{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:25:30Z","timestamp":1777407930305,"version":"3.51.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u00a0<\/jats:title>\n                  <jats:p>Skeletal fluorosis is rare and occurs secondary to chronic high amounts of fluoride consumption, manifesting as diffuse osteosclerosis, skeletal pain, connective tissue calcification, and increased fracture risk. Methoxyflurane is a volatile, fluorinated hydrocarbon-inhaled analgesic, and the maximum recommended dose is 15\u00a0mL (99.9 % w\/w) per wk. A rodent study found increased skeletal fluoride after methoxyflurane exposure. However, skeletal fluorosis secondary to methoxyflurane use in humans has rarely been reported. We present the case of a 47-yr-old female with diffuse osteosclerosis secondary to fluorosis from methoxyflurane use for chronic pain, presenting with 3 yr of generalized bony pain and multiple fragility fractures. Lumbar spine BMD was elevated. CT and radiographs demonstrated new-onset marked diffuse osteosclerosis, with calcification of interosseous membranes and ligaments, and a bone scan demonstrated a grossly increased uptake throughout the skeleton. Biochemistry revealed an elevated alkaline phosphatase and bone turnover markers, mild secondary hyperparathyroidism with vitamin D deficiency, and mild renal impairment. Zoledronic acid, prescribed for presumed Paget\u2019s disease, severely exacerbated bony pain. Urinary fluoride was elevated (7.3\u00a0mg\/L; reference range\u2009&amp;lt;\u20093.0\u00a0mg\/L) and the patient revealed using methoxyflurane 9\u00a0mL per wk for 8 yr for chronic pain. A decalcified bone biopsy revealed haphazardly arranged cement lines and osteocytes lacunae and canaliculi, which was consistent with an osteosclerotic process. Focal subtle basophilic stippling around osteocyte lacunae was suggestive of fluorosis. Although fluorosis is not a histological diagnosis, the presence of compatible histology features was supportive of the diagnosis in this case with clinical\u2013radiological\u2013pathological correlation. Skeletal fluorosis should be considered as a cause of acquired diffuse osteosclerosis. Methoxyflurane should not be recommended for chronic pain. The risk of repeated low-dose exposure to fluoride from methoxyflurane use as analgesia may be greater than expected, and the maximum recommended dose for methoxyflurane may require re-evaluation to minimize skeletal complications.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Abbreviated abstract<\/jats:title>\n                  <jats:p>Skeletal fluorosis is rare and occurs secondary to chronic high amounts of fluoride consumption, manifesting as diffuse osteosclerosis, skeletal pain, connective tissue calcification, and increased fracture risk. We present the case of a 47-yr-old female with skeletal fluorosis secondary to long-term methoxyflurane for chronic pain. The risk of repeated low-dose exposure to fluoride from methoxyflurane use for analgesia may be greater than expected, and the maximum recommended dose for methoxyflurane may require re-evaluation to minimize skeletal complications.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jbmrpl\/ziae032","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T06:15:40Z","timestamp":1709705740000},"source":"Crossref","is-referenced-by-count":4,"title":["Skeletal fluorosis secondary to methoxyflurane use for chronic pain"],"prefix":"10.1093","volume":"8","author":[{"given":"Yeung-Ae","family":"Park","sequence":"first","affiliation":[{"name":"Department of Diabetes & Endocrinology, Royal Melbourne Hospital , Melbourne, Victoria 3052 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter E","family":"Plehwe","sequence":"additional","affiliation":[{"name":"The Epworth Centre , Richmond, Victoria 3121 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kapilan","family":"Varatharajah","sequence":"additional","affiliation":[{"name":"Department of Radiology, Royal Melbourne Hospital , Melbourne, Victoria 3052 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Pathology, Royal Melbourne Hospital , Melbourne, Victoria 3052 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Christie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Royal Melbourne Hospital , Melbourne, Victoria 3052 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Diabetes & Endocrinology, Royal Melbourne Hospital , Melbourne, Victoria 3052 , Australia"},{"name":"Department of Medicine, Royal Melbourne Hospital, University of Melbourne , Parkville 3052 , Australia"},{"name":"Department of Diabetes & Endocrinology, Western Health , Melbourne, Victoria 3021 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"2024040419221750700_ref1","first-page":"1","article-title":"The metabolism and toxicity of fluoride","volume":"16 Rev 2","author":"Whitford","year":"1996","journal-title":"Monogr Oral Sci"},{"key":"2024040419221750700_ref2","volume-title":"The National Academies Collection: Reports funded by National Institutes of Health. 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