June 23, 2015
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Hyponatremia increases risk for osteoporosis, fragility fracture

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Recent and sustained hyponatremia, even when mild, can increase the risk for both osteoporosis and fragility fracture, according to research in The Journal of Clinical Endocrinology & Metabolism.

In a matched case-control study, researchers expanded on previous studies that measured only a single serum sodium value in patients with osteoporosis or fragility fracture, and included the variable of chronic hyponatremia during at least 1 year to better evaluate risk.

“The present study provides further evidence that the association between hyponatremia and osteoporosis is dose-dependent (more severe hyponatremia results in higher elevated risk) and time-dependent (chronic hyponatremia carries higher risk than prior hyponatremia alone),” the researchers wrote. “Furthermore, the present finding that recent hyponatremia carries higher odds of osteoporosis than prior hyponatremia supports the hypothesis that hyponatremia-induced bone loss is reversible.”

Sister Grace Miriam (Rachel) Usala, RSM, MS, of Georgetown University Medical Center in Washington, D.C., and colleagues analyzed data from 30,517 osteoporosis cases and 46,256 fragility fracture cases from the MedStar Health electronic database, matched for age, sex, race and patient record length with 30,517 controls without osteoporosis and 46,256 controls without fragility fractures. Researchers reviewed patients’ serum sodium values and performed multivariate logistic regression analyses based on four models: prior, chronic, recent and an interaction of recent and chronic hyponatremia variables.

Researchers found that patients with chronic hyponatremia had the largest OR for incident osteoporosis (3.97; 95% CI, 3.59-4.39), but that the odds of osteoporosis for a patient with both chronic and recent hyponatremia were higher by a factor of 12.09 (95% CI, 9.34-15.66) vs. patients without chronic or recent hyponatremia.

“This model also suggest that, compared to those without either chronic or recent hyponatremia, the odds of experiencing osteoporosis increased almost 2.4-fold if the patient had only recent hyponatremia and almost threefold if the patient had only chronic hyponatremia,” the researchers wrote.

Results for fragility fractures and hyponatremia were similar. Researchers found that patients with chronic hyponatremia had the largest OR for incident fragility fracture (4.61; 95% CI, 4.15-5.11), but that the odds of fragility fracture for a patient with both chronic and recent hyponatremia were higher by a factor of 11.21 (95% CI, 8.81-14.26) vs. patients without chronic or recent hyponatremia.

“Our findings demonstrate that recent hyponatremia is an even greater risk factor for fragility fracture than prior hyponatremia alone,” the researchers wrote. “Thus, the association between hyponatremia and fragility fracture may not be merely related to chronic bone loss, but also due to a more acute process, such as hyponatremia-induced gait instability leading to increased falls.”

The findings demonstrate that different types of hyponatremia are associated with different levels of risk for osteoporosis and fragility fracture, and clinicians should distinguish among a short and proximate hyponatremic event, a chronic pattern and a brief episode in the distant past, according to researchers.

“More studies, such as prospective trials of reversal of hyponatremia with monitoring of bone quality, falls and fractures, are warranted to evaluate whether treatment of a highly prevalent electrolyte disorder could result in improved patient outcomes,” the researchers wrote. by Regina Schaffer

Disclosure: Usala reports no relevant financial disclosures. One study author reports receiving grant support from Otsuka America Pharmaceutical Inc., as well as non-CME-related fees from Cardiokine, Cornerstone Therapeutics, Ferring Pharmaceuticals and Otsuka America.