Table 2 Hyponatremia, osteoporosis, and fractures: characteristics of the studies included in the review
From: Hyponatremia and aging-related diseases: key player or innocent bystander? A systematic review
Study | Study design | Sodium level | Definition of hyponatremia used | Time of sodium measurement | Participants (number) | Age of participants (years) | Gender | Etiology of hyponatremia | Scores | Diuretics | Main outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|
Gankam Kengne et al. (2008) [10] | Case control | 131 ± 3 mEq/l (mean ± SD) in hyponatremia group | Serum sodium  < 135 mEq/l | Single at admission (pretreatment) | 513 | 81 (8) Mean (SD) | 74.1% F | Idiopathic SIADH (35%), diuretics (35%), SSRI (16%), salt depletion (6%), secondary SIADH (4%), potomania (3%), antiepileptic drugs (1%) | - | Type and dosage of diuretic not specified | Prevalence of hyponatremia in fractures |
Sandhu et al. (2009) [36] | Cross-sectional | 131 ± 2 mEq/l (mean ± SD) in fracture group | Serum sodium  < 135 mEq/l | Single at baseline | 1609 | 79.2 (8.2) Mean (SD) | 75.3% F | Hyponatremia associated with central nervous system disease, lung disease, thyroid disorders, diuretic, or antidepressant use | - | Type and dosage of diuretic not specified | Incidence of hyponatremia in patient with fracture |
Kinsella et al. (2010) [19] | Cross-sectional | 140.6 ± 3.0 mEq/l (total mean ± SD) | Serum sodium  < 135 mEq/l | Within 1 year before DXA | 1408 | 61 (11) Mean (SD) | 100% F | Not evaluated | BMD, DXA | Not evaluated | Incidence of fractures |
Chow et al. (2011) [37] | Retrospective cohort | 116 ± 7 mEq/l (mean ± SD) in the thiazide-induced group | Serum sodium  < 135 mEq/l | Record of hyponatremia | 439 | 76 (9) Mean (SD) | 70.4% F | Thiazide-induced hyponatremia | - | Thiazide, dosage not reported | Prevalence of fracture in patients with thiazide-induced hyponatremia |
Hoorn et al. (2011) [4] | Prospective cohort | 140.2 ± 3.3 mEq/l (total mean ± SD) | Serum sodium  < 136 mEq/l | Single at baseline | 5208 | 70.3 (9.1) Mean (SD) | 61.5% F | Not evaluated | - | Thiazides, loop diuretics, potassium-sparing diuretics. Dosage not reported | Incidence of fractures, falls, mortality in the community |
Tolouian et al. (2012) [38] | Case control | 137.4 ± 3.8 mEq/l (mean ± SD) in hyponatremia group | Serum sodium  < 135 mEq/l | Single at baseline | 293 | 81.6 (8.4) Mean (SD) | 63.1% F | Not evaluated | - | Not evaluated | Prevalence of hyponatremia in hip fracture |
Arampatzis et al. (2013) [39] | Cross-sectional | 139 ± 4 mEq/l (mean ± SD) in hyponatremia group | Serum sodium  < 132 mEq/l | Single at admission | 10,823 | 73 (12) Mean (SD) | 63% F | Hyponatremia related to diuretic use | - | Thiazides, loop diuretics, spironolactone, amiloride. Dosages not reported | Prevalence of fractures in hyponatremic (loop diuretics users) |
Hagino et al. (2013) [40] | Case control | 132 ± 2.3 mEq/l (mean ± SD) in hyponatremia group | Serum sodium  < 135 mEq/l | Single at admission | 512 | 86.7 (6.6) Mean (SD) | 75.5% F | Hyponatremia related to heart failure, liver failure, and diabetes | - | Not evaluated | Prevalence of hyponatremia at in hip fracture |
Afshinnia et al. (2015) [41] | Cross-sectional | 140.2 ± 2.3 mEq/l (total mean ± SD) | Serum sodium  ≤ 135 mEq/l | Time averaged | 24,784 | 61 (14) Mean (SD) | 81.6% F | Hyponatremia related to diuretics use and liver cirrhosis | BMD, DXA | Thiazides, loop diuretics. Dosage not reported | Prevalence of osteoporosis |
Ganguli et al. (2015) [29] | Retrospective chart review | 131.2 ± 4.5 mEq/l (initial hyponatremia) 130.4 ± 3.5 mEq/l (persistent hyponatremia) | Serum sodium  < 136 mEq/l | At baseline, at least 2 or more than 6 consecutive measurements | 608 | 84.3 (9.3) Mean (SD) | 77.1% F | Euvolemic (69.8%): main causes were thiazides and SSRI use, idiopathic SIADH; hypervolemic (9.4%): main cause was end-stage renal disease and congestive heart failure; hypovolemic (20.7%): main causes were diarrhea and diuretics (furosemide and thiazide) | - | Thiazides, furosemide. Dosage not reported | Incidence of falls, fractures due to falls, hospitalization, mortality |
Holm et al. (2015) [42] | Retrospective cohort | 141.5 ± 2.8 mEq/l (total mean ± SD) | Serum sodium  < 136 mEq/l | Single at baseline | 5610 | 61.4 (11.7) Mean (SD) | 100% F | Hyponatremia related to diuretic use, liver disease, congestive heart disease, diabetes, malignancy | BMD, DXA | Thiazides, loop diuretics, potassium-sparing diuretics. Dosage not reported | Prevalence of osteoporosis |
Jamal et al. (2015) [43] | Prospective cohort | 132.3 ± 1.8 mEq/l (mean ± SD) in hyponatremia group | Serum sodium  < 135 mEq/l | Single at baseline | 5122 | 76.8 (7.0) Mean (SD) | 100% M | Hyponatremia related to congestive heart failure, diabetes | BMD, DXA | Thiazides, non-thiazides. Dosage not reported | Prevalence of morphometric fractures |
Kruse et al. (2015) [20] | Cross-sectional | 139.4 ± 3.08 MEq/l (total mean ± SD) | Serum sodium  < 135 mEq/l | Within 14 days before or after DXA | 1575 | 63.13 (13.6) Mean (SD) | 77.2% F | Hyponatremia related to liver insufficiency, ischemic heart disease, diabetes, malignancy, chronic kidney disease | BMD, DXA | Thiazides, loop diuretics. Dosage not reported | Prevalence of osteoporosis |
Usala et al. (2015) [44] | Case control | Not reported | Serum sodium  < 135 mEq/l | At least 1 measurement | 139,594 | 65.9 (14.7) Mean (SD) | 88.3% F | Not evaluated | ICD-9-CM | Thiazides, loop diuretics. Dosage not reported | Incidence of osteoporosis and fragility fractures |
Ayus et al. (2016) [45] | Retrospective cohort | 132 ± 5 (mean ± SD) in hyponatremia group | Serum sodium < 135 mEq/l | At least on 2 or more consecutive measurements for > 90 days | 31,527 | 78 (12) Mean (SD) | 71.5% F | Hyponatremia related to heart failure, chronic kidney disease, liver failure, diabetes, diuretic use | - | Thiazides. Dosage not reported | Incidence of hip fracture |
Hosseini et al. (2018) [34] | Prospective cohort | 140 ± 2.3 mEq/l (mean ± SD) in fracture group | Serum sodium ≤ 137 mEq/l | Single at baseline | 1113 | 68.6 (6.8) Mean (SD) | 44.1% F | Not available | BMD, DXA | Patient under thiazides was excluded. Dosage not reported | Incidence of bone fracture and falls |
Adams et al. (2019) [46] | Retrospective cohort | 139 mEq/l (total median) | Serum sodium < 135 mEq/l | Time averaged | 341,003 | 63.3 Median | 67% F | Hyponatremia related to cardiovascular disease, diabetes, diuretic use | BMD, DXA | Thiazides. Dosage not reported | Prevalence of osteoporosis |
Nigwekar et al. (2019) [47] | Case control | Not reported | Serum sodium < 135 mEq/l | At least two measurements separated by at least 90 days | 5751 | 84 (9) Mean (SD) | 61% F | Hyponatremia related to congestive heart failure, cirrhosis, diabetes, diuretic use | - | Type and dosage of diuretic non specified | Prevalence of hyponatremia in hip fracture |
Schiara et al. (2020) [21] | Case–control and prospective cohort | 129.9 ± 4.7 mEq/l (mean ± SD) in hyponatremia prospective group | Serum sodium < 135 mEq/l | Single at admission | 2768 (case control) 284 (cohort) | 83 (7) Mean (SD) | 77.8% F | Not evaluated | - | Thiazides. Dosage not reported | Prevalence of hyponatremia and hypokalemia, mortality |