Association Between Hyponatremia, Osteoporosis, and Fracture: A Systematic Review and Meta-analysis

Context: Hyponatremia is the most common electrolyte disorder. Recent research shows that it may associate with osteoporosis and fracture. However, whether it directly associates or is a surrogate marker of other causes is still unclear. Objectives: To explore the hypothesis of an association of osteoporosis or fracture with hyponatremia. Data Sources: MEDLINE and EMBASE databases from inception to October 2015. Study Selection: The inclusion criteria were published studies evaluating bone mineral density, risk or prevalence of osteoporosis or fracture in patients with hyponatremia. Data Extraction: Both authors independently reviewed titles and abstracts of all citations that were identified. Data Synthesis: A meta-analysis using a random-effects model comparing between hyponatremia and normal serum sodium groups was performed. We calculated pooled mean difference in bone mineral density, pooled hazard ratio (HR) or odds ratio (OR) of fracture and osteoporosis. Factors that may predict these associations were evaluated in subgroup analysis and meta-regression. From 29 full-text articles, 15 observational studies involving 212 889 participants met our inclusion criteria. Twelve studies were included in the meta-analysis. There was a significant association with fracture and osteoporosis in patients with hyponatremia with OR of fracture = 1.99 (95% confidence interval, 1.50-2.63; p < .001) for studies that reported OR, and increase risk of fracture with HR = 1.62 (95% confidence interval, 1.28-2.05; P < .001) for studies that reported HR. Conclusions: Hyponatremia significantly associates with osteoporosis and fracture. More prospective studies evaluating osteoporosis and fracture risk reduction after hyponatremia correction should be performed.