title: Analog Method for Radiographic Assessment of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva.
abstract: Severe progressive multifocal heterotopic ossification (HO) is a rare occurrence seen predominantly in patients who have fibrodysplasia ossificans progressiva (FOP) and is difficult to quantitate owing to patient-, disease-, logistical-, and radiation-related issues. The purpose of this study was to develop and validate a scoring system based on plain radiographs for quantitative assessment of HO lesions in patients with FOP.
  
  
  
  Institutional review board approval was obtained from the University of Pennsylvania, and all data comply with Health Insurance Portability and Accountability Act regulations. The University of Pennsylvania Institutional Animal Care and Use Committee approved the use of mice in this study. First, we used a mouse model of FOP-like HO to validate a semiquantitative analog scale for estimating relative heterotopic bone volume. Second, we used this validated scale to estimate the relative amount of HO from a retrospective analysis of plain radiographs from 63 patients with classic FOP. Finally, the scale was applied to a retrospective analysis of computed tomographic images from three patients with FOP.
  
  
  
  In the FOP-mouse model, the observed rating on the analog scale is highly correlated to heterotopic bone volumes measured by microcomputed tomography (R2= 0.89). The scoring system that was applied to radiographs of patients with FOP captured the clinical range of HO typically present at all axial and appendicular sites. Analysis of computed tomographic scans of patients with FOP found that observed radiograph ratings were highly correlated with HO volume (R2= 0.80).
  
  
  
  The scoring system described here could enable practical, quantitative assessment of HO in clinical trials to evaluate new treatment modalities, especially for FOP. The development of the six-point analog scale described here provides and validates a much-needed, reproducible, and quantifiable method for describing and assessing HO in patients with FOP. This scale has the potential to be a key descriptor that can inform patients with FOP and clinicians about disease progression and response of HO lesions to interventions and treatments.
authors.affiliation: Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104; Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104. Electronic address: chamith@mail.med.upenn.edu.
authors.forename: Chamith S
authors.initials: CS
authors.lastname: Rajapakse
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Carter
authors.initials: C
authors.lastname: Lindborg
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Newman
authors.affiliation: Department of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kobe
authors.affiliation: The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Gregory
authors.initials: G
authors.lastname: Chang
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Radiology, NYU Langone Medical Center, New York, New York.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
authors.affiliation: Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
authors.affiliation: Division of Geriatric Medicine & Gerontology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Pignolo
mesh_terms: D000293:Adolescent; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002648:Child; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009221:Myositis Ossificans / Q000150:complications / Q000000981:diagnostic imaging*; D009999:Ossification, Heterotopic / Q000000981:diagnostic imaging* / Q000209:etiology; D015203:Reproducibility of Results; D012189:Retrospective Studies; D055114:X-Ray Microtomography / Q000379:methods*
keywords: Heterotopic bone; fibrodysplasia ossificans progressiva