Association of hyponatremia with bone mineral density and fractures: a narrative review

Recent studies suggest a possible association of hyponatremia with osteoporosis, falls and bone fractures. The objectives of this narrative review were to further explore this association and the related pathophysiological mechanisms and to suggest a practical approach to patients with osteoporosis or chronic hyponatremia in clinical practice. We conducted an extensive PubMed search until October 2022 with the combination of the following keywords: 'hyponatremia' or 'sodium' or 'SIADH' and 'fractures' or 'bone' or 'osteoporosis', as MeSH Terms. Review of numerous observational studies confirms a significant independent association of, even mild, hyponatremia with two- to three-fold increase in the occurrence of bone fractures. Hyponatremia is a risk factor for osteoporosis with a predilection to affect the hip, while the magnitude of association depends on the severity and chronicity of hyponatremia. Chronic hyponatremia also increases the risk for falls by inducing gait instability and neurocognitive deficits. Besides the detrimental impact of hyponatremia on bone mineral density and risk of falls, it also induces changes in bone quality. Emerging evidence suggests that acute hyponatremia shifts bone turnover dynamics towards less bone formation, while hyponatremia correction increases bone formation. The key unanswered question whether treatment of hyponatremia could improve osteoporosis and lower fracture risk highlights the need for prospective studies, evaluating the impact of sodium normalization on bone metabolism and occurrence of fractures. Recommendations for clinical approach should include measurement of serum sodium in all individuals with fracture or osteoporosis. Also, hyponatremia, as an independent risk factor for fracture, should be taken into consideration when estimating the likelihood for future fragility fracture and in clinical decision-making about pharmacological therapy of osteoporosis. Until it is proven that normalization of sodium can lower fracture occurrence, correcting hyponatremia cannot be universally recommended on this basis, but should be decided on a case-by-case basis.