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Acquired Osteomalacia Associated with Autoantibodies against PHEX
Article Number: SIS506217AI220525
22nd May, 2025
Author(s):
Yoshitomo Hoshino, M.D.; Kazuo Okamoto, Ph.D.; Tomohiro Ogawa; Hajime Kato, M.D., Ph.D.; Koki Irie, M.D., et al.
Abstract:
Tumor-induced osteomalacia is the most common acquired form of fibroblast growth factor 23-related hypophosphatemic rickets-osteomalacia (FGF23rHR). However, in 27% to 45% of cases, causative tumors remain undetectable. This study investigated the possibility that unidentified cases might be linked to autoantibodies against key phosphate-regulating proteins.
Among 13 patients with unexplained FGF23rHR, five (38%) exhibited autoantibodies targeting PHEX (phosphate-regulating endopeptidase X-linked), a protein involved in phosphate homeostasis. These findings suggest that autoimmune mechanisms rather than tumor-secreted FGF23 could contribute to acquired osteomalacia. Flow cytometry and luciferase immunoprecipitation system assays confirmed the presence of PHEX autoantibodies, distinguishing affected patients from those with other forms of hypophosphatemia. One patient also had multiple autoimmune disorders, including Graves' disease and systemic lupus erythematosus.
The authors propose that early antibody screening might reduce unnecessary tumor searches and facilitate prompt initiation of targeted therapies like burosumab (an anti-FGF23 monoclonal antibody) or immunosuppressive interventions. These cases represent a novel autoimmune subset of acquired osteomalacia.