI）（r = -0.230，p = 0.001）显著相关。与中年男性（年龄≤59岁，n = 98）相比，老年男性（年龄>59岁，n = 96）的血清OPG水平显著更高（4.6 pmol/L对5.4 pmol/L；p < 0.001），而sRANKL水平更低（0.226 pmol/L对0.167 pmol/L；p = 0.048）。老年男性的血清OPG水平与胱抑素C（斯皮尔曼等级相关系数 = 0.322，p = 0.002）和E2（斯皮尔曼等级相关系数 = 0.211，p = 0.043）之间存在显著相关性。在回归模型中纳入胱抑素C和E2后发现，胱抑素C（标准回归系数（β） = 0.345；p = 0.002）是老年男性血清OPG水平的唯一显著预测因子。
本研究结果表明，除年龄（是更强的预测因子）外，胱抑素C、FTI和E2等其他可改变因素也是OPG的显著预测因子，并且胱抑素C与OPG之间的关联在年龄增长（老年组）时更为明显。因此，胱抑素C是独立于年龄、FTI和E2的OPG的显著预测因子。
