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Tumor induced osteomalacia: a systematic review and individual patient's data analysis.

CONTEXT: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome, usually caused by small, benign and slow-growing phosphaturic mesenchymal tumors. Clinically, TIO is characterized by renal phosphate leak, causing hypophosphatemia and osteomalacia. This review was performed to assess the clinical characteristics of TIO patients described worldwide so far.

EVIDENCE ACQUISITION: On 06/26/2021, a systematic search was performed in Medline, Google Scholar, Google book, and Cochrane Library using the terms: "tumor induced osteomalacia", "oncogenic osteomalacia", "hypophosphatemia". There were no language restrictions. This review was performed according to PRISMA criteria.

EVIDENCE RESULTS: Overall, 1725 TIO cases were collected. TIO was more frequent in adult men, who showed a higher incidence of fractures compared to TIO women. The TIO causing neoplasms were identified in 1493 patients. The somatostatin receptor-based imaging modalities have the highest sensitivity for the identification of TIO-causing neoplasms. TIO causing neoplasms were equally located in bone and soft tissues; these latter showed a higher prevalence of fractures and deformities. The surgery is the preferred TIO definitive treatment (successful in >90% of patients). Promising non-surgical therapies are treatments with burosumab in TIO patients with elevated Fibroblast Growth Factor-23 levels, and with radiolabeled somatostatin analogs in patients with TIO-causing neoplasm identified by somatostatin receptor-based imaging techniques.

CONCLUSION: TIO occurs preferentially in adult men. The TIO clinical expressiveness is more severe in men as well as in patients with TIO-causing neoplasms located to soft tissues. Treatments with burosumab and with radiolabeled somatostatin analogs are the most promising non-surgical therapies.

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