There is a high prevalence of chronic
hyponatremia in the elderly, frequently owing to the syndrome of inappropriate
antidiuretic hormone secretion (
SIADH). Recent reports have shown that even mild
hyponatremia is associated with impaired gait stability and increased falls. An increased risk of falls among elderly hyponatremic patients represents a risk factor for fractures, which would be further amplified if
hyponatremia also contributed metabolically to bone loss. To evaluate this possibility, we studied a rat model of
SIADH and analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III). In rats, dual-energy X-ray absorptiometry (DXA) analysis of excised femurs established that
hyponatremia for 3 months significantly reduced bone mineral density by approximately 30% compared with normonatremic control rats. Moreover, micro-computed tomography (microCT) and histomorphometric analyses indicated that
hyponatremia markedly reduced both trabecular and cortical bone via increased
bone resorption and decreased bone formation. Analysis of data from adults in NHANES III by linear regression models showed that mild
hyponatremia is associated with increased odds of
osteoporosis (T-score -2.5 or less) at the hip [odds ratio (OR) = 2.85; 95% confidence interval (CI) 1.03-7.86; p < .01]; all models were adjusted for age, sex, race, body mass index (BMI), physical activity, history of
diuretic use, history of smoking, and serum
25-hydroxyvitamin D [25(
OH)D] levels. Our results represent the first demonstration that chronic
hyponatremia causes a substantial reduction of bone mass. Cross-sectional human data showing that
hyponatremia is associated with significantly increased odds of
osteoporosis are consistent with the experimental data in rodents. Our combined results suggest that bone quality should be assessed in all patients with chronic
hyponatremia.