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      Hyponatremia and bone: an emerging relationship.

      Nature reviews. Endocrinology
      Springer Nature America, Inc

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          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.

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          Most cited references37

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          Osteoporosis: now and the future.

          Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This overview discusses these novel therapies and explains their underlying physiology. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.

            Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.
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              Incidence and prevalence of hyponatremia.

              Hyponatremia is the most common electrolyte abnormality encountered in clinical practice. The reported frequency of the disorder is determined by a number of factors, including the definition of hyponatremia, the frequency of testing, the healthcare setting, and the patient population. This review focuses on the incidence and prevalence of hyponatremia. In acute hospital care, particular attention is given to admission versus hospital-acquired hyponatremia. Although less well studied, the epidemiology of hyponatremia in the ambulatory-based setting and the geriatric/nursing home population is also summarized. Finally, the frequency of hyponatremia occurring in special clinical conditions--including congestive heart failure, cirrhosis, pneumonia, and acquired immunodeficiency syndrome--as well as in marathon runners will be reviewed. Substantial additional work is still required to determine the true occurrence of hyponatremia in the various clinical settings. Beyond the phenomenologic value, advances in the epidemiology of hyponatremia should also provide insights in the prognostic implications as well as the preventive and management strategies of the disorder in various clinical settings.
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                Author and article information

                Journal
                22024973
                10.1038/nrendo.2011.173

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