![]() 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. An additional direct effect of AVP on bone remodeling has also been recently suggested. The mechanisms through which this occurs are not yet completely understood, but prominently involve increased bone osteoclast formation and activity. 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. In particular, hyponatremia has been shown to increase gait instability, falls, and fracture risk. Hyponatremia, even when relatively mild, leads to increased morbidity and mortality in diverse clinical scenarios. 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. Consequently, changes in total body sodium content are not always accurately reflected by the ECF. Extracellular fluid (ECF) sodium concentrations () 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). This paper reviews our current understanding of the mechanisms by which WNT signalng regulates bone homeostasis.Sodium balance is primarily regulated through the renin-angiotensin-aldosterone system. The pathway is now the target for therapeutic intervention to restore bone strength in millions of patients at risk for fracture. The importance of WNT signaling for bone has also been highlighted since then in the general population in numerous genome-wide association studies. Mouse genetics confirmed the importance of canonical Wnt signaling in the regulation of bone homeostasis, with activation of the pathway leading to increased, and inhibition leading to decreased, bone mass and strength. A decade ago, rare human mutations affecting bone negatively (osteoporosis-pseudoglioma syndrome) or positively (high-bone mass phenotype, sclerosteosis and Van Buchem disease) have been identified and found to all reside in components of the canonical WNT signaling machinery. Low bone mass and strength lead to fragility fractures, for example, in elderly individuals affected by osteoporosis or children with osteogenesis imperfecta. ![]()
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December 2022
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