Higher Fracture Rates Seen Among Elderly With Mild Hyponatremia

November 23, 2010 (Denver, Colorado) — Elderly patients who are even mildly hyponatremic have a significantly higher risk for falls and fractures than those with normal sodium levels, according to research presented here at Renal Week 2010: American Society of Nephrology 43rd Annual Meeting.

Dutch researchers evaluated data from The Rotterdam Study, a population-based cohort of 5208 elderly patients, and found that in the 339 (7%) subjects with hyponatremia, the risk for vertebral fractures or vertebral compression fractures was 61% higher than in those with sodium levels in the normal range, and the risk for nonspinal fractures, such as hip fractures, was 39% higher.

The researchers also found that 24% of subjects with hyponatremia had experienced recent falls, compared with 16% of those who were normonatremic, and patients who were hyponatremic had a 21% increased risk for death during the study's mean follow-up period of 7.4 years.

Despite the increased risk for falls and fractures, the bone mineral density of hyponatremic subjects was not significantly different than that of those who were normonatremic.

"The normal assumption would be that the higher fracture risk was mediated through an effect on bone mineral density or osteoporosis, but in this study, we were unable to reproduce such an association," said lead author Ewout J. Hoorn, MD, PhD, from the Erasmus Medical Center, Rotterdam, the Netherlands.

The researchers found that subjects with hyponatremia were older (73.5 ± 10.3 years vs 70.0 ± 9.0 years; P < .001), had a higher prevalence of type 2 diabetes mellitus (22.2% vs 10.3%; P < .001), and had a higher use of diuretics (36.9% vs 21.3%; P < .001).

The increased risk for incident nonvertebral fractures among subjects with hyponatremia (hazard ratio, 1.39; 95% confidence interval, 1.11 - 1.73; P = .004) was evident after adjustment for age, sex, and body mass index. Adjustments for disability index, use of diuretics or psycholeptics, recent falls, and prevalent diabetes did not modify the results.

The absence of an association between fractures and low bone mineral density raises the question of whether other aspects of hyponatremia somehow increase the risk, Dr. Hoorn said.

One theory, he speculated, involves the concept of sodium-gated channels and bone regeneration, first described in a paper in 1984.

The paper "demonstrated that damaged bone contains ionic currents, including sodium currents, and it gets even more interesting with the discovery of so-called voltage-gated sodium channels that are important for regeneration," Dr. Hoorn explained.

"If you cut off the tail of a frog, it regenerates normally; however, if you inhibit the voltage-gated sodium channels, it does not regenerate normally. Interestingly, voltage-gated sodium channels are highly expressed in bone and are sensitive to changes in extracellular osmolality."

"If sodium currents are important for the microdamage of bone, and if the lower serum osmolality found in hyponatremia inhibits voltage-gated sodium channels, which are important for regeneration, this might provide a mechanism by which hyponatremia might increase fracture," Dr. Hoorn said. "It's speculative, but I thought it was interesting."

The findings, if confirmed in further studies, suggest that screening for hyponatremia might be useful in reducing fracture risk in the elderly.

"Mild hyponatremia appears to be a new risk factor for fractures in the elderly, and if replicated, screening and treatment for hyponatremia might prevent fractures," Dr. Hoorn said.

More studies are needed to determine the nature of the association, but clinicians are already taking greater notice of the condition and its potential relation to fractures, according to Kenneth R. Hallows, MD, associate professor of medicine, cell biology, and physiology at the University of Pittsburgh School of Medicine in Pennsylvania, who moderated the session.

"I believe that there is a growing awareness of the issue of hyponatremia and the risk of falls and fractures in the elderly, at least among nephrologists and geriatricians. This study should help give the issue more visibility," said Dr. Hallows.

"Regarding the issue of screening, many patients in this age range who visit a physician regularly get frequent (e.g., yearly) chemistry panels that would detect hyponatremia. It may be reasonable for elderly patients who are at higher risk for hyponatremia (e.g., those on thiazide diuretics, or with heart failure or chronic kidney disease) to be screened more frequently," Dr. Hallows noted.

"In general, I believe that increased education and awareness on the part of physicians treating elderly patients who present with mild hyponatremia about the association of increased falls and fractures with this condition could lead to improved outcomes," he added.

Dr. Hoorn and Dr. Hallows have disclosed no relevant financial relationships.

Renal Week 2010: American Society of Nephrology 43rd Annual Meeting. Abstract FC232. Presented November 19, 2010.