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However, in a substantial subset of patients with acquired FGF23-related hypophosphatemic osteomalacia, phosphaturic mesenchymal tumors (PMTs) remain undetectable despite extensive imaging studies. A recent study identified autoantibodies against PHEX, the gene responsible for XLH, in 5 of 13 patients with acquired FGF23-related osteomalacia without detectable PMTs, thereby defining a novel disease entity termed autoimmune osteomalacia (AIO). Clinically, AIO presents with milder disease activity than TIO, comparable in severity to XLH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>Some patients exhibited concomitant autoimmune disorders, and whole-genome sequencing revealed rare variants in autoimmune susceptibility genes, suggesting a genetic predisposition. Therapeutic options include burosumab and, potentially, immunosuppressive therapy such as glucocorticoids. Long-term follow-up indicates that AIO patients may develop ectopic ossifi cation, similar to XLH. Anti-PHEX autoantibodies were detected using both luciferase immunoprecipitation systems and fl ow cytometry, underscoring the importance of complementary methods for detecting antibodies against native conformational epitopes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Recognition of AIO should be particularly considered in patients with acquired FGF23-related hypophosphatemia who have undetectable PMTs, relatively mild disease activity, and concurrent autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00774-026-01697-0","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T16:43:11Z","timestamp":1771087391000},"page":"269-275","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Autoimmune osteomalacia: a novel FGF23-related hypophosphatemic osteomalacia"],"prefix":"10.1007","volume":"44","author":[{"given":"Yoshitomo","family":"Hoshino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-5372","authenticated-orcid":false,"given":"Nobuaki","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"1697_CR1","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1359\/JBMR.0301264","volume":"19","author":"T Shimada","year":"2004","unstructured":"Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. 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The other author has nothing to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All participants gave written informed consent prior to being enrolled in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}