Complications and Management of Hyponatremia

Richard H. Sterns; Stephen M. Silver


Curr Opin Nephrol Hypertens. 2016;25(2):114-119. 

In This Article

Hyponatremia and Bone

Because a large fraction of body sodium is stored in bone, the skeleton can serve as a sodium reservoir that can be mobilized in response to homeostatic stress.[4,16,17] Hyponatremia promotes bone loss by increasing the number and activity of osteoclasts and by favoring differentiation of mesenchymal stromal cells into adipocytes (which inhibit bone formation) rather than osteoblasts.[16,17] These effects appear to be mediated by a specific extracellular sodium detector and are independent of osmolality. Chronic hyponatremia directly promotes bone loss in experimental animals and is an independent risk factor for osteoporosis and fractures in humans.[17–23] A matched case-controlled study in more than 2.9 million patients found that hyponatremia lasting for more than a year is associated with a four-fold increase in the odds of having osteoporosis.[23] The association was both dose dependent (more severe hyponatremia associated with greater risk) and time dependent (more chronic hyponatremia associated with greater risk). Patients with remote hyponatremia had a lower risk than patients with more recent hyponatremia, consistent with findings of a recent case report suggesting bone mass recovers if hyponatremia is reversed.[24] A young man with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) caused by a vasopressin-secreting esthesioneuroblastoma presented with severe osteoporosis complicated by vertebral fracture; bone density improved after surgical excision of the tumor and resolution of hyponatremia.

In addition to its effect on bone mineral, chronic hyponatremia is associated with gait instability and falls in the elderly, contributing to an increased risk of fractures.[18,19,21,22] Depletion of intracellular glutamate, an excitatory neurotransmitter, could be responsible for some of these findings; chronically hyponatremic rats exhibit an ataxic gait and evidence of cognitive impairment, which is associated with elevated extracellular glutamate in the hippocampus.[5,25]