血清骨硬化蛋白、成纤维生长因子23水平与老年2型糖尿病患者骨代谢异常及骨质疏松风险的关系

Association of serum sclerostin and fibroblast growth factor 23 levels with bone metabolic abnormalities and osteoporosis risk in elderly patients with type 2 diabetes mellitus

摘要:

目的 探讨血清骨硬化蛋白（SOST）及成纤维生长因子23（FGF23）水平与老年2型糖尿病患者骨代谢异常及骨质疏松风险的关系，并评估其在骨质疏松风险预测中的临床价值。方法 选取2023年1月—2025年1月北京中医药大学东方医院秦皇岛医院就诊的老年2型糖尿病患者96例，依据双能X射线吸收法（DEXA）检测所得骨密度（BMD）数值，按照相关诊断标准将研究对象划分为骨量正常组32例、骨量减少组34例及骨质疏松组30例。比较3组血清SOST、FGF23及骨代谢相关指标水平差异，分析其与BMD及骨形成标志物的相关性，并采用受试者工作特征（ROC）曲线评估SOST、FGF23单项及联合预测骨质疏松风险的效能。结果 骨量正常组、骨量减少组和骨质疏松组年龄、糖尿病病程和糖化血红蛋白（HbA1c）水平比较，差异均有统计学意义（P <0.05）；年龄和糖尿病病程两两比较均有统计学意义（P <0.05），随骨密度降低呈逐渐升高趋势。骨量正常组、骨量减少组和骨质疏松组SOST水平和FGF23水平比较，差异均有统计学意义（P <0.05）；SOST和FGF23水平两两比较均有统计学意义（P <0.05），SOST水平逐级降低，FGF23水平逐级升高。骨量正常组、骨量减少组和骨质疏松组腰椎L_2～4 BMD、股骨颈BMD、骨钙素（BGP）及骨碱性磷酸酶（BALP）水平比较，差异均有统计学意义（P <0.05）；各指标两两比较差异均有统计学意义（P <0.05）。腰椎L_2～4 BMD、股骨颈BMD、BGP及BALP水平均随骨量下降呈逐级降低趋势。Pearson相关性分析结果显示：血清SOST水平与腰椎L_2～4 BMD、股骨颈BMD、BGP、BALP均呈正相关（r =0.457、0.456、0.348、0.327，P <0.05），血清FGF23水平与腰椎L_2～4 BMD、股骨颈BMD、BGP、BALP均呈负相关（r =-0.469、-0.335、-0.305、-0.292，P <0.05）。年龄增加［O^R =1.324（95% CI：1.018，1.722）］、糖尿病病程延长［O^R =1.657（95% CI：1.125，2.442）］、HbA1c升高［O^R =6.565（95% CI：1.503，28.677）］、FGF23升高［O^R =1.082（95% CI：1.016，1.153）］均为老年2型糖尿病患者发生骨质疏松的危险因素，SOST升高［O^R =0.318（95% CI：0.109，0.925）］为其保护因素（均P <0.05）。SOST与FGF23联合检测诊断骨质疏松的曲线下面积为0.927（95% CI：0.868，0.986），敏感性为90.0%，特异性为81.2%，约登指数为0.712。结论 血清SOST降低、FGF23升高与老年2型糖尿病患者骨密度下降及骨代谢异常密切相关，二者联合检测对骨质疏松风险评估具有较高预测价值。

Abstract:

Objective To explore the relationships of circulating sclerostin (SOST) and fibroblast growth factor 23 (FGF23) with alterations in bone metabolism among older individuals with type 2 diabetes, and to assess their utility in identifying patients at high risk for osteoporosis.Methods Ninety-six elderly patients with type 2 diabetes admitted to our hospital from January 2023 to January 2025 were included. According to bone mineral density values obtained using dual-energy X-ray absorptiometry, subjects were stratified into three subgroups: normal bone mass (n = 32), osteopenia (n = 34), and osteoporosis (n = 30). Serum concentrations of SOST and FGF23, together with bone metabolic indices, were compared across groups. Associations between these biomarkers and bone mineral density at different skeletal sites as well as markers of bone formation were evaluated. Receiver operating characteristic curve analysis was applied to determine the discriminative performance of SOST, FGF23, and their combined model for osteoporosis.Results There were statistically significant differences in age, duration of diabetes, and glycated hemoglobin (HbA1c) levels among the normal bone mass group, osteopenia group, and osteoporosis group (P < 0.05). Age and duration of diabetes showed significant pairwise differences among the three groups (P < 0.05), with gradually increasing trends as bone density decreased. Significant differences were observed in serum SOST and FGF23 levels among the three groups (P < 0.05). Pairwise comparisons also showed statistically significant differences (P < 0.05), with SOST levels decreasing progressively and FGF23 levels increasing progressively. Significant differences were also found in lumbar L_2-4 BMD, femoral neck BMD, bone gla protein (BGP), and bone alkaline phosphatase (BALP) levels among the three groups (P < 0.05), and all indicators showed progressively decreasing trends with declining bone mass. Pearson correlation analysis demonstrated that serum SOST levels were positively correlated with lumbar L_2-4 BMD and femoral neck BMD (r = 0.457 and 0.456, respectively; P < 0.001), and were also positively correlated with BGP and BALP levels (r = 0.348 and 0.327, respectively; P < 0.05). Serum FGF23 levels were negatively correlated with lumbar L_2-4 BMD and femoral neck BMD (r = -0.469 and -0.335, respectively; P < 0.05), and were also negatively correlated with BGP and BALP levels (r = -0.305 and -0.292, respectively; P < 0.05). Increased age [O^R = 1.324 (95% CI: 1.018, 1.722) ], longer duration of diabetes [O^R = 1.657 (95% CI: 1.125, 2.442) ], elevated HbA1c [O^R = 6.565 (95% CI: 1.503, 28.677) ], and increased FGF23 [O^R = 1.082 (95% CI: 1.016, 1.153) ] were identified as risk factors for osteoporosis in elderly patients with T2DM, whereas elevated SOST [O^R = 0.318 (95% CI: 0.109, 0.925) ] was identified as a protective factor. The area under the curve (AUC) for the combined detection of SOST and FGF23 in diagnosing osteoporosis was 0.927 (95% CI: 0.868, 0.986), with a sensitivity of 90.0%, specificity of 81.2%, and Youden index of 0.712.Conclusion Decreased serum SOST and elevated FGF23 levels are closely associated with reduced bone mineral density and bone metabolic abnormalities in elderly patients with T2DM. Combined assessment of these two biomarkers provides substantial value for osteoporosis risk stratification.