Mild prolonged hyponatremia is independently associated with an increased risk of hip fracture among individuals older than 60 years, according to a new study.

Juan Carlos Ayus, MD, the Renal Consultants of Houston in Texas and the Italian Hospital of Buenos Aires (IHBA) in Buenos Aires, Argentina, retrospectively studied of 31,527 patients older than 60 years who had 2 or more measurements of plasma sodium levels during 2005–2012. Of these, 228 (0.9%) had prolonged chronic hyponatremia, defined as a sodium level below 135 mmol/L for more than 90 days. The mean plasma sodium level was 132 mmol/L in the hyponatremic patients and 139 mmol/L in the normonatremic patients.

Hip fractures occurred in 7 (3%) of the 228 hyponatremic patients and 411 (1%) of the 31,299 normonatremic. In adjusted analyses, prolonged chronic hyponatremia was associated with a 4.5 times increased risk of hip fracture compared with normonatremia, Dr. Ayus’ team reported online ahead of print in Nephrology Dialysis Transplantation. Chronic moderate hyponatremia (sodium level less than 130 mmol/L) was associated with 7.6 times higher risk.

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The findings suggest that duration of hyponatremia is an additional risk for hip fracture, the authors concluded. “Although the present study cannot establish a causal relationship, the results raise questions about the current indication for the treatment of mild hyponatremia in older patients and suggest the need for interventional studies to evaluate whether systematic surveillance and active correction of mild hyponatremia could help to reduce hip fractures in the elderly.”

The investigators described 2 proposed mechanisms by which hyponatremia contributes to bone fractures: by causing subtle neurologic impairment, with gait abnormalities and falls, and by contributing directly to osteoporosis and increased bone fragility. Animals studies have shown that prolonged chronic hyponatremia (3 months’ duration) leads to abnormal bone histomorphology and decreased bone mineral density, but no human studies have examined whether hyponatremia duration contributes to bone abnormalities, they pointed out.

“In the present study, all hip fractures were caused by a mechanical fall, suggesting abnormal gait was present in these subjects,” the authors wrote.

Dr. Ayus and his colleagues explained that the brain adapts to chronic hyponatremia with the loss of osmolytes, such as glutamate, a neurotransmitter involved in gait function. “Thus, loss of glutamate may play a role in gait abnormalities that lead to falls in patients with chronic hyponatremia.”

The study population consisted of patients receiving care at IHBA, a general tertiary-level hospital. The patients with chronic hyponatremia were older than those with normonatremia (mean 78 vs. 70 years). The median follow-up times for the hyponatremic and normonatremic groups were 510 days and 1,421 days, respectively. The hyponatremic patients had a higher incidence of previous fractures (17% vs. 12%) and alcohol use (2.6% vs. 0.8%), factors known to increase fracture risk.

In a separate study of Danish patients published recently in Bone (2016;84:9-14), researchers found that chronic mild hyponatremia (sodium level 130–137 mmol/L) was associated with lower bone mineral content and bone mineral density in nearly all regions of the hip as ascertained by multiple serial dual-energy X-ray absorptiometry scans.