Chronic Hyponatremia Is a Risk Factor for Hip Fracture in Older Patients with CKD

Increasing evidence suggests hyponatremia is a risk factor for bone disease in the general population and for bone fracture among those who fall. Also, Sagar U. Nigwekara, MD, MMSc, nephrologist in the Division of Nephrology at Massachusetts General Hospital, and colleagues recently reported in Nephrology Dialysis Transplantation that mild chronic prolonged hyponatremia is a significant risk factor for hip fractures in older patients without chronic kidney disease (CKD).

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Adding to that research, Dr. Nigwekara and colleagues have determined that chronic prolonged hyponatremia is associated with increased hip fracture risk in older patients with CKD, a population that has a high prevalence of hyponatremia and high fracture risk. Their report appears in Bone.

Study Methods

The researchers conducted a case-control study on 1,236 cases using a patient registry maintained by Mass General and its partner hospitals. These patients were older than 60 years of age, had CKD and experienced a hip fracture due to minor trauma between January 1, 2006, and December 31, 2013. Patients were excluded if they were receiving dialysis or had received a transplant.

The control group consisted of 4,515 CKD patients older than 60 who had no hip fracture during the study period and matched the cases on age, sex and race.

Subjects were considered to have chronic prolonged hyponatremia if serum sodium was <135 mEq/L on at least two occasions, separated by at least 90 days, prior to the hip fracture (cases) or at any time during the study period (controls).

Prevalence of Hyponatremia

In the comparison of cases and controls:

• Chronic prolonged hyponatremia was present in 21% vs. 10% (P < .001)
• The hyponatremia was mild (serum sodium 131–134 mEq/L) in 77% and 79%
• Patients having at least one episode of hyponatremia occurred in 53% vs. 41% (P < .001)
• Chronic hyponatremia lasted ≥180 days in 16% vs. 7% (P < .001)

Hyponatremia and Risk of Hip Fracture

In a multivariate model adjusted for comorbidities, medications and laboratory parameters, chronic prolonged hyponatremia was associated with higher odds of hip fracture (OR, 1.36; 95% CI, 1.04–1.78).

Chronic prolonged hyponatremia persisted as a significant risk factor for hip fracture in stratified analyses:

• With osteoporosis—OR, 2.45
• Without osteoporosis—OR, 2.38
• With a history of falling—OR, 1.57
• Without a history of falling—OR, 1.76
• Age >70—OR, 2.24
• Age ≤70—OR, 4.02

Compared with patients who had severe hyponatremia (serum sodium <130 mEq/L), patients with mild or moderate hyponatremia had comparable risks of hip fracture. A single episode of hyponatremia was not significantly associated with a higher risk in a multivariate-adjusted model.

Clinical Application

It's notable that more than three-quarters of patients in this study had only mild hyponatremia, which was as much a risk factor for hip fracture as severe hyponatremia. A potential mechanism is diminished bone quality due to chronically low sodium concentration.

Mild chronic hyponatremia has conventionally been considered benign, so it may not receive enough attention in clinical practice. Chronic hyponatremia should be addressed as a potentially modifiable risk factor for hip fracture in all older patients who have CKD. The chronicity of hyponatremia appears to be a key consideration since a single episode of hyponatremia was not associated with increased fracture risk.

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