Normalization of hyponatremia in hospitalized patients decreases osteoclast activity

Objective Hyponatremia, the most common electrolyte disorder in hospitalized patients, has been largely associated with increased risk of osteoporosis. Preclinical studies suggest that hyponatremia stimulates osteoclast activity. This study evaluated whether normalization of hyponatremia impacts osteoclast activity. Design In this prospective, observational study we included patients with serum sodium <135 mmol/l hospitalized at the University Hospital of Basel, Switzerland, between 03/2020 and 02/2025. Premenopausal status, steroid therapy, hypogonadism, fractures, hyperparathyroidism or anti-osteoporotic treatments were exclusion criteria. Methods Sodium and markers of bone resorption (CTX) and bone formation (P1NP) were measured at baseline and after 10 (±3) days and compared between patients who achieved normonatremia versus those who remained hyponatremic. A multivariable model was implemented to adjust for age, sex, BMI, comorbidities, smoking habits, vitamin D levels and volume status. Results Forty-one patients (65.8% male, mean age 68.6, standard deviation 16.6 years) completed the study. Median (IQR) sodium at baseline was 130 mmol/l (127-132), with 60% of patients having mild hyponatremia. Serum-CTX at baseline in patients with persistent hyponatremia at day10 (n=19, 46.3%) and patients reaching normonatremia (n=22, 53.7%) were similar (median (IQR) 0.41 (0.29-0.53) vs 0.41 (0.37-0.66) ng/ml, p=0.35), whereas they differed at day 10 (0.54 (0.37-0.58) vs 0.35 ng/ml (0.26-0.45), p=0.02). The multivariable linear model showed an association between normonatremia on day 10 and a decrease in CTX (β-coefficient -0.18, 95% CI -0.30 to -0.08, p=0.002). P1NP showed no differences between patients with persistent and normalized sodium at both baseline and day10 (p>0.05). Conclusions In hospitalized patients with hyponatremia, sodium normalization is associated with attenuated osteoclast activity. Correction of even mild hyponatremia could thus be beneficial for counteracting bone loss.