A Retrospective Cohort of Tumor-Induced Osteomalacia and Case Series of Malignant Disease.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare condition with evidence mostly derived from case reports and case series.

OBJECTIVE

We aimed to describe the clinical characteristics of a large cohort of patients diagnosed with TIO, with a focus on patients with nonlocalizing and malignant TIO.

METHODS

This is a retrospective cohort of patients with TIO in an academic medical center, diagnosed between January 1998 and May 2023. We describe their demographics, biochemistries, tumor features, localization, treatment, and complications.

RESULTS

Of 68 patients diagnosed with TIO, 49 (72%) were localizing and 5 (7.4%) were malignant. Of 50 patients who attempted localizing procedures, 29 (58%) achieved cure. Twenty (40%) had persistent disease due to the wrong tumor targeted, or refractory or recurrent tumors, despite up to 6 procedural attempts. There was no difference in demographics, phosphorus, or baseline fibroblast growth factor-23 (FGF23) levels between localizing vs nonlocalizing groups, and malignant vs nonmalignant groups. The lower extremity was the commonest site of localization (37%), with 47% in bone and 53% in soft tissue. Sixty percent of malignant cases were located in the trunk. Tumor size correlated with peak FGF23 (R = 0.566, P < .001) but was not associated with malignancy risk (P = .479). A cut-off FGF23 of >20 times upper limit of normal in the presence of normal renal function (P = .025) and recurrence after initial cure (P = .013) were factors significantly associated with malignancy. The nonlocalizing group had lower survival than the localizing group (P = .0097).

CONCLUSION

TIO is a condition with significant morbidity. Very high FGF23 levels and disease recurrence are associated with malignant disease. Reasons behind the observation of higher mortality in nonlocalizing TIO should be further explored.