Bone Abstracts

Background: X-linked hypophosphataemia (XLH) is a rare bone disorder affecting around 1 in 20,000 people in the UK. Adults XLH have reported that stiffness is rarely included in clinicians assessments, despite stiffness being a common experience for those living with XLH. Burosumab is a treatment blocking the activity of FGF23 which is overactive in XLH; it became available to all adults with XLH in November 2024. Clinical trials have indicated that Burosumab reduces stiffness; in this study, real world data has been used to characterise the stiffness and understand the impact of using Burosumab.

Method: The Rare and UnDiagnosed studY (RUDY) is a patient driven data collection platform for rare diseases. Adults with a self-reported diagnosis of XLH are asked to answer questionnaires about their general health, disease activity and wellbeing. Participants were included in this analysis if they had completed painDETECT, an assessment of stiffness, which included a body map and a current medication form. Hierarchical clustering was used to identify clusters of stiff or painful joint stiffness locations. The number of clusters selected was based on the Silhouette score, the Gap statistic, and a visual inspection of the dendrogram.

Results: 33 adults with XLH had complete stiffness data. A higher prevalence of stiffness in adults not on Burosumab was identified, especially at the shoulder, wrist and ankle. Of the patients with reported stiffness, 100% of non-Burosumab users reported severe and extreme stiffness compared with approximately 38.5% of Burosumab users (P 0.01). Stiffness of ≥2 hours was also more common in non-Burosumab users overall. Four distinct stiffness clusters were identified with a low Silhouette score of 0.21, and a specific cluster for spine and shoulder stiffness.

Conclusion: Stiffness is common in adults with XLH and should be included within clinical assessments. Stiffness in the non-weight-bearing joints of the upper limb was especially problematic in those who had never received Burosumab. Stiffness was as common in those with and without Burosumab treatment at the hip; this could suggest an alternative aetiology. This analysis suggests Burosumab is an effective treatment for stiffness, particularly in reducing its severity.