Hypophosphatasia (HPP) is the rare inherited metabolic disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. TNSALP deficiency leads to extracellular excess of inorganic pyrophosphate, a bone mineralization inhibitor. Here, we report the validity and reproducibility of a novel scale to quantify HPP-specific radiographic changes in pediatric patients.
The Radiographic Global Impression of Change (RGI-C) is a seven-point scale (−3=severe worsening, 0=no change; +3=near/complete healing), designed for comprehensive evaluation of HPP skeletal health. Sequential radiographic studies (chest (<5 years only), knees, wrists) are assessed for improvement or worsening using age-specific hallmarks of HPP developed by expert consensus. Age-specific features include gracile and/or absent bones and chest deformity (patients <5 years), and osteopenia, popcorn calcification, and physeal corner defects (patients ≥5 years). Features common to both age groups include metadiaphyseal sclerosis, apparent physeal widening, and metaphyseal radiolucencies and/or fraying. Inter-/intra-rater agreements for six raters across three studies were assessed using intraclass correlation defects coefficients (ICC) and weighted kappa coefficients (KC). Concurrent validity was assessed via correlation between RGI-C scores and simultaneous changes from baseline in: Rickets Severity Scale (RSS); Pediatric Outcomes Data Collection Instrument (PODCI) Global Function scale; Child Health Assessment Questionnaire (CHAQ) Disability Index; 6 Minute Walk test (6MWT); and height z-scores (children ≥5 years).
ICC revealed moderate-to-good inter-rater agreement for patients <5 years (0.65, 227 radiographs; P<0.0001) and ≥5 years (0.57, 136 radiographs; P<0.0001). Most raters achieved substantial (n=4, KC>0.6) or near-perfect (N=4, KC>0.8) intra-rater agreement. Linear regression revealed significant correlations with all measured parameters (Table 1). The RGI-C scale is a valid, reproducible measure for assessing clinically important changes in skeletal manifestations of HPP in pediatric patients.
|Measure||Number of data points||Pearson correlation®||P value|
14 - 17 May 2016
European Calcified Tissue Society