{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:50:44Z","timestamp":1790142644956,"version":"4.0.1"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Introduction<\/jats:title><jats:p>Cobalt is a mitochondrial toxin, clinical cobaltism manifests with constitutional, neurologic, and cardiovascular symptomatology. Cobalt\u2019s severe toxidrome is known through case reports from extreme wear or corrosion of cobalt-chromium arthroplasty components. However, the spectrum and epidemiology of orthopedic-implant cobaltism and its relationship to duration and degree of cobalt exposure are not well defined.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>The relationship of urine-cobalt concentration and duration of exposure to cobalt-chromium joint implants and cobaltism symptomatology were prospectively studied in 229 patients. Subjects received a Cobaltism-Symptom-Inventory-Score (CSIS) based on a protocolized interview and examination followed by a spot urine-cobalt measurement.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>129 (56%) subjects were cobalturic (urine-cobalt \u22651.0 ppb). 122 (53%) subjects had a CSIS of &gt;2, this status significantly associates with cobalturia. Median [IQR] urine-cobalt in the subjects with a CSIS &gt;2 was 4.1[1.1\u201317.0] ppb compared to 0.5[0.5\u20131.4] ppb in subjects with CSIS \u2264 2. Cobalturia has a sensitivity of 0.69, a specificity of 0.77, and a positive predictive value of 0.74 for a CSIS of &gt;2. The product of years-exposed to a cobalt-chromium implant and urine-cobalt by quartiles significantly positively associates with the Cobaltism-Symptom-Inventory-Score.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>A urine-cobalt of \u22651 ppb likely indicates adverse systemic exposure to orthopedic-implant generated cobalt. Cobaltism severity as quantified by the CSIS significantly correlates with the product of spot urine-cobalt concentration and years-exposed to a cobalt-chromium orthopedic-implant indicating a dose-response relationship. Medical provider and public awareness of orthopedic-implant cobaltism is vital because tens-of-millions are at-risk and early cobaltism is reversible. Further use of cobalt-chromium orthopedic-implants should be questioned given cobaltism becomes clinically apparent at a spot urine-cobalt of 1 ppb or greater. Monitoring of patients with high-risk cobalt-chromium orthopedic-implants appears to be indicated.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0295203","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T18:26:17Z","timestamp":1703183177000},"page":"e0295203","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The association of cobalturia with cobaltism symptoms a prospective blinded study of 229 post-arthroplasty patients"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-3213","authenticated-orcid":true,"given":"Stephen S.","family":"Tower","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford D.","family":"Gessner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina S.","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2579-7875","authenticated-orcid":true,"given":"Robert L.","family":"Bridges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"pone.0295203.ref001","volume-title":"Trace Elements in the Environment","author":"IC Smith","year":"1981"},{"key":"pone.0295203.ref002","article-title":"A Systematic Review of Systemic Cobaltism After Wear or Corrosion of Chrome-Cobalt Hip Implants","author":"BD Gessner","year":"2015","journal-title":"J Patient Saf"},{"issue":"3","key":"pone.0295203.ref003","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1530\/EOR-21-0098","article-title":"Prosthetic hip-associated cobalt toxicity: a systematic review of case series and case reports","volume":"7","author":"J Crutsen","year":"2022","journal-title":"EFORT Open Reviews"},{"issue":"8","key":"pone.0295203.ref004","doi-asserted-by":"crossref","first-page":"e2121758","DOI":"10.1001\/jamanetworkopen.2021.21758","article-title":"Prevalence of Cobalturia Among Adults With Joint Replacements","volume":"4","author":"SS Tower","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"8","key":"pone.0295203.ref005","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1007\/s11999-017-5377-7","article-title":"Increase in total joint arthroplasty projected from 2014 to 2046 in Australia: a conservative local model with international implications","volume":"475","author":"M Inacio","year":"2017","journal-title":"Clinical Orthopaedics and Related Research\u00ae"},{"key":"pone.0295203.ref006","article-title":"Neurotoxicity of cobalt","author":"S Catalani","year":"2011","journal-title":"Human & experimental toxicology"},{"issue":"2","key":"pone.0295203.ref007","doi-asserted-by":"crossref","first-page":"2309499020905993","DOI":"10.1177\/2309499020905993","article-title":"Cobalt-related cardiomyopathy: A real concern! 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