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

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.