Epidemiology of Tumor-Induced Osteomalacia in Denmark

Bo Abrahamsen,Christopher D Smith,Salvatore Minisola

doi:10.1007/s00223-021-00843-2

Abstract

Tumor-induced osteomalacia (TIO) is a rare, acquired condition of phosphate wasting due to phosphaturic mesenchymal tumors. Because the incidence and prevalence of TIO is unknown, we conducted an observational cohort study using national Danish health registers for the period 2008 to 2018 to obtain such information. The study also aimed to describe the demographics of the TIO population and the prognosis. The operational definition was based on hypophosphatemia or adult osteomalacia diagnoses, combined with prescriptions used in the initial management and procedures consistent with advanced imaging used for locating tumors. The incidence of TIO in Denmark was found to be below 0.13 per 100,000 person years for the total population of the country and 0.10 per 100,000 in adult-onset disease. The prevalence of TIO was estimated to be no more than 0.70 per 100,000 persons for the total population and 0.43 per 100,000 in adults. In 2018, there were a maximum of nine new cases of TIO in Danish adults. Mortality was low but few patients fulfilled the protocol cure criterion during the observation period. TIO has no ICD-10 code and limitations to the study include lack of information on serum biochemistry and on the use of phosphate supplements. Strengths include the use of long-term longitudinal, national hospital and prescription data from a country with universal healthcare. Given the very small patient population with TIO and the known delay to diagnosis and cure, management of patients with suspected TIO should be centralized.

Highlights

Tumor-induced osteomalacia (TIO) is a rare, acquired condition of phosphate wasting due to FGF23 secreting tumors [1]
A total of 918 cases (Fig. 1) of possible TIO were identified as consulting in the time period 2008–2018, after removal of 5 cases with no linkable Danish ID record and 3 that had not been resident in the country for one year, and 37 cases that were coded as familial hypophosphatemia (ICD-10 code E833A1)
We considered patients cured of TIO once a record had been made of them undergoing tumor surgery or radiotherapy in Denmark and no longer filling prescriptions for alphahydroxylated vitamin D treatment

Summary

Introduction

Tumor-induced osteomalacia (TIO) is a rare, acquired condition of phosphate wasting due to FGF23 secreting tumors [1]. It is not clear from the paper how selective sampling of specialist hospitals, their weighting to the results and the potential for the same patient to have been seen in more than one hospital—leading to double counting- was addressed in the study It is unclear how sampling and calculation of incidence accounted for the difference in duration of the two diseases as XLH is a chronic condition whereas many cases of TIO are open to surgical cure. An important opportunity to differentiate TIO from other phosphate wasting diseases in register data is that functional and anatomical imaging will be required to locate the FGF23-secreting tumor while this will not be the case for competing causes of hypophosphatemia [1, 2]. The Danish health databases provide a unique opportunity to provide reliable estimates of TIO incidence, prevalence and prognosis

Objective

Study Design

Results

Discussion