Hyponatremia Is a Risk Factor for Fractures in the Elderly

Fran Lowry

October 25, 2010

October 25, 2010 (Toronto, Ontario) — Mild hyponatremia is an important risk factor for fractures in the elderly, according to new research presented here at the American Society for Bone and Mineral Research 2010 Annual Meeting.

"Decreased serum sodium levels are considered to be a benign condition," said Carola Zillikens, MD, PhD, from Erasmus University Medical Center, Rotterdam, the Netherlands. "But recent data suggest this may not be the case. Mild hyponatremia has been linked to fractures [because of the] increased risk of falling or decreased bone mineral density."

She and her colleagues investigated the relation between decreased serum sodium and fractures in participants of the Rotterdam study, a prospective, population-based study of 5208 participants, 55 years and older, who had serum sodium levels measured at study entry. The mean age was 70 years, and 23% of the cohort was smokers and 16.5% used diuretics.

At baseline, 194 individuals were found to have vertebral fractures on x-ray. Another 139 fractures occurred during the mean follow-up of 6.4 years.

Hyponatremia, defined as a serum sodium level of 136 mmol/L or less, was detected in 399 participants (7.7%). Subjects with hyponatremia were significantly older (mean age, 74 vs 70 years; P < .001), had more recent falls (24% vs 16%; P < .01), had a higher prevalence of type 2 diabetes (22% vs 10%; P < .001), and were more likely to use diuretics (37% vs 21%; P < .001).

The investigators found that hyponatremia was associated with a nearly 40% increased risk for incident nonvertebral fractures (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.11 - 1.73; P = .004) after adjustment for age, sex, and body mass index. Further adjustment for disability, use of diuretics and psycholeptics, history of recent falls, and diabetes did not change these results, Dr. Zillikens said.

The researchers also found that the risk for both prevalent and incident vertebral fractures among subjects with hyponatremia was about 60% higher after adjustment for all variables (HR, 1.61; 95% CI, 1.00 - 2.59; P = .049).

Hyponatremia was not related to femoral neck or lumbar spine bone mineral density.

"Treating hyponatremia may be one way to prevent falls and fractures, but we really can't say yet whether this should be standard practice," Dr. Zillikens told Medscape Medical News. "Our data have to be replicated in other prospective studies. If they are, then I think it would be reasonable, when elderly people fracture, that they be tested for hyponatremia to see if that may be an underlying cause."

It is too soon to recommend general screening in the elderly for hyponatremia, she added. "I think it is important that these results are replicated and that others find the same association."

Jerilynn Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, told Medscape Medical News that she found the study fascinating. "My thoughts are that the hyponatremia–fracture link has to do with some relationship with the rennin angiotensin aldosterone pathway, and also with increased inflammation or oxidative stress."

Elizabeth Barrett-Connor, MD, from the University of California at San Diego, told Medscape Medical News that the observation that mild hyponatremia is linked to fractures is an original one.

There could be many explanations for the association, she added.

"There could be lots of different mechanisms. It's certainly exciting, but I don't know what it means," Dr. Barrett-Connor, who was one of the moderators of the session, confessed. "First, we need to see if somebody else can find it again, because the first time somebody shows something, you're never sure whether this is due to chance or not, nor are you sure of what the mechanisms are. The speaker was very good at listing a whole lot of things. She tried to adjust for them, but adjustments are never perfect."

Dr. Zillikens, Dr. Prior, and Dr. Barrett-Connor have disclosed no relevant financial relationships.

American Society for Bone and Mineral Research (ASBMR) 2010 Annual Meeting: Abstract 1092. Presented October 17, 2010.