Hyponatremia and aging-related diseases: key player or innocent bystander? A systematic review

Hyponatremia is frequent in older age; whether it is a key player, a surrogate marker, or an innocent bystander in age-related diseases is still unclear.

To understand the role of hyponatremia in falls, osteoporosis, fractures, and cognitive impairment in old patients.

Eligibility criteria for study inclusions were: written in English, peer-reviewed observational and intervention studies, clinical trial, prospective and retrospective controlled cohort studies, and case-controlled studies without limitations regarding the date of publication.

Protocol available on the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021218389). MEDLINE, Embase, and PsycINFO were searched. Final search done on August 8, 2021. Risk-of-bias assessment: Risk-of-Bias Assessment tool for Non-randomized Studies (RoBANS) and the Bradford Hill's criteria for causality.

Includes studies: One-hundred thirty-five articles retained for the revision. Synthesis of results - Falls: Eleven studies were included. Strong association between hyponatremia and falls in all the studies was found. Osteoporosis and fractures: nineteen articles were included. The association between hyponatremia and osteoporosis is unclear. Cognitive impairment: Five articles were included. No association between hyponatremia and cognitive impairment was found.

Interpretation: Falls, osteoporosis, and fractures are multifactorial. Hyponatremia is not temporally related with the outcomes; we suggest that hyponatremia may be regarded as a marker of unhealthy aging and a confounder instead of a causal factor or an innocent bystander for falls and fractures. Concerning cognitive impairment, there are no evidence supporting a real role of hyponatremia to be regarded as an innocent bystander in neurodegeneration.