ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 66 OC5.6 | DOI: 10.1530/endoabs.66.OC5.6

Monitoring and long-term disease activity in children with X-linked hypophosphataemia on conventional therapy

Suma Uday1,2, Nick Shaw1,2, Zulf Mughal3, Tabitha Randell4, Wolfgang Högler5,2, Rui Santos6 & Raja Padidela3

1Birmingham Women’s and Children’s Hospital, Birmingham, UK; 2IMSR, University of Birmingham, Birmingham, UK; 3Manchester Children’s Hospital, Manchester, UK; 4Nottingham Children’s Hospital, Nottingham, UK; 5Johannes Kepler University, Linz, Austria; 6Evelina London Children’s Hospital, London, UK

Background: Conventional treatment of X-linked hypophosphataemic rickets (XLH) involves administration of oral phosphate and vitamin D analogues. Newer therapies such as Anti Fibroblast Growth Factor 23 antibodies (burosumab) have now become available. An important treatment goal is to heal rickets; assessed by normalisation of serum alkaline phosphatase (ALP) levels and resolution of radiological signs of rickets.

Objectives: (1) Assess disease severity on wrist and knee radiographs as determined by rickets severity scores (RSS) and Thacher scores on conventional therapy. (2) Determine the usefulness of serum ALP in assessing rickets severity on radiographs

Methods: Data was collected, retrospectively from case notes and electronic database, as part of National Institute for Heath and Care Excellence review of burosumab. Patients from 3 UK tertiary centres, with a confirmed diagnosis of XLH (PHEX mutation in the patient or family member) and ≥ 3 radiographs were included. Radiographs were scored for RSS and Thacher scores by a consultant in metabolic bone disease (RP) and radiologist (RS). Due to different assays used for ALP measurements, ALP z scores were calculated using age- and sex-specific mean/standard deviation (S.D.) CALIPER reference data. Spearman’s correlation was used to determine the relation between ALP z scores and Knee RSS and Thacher scores.

Results: Forty (male=12) patients with a median age of 9.3 years (range 0.8–18.9) were identified. Median age at diagnosis was 1.17 years (range 0.2–11.7). The majority (48%, n=19) were diagnosed in infancy. The median follow-up duration was 7.2 years (range 0.6–18.7). The mean±S.D. knee RSS and Thacher score at baseline were 1.9±1.2 (n=19) and 3.3±1.3 (n=8) respectively and at most recent follow up visit were 1.6±1.0 (n=26) and 2.4 ±1.6 (n=6). The mean±S.D. ALP z score at diagnosis and most recent visit were 4.2±2.9 (n=36) and 4.1±2.7 (n=34). There was no significant correlation between ALP z score and knee RSS (r=0.17) or wrist RSS (r=0.32) or Thacher scores (r= 0.14).

Conclusions: (1) Conventional therapy was not effective in significantly improving biochemical and radiological features of disease. (2) Lack of association of serum ALP with RSS limits its value as the sole indicator of rickets activity.

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