Bone Abstracts

Several independent international studies have shown increased bone fracture rates in patients with hyponatremia (HN). A likely major contributor to this finding is gait instability and increased falls in HN patients. Studies in experimental animals have also demonstrated HN-induced bone loss, and analysis of human subjects in NHANES III showed a significantly increased odds ratio for osteoporosis by hip DXA in the HN subjects in this database. In vitro studies of the mechanisms underlying HN-induced osteoporosis have implicated a resorptive osteoporosis due to osteoclast sensing of serum and extracellular fluid sodium concentration (Na⁺) with subsequent stimulation of osteoclast proliferation and resorptive activity; this pathophysiology occurs independently of vasopressin levels. In considering the teleological basis for osteoclast activation by low extracellular (Na⁺), it is notable that bone mineral is rich in sodium, upto 40% of which is exchangeable with circulating sodium within a relatively short time. We therefore hypothesize that bone acts as a sodium storage reservoir that can be mobilized to maintain the sodium content of the ECF at levels adequate to maintain blood volume, blood pressure and tissue perfusion during times of sodium deficiency, similar to the release of bone calcium to maintain calcium homeostasis during calcium 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. This talk will review current data regarding the pathophysiology of HN-induced osteoporosis, discuss the role of bone in maintaining sodium homeostasis, and present new data regarding the prevalence and potential impact of HN on osteoporosis and fragility fractures that support our hypothesis that HN is a significant and clinically important risk factor for osteoporosis and bone fractures.