Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population

Usala, Rachel L.; Fernandez, Stephen; Méte, Mihriye; Cowen, Laura E.; Shara, Nawar; Barsony, Julianna; Verbalis, Joseph G.

doi:10.1210/jc.2015-1261

Cited by 114 publications

(76 citation statements)

References 31 publications

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“…These last two drug classes are associated with altered metabolism and absorption of calcium, phosphate, and vitamin D, and trabecular bone loss at the spine and femoral neck (6, 13-17). In addition, hyponatremia, an emerging contributor to osteoporosis, has been reported after allo-HSCT (18-20). …”

Section: Introductionmentioning

confidence: 99%

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

Pirsl

Curtis

Steinberg

et al. 2016

Biology of Blood and Marrow Transplantation

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The NIH Chronic Graft-versus-Host Disease (cGVHD) Consensus Project Ancillary and Supportive Care Guidelines recommend annual assessment of bone mineral density (BMD) to monitor bone health. The study of osteoporosis in patients with cGVHD has been limited to small numbers of patients and the guidelines are based on experiences in other chronic diseases and expert opinion. We hypothesized that the prevalence of osteoporosis is high in a cohort of 258 patients with moderate to severe cGVHD due to prolonged exposure to risk factors for osteoporosis after allogeneic hematopoietic stem cell transplantation. We defined osteoporosis using BMD criteria (T-score ≤ -2.5) at three anatomical sites (femoral neck – FN, lumbar spine – LS, total hip – TH) and characterized risk factors through univariate and multivariate analyses. We found that low body weight (FN p<0.0001, LS p=0.0002, TH p<0.0001), malnutrition (FN p=0.0002, LS p=0.03, TH p=0.0076), higher platelet count (FN p=0.0065, TH p=0.0025), higher average NIH organ score (FN p=0.038), higher prednisone dose (LS p=0.032), lower complement component 3 (LS p=0.0073), and physical inactivity (FN p=0.01) were associated with osteoporosis in one or more site. T-scores were significantly lower in the FN than in the other two sites (p<0.0001 for both). The prevalence of osteoporosis and osteopenia was high (17% and 60%, respectively), supporting current recommendations for frequent monitoring of BMD. The association of higher platelet count in cGVHD patients with osteoporosis has not been previously reported and presents a new area of interest in the study of osteoporosis after allogeneic hematopoietic stem cell transplantation.

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Section: Introductionmentioning

confidence: 99%

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

Pirsl

Curtis

Steinberg

et al. 2016

Biology of Blood and Marrow Transplantation

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“…As has been described in other studies, PH was associated with older age, systemic hypertension, diabetes, and a history of heart failure (HF). 5,7 Multivariable analysis found that older age, lower hemoglobin, lower left ventricular ejection fraction, and the presence of left ventricular hypertrophy were independently associated with PH. The presence of PH was associated with a 38% increased risk of overall mortality and a 23% increased risk of cardiovascular events (HF, myocardial infarction, cerebrovascular accident, and peripheral vascular disease).…”

Section: Disclosuresmentioning

confidence: 99%

“…Furthermore, in population-based studies, chronic hyponatremia associates with bone fracture risk [6][7][8] ; however, whether this is a consequence of a neurologic phenotype predisposing to falls 9 or of a bone phenotype predisposing to fracture 10 (or perhaps a combination of both) remains unclear.…”

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confidence: 99%

Modeling the Neurologic and Cognitive Effects of Hyponatremia

Cohen

2016

Journal of the American Society of Nephrology

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Acute hyponatremia causes swelling of brain cells and, if of a sufficient degree, increased intracranial pressure. This is a consequence of the relative impermeability of the blood-brain barrier to sodium ions 1 ; this principle underlies the clinical utility of hypertonic NaCl infusion in the treatment of the cerebral edema accompanying traumatic brain injury or stroke. That acute hyponatremic brain swelling should cause neurologic symptoms is unsurprising. Brain swelling is absent in chronic hyponatremia, in contrast, and the basis for the neurologic and cognitive symptoms in this context is less clear.There is an emerging view that even mild-to-moderate degrees of chronic hyponatremia cause neurologic symptoms and that reversal of hyponatremia ameliorates them. 2 Data in support of this attractive hypothesis are few. Renneboog et al. tested gait and coordination in 16 patients with syndrome of inappropriate antidiuresis (SIAD) both on and off their chronic therapy (with mean plasma sodium concentrations of 138 and 128 mEq/L, respectively). 3 They reported that the total traveled way, an index of balance performance and gait instability, was abnormal under hyponatremic conditions but normalized after correction of hyponatremia. All participants were outpatients at the time of evaluation; therefore, there was no confounding by acute medical comorbidity. To eliminate an additional potential source of bias, and in support of reversibility, half were initially tested on treatment, and half were tested in the untreated state.Additional evidence comes from the Study of Ascending Levels of Tolvaptan in Hyponatremia-I (SALT-I) and SALT-II trials. 4 These studies tested the effect of the vasopressin V 2 -receptor antagonist, tolvaptan, on plasma sodium concentration in hyponatremic participants with an initial plasma sodium concentration ,135 mEq/L. One secondary end point was a 12-Item Short Form Health Survey (SF-12) score. The SF-12 is a proprietary instrument that quantifies study participants' self-reported well-being using 12 general questions addressing mood and health-related limitations on activity. 5 After 30 days of tolvaptan treatment, during which the mean plasma sodium concentration increased from 129 to 136 mEq/L, the mental component of the SF-12 score significantly improved (P50.02), whereas the physical component was unaffected. This metric is subjective (i.e., self-reported) and emphasizes feelings of depression and anxiety; it does not directly assess cognitive performance or neurologic deficit. In addition, there was no control for the order of treatment; all participants were initially tested when hyponatremic and then tested again after tolvaptan treatment. Nonetheless, these findings in a moderately large randomized controlled trial are consistent with a reversible neuropsychiatric effect of even mild hyponatremia.Furthermore, in population-based studies, chronic hyponatremia associates with bone fracture risk 6-8 ; however, whether this is a consequence of a neurologic phenotype predisposing to...

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“…1 It has been detected as the most frequent electrolyte disorder in clinical medicine. 2,3 Mild hyponatraemia is seldom associated with any specific features and symptoms usually relate to the underlying cause of the hyponatraemia. Severity of symptoms depends on rate of fall of plasma sodium concentration as well as absolute value.…”

Section: Introductionmentioning

confidence: 99%

Hyponatraemia in Acute Confusional States and Coma

Dan

Acherjya²,

Chowdhury

et al. 2018

J. Medicine

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ound: ound: Though hyponatraemia is a common scenario in our daily clinical practice, the mortality and morbidity are very high without early detection and prompt treatment. Both under and over treatment of hyponatraemia may cause permanent brain damage. Proper and meticulous treatment may prevent development of permanent brain disorder. So, a study was carried out to see the prevalence of hyponatraemia in acute confusional states and coma. The effect of hyponatraemia on consciousness level was also observed. (60) cases with acute confusional state and coma were recruited in our study. Among 60 patients with acute confusional states including coma, 85% (51) patients were presented with hyponatraemia. In the study, mild, moderate and severe hyponatraemia were 20%, 13.33% and 51.67% respectively. Of the total study population, 31.67%, 33.33% and 35% presented with coma, stupor and drowsiness respectively. Severe hyponatraemia was found in 68.42% in comatose, 50% in stuporous and 38.1% in drowsy patients. 47.06% of hyponatraemic patients were noticed in several intracranial disorders. Hepatic encephalopathy, gastrointestinal disorders, chronic renal failure and ischemic heart disease comprised 13.73%, 11.76%, 9.80% and 5.89% respectively. Diabetic ketoacidosis and hypoglycaemic shock comprised 3. 92% each and congestive heart failure and acute respiratory distress syndrome comprised 1.96% each of hyponatraemic patients. Conclusions:Conclusions: Conclusions: Conclusions: Conclusions: Hyponatraemia is a common clinical problem in our day to day clinical practice. If neglected this may result in permanent brain malfunction which may be prevented with earlier detection and correction under meticulous supervision. K K K K Ke e e e eyw yw yw yw ywor or or

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Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population

Abstract: These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes.

Cited by 114 publications

References 31 publications

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease

Modeling the Neurologic and Cognitive Effects of Hyponatremia

Hyponatraemia in Acute Confusional States and Coma

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