Mild Hyponatremia as a Risk Factor for Fractures: The Rotterdam Study

Recent studies suggest that mild hyponatremia is associated with fractures, but prospective studies are lacking. We studied whether hyponatremia is associated with fractures, falls, and/or bone mineral density (BMD). A total of 5208 elderly subjects with serum sodium assessed at baseline were included from the prospective population-based Rotterdam Study. The following data were analyzed: BMD, vertebral fractures (mean follow-up 6.4 years), nonvertebral fractures (7.4 years), recent falls, comorbidity, medication, and mortality. Hyponatremia was detected in 399 subjects (7.7%, 133.4 +/- 2.0 mmol/L). Subjects with hyponatremia were older (73.5 +/- 10.3 years versus 70.0 +/- 9.0 years, p<.001), had more recent falls (23.8% versus16.4%, p<.01), higher type 2 diabetes mellitus prevalence (22.2% versus 10.3%, p<.001), and more often used diuretics (31.1% versus 15.0%, p<.001). Hyponatremia was not associated with lower BMD but was associated with increased risk of incident nonvertebral fractures [hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.73, p=.004] after adjustment for age, sex, and body mass index. Further adjustments for disability index, use of diuretics, use of psycholeptics, recent falls, and diabetes did not modify results. In the fully adjusted model, subjects with hyponatremia also had increased risk of vertebral fractures at baseline [odds ratio (OR)=1.78, 95% CI 1.04-3.06, p=.037] but not at follow-up. Finally, all-cause mortality was higher in subjects with hyponatremia (HR=1.21, 95% CI 1.03-1.43, p=.022). It is concluded that mild hyponatremia in the elderly is associated with an increased risk of vertebral fractures and incident nonvertebral fractures but not with BMD. Increased fracture risk in hyponatremia also was independent of recent falls, pointing toward a possible effect on bone quality. (C) 2011 American Society for Bone and Mineral Research.