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

Abstract

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.

The Influence of Hyponatremia and Hypokalemia on the Risk of Fractures in Various Anatomical Regions among Adult Trauma Patients: A Propensity Score-Matched Analysis

“…Second, the usage of drugs and nutritional state in this study population are unclear, which may contribute to bias in the interpretation of the data. Third, some diseases, such as hypophosphatemia or metabolic alkalosis [47], syndrome of inappropriate antidiuretic hormone secretion (SIADH) [11,25], primary hyperaldosteronism [48,49], Cushing syndrome [50][51][52], and Bartter syndrome [53], may be strongly linked to hyponatremia or hypokalemia and fracture incidence but were not excluded or analyzed in this study. Finally, the study is confined to a single trauma center, potentially limiting the generalizability of its findings to broader populations.…”

“…Additionally, certain authors have suggested that hyponatremia and hypokalemia should be regarded as indicators of compromised health rather than as isolated risk factors for fractures [20]. Furthermore, although hip fractures are consistently identified as the most prevalent among patients with hyponatremia [4,[22][23][24][25], no distinct order is established regarding the ranking of other fracture sites. Furthermore, there are also no published reports concerning the location of fractures associated with hypokalemia.…”