Abstract
Hyponatremia is the most common electrolyte disorder and is mainly known for its neurological complications. New studies suggest previously unrecognized complications of hyponatremia, including falls, osteoporosis and fractures. Because these novel associations are mainly derived from epidemiological studies, it remains unclear whether hyponatremia has a direct effect on bone or whether it is a surrogate marker of another etiology. However, one animal and one in vitro study now show that hyponatremia can have direct effects on bone, mainly via activation of osteoclasts. The association between hyponatremia and fractures appears to be independent of osteoporosis (defined as low BMD). Also, data suggest that this association cannot be fully explained by the possibility that hyponatremia predisposes to falls. Hyponatremia, therefore, also has an effect on bone quality that is not captured by BMD. Here, the emerging relationship between hyponatremia and bone is reviewed, with special emphasis on possible mechanisms, unanswered questions and clinical implications.
Key Points
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Recent studies suggest that hyponatremia, the most common electrolyte disorder, affects not only the brain but also bone
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Several epidemiological studies have identified associations between hyponatremia and increased risk of falls and fractures and, in one study, with decreased BMD
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The associations between mild hyponatremia and increased fracture risk cannot be fully explained by increased risk of falling and appear to be independent of BMD
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One animal study and one cell culture study found that a low sodium concentration in serum or medium increased osteoclast activity
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Hyponatremia could be a new clinical risk factor for osteoporosis and fractures
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Future studies are needed to show whether the relationship between hyponatremia and fractures is causal and whether correction of hyponatremia reduces fracture risk
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E. J. Hoorn researched the data for the article. E. J. Hoorn, R. Zietse and M. C. Zillikens provided a substantial contribution to discussions of the content. E. J. Hoorn, G. Liamis and M. C. Zillikens contributed equally to writing the article. All authors reviewed and/or edited the manuscript before submission.
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Hoorn, E., Liamis, G., Zietse, R. et al. Hyponatremia and bone: an emerging relationship. Nat Rev Endocrinol 8, 33–39 (2012). https://doi.org/10.1038/nrendo.2011.173
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DOI: https://doi.org/10.1038/nrendo.2011.173
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