Chronic hyponatremia and association with osteoporosis among a large racially/ethnically diverse population

  • A. L. AdamsEmail author
  • B. H. Li
  • S. Bhandari
  • S. Kamat
  • S. Sundar
  • H. Krasa
  • C. M. Rhee
  • K. Kalantar-Zadeh
  • S. J. Jacobsen
  • J. J. SimEmail author
Original Article



Chronic hyponatremia may contribute to decreased bone density. We studied 341,003 men and women who underwent DXA testing and observed that individuals with chronic hyponatremia (sodium < 135 mEq/L) had an 11% greater likelihood of having osteoporosis. There was a dose-dependent effect with lower sodium and stronger association with osteoporosis.


Chronic hyponatremia has been associated with both neurologic deficits and increased risk of gait abnormalities leading to falls and resultant bone fractures. Whether chronic hyponatremia contributes to decreased bone density is uncertain. We evaluated whether chronic, mild hyponatremia based on serial sodium measurements was associated with increased risk of osteoporosis within a large, ethnically diverse population.


This is a retrospective cohort study between January 1, 1998 and December 31, 2014 within Kaiser Permanente Southern California, an integrated healthcare delivery system. Men and women were aged ≥ 55 years with ≥ 2 serum sodium measurements prior to dual-energy X-ray absorptiometry (DXA) testing. Time-weighted (TW) mean sodium values were calculated by using the proportion of time (weight) elapsed between sodium measurements and defined as < 135 mEq/L. Osteoporosis defined as any T-score value ≤ − 2.5 of lumbar spine, femoral neck, or hip.


Among 341,003 individuals with 3,330,903 sodium measurements, 11,539 (3.4%) had chronic hyponatremia and 151,505 (44.4%) had osteoporosis. Chronic hyponatremic individuals had an osteoporosis RR (95% CI) of 1.11 (1.09, 1.13) compared to those with normonatremia. A TW mean sodium increase of 3 mEq/L was associated with a lower risk of osteoporosis [adjusted RR (95% CI) 0.95 (0.93, 0.96)]. A similar association was observed when the arithmetic mean sodium value was used for comparison.


We observed a modest increase in risk for osteoporosis in people with chronic hyponatremia. There was also a graded association between higher TW mean sodium values and lower risk of osteoporosis. Our findings underscore the premise that chronic hyponatremia may lead to adverse physiological effects and responses which deserves better understanding.


Chronic hyponatremia Diverse population Osteoporosis 


Financial support

This study was funded and supported by Otsuka Pharmaceutical Development & Commercialization, Inc.

Compliance with ethical standards

Conflicts of interest

A. Adams, B. Li, S. Bhandari, C. Rhee, K. Kalantar-Zadeh, S. Jacobsen, and J. Sim report no conflicts of interest relevant to this manuscript. H. Krasa, S. Kamat, and S. Sundar are employees of Otsuka Pharmaceutical Development & Commercialization, Inc., who has a treatment for hyponatremia.

Supplementary material

198_2018_4832_MOESM1_ESM.docx (67 kb)
ESM 1 (DOCX 67 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.Department of Research and EvaluationKaiser Permanente Southern CaliforniaPasadenaUSA
  2. 2.Division of Nephrology and HypertensionKaiser Permanente Los Angeles Medical CenterLos AngelesUSA
  3. 3.Otsuka Pharmaceuticals Development and Commercialization, Inc.San FranciscoUSA
  4. 4.Division of Nephrology and HypertensionUC Irvine Medical CenterIrvineUSA

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