ArticleThe Journal of biological chemistry2011
Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03371199 (The Effect of Normalization of Sodium on Bone Markers in Patients With Epilepsy. A Randomized Single-blinded Placebo-controlled Trial.), which is not on this map. Cited by 106 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effect of Normalization of Sodium on Bone Markers in Patients With Epilepsy. A Randomized Single-blinded Placebo-controlled Trial.
Who cites it
106 citing papers in PubMed, 6 syntheses or guidelines pooled it, 186 citations in OpenAlex.
- Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- Association of Preoperative Hyponatremia With Surgical Outcomes: A Systematic Review and Meta-analysis of 32 Observational Studies.The Journal of clinical endocrinology and metabolism · 2023Pooled it
- The Extraglycemic Effect of SGLT-2is on Mineral and Bone Metabolism and Bone Fracture.Frontiers in endocrinology · 2022Pooled it
- Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis.PloS one · 2015Pooled it
- Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis.PloS one · 2013Pooled it
- Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia.The American journal of medicine · 2011Pooled it
- Effect of salt substitution on fracture-a secondary analysis of the Salt Substitute and Stroke Study (SSaSS).BMC medicine · 2024Trial
- An Increase in Plasma Sodium Levels Is Associated With an Increase in Osteoblast Function in Chronic SIAD.The Journal of clinical endocrinology and metabolism · 2023Trial
- Chronic hyponatremia and skeletal vulnerability: bone loss, fragility fracture risk, and therapeutic uncertainties.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Preoperative natremia and AKI after cardiac surgery: an international multicenter prospective cohort study.Journal of anesthesia, analgesia and critical care · 2026Article
- Hyponatraemia in Neck of Femur Fracture: A Narrative Review of Epidemiology, Pathophysiology, and Outcomes.Geriatrics (Basel, Switzerland) · 2026Review
- Perioperative hyponatremia in total joint arthroplasty: A systematic review of prevalence, risk factors, outcomes, and management.Journal of orthopaedics · 2026Review
- Fracture risks in patients with arginine vasopressin deficiency: a nationwide matched cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Insights into vitamin C in musculoskeletal physiology and disorders: mechanisms and translational perspectives.Frontiers in immunology · 2026Review
- Cognition and fall assessment after recovery from syndrome of inappropriate anti diuresis.Endocrine · 2025Article
- Chronic Hyponatremia Potentiates Innate Anxiety-Like Behaviors Through the Dysfunction of Monoaminergic Neurons in Mice.Molecular neurobiology · 2025Article
- Role of oxidative/nitrosative stress in dysfunction of rat's intracerebral parenchymal arterioles in low sodium environment in the presence of vasopressin.Pflugers Archiv : European journal of physiology · 2025Article
- Dynamic Prediction and Intervention of Serum Sodium in Patients with Stroke Based on Attention Mechanism Model.Journal of healthcare informatics research · 2025Article
- Roles of Insulin-Like Growth Factor-1 in Muscle Wasting and Osteopenia in Mice with Hyponatremia.Calcified tissue international · 2025Article
- Mild Hyponatremia Is Not Associated With Degradation of Trabecular Bone Microarchitecture Despite Bone Mass Loss.The Journal of clinical endocrinology and metabolism · 2025Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Our recent animal and human studies revealed that chronic hyponatremia is a previously unrecognized cause of osteoporosis that is associated with increased osteoclast numbers in a rat model of the human disease of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We used cellular and molecular approaches to demonstrate that sustained low extracellular sodium ion concentrations ([Na(+)]) directly stimulate osteoclastogenesis and resorptive activity and to explore the mechanisms underlying this effect. Assays on murine preosteoclastic RAW 264.7 cells and on primary bone marrow monocytes both indicated that lowering the medium [Na(+)] dose-dependently increased osteoclast formation and resorptive activity. Low [Na(+)], rather than low osmolality, triggered these effects. Chronic reduction of [Na(+)] dose-dependently decreased intracellular calcium without depleting endoplasmic reticulum calcium stores. Moreover, we found that reduction of [Na(+)] dose-dependently decreased cellular uptake of radiolabeled ascorbic acid, and reduction of ascorbic acid in the culture medium mimicked the osteoclastogenic effect of low [Na(+)]. We also detected downstream effects of reduced ascorbic acid uptake, namely evidence of hyponatremia-induced oxidative stress. This was manifested by increased intracellular free oxygen radical accumulation and proportional changes in protein expression and phosphorylation, as indicated by Western blot analysis from cellular extracts and by increased serum 8-hydroxy-2'-deoxyguanosine levels in vivo in rats. Our results therefore reveal novel sodium signaling mechanisms in osteoclasts that may serve to mobilize sodium from bone stores during prolonged hyponatremia, thereby leading to a resorptive osteoporosis in patients with SIADH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.