Endocrine Abstracts

Burosumab has become available as a treatment for children with X-linked hypophosphatemia (XLH) and is a recombinant fully human IgG1 against FGF23. By binding to the active FGF23, burosumab inhibits its effect and symptoms (growth retardation, rickets, enthesiopathy, low phosphate) may improve, however, not in all children. Concomitantly paediatricians are keen to measure FGF23, in treated children, to avoid overtreatment with burosumab, associated with potential calcification risk. Samples from treated patients were sent for c-terminal FGF23 analysis as part of the clinical request. On suspicion of an assay interference, the clinician/patients authorised the analysis of the samples further. Control samples were provided fully anonymised as leftover material from the clinical laboratory. FGF23 was measured using cFGF23 (Immutopics, detecting both intact and c-terminal fragment) and iFGF23 (DiaSorin) immunoassays. Antibodies used for western-blot were anti-human IgG-Fc and anti-human cFGF23 (186-206). Serial dilution demonstrated a positive interference of burosumab in the cFGF23 assay and a negative interference in the iFGF23 assay. We immunoprecipitated burosumab using magnetic beads. IgG and iFGF23 were present in the precipitated fraction but only iFGF23 was detectable in the supernatant. In neither compartment was cFGF23 detected. Supernatants were submitted to FGF23 total assay and elevated concentrations were observed (RR:<100RU/mL). Only iFGF23 was detected by western-blot suggesting that either there is no free cFGF23 or the technique is not sensitive enough to detect the circulating cFGF23 fragments. The presence of sufficient circulating intact FGF23 and absence of cFGF23 in treated patients could explain the persistence of some symptoms of XLH. In future, we may be able to correlate outcome with circulating concentrations of free iFGF23. The changes in efficacy of Burosumab in older children and adolescents may partly reflect a requirement for an increased dose of burosumab to fully capture iFGF23.