Tumor-Induced Osteomalacia in Patients With Malignancy: A Meta-analysis and Systematic Review of Case Reports

Abstract

Context Tumour induced osteomalacia (TIO) due to FGF23 overexpression is becoming recognized in patients with malignancy. The condition may be underdiagnosed, with a scarce medical literature. Objective To perform a meta-analysis of case reports to allow a better understanding of malignant TIO and its clinical implications. Methods Full-texts were selected according to strict inclusion criteria. All case reports were included where patients had hypophosphatemia, malignant TIO, and FGF23 blood levels. 32/275 eligible studies (n = 34 patients) met inclusion criteria. A list of desired data was extracted and graded for methodological quality. Results Prostate adenocarcinoma (n = 9) were the most tumours reported. 25/34 patients had a metastatic disease and a poor clinical outcome was reported for 15/28 patients. The median levels of blood phosphate and C-terminal FGF23 (cFGF23) were 0.40 mmol/L and 788.5 RU/mL respectively. For most of patients, blood PTH was elevated or within range, and calcitriol levels were inappropriately low or normal. Alkaline phosphatase concentrations were increased for 20/22 patients. The cFGF23 values were significantly higher for patients with a poor clinical outcome when compared to other patients (1685 vs 357.5 RU/mL). In case of prostate cancer, cFGF23 levels were significantly lower (429.4 RU/mL) than for other malignancies (1007.5 RU/mL). Conclusion We report for the first time a detailed description of the clinical and biological characteristics of malignant TIO. In this context, FGF23 blood measurement would be of value for the diagnostic work-up, prognostication and follow-up of patients.