ESPE Abstracts

Background: X-linked hypophosphatemia (XLH) is a rare metabolic bone disease which is caused by inactivating mutations in Phosphate-regulating neutral endopeptidase, X-linked (PHEX). Due to dysregulation of Fibroblast growth factor 23 (FGF-23), increased systemic levels of FGF-23 lead to chronic renal phosphate wasting and to impaired activation of 25OH-Vitamin D (25OHD). As a result, patients suffer from multiple musculoskeletal symptoms such as long bone deformities, short stature, bone pain, muscle weakness, dental abscesses, and fatigue. Conventional treatment with phosphate supplements and active vitamin D derivatives as well as FGF23-blocking antibody treatment are used to ameliorate symptoms in patients with XLH. To date, detailed data on QoL in well-defined XLH cohorts including treatment associated changes are sparse.

Methods: The German version of PedsQL^TM was performed by 16 pediatric patients with confirmed XLH (f: m = 10:6, conventional treatment n=15, Burosumab m=1). Comparison with an osteogenesis imperfecta (OI) cohort, historic data on healthy children and patients with achondroplasia were used for comparison. Patients switching from conventional to Burosumab treatment (n=5) were investigaed regarding changes of treatment-relevant parameters including QoL domains.

Results: Physical QoL was substantially reduced in the investigated XLH patients (-17.8% vs. historic healthy cohort), comparable to patients with achondroplasia (-19.1 vs. historic healthy cohort) and exceeded QoL impairment of patients with non-deforming Osteogenesis imperfecta (-11.8% vs. historic healthy cohort). BMI SDS and the number of osteotomies was negatively associated with physical QoL (BMI SDS: P=0.033; osteotomies: P=0.049). Disease specific factors such as age, alkaline phosphatase (ALP) or the rickets severity score (RSS) did not predict QoL. After a mean Burosumab treatment duration of 15 +/-3 months patients revealed an increase of +14% (+/-13) in physical Qol, as well as improvement of biochemical and radiographic parameters for rickets severity.

Conclusions: Impairment of QoL in patients with XLH is found in the range of patients with severe skeletal dysplasias such as achondroplasia. Lower physical wellbeing scores as compared to patients with osteogenesis imperfecta point to an often underestimated disease burden. Associations of BMI and the numbers of osteotomies with physical QoL suggest an impact of metabolic factors and burden of surgical interventions in this cohort. While data are limited, improvement of physical QoL under >1 year of Burosumab treatment raises the prospect of sustained amelioration of disease burden in this vulnerable cohort.