Effect of hyponatremia normalization on osteoblast function in patients with SIAD.
Summary: This study assessed whether correction of hyponatremia (sodium level in the blood is below normal) had an impact on bone metabolism (cooperation of bone cells including osteoblasts, osteoclasts, and osteocytes in order to maintain bone tissue quantity and the integrity of bone structure) in hospitalized patients with the syndrome of inappropriate antidiuresis (when an excessive amount of antidiuretic hormone is released resulting in water retention and a low sodium level; SIAD).
Conclusion: Correction of hyponatremia (sodium level in the blood is below normal) in hospitalized patients with the syndrome of inappropriate antidiuresis (when an excessive amount of antidiuretic hormone is released resulting in water retention and a low sodium level) might have a positive impact on osteoblast (a bone-forming cell) function.
Objective: Hyponatremia is associated with an increased risk of bone fragility 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 assess whether and how correction of hyponatremia in hospitalized patients with the syndrome of inappropriate antidiuresis (SIAD) has an impact on bone metabolism.
Methods: This was a predefined secondary analysis of 88 hospitalized patients with SIAD undergoing a randomized treatment with SGLT-2 inhibitors or placebo for 4 days. Biochemical markers of bone resorption (CTX) and bone formation (PINP) were collected in serum at baseline and after the intervention (day 5). Bone formation index (defined as PINP/CTX) and its difference between day 5 and baseline 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. These 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 normonatremic 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.