Sodium homeostasis and bone.

Abstract

Sodium balance is primarily regulated through the renin-angiotensin-aldosterone system. Extracellular fluid (ECF) sodium concentrations ([Na]) reflect the overall body sodium content, but are also influenced by the osmoregulatory system, which is regulated by the posterior pituitary hormone arginine vasopressin (AVP). Consequently, changes in total body sodium content are not always accurately reflected by the ECF [Na]. This review summarizes the growing evidence base suggesting that skeletal bone, which is rich in sodium, may play a key role in overall body sodium homeostasis. Hyponatremia, even when relatively mild, leads to increased morbidity and mortality in diverse clinical scenarios. In particular, hyponatremia has been shown to increase gait instability, falls, and fracture risk. It now appears likely that at least part of the fracture risk is because of the adverse effects of hyponatremia on bone density and quality. The mechanisms through which this occurs are not yet completely understood, but prominently involve increased bone osteoclast formation and activity. An additional direct effect of AVP on bone remodeling has also been recently suggested. Recent evidence expands upon the previously accepted concepts of body sodium homeostasis and suggests that sodium balance can be augmented by inputs from skeletal bone, which acts as a sodium-rich reservoir that can be deployed during times of sodium deficiency. However, this evolutionarily adaptive mechanism to maintain sodium homeostasis during times of environmental sodium deprivation also has adverse consequences by negatively impacting bone quality and increasing fracture risk.