- In a case-control study of patients over age 60 who had chronic kidney disease, chronic prolonged hyponatremia was associated with 36% higher odds of hip fracture, even after adjustment for comorbidities, medications and laboratory parameters
- Hip fracture risk tied to chronic prolonged hyponatremia was increased in stratified analyses of patients with and without osteoporosis, with or without falls and over or under age 70
- Severe hyponatremia was not a prerequisite for fracture risk
- The chronicity of hyponatremia appears to be a key consideration, in that a single episode of hyponatremia was not associated with increased fracture risk
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. Nigwekar, MD, MMSc, nephrologist at 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).
Adding to that research, Dr. Nigwekar 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.
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 who 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.
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.