Introduction: Conventional treatment of X-linked hypophosphataemic rickets (XLH) involves administration of oral phosphate and vitamin D analogues. An important treatment goal is to heal rickets which is assessed by normalisation of serum alkaline phosphatase (ALP) levels and resolution of radiological signs of rickets.
Objectives: To determine the usefulness of serum ALP in assessing disease severity on wrist and knee radiographs as determined by rickets severity scores (RSS) and Thacher scores.
Methods: Patients from 3 UK tertiary centres, with a confirmed diagnosis of XLH (documented PHEXmutation in the patient or family member) and ≥ 3 radiographs were included. Data was collected retrospectively from case notes and electronic database. 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 (SD) lab specific reference data. Wilcoxon Signed Ranks test was used to compare knee and wrist RSS. 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 within the first year of life. The median follow-up duration was 7.2 years (range 0.6-18.7). The mean ±SD 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±SD ALP z score at diagnosis and most recent visit were 4.2±2.9 (n=36) and 4.1±2.7 (n=34). The wrist RSS was significantly lower than the knee (P<0.001). 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 between serum ALP and rickets severity on radiographs limits the value of serum ALP as the sole indicator of rickets activity.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology