Validation of the Radiographic Global Impression of Change (RGI-C) score to assess healing of rickets in pediatric X-linked hypophosphatemia (XLH).

Abstract

BACKGROUND:

Rickets is a primary manifestation of pediatric X-linked hypophosphatemia (XLH) - a rare progressive hereditary phosphate-wasting disease. Severity is quantified from radiographs using the Rickets Severity Scale (RSS). The Radiographic Global Impression of Change (RGI-C) is a complementary assessment in which a change score is assigned based on differences in the appearance of rickets on pairs of radiographs compared side by side.

OBJECTIVE:

The current study evaluated the reliability, validity, and sensitivity to change of the RGI-C specifically in pediatric XLH.

METHODS:

The reliability, validity, and sensitivity to change of the RGI-C were evaluated using data from two studies in pediatric XLH (113 children aged 1-12 years) in which burosumab treatment significantly improved rickets severity. Intra-rater and inter-rater reliability were assessed by three pediatric radiologists.

RESULTS:

Intra-rater reliability for RGI-C global score was >90% for agreement within 1 point, with weighted kappa values >0.5, indicating moderate to almost perfect agreement. Inter-rater reliability was also >90% (0.47-0.52 for all reader pairs; moderate agreement). The RGI-C global score showed significant relationships with changes from baseline to week 64 in serum phosphorus (r = -0.397), alkaline phosphatase (-0.611), total RSS (-0.672), standing height (0.268), and patient-reported global functioning (0.306) and comfort/pain functioning (0.409). Based on standardized response means, RGI-C global scores were sensitive to change in RSS, differentiating between those considered improved and greatly improved. Results for validity and sensitivity to change were similar for the RGI-C wrist, knee, and standing long leg scores.

CONCLUSION:

The RGI-C is a reliable, valid, and sensitive measure in pediatric XLH, and complementary to the RSS.

• Authors: Ruth Lim, Randheer Shailam, Rebecca Hulett, Alison Skrinar, Annabel Nixon, Angela Williams, Mark Nixon, Tom D Thacher
• Journal: Bone (Bone) Vol. 148 Pg. 115964 (07 2021) ISSN: 1873-2763 [Electronic] United States
• PMID: 33878504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Alkaline Phosphatase

Topics

• Alkaline Phosphatase
• Antibodies, Monoclonal
• Child
• Familial Hypophosphatemic Rickets (diagnostic imaging, drug therapy)
• Humans
• Immunoglobulin G
• Reproducibility of Results