X-linked hypophosphatemia (XLH, MIM 307800) is a rare hereditary disorder of bone metabolism characterized by growth impairment, leading to bone deformities and short stature and beside others to muscle function deficits. XLH is caused by defect of endopeptidase PHEX leading to high levels of FGF-23 and thereby renal phosphate wasting. While conventional treatment includes substitution of phosphate and 1-25 OH-Vitamin D, now a treatment with a FGF-23 antibody (burosumab) is available, normalizing serum phosphate. We present prospective observational data of patients, with a detailed assessment of muscle function during conventional therapy and after changing to burosumab. In eleven paediatric patients treatment with burosumab was initiated after approval by the European Medical Agency. We monitored this patients at five specific timepoints related to treatment (during conventional therapy (t1); wash out/no treatment (t2); three months (t3), 12 months (t4), 24 months (t5) after initiation of burosumab treatment). Monitoring included clinical/radiological follow up (auxiology, clinical chemistry, x-ray of the palm) and a defined set of muscle function tests (grip force, two-legged-jump (2LJ), chair rising test (CRT)). In eleven patients (age: 9.6 ± 3.4 years) treatment with burosumab was initiated. During conventional therapy most clinical and functional parameters were outside of the age and gender specific reference range. Height standard deviation score (SDS) improved from -2.71 (t1) to -2.24 (t5) while BMI-SDS did not change. Although serum anorganic phosphate only increased slightly, from 0.53 (± 0.12) times lower fold of age/gender specific reference values to 0.69 (± 0.14), alkaline phosphatase normalized from 1.45 (± 0.37) times upper fold of age related reference values to 0.94 (±0.24). Regarding muscle function, there was a trend, but no significant improvement of grip strength SDS (neither age (-0.18 (t1) to 0.21 (t5)) or height corrected (1.68 (t1) to 1.84 (t5))), nor in force, power or the Esslinger Fitness Index (E.F.I) in 2LJ or CRT. Nevertheless, there is a strong trend to an improved average time per test SDS for CRT (2.86 SDS (t1) to 0.34 SDS (t5). Signs of rickets, radiologically assessed by Thatcher-Score improved over time. Real-life observations support recent findings of improvement of clinical parameters in patients with XLH treated with burosumab. We could confirm and extend knowledge about muscle function deficits during conventional therapy. Additionally, we could show moderate improvements in muscle function after initiation of burosumab treatment. Further studies are needed to investigate the influence of phosphate homoeostasis on muscle function in XLH.
15 Sep 2022 - 17 Sep 2022