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Hyponatremia, a risk factor for osteoporosis and fractures in women

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Abstract

Summary

Hyponatremia has been linked to an increased risk of osteoporosis and fractures. We found an increased hazard ratio of major osteoporotic fractures adjusted for potential confounders, including osteoporosis and medication. A reduced BMD was not sufficiently explaining the association. Our data indicate that hyponatremia should be considered a risk factor for osteoporosis and fractures.

Introduction

Hyponatremia is the most common electrolyte disorder in clinical practice and could be a risk factor for both osteoporosis and fractures. Mild hyponatremia has traditionally been regarded as a benign and asymptomatic condition; however, data from large population and animal studies have led to a reappraisal of this view. The purpose of this study was to evaluate the association of hyponatremia with osteoporosis and major osteoporotic fractures (MOF) in women.

Methods

This is a historical cohort study with fracture follow-up. The study consisted of 5610 patients with available serum sodium and a bone density measurement. Information on potential risk factor was obtained through a questionnaire. Additional information on medication, comorbidities, and fractures was obtained through national registries.

Results

Hyponatremia was associated with significant lower T-scores at total hip and a borderline significant lower T-score at femoral neck in the multivariate analysis. No association was found between hyponatremia and the lumbar spine T-score. Hyponatremia was associated with an increased hazard ratio of sustaining a MOF in the period from 6 months prior to 12 months after serum sodium measurement. Finally, data showed a relationship with increasing serum sodium and an increasing T-score estimate and a decreasing hazard ratio of MOF.

Conclusions

Our data suggest that hyponatremia in women increases the risk of osteoporosis and MOF. The increased risk of MOF was independent of osteoporosis.

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Author information

Author notes

    Authors and Affiliations

    1. Department of Endocrinology, Copenhagen University Hospital Hvidovre, Kettegaards Allé 30, DK-2650, Hvidovre, Denmark

      J. P. Holm, A. O. S. Amar, L. Hyldstrup & J. E. B. Jensen

    Authors
    1. J. P. Holm
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    2. A. O. S. Amar
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    3. L. Hyldstrup
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    4. J. E. B. Jensen
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    Corresponding author

    Correspondence to A. O. S. Amar.

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    Conflicts of interest

    J. P. Holm has participated as a subinvestigator in studies by MSD and Amgen. A.O.S Amar none. L. Hyldstrup has been giving lectures sponsored by: Novartis, Lilly, Takeda/Nycomed, Novo-Nordisk, Amgen, GlaxoSmithKline, Servier, MSD, Ferrosan, Pfizer, PharmaVinci and Renapharma. Currently advisory board member for Amgen. J.E.B. Jensen : board membership Amgen, Eli Lilly, MSD, Novartis, Nycomed. Payment for lectures Amgen, Eli Lilly and MSD.

    Additional information

    J. P. Holm and A. O. S. Amar contributed equally to this work.

    Appendices

    Appendix 1

    Definition of fractures

     

    ICD-8

    ICD-10

    MOF

    Spine

    805xx, 806xx

    S120–S122, S127, S220, S221, S320–322, S327, S327A, S328A, S328, M484, M48, T08

    Lower arm

    813xx plus 81248, 81258, 81298

    S52

    Upper arm

    810xx, 811xx, 812xx. minus 81248, 81258, 81298

    S42

    Hip

    820xx

    S720–S722

    Definition of alcohol-related diagnosis

     

    ICD-8

    ICD-10

    Alcohol-related diagnosis

    291xx, 57109, 57110, 303xx

    E244, G312, G621, G721, I426, K292, K860, O354, P043, Q860, K70, F10, T51, Z502, Z714, Z721, 5852

    Definition of medication

     

    ATC

    Thiazides

    C03A, C03EA, C09B, C09BA, C09DA

    Loop diuretics

    C03C, C03EB

    Potassium sparing diuretics

    C03, C07B, C03EA, C03EB

    Systemic glucocorticoids

    H02AB

    Bisphosphonates

    M05BA, M05BB,

    Strontium ranelate

    M05BX03, M05BX53

    PTH analogues

    H05AA01, H05AA02, H05AA03

    Denosumab

    M05BX04

    Raloxifen

    G03XC01

    ACE Inhibitors

    C09A, C09B

    Angiotensin II receptor blockers

    C09C, C09D

    SSRI

    NO6AB

    Definition of Charlson index

    Comorbidities in Charlson index

    ICD-8

    ICD-10

    Score

    Myocardial infarction

    410

    121, 122, 123

    1

    Congestive heart failure

    427.09, 427.10, 427.11, 427.19, 428.99, 782.49

    I50, I11.0, I13.0, I13.2

    1

    Peripheral vascular disease

    440–445

    I70, I71, I72, I73, I74, I77

    1

    Cerebrovascular disease

    430–438

    I60–I69, G45, G46

    1

    Dementia

    290.09–290.19, 293.09

    F00–F03, F05.1, G30

    1

    Chronic pulmonary disease

    490–493, 515–518

    J40–J47, J60–J67, J68.4, J70.1, J70.3, J84.1, J92.0, J96.1, J98.2, J98.3

    1

    Connective tissue disease

    712, 716, 734, 446, 139.99

    M05, M06, M08, M09, M30–M36, D86

    1

    Ulcer disease

    530.91, 530.98, 531–534

    K22.1, K25–K28

    1

    Diabetes mellitus type 1 and 2

    249.00, 249.06, 249.07, 249.09, 250.00, 250.06, 250.07, 250.09

    E10.0, E10.1, E10.9, E11.0, E11.1, E11.9

    1

    Hemiplegia

    344

    G81, G82

    2

    Moderate to severe renal disease

    403, 404,580–584, 590.09, 593.19, 753.10–753.19, 792

    I12, I13, N00–N05, N07, N11, N14, N17–N19, Q61

    2

    Diabetes mellitus type 1 and 2 with end organ damage

    249.01–249.05, 249.08, 250.01–250.05, 250.08

    E10.2–E10.8, E11.2–E11.8

    2

    Any tumor

    140–194

    C00–C75

    2

    Leukemia

    204–207

    C91–C95

    2

    Lymphoma

    200–203

    C81–C85, C88, C90, C96

    2

    Metastatic solid tumor

    195–199

    C76–C80

    6

    AIDS

    79.83

    B21–B24

    6

    Mild liver disease

    571, 573.01, 573.04

    B18, K70.0–K70.3, K70.9, K71, K73, K74, K76.0

    1

    Moderate to severe liver disease

    70.00, 70.02, 70.04, 70.06, 70.08, 573.00, 456

    B15.0, B16.0, B16.2, B19.0, K70.4, K72, K76.6, I85

    3

    Appendix 2

    Table 6

    Table 6 Estimates and p values from multiple regression analysis of T-scores
    Full size table

    Appendix 3

    Table 7

    Table 7 Hazard ratios for MOF in the final model with and without osteoporosis
    Full size table

    Appendix 4

    Table 8

    Table 8 Estimates and p values from multiple regression analysis of T-scores with sodium as a continuous parameter
    Full size table

    Appendix 5

    Table 9.

    Table 9 Hazard ratios for MOF with sodium as a continuous parameter, in the final model with and without osteoporosis
    Full size table

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    Holm, J.P., Amar, A.O.S., Hyldstrup, L. et al. Hyponatremia, a risk factor for osteoporosis and fractures in women. Osteoporos Int 27, 989–1001 (2016). https://doi.org/10.1007/s00198-015-3370-0

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