{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:07:19Z","timestamp":1789016839124,"version":"build-2803163510"},"reference-count":110,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019000","name":"Ministry of National Defense, Medical Affairs Bureau","doi-asserted-by":"crossref","award":["MND-MAB-E-115253"],"award-info":[{"award-number":["MND-MAB-E-115253"]}],"id":[{"id":"10.13039\/501100019000","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100025478","name":"Taoyuan Armed Forces General Hospital","doi-asserted-by":"crossref","award":["TYAFGH-D-115024"],"award-info":[{"award-number":["TYAFGH-D-115024"]}],"id":[{"id":"10.13039\/501100025478","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100025478","name":"Taoyuan Armed Forces General Hospital","doi-asserted-by":"crossref","award":["TYAFGH-E-115051"],"award-info":[{"award-number":["TYAFGH-E-115051"]}],"id":[{"id":"10.13039\/501100025478","id-type":"DOI","asserted-by":"crossref"}]},{"award":["TYAFGH-D-115024"],"award-info":[{"award-number":["TYAFGH-D-115024"]}],"id":[{"id":"https:\/\/ror.org\/01p01k535","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TYAFGH-E-115051"],"award-info":[{"award-number":["TYAFGH-E-115051"]}],"id":[{"id":"https:\/\/ror.org\/01p01k535","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Teh-Tzer Study Group for Human Medical Research Foundation","award":["B1141003"],"award-info":[{"award-number":["B1141003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Chronic kidney disease\u2013mineral and bone disorder (CKD-MBD) confers a substantial fracture burden that is only partly addressed by therapies targeting phosphate, parathyroid hormone, and vitamin D. Redox dysregulation may represent a complementary mechanism: reactive oxygen species (ROS) are required for receptor activator of nuclear factor-\u03baB ligand (RANKL)-dependent osteoclastogenesis, whereas excessive ROS impair Wnt\/\u03b2-catenin signalling in osteoblast precursors and promote osteocyte dysfunction. Uremic toxins, inflammation, and dialysis further increase oxidative stress. Molecular hydrogen (H2) is a highly diffusible redox modulator that has been proposed to limit damaging radical-chain reactions while preserving physiological oxidant signalling. In non-uremic skeletal models, H2 consistently suppresses osteoclast differentiation and bone loss, but evidence for osteoblast rescue is heterogeneous. In CKD and dialysis, H2-based interventions have shown signals of reduced oxidative stress and symptomatic benefit; however, human evidence is predominantly observational, and no study identified in this review assessed a bone-specific endpoint. We therefore integrate uremic bone redox biology with H2 pharmacology and propose a turnover-state-dependent model in which H2 may restrain excessive resorption in high-turnover disease, while its net effect in low-turnover adynamic bone remains uncertain because potential osteoblast rescue competes with anti-osteoclastic activity established only in non-uremic models. H2 should therefore be considered an experimental, mechanistically differentiated strategy requiring direct evaluation in uremic models and turnover-stratified clinical trials with parallel skeletal and vascular safety endpoints.<\/jats:p>","DOI":"10.3390\/antiox15091137","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:46:04Z","timestamp":1788885964000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Hydrogen and the Uremic Skeleton: A Critical Review and Turnover-State-Dependent Redox Hypothesis in CKD-MBD"],"prefix":"10.3390","volume":"15","author":[{"given":"Po-Jen","family":"Hsiao","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan"},{"name":"Department of Life Sciences, National Central University, Taoyuan 320317, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Tsai","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan"},{"name":"Cardiovascular Division, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Fang","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-0162","authenticated-orcid":false,"given":"Jenq-Shyong","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yen","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan"},{"name":"Cardiovascular Division, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Chi","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan"},{"name":"Cardiovascular Division, Tri-Service General Hospital, National Defense Medical University, Taipei 11490, Taiwan"},{"name":"School of Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan"},{"name":"Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300044, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23143, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City 24352, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1038\/sj.ki.5000414","article-title":"Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"69","author":"Moe","year":"2006","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S2213-8587(14)70059-2","article-title":"Bone: A new endocrine organ at the heart of chronic kidney disease and mineral and bone disorders","volume":"2","author":"Vervloet","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.kint.2024.11.013","article-title":"Chronic kidney disease-mineral and bone disorder: Conclusions from a Kidney Disease: Improving Global 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