Recent research progress on the etiology and pathogenesis of tumor-induced osteomalacia: A review

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder characterized by an insidious onset, while its underlying pathogenesis has not yet been fully explored. Identifying and accurately localizing the causative tumors in TIO remains highly challenging in clinical practice. Although complete surgical excision following precise diagnosis is currently considered the most effective treatment approach, surgical management strategies still require optimization, and recurrence may occur even after tumor resection. TIO is primarily recognized as a metabolic bone disease driven by excessive secretion of fibroblast growth factor 23 (FGF23) by tumors; however, its detailed etiological features and molecular pathogenic mechanisms remain unclear. Besides FGF23, other phosphate-regulating hormones and pathogenic genes are also believed to participate in disease development. A clearer understanding of FGF23-mediated phosphate regulation, including hormone secretion, circulation, transport, and interactions with target organs, is critical for early diagnosis and the development of effective therapeutic strategies. Further investigation into the mechanisms responsible for refractory and recurrent TIO is also needed. Integrated multi-omics approaches are expected to provide deeper insight into the complex pathogenic basis of TIO, supporting the development of improved diagnostic and therapeutic strategies. This review summarizes recent progress in understanding the etiology and pathogenesis of TIO, intending to improve disease comprehension and facilitate more effective clinical diagnosis and treatment.