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Hyponatremia increases fracture risk in diabetes

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January 10, 2019

Hyponatremia in adults with diabetes is associated with a threefold increased risk for osteoporosis and a sixfold increased risk for fragility fracture, independent of the degree of hyperglycemia, according to findings from a matched case-control study.

Sister Grace Miriam (Rachel) Usala

“Hyponatremia is strongly associated with osteoporosis and fragility fracture in this case-control study among patients with diabetes mellitus matched by degree of glycemic control,” Sister Grace Miriam (Rachel) Usala, RSM, MS, an internal medicine resident physician at Georgetown University Medical Center in Washington, D.C., told Endocrine Today. “These findings support our hypothesis that biological processes stimulated by translocational hyponatremia to maintain osmotic homeostasis in hyperglycemic patients have negative consequences by contributing to increased risk for fragility fracture. Building on previous epidemiological and experimental data, our data suggest that hyponatremia increases risk for fracture by two mechanisms: increased bone resorption compromising bone quality and predisposition for gait instability that contributes to increased mechanical falls and fractures.”

Usala and colleagues analyzed electronic health records data from 823 patients with at least one diagnosis of osteoporosis and 840 patients with at least one diagnosis of fragility fracture, all with diabetes, from the MedStar Health database. Researchers matched those patients by characteristics including age, sex, race and age at first HbA1c of at least 6.5% with control patients with diabetes but without osteoporosis (n = 823) and without fragility fractures (n = 840). Case or control exposure to hyponatremia was defined as having at least one serum sodium measurement of less than 135 mmol/L. Researchers used conditional logistic regression analysis to estimate the change in risk for osteoporosis and fractures, given the categories of an exposure variable.

Within the cohort, most case patients and control patients with osteoporosis were women (89.4%), had type 2 diabetes (95.7%) and had a mean age of 67 years at first encounter, with an HbA1c of at least 6.5%.

Researchers found that the OR associating hyponatremia with osteoporosis was greater than any other variable analyzed (OR = 3.09; 95% CI, 1.37-6.98), including prior fracture, tobacco use, liver disease, pulmonary disease or glucocorticoid use. Similarly, the OR associating hyponatremia with fragility fracture was also greater than other variables (OR = 6.41; 95% CI, 2.44-16.82).

Usala noted that the findings are hypothesis-generating; however, there are potential clinical implications.

“First, our findings reaffirm that hyperglycemia-induced translocational hyponatremia is a true hyponatremia and not an artifact, such as pseudohyponatremia,” Usala said. “Second, the findings challenge the prevailing concept that hyperglycemia-induced hyponatremia is of no clinical significance, since translocational hyponatremia was associated with increased risk of osteoporosis and fractures independent of well-matched indices of glycemic control. Third, the findings suggest that biological processes directed toward maintaining osmotic homeostasis represent yet another potential risk factor associated with the well-known increased incidence of osteoporosis and fragility fracture among patients with diabetes mellitus.” – by Regina Schaffer

For more information:

Sister Grace Miriam (Rachel) Usala, RSM, MS, can be reached at Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, D.C. 20007; email: rlu4@georgetown.edu.

Disclosures: One of the study authors reports he has received research grant support or noncontinuing medical education-related fees from Corcept Therapeutics, Ferring Pharmaceuticals and Otsuka Pharmaceutical. Usala reports no relevant financial disclosures.