{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:17:36Z","timestamp":1789827456844,"version":"4.0.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:00:00Z","timestamp":1670025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:00:00Z","timestamp":1670025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR057374"],"award-info":[{"award-number":["AR057374"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Orphan Disease Center, Million Dollar Bike Ride Grant Program"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder involving skeletal dysplasia and heterotopic ossification (HO) of muscle and connective tissue. We aimed to define a novel biomarker in FOP that enables reliable assessment of musculoskeletal tissue integrity. Considering logistical difficulties that FOP patients often face, our goal was to identify an at-home biomarker technique. Electrical impedance myography (EIM) is a non-invasive, portable method that can inform on muscle health. 15 FOP patients (age 10\u201352) and 13 healthy controls were assessed. Using EIM, multiple muscle groups were characterized per participant in a 45-min period. The Cumulative Analogue Joint Involvement Scale (CAJIS) was implemented to determine mobility burden severity. We additionally evaluated physical activity levels via a Patient-Reported Outcomes Measurement Information System (PROMIS)-based questionnaire. Relative to controls, FOP patients demonstrated significantly lower regional and whole-body phase values at 50\u00a0kHz and 100\u00a0kHz, indicating more diseased muscle tissue. Lower whole-body phase and reactance values, and higher resistance values, were associated with greater FOP burden (CAJIS score range: 4\u201330) and lower physical activity levels at 50\u00a0kHz and 100\u00a0kHz. This study points to the potential utility of EIM as a clinical biomarker tool capable of characterizing muscle integrity in FOP.<\/jats:p>","DOI":"10.1038\/s41598-022-25610-7","type":"journal-article","created":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T07:03:29Z","timestamp":1670051009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diminished muscle integrity in patients with fibrodysplasia ossificans progressiva assessed with at-home electrical impedance myography"],"prefix":"10.1038","volume":"12","author":[{"given":"Alexander","family":"Farid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Golden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Robicheau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seward B.","family":"Rutkove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymin","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"key":"25610_CR1","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/978-90-481-9485-8_19","volume":"686","author":"A Morales-Piga","year":"2010","unstructured":"Morales-Piga, A. & Kaplan, F. S. Osteochondral diseases and fibrodysplasia ossificans progressiva. Adv. Exp. Med. Biol. 686, 335\u2013348. https:\/\/doi.org\/10.1007\/978-90-481-9485-8_19 (2010).","journal-title":"Adv. Exp. Med. Biol."},{"key":"25610_CR2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13023-017-0674-5","volume":"12","author":"G Baujat","year":"2017","unstructured":"Baujat, G. et al. Prevalence of fibrodysplasia ossificans progressiva (FOP) in France: An estimate based on a record linkage of two national databases. Orphanet. J. Rare Dis. 12, 123. https:\/\/doi.org\/10.1186\/s13023-017-0674-5 (2017).","journal-title":"Orphanet. J. Rare Dis."},{"key":"25610_CR3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1136\/jmg.19.1.35","volume":"19","author":"JM Connor","year":"1982","unstructured":"Connor, J. M. & Evans, D. A. Genetic aspects of fibrodysplasia ossificans progressiva. J. Med. Genet. 19, 35\u201339. https:\/\/doi.org\/10.1136\/jmg.19.1.35 (1982).","journal-title":"J. Med. Genet."},{"key":"25610_CR4","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1159\/000365770","volume":"5","author":"I Huning","year":"2014","unstructured":"Huning, I. & Gillessen-Kaesbach, G. Fibrodysplasia ossificans progressiva: Clinical course, genetic mutations and genotype-phenotype correlation. Mol. Syndromol. 5, 201\u2013211. https:\/\/doi.org\/10.1159\/000365770 (2014).","journal-title":"Mol. Syndromol."},{"key":"25610_CR5","doi-asserted-by":"publisher","first-page":"303ra137","DOI":"10.1126\/scitranslmed.aac4358","volume":"7","author":"SJ Hatsell","year":"2015","unstructured":"Hatsell, S. J. et al. ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci. Transl. Med. 7, 303ra137. https:\/\/doi.org\/10.1126\/scitranslmed.aac4358 (2015).","journal-title":"Sci. Transl. 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Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP). Bone 109, 153\u2013157. https:\/\/doi.org\/10.1016\/j.bone.2017.09.016 (2018).","journal-title":"Bone"},{"key":"25610_CR34","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.jtemb.2016.10.001","volume":"39","author":"L Hildebrand","year":"2017","unstructured":"Hildebrand, L. et al. Trace element and cytokine concentrations in patients with fibrodysplasia ossificans progressiva (FOP): A case control study. J. Trace Elem. Med. Biol. 39, 186\u2013192. https:\/\/doi.org\/10.1016\/j.jtemb.2016.10.001 (2017).","journal-title":"J. Trace Elem. Med. Biol."},{"key":"25610_CR35","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1111\/bcp.13777","volume":"85","author":"EC Hsiao","year":"2019","unstructured":"Hsiao, E. C. et al. 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KC is the founder of BioSAS Consulting. SBR has equity in and serves a consultant and scientific advisor to Myolex, Inc., and Haystack Diagnostics, Inc., companies that design impedance devices for clinical and research use; he is also a member of the Myolex's Board of Directors. The companies also have an option to license patented impedance technology of which SBR is named as an inventor. PBY is a co-founder of Keros Therapeutics, which develops therapeutics for hematological and musculoskeletal diseases which target TGF-\u00df signaling pathways. SBR is compensated for work on the company\u2019s scientific advisory board and owns equity in the publicly-traded company. All other authors have nothing to disclose. All authors approved the manuscript.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20908"}}