OR2805 Plasma Sodium Increase Is Associated With An Increase In Bone Formation In Outpatients With Chronic SIAD—A Predefined Secondary Analysis Of The SANDx Trial
Authors: Monnerat Sophie , Refardt Julie , Meier Christian , Christ-Crain Mirjam 
Published: October 2023

Abstract
Disclosure: S. Monnerat: None. J. Refardt: None. C. Meier: None. M. Christ-Crain: None.
INTRODUCTION Hyponatremia is the most common electrolyte disorder encountered in clinical practice and is associated with increased mortality and morbidity, including an increased risk for osteoporosis and fragility fractures. Preclinical studies suggest that hyponatremia upregulates osteoclasts. In a previous analysis of 88 hospitalized patients with a syndrome of inappropriate antidiuresis (SIAD), we observed that hyponatremia normalization after 4 days had a positive impact on osteoblast function. METHODS This is a secondary analysis of a double-blind, crossover, placebo-controlled trial investigating the effect of 4-week treatment with empagliflozin 25mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). Two patients with an antiresorptive osteoporosis treatment and 1 patient with recent hip arthroplasty were excluded (n=11). The primary objective was to investigate the relationship between the change in bone formation index (BFI), defined as PINP/CTX, and the change in plasma sodium levels. Secondary objectives included the relationship between the change in the osteoblasts markers procollagen type 1 N (P1NP) and osteocalcin and the osteoclasts markers C-telopeptide crosslink (CTX), and the change in plasma sodium levels over the treatment period. Linear mixed models and Spearman correlation were computed. RESULTS Six out of the 11 outpatients with a chronic SIAD were female (median [IQR] age 73 years [66, 78]). At baseline, median [IQR] CTX concentration was 0.47 ug/L [0.29, 0.65], median [IQR] osteocalcin was 18.00 ug/L [13.95, 25.87] and median [IQR] P1NP was 64.64 ug/L [45.62, 68.45]. The calculated median BFI [IQR] was 131.86 [96.21, 168.73]. A sodium increase of 1 mmol/L was associated with an increase of 5.21 in BFI (95%-CI: 1.41, 9.00, p = 0.013) and with an increase of 1.48 ug/L in P1NP (95%-CI: 0.26, 2.62, p = 0.03). Plasma sodium concentration was not associated with a change in osteocalcin (β = 0.32; 95%-CI: -0.09, 0.72, p = 0.18), nor with a change in CTX (β = 0.003; 95%-CI: -0.008, 0.014, p = 0.324). Empagliflozin was not a significant predictor for the change of any bone markers and there was no interaction between treatment allocation and sodium. Changes in plasma sodium were positively correlated with changes in BFI and P1NP (BFI: ρ = 0.55, p &lt; 0.001; P1NP: ρ = 0.45, p = 0.004) but not with CTX and osteocalcin (CTX: ρ = -0.21, p = 0.184; Osteocalcin: ρ = 0.34, p = 0.149). CONCLUSION An increase in plasma sodium levels in outpatients with chronic SIAD was associated with an increase in bone formation index (P1NP/CTX), which seemed to be triggered by an increase in P1NP, a surrogate marker of osteoblast function. This supports the importance of treating hyponatremia, particularly in older adults in whom chronic hyponatremia is also associated with falls.
Presentation: Sunday, June 18, 2023