Effect of hyponatremia normalization on osteoblast function in patients with SIAD

Abstract

Objective: Hyponatremia is associated with an increased risk of bone frag ility and fractures. Many studies suggest that hyponatremia stimulates osteoclast activation, whereas other studies rather reveal a possible role of acute hyponatremia in impairing osteoblast function. We aimed to asse ss whether and how correction of hyponatremia in hospitalized patients with the syndrome of inappropriate antidi uresis (SIAD) has an impact on bone metabolism. Design and Methods: This was a predefined secondary analysis of 88 hospitalized pat ients with SIAD undergoing a randomized treatment with SGLT-2 inhibitors or placebo for 4 da ys. Biochemical markers of bone resorption (CTX) and bone formation (PINP) were collected in serum at baseline and a fter the intervention (day 5). Bone formation index (defined as PINP/CTX) and its difference between day 5 and baseli ne were calculated. Patients with steroid therapy (n = 6), fractures (n = 10), or whose data were missing (n = 4) were excluded from the analysis. Results: Out of 68 patients, 27 (39.7%) were normonatremic at day 5. Th ese patients showed an increase in serum PINP (P = 0.04), whereas persistent hyponatremic patients did not (P = 0.38), with a relevant difference between these two subgroups (P = 0.005). Serum CTX increased similarly in the two groups ( P = 0.43). This produced a 47.9 points higher PINP/CTX difference between discharge and admission in no rmonatremic patients (95% CI: 17.0-78.7, P = 0.003) compared to patients with persistent hyponatremia, independent of age, sex, BMI, smoking habits, randomization arm, and baseline cortisol levels. Conclusions: Our predefined post hoc analysis shows that correction of hyponatremia in hospitalized patients with SIAD might have a positive impact on osteoblast function.