Department of Endocrinology and Metabolism, The First Affliated Hospital of Shihezi University, Hongshan Sub-District, Shihezi, 832000, Xinjiang, China.
School of Medicine, Shihezi University, Shihezi, 832000, Xinjiang, China.
J Orthop Surg Res. 2024 Nov 1;19(1):706. doi: 10.1186/s13018-024-05162-4.
The aim was to investigate the relationship between metabolic indices and abnormal bone mass (ABM), analyse the association between osteoprotegerin (OPG) gene mutations and ABM, and explore the interaction effect of type 2 diabetes mellitus (T2DM) and OPG gene mutations on bone mineral density (BMD) in postmenopausal women to provide a new supplementary index and a reliable basis for the early identification of osteoporosis (OP) in postmenopausal women in the clinical setting.
Postmenopausal women hospitalized within the Department of Endocrinology of the First Affiliated Sanatorium of Shihezi University from June 2021 to March 2023 were retrospectively analysed, and the bone mineral density of lumbar vertebrae 1-4 (BMD (L1-4)) of the studied subjects was measured once via twin-energy X-ray absorptiometry. The studied subjects were divided into a normal bone mass (NBM) group and an ABM group according to their bone mineral density, and the general data of the studied subjects were recorded once. Blood biochemical indices were determined, and genotyping of the rs4355801 locus of the OPG gene was performed. Differences in the overall data and biochemical indices of the two groups were evaluated via the rank-sum test, and the relationship between blood glucose levels and mutations of the rs4355801 locus of the OPG gene and ABM or BMD (L1-4) was evaluated via binary logistic regression analysis or linear regression analysis. A bootstrap test was performed to test whether uric acid (UA) levels mediate the association between blood glucose levels and BMD (L1-4). Simple effect analysis was performed to analyse the interaction between T2DM and mutations at the rs4355801 locus of the OPG gene on BMD (L1-4).
① After adjusting for confounding factors, the risk of ABM increased by 50% (95% CI 21-85%) for each unit increase in fasting plasma glucose (FPG) levels and 31% (95% CI 2-69%) for each unit increase in glycosylated haemoglobin (HbA1c) levels (both P < 0.05). FPG levels were negatively correlated with BMD (L1-4) (both P < 0.05), and uric acid in blood sugar and BMD (L1-4) played a significant mediating role in the model; this mediation accounted for 21% of the variance. ② After adjusting for confounding factors, women with the mutant genotypes GA and GG + GA of the OPG gene rs4355801 locus had a lower risk of ABM than did those with the wild-type genotype AA (OR = 0.71, 95% CI = 0.52-1.00; OR = 0.51, 95% CI = 0.28-0.92, P < 0.05). The mutant genotypes GG, GA and GG + GA were positively correlated with BMD (L1-4) (all P < 0.05). The interaction between T2DM and mutations in the OPG gene rs4355801 locus had an effect on BMD (L1-4), and this site mutation weakened the increase in blood glucose levels and led to an increase in the risk of ABM (P < 0.05).
Elevated blood glucose levels in postmenopausal women were associated with an increased risk of ABM, and UA played a mediating role in the relationship FPG levels and BMD (L1-4), accounting for 21% of the variance. Mutations at the rs4355801 locus of the OPG gene were associated with a reduced risk of ABM in postmenopausal women. The interaction between T2DM and mutations at the rs4355801 locus of the OPG gene in postmenopausal women affects BMD (L1-4), and mutations at this locus attenuate the increased risk of ABM due to elevated blood glucose levels.
探讨代谢指标与异常骨量（ABM）的关系，分析骨保护素（OPG）基因突变与 ABM 的相关性，并探讨 2 型糖尿病（T2DM）与 OPG 基因突变对绝经后妇女骨密度（BMD）的交互作用，为绝经后妇女骨质疏松症（OP）的早期识别提供新的补充指标和可靠依据。
回顾性分析 2021 年 6 月至 2023 年 3 月在石河子大学第一附属医院内分泌科住院的绝经后妇女，采用双能 X 线吸收法（DXA）测量研究对象腰椎 1-4 骨密度（BMD（L1-4））一次。根据骨密度将研究对象分为正常骨量（NBM）组和 ABM 组，记录研究对象的一般资料。测定血生化指标，并对 OPG 基因 rs4355801 位点进行基因分型。采用秩和检验比较两组的总体数据和生化指标差异，采用二元 logistic 回归分析或线性回归分析评估血糖水平与 OPG 基因 rs4355801 位点突变与 ABM 或 BMD（L1-4）的关系。采用 bootstrap 检验检验血尿酸（UA）水平是否介导血糖水平与 BMD（L1-4）之间的关系。采用简单效应分析分析 T2DM 与 OPG 基因 rs4355801 位点突变对 BMD（L1-4）的交互作用。
① 调整混杂因素后，空腹血糖（FPG）水平每增加 1 单位，ABM 风险增加 50%（95%CI 21%-85%），糖化血红蛋白（HbA1c）水平每增加 1 单位，ABM 风险增加 31%（95%CI 2%-69%）（均 P<0.05）。FPG 水平与 BMD（L1-4）呈负相关（均 P<0.05），血糖与 BMD（L1-4）之间的尿酸有显著的中介作用，该中介作用占模型方差的 21%。② 调整混杂因素后，OPG 基因 rs4355801 位点 GA 和 GG+GA 突变基因型的女性发生 ABM 的风险低于 AA 野生型基因型（OR=0.71，95%CI=0.52-1.00；OR=0.51，95%CI=0.28-0.92，P<0.05）。突变基因型 GG、GA 和 GG+GA 与 BMD（L1-4）呈正相关（均 P<0.05）。T2DM 与 OPG 基因 rs4355801 位点突变的交互作用对 BMD（L1-4）有影响，该位点突变减弱了血糖升高导致的 ABM 风险增加（P<0.05）。
绝经后妇女血糖水平升高与 ABM 风险增加相关，UA 在 FPG 水平与 BMD（L1-4）之间的关系中起中介作用，占方差的 21%。OPG 基因 rs4355801 位点突变与绝经后妇女 ABM 风险降低有关。T2DM 与 OPG 基因 rs4355801 位点突变在绝经后妇女中的交互作用影响 BMD（L1-4），该位点突变减弱了血糖升高导致的 ABM 风险增加。
