Hyponatremia is Associated with Increased Osteoporosis and Bone Fractures in Diabetics with Matched Glycemic Control: Supplemental Materials

Hyponatremia is Associated with Increased Osteoporosis and Bone Fractures in Diabetics with Matched Glycemic Control Abstract Purpose Patients with diabetes mellitus are at increased risk for bone fragility fracture secondary to multiple mechanisms. Hyperglycemia can induce true dilutional hyponatremia. Hyponatremia is associated with gait instability, osteoporosis, and increased falls and bone fractures, and studies suggest that compromised bone quality with hyponatremia may be independent of plasma osmolality. We performed a case-control study of patients with diabetes mellitus matched by median glycated hemoglobin (HbA1c) to assess whether hyponatremia was associated with increased risk of osteoporosis and/or fragility fracture. Methods Osteoporosis (n=823) and fragility fracture (n=840) cases from the MedStar Health database were matched on age of first HbA1c ≥ 6.5%, sex, race, median HbA1c over an interval from first HbA1c ≥ 6.5% to the end of the encounter window, diabetic encounter window length, and type 1 versus type 2 diabetes mellitus with controls without osteoporosis (n=823) and without fragility fractures (n=840), respectively. Clinical variables, including coefficient of glucose variation and hyponatremia (defined as serum [Na+] <135mmol/dL within 30-days of the end of the diabetic window), were included in a multivariate analysis. Results Multivariate conditional logistic regression models demonstrated that hyponatremia within thirty days of the outcome measure was independently associated with osteoporosis and fragility fractures (osteoporosis OR 3.09, 95% CI 1.37-6.98; fracture OR 6.41, 95% CI 2.44-16.82). Conclusions Our analyses support the hypothesis that hyponatremia is an additional risk factor for osteoporosis and fragility fracture among patients with diabetes mellitus.

低钠血症与血糖匹配的糖尿病患者骨质疏松及骨折风险升高相关

摘要

目的：糖尿病患者因多种病理机制，发生骨脆性骨折的风险升高。高血糖可诱导真性稀释性低钠血症。低钠血症与步态不稳、骨质疏松、跌倒及骨折风险升高相关，现有研究提示，低钠血症所致的骨质质量下降可能不依赖于血浆渗透压。本研究开展了一项病例对照研究，以糖化血红蛋白（HbA1c）中位数作为匹配标准，旨在探讨低钠血症是否与骨质疏松和/或脆性骨折风险升高存在关联。

方法：从MedStar健康数据库中纳入骨质疏松病例组（n=823）与脆性骨折病例组（n=840），分别与无骨质疏松（n=823）、无脆性骨折的对照组进行匹配，匹配变量包括首次糖化血红蛋白≥6.5%的年龄、性别、种族、首次糖化血红蛋白≥6.5%至研究随访窗口结束期间的中位糖化血红蛋白水平、糖尿病随访窗口时长，以及1型与2型糖尿病分型。本研究纳入血糖变异系数、低钠血症（定义为糖尿病随访窗口结束后30天内血清钠浓度[Na+]<135mmol/dL）等临床变量，开展多因素分析。

结果：多因素条件logistic回归模型结果显示，结局指标评估前30天内出现的低钠血症与骨质疏松及脆性骨折独立相关（骨质疏松：比值比OR=3.09，95%置信区间CI=1.37~6.98；骨折：OR=6.41，95%CI=2.44~16.82）。

结论：本研究分析结果支持以下假说：低钠血症是糖尿病患者发生骨质疏松及脆性骨折的额外独立危险因素。