Hyponatremia and Fractures: Findings From the MrOS Study

Abstract

Hyponatremia may be a risk factor for fracture. To determine the relationship between hyponatremia and fracture we conducted cross-sectional and longitudinal analyses using data from the Osteoporotic Fractures in Men Study (MrOS). The MrOS study enrolled 5122 community dwelling men aged ≥ 65 years from six centers across the United States. We excluded men taking bisphosphonates, those with unknown medication history, those without serum sodium measures, or those with out of range assays for serum sodium. Serum sodium was measured at study entry. Subjects were followed for fractures (nonspine (including hip), hip, and incident and prevalent morphometric) for up to 9 years. We used cox proportional hazards models to analyze the association between serum sodium levels (<135mmol/L versus ≥135mmol/L) and risk of nonspine and hip fractures, with results presented as hazard ratios (HR) and 95% confidence intervals (CI). We examined the association between morphometric vertebral fractures and serum sodium using logistic regression models, presented as odds ratios (OR) and 95% CI. Hyponatremia was observed in 64 men (1.2% of the cohort). After adjusting for age, BMI, study center, and other covariates, we found that, compared to men with serum sodium ≥ 135mmol/L, those with serum sodium <135mmol/L, had an increased risk hip fracture (HR=3.04; 95% CI: 1.37 to 6.75), prevalent (OR=2.46; 95% CI: 1.22 to 4.95) and incident (OR=3.53; 95% CI: 1.35 to 9.19) morphometric spine fractures but not nonspine fractures (OR=1.44; 95% CI: 0.85 to 2.44). Adjusting for bone mineral density did not change our findings. Our data demonstrate that hyponatremia is associated with up to a doubling in the risk of hip and morphometric spine fractures, independent of BMD. Further studies, to determine how hyponatremia causes fractures and if correction of hyponatremia decreases fractures, are needed.

Mild Chronic Hyponatremia in the Ambulatory Setting

“…Most recently, Jamal et al (26) studied the association of hyponatremia with fractures among 5122 elderly communitydwelling men using data from the Osteoporotic Fractures in Men Study. Baseline prevalence of hyponatremia was 1.25%.…”

Bone Mineral Density and Osteoporosis in Hyponatremic Versus Normonatremic Patients: A Retrospective 12-Month Analysis

“…Hence, the likelihood of hyponatremia to lead to fractures through other effects on bone such as decreased bone quality, which is not captured by BMD, has also been emphasized (8). In a longitudinal analysis of data from the Osteoporotic Fractures in Men Study (MrOS), it was reported that after adjusting for age, BMI, study center, and other covariates, hyponatremia was associated with up to a doubling in the risk of hip and morphometric spine fractures, independent of BMD (25). Accordingly, aside from reduction in BMD, chronic hyponatremia has also been associated with increased fracture rates in elderly (4,8,11,(14)(15)(16) and with metabolic bone loss through an uncoupling of bone resorption and formation in rats indicating the effect of hyponatremia on bone quality (10).…”

Modeling the Neurologic and Cognitive Effects of Hyponatremia

“…First, the study utilizes ePASP as a proxy for invasive hemodynamic measures. While echocardiography provides a reliable estimate of ePASP, 8 its utility as a tool for…”

“…Furthermore, in population-based studies, chronic hyponatremia associates with bone fracture risk [6][7][8] ; however, whether this is a consequence of a neurologic phenotype predisposing to falls 9 or of a bone phenotype predisposing to fracture 10 (or perhaps a combination of both) remains unclear.…”