Wang Na, Xue Peng, Wu Xuelun, Ma Jianxia, Wang Yan, Li Yukun
a Department of Endocrinology , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
b Key Laboratory of Orthopedic Biomechanics of Hebei Province , The Third Hospital of Hebei Medical University , Shijiazhuang , China.
Endocr Res. 2018 Feb;43(1):29-38. doi: 10.1080/07435800.2017.1373662. Epub 2017 Oct 3.
This study aimed to investigate the role of sclerostin and dkk1 in the bone metabolism of type 2 diabetic patients.
This cross-sectional study included 95 inpatients with type 2 diabetes mellitus. We divided the patients into three groups (i.e., the normal bone mineral density (BMD) group, osteopenia group and osteoporosis group) based on their different BMD levels and measured the serum levels of sclerostin, dkk1, 25-hydroxyvitamin D (25OHD), bone turnover markers and other biochemical data in each group.
Significantly increased levels of serum sclerostin and dkk1 were found in the osteoporosis group, even when the male and female cohorts were considered separately. Ordinal logistic regression analysis suggested that the levels of serum sclerostin were independently associated with the presence of osteopenia and osteoporosis after adjusting for age, gender and 25OHD (sclerostin: OR = 1.02, p = 0.001). The areal BMDs were negatively correlated with the levels of serum sclerostin and dkk1 and positively correlated with 25OHD. In addition, age, glycosylated hemoglobin and serum sclerostin levels were predictors for N-terminal propeptide of type 1 procollagen and serum dkk1 levels were the only predictors for crosslinked carboxyterminal telopeptide in type 1 collagen.
The sclerostin and dkk1 levels increased in conjunction with the reduction of BMD, confirming that the Wnts, inhibited by sclerostin and dkk1, were potentially responsible for bone fragility in type 2 diabetes patients with osteoporosis. Note that the serum sclerostin levels were predictors for bone formation, while the DKK1 levels predicted bone resorption.
本研究旨在探讨硬化蛋白和 Dickkopf-1（DKK1）在 2 型糖尿病患者骨代谢中的作用。
这项横断面研究纳入了 95 例 2 型糖尿病住院患者。我们根据患者不同的骨密度（BMD）水平将其分为三组（即正常骨密度组、骨量减少组和骨质疏松组），并测量了每组患者血清中硬化蛋白、DKK1、25-羟基维生素 D（25OHD）、骨转换标志物及其他生化数据。
骨质疏松组血清硬化蛋白和 DKK1 水平显著升高，即便分别考虑男性和女性队列亦是如此。有序逻辑回归分析表明，在校正年龄、性别和 25OHD 后，血清硬化蛋白水平与骨量减少和骨质疏松的存在独立相关（硬化蛋白：比值比（OR）=1.02，p = 0.001）。面积骨密度与血清硬化蛋白和 DKK-1 水平呈负相关，与 25OHD 呈正相关。此外，年龄、糖化血红蛋白和血清硬化蛋白水平是 I 型前胶原氨基端前肽的预测指标，而血清 DKK1 水平是 I 型胶原交联羧基末端肽的唯一预测指标。
硬化蛋白和 DKK1 水平随着骨密度降低而升高，证实受硬化蛋白和 DKK1 抑制的 Wnt 信号通路可能是 2 型糖尿病骨质疏松患者骨脆性的原因。需注意，血清硬化蛋白水平是骨形成的预测指标，而 DKK1 水平预测骨吸收。
