Background 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. Objective: To understand the role of hyponatremia in falls, osteoporosis, fractures, and cognitive impairment in old patients. Method 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. Information sources: 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. Results 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. Discussion 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.
Purpose. 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. Method. To further understand the role of hyponatremia in falls, osteoporosis, fractures, and cognitive impairment in old patients, we conducted a systematic literature review. The protocol of this study is available on the International prospective register of systematic reviews (PROSPERO, number CRD42021218389). MEDLINE, EMBASE and PsycINFO database were searched. Three reviewers identified studies meeting inclusion criteria and check decisions. Each study was independently evaluated by two reviewers, discrepancies between the two reviewers were solved by the third. Two hundred and fifteen articles were retrieved. Thirty-two were included in the review. Results. The majority of the studies found a significant association between hyponatremia and falls even after correction for confounding factors. Some studies suggested an association between persistent hyponatremia and increased osteoporosis and fracture risk. On the contrary, the evidence of an association between hyponatremia and cognitive impairment is lacking. Conclusion. Here we suggest that hyponatremia may be regarded as a marker of unhealthy aging and a confounder rather than a causal factor or an innocent bystander for falls and fractures. As regards cognitive impairment, the evidence provided until now, are not sufficient to explain a real role of hyponatremia that may be regarded rather as an innocent bystander in neurodegeneration.
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