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Bone. 2019 Feb 14;122:76-81. doi: 10.1016/j.bone.2019.02.010. [Epub ahead of print]

Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: Utility of the radiographic Rickets Severity Score.

Author information

1
Mayo Clinic, Rochester, MN, USA. Electronic address: Thacher.Thomas@mayo.edu.
2
MRC/Wits Developmental Pathways for Health Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
3
Mayo Clinic, Rochester, MN, USA.
4
Ultragenyx Pharmaceutical Inc., Novato, CA, USA.
5
Yale University School of Medicine, New Haven, CT, USA.

Abstract

The Rickets Severity Score (RSS) was used to evaluate X-linked hypophosphatemic rickets (XLH), a genetic disorder mediated by increased circulating FGF23. The reliability of the RSS was assessed using data from a randomized, phase 2 clinical trial that evaluated the effects of burosumab, a fully human anti-FGF23 monoclonal antibody, in 52 children with XLH ages 5 to 12 years. Bilateral knee and wrist radiographs were obtained at baseline, week 40, and week 64. We evaluated the relationships of the RSS to the Radiographic Global Impression of Change (RGI-C), serum alkaline phosphatase (ALP), height Z-score, 6-minute walk test (6MWT) percent predicted, and the Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI). The RSS showed moderate-to-substantial inter-rater reliability (weighted kappa, 0.45-0.65; Pearson correlation coefficient (r), 0.83-0.89) and substantial intra-rater reliability (weighted Kappa, 0.66; r = 0.91). Baseline RSS correlated with serum ALP (r = 0.47). Baseline RSS identified two subgroups (higher [RSS ≥1.5] and lower RSS [RSS <1.5]) that discriminated between subjects with greater and lesser rachitic disease. Higher RSS was associated with more severe clinical features, including impaired growth (Z-score, -2.12 vs -1.44) and walking ability (6MWT percent predicted, 77% vs 86%), more severe self-reported pain (29.9 [more severe] vs 45.3 [less severe]) and less physical function (29.6 [more severe] vs 40.9 [less severe]). During burosumab treatment, greater reductions in RSS corresponded to higher RGI-C global scores (r = -0.65). Improvements in RSS correlated with decreased serum ALP (r = 0.47). These results show the reliability of the RSS in XLH, and demonstrate that higher RSS values are associated with greater biochemical, clinical, and functional impairments in children with XLH.

KEYWORDS:

Children; Clinical trial; Metabolic bone disease; Radiology; Validation

PMID:
30772600
DOI:
10.1016/j.bone.2019.02.010
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