TY - JOUR
T1 - Analog Method for Radiographic Assessment of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva
AU - Rajapakse, Chamith S.
AU - Lindborg, Carter
AU - Wang, Haitao
AU - Newman, Benjamin T.
AU - Kobe, Elizabeth A.
AU - Chang, Gregory
AU - Shore, Eileen M.
AU - Kaplan, Frederick S.
AU - Pignolo, Robert J.
N1 - Funding Information:
We acknowledge Meiqi Xu for ACVR1 genotyping to confirm patients with classic FOP. This work was supported in part by the International Fibrodysplasia Ossificans Progressiva Association (IFOPA), the Center for Research in FOP and Related Disorders, the Ian Cali Endowment for FOP Research, the Whitney Weldon Endowment for FOP Research, the Isaac and Rose Nassau Professorship of Orthopaedic Molecular Medicine (to FSK), the Cali-Weldon Research Professorship in FOP (to EMS), the Ian Cali Distinguished Clinician-Scientist (to RJP), the McGuire FOP Fund, the Ashley Martucci FOP Research Fund, the Penn Center for Musculoskeletal Disorders, and the National Institutes of Health (NIH R01 AR41916, R01 AR068382, and K25 AR060283).
Publisher Copyright:
© 2017 The Association of University Radiologists
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Rationale and Objectives 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. Materials and Methods 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. Results 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). Conclusions 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.
AB - Rationale and Objectives 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. Materials and Methods 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. Results 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). Conclusions 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.
KW - Heterotopic bone
KW - fibrodysplasia ossificans progressiva
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U2 - 10.1016/j.acra.2016.10.010
DO - 10.1016/j.acra.2016.10.010
M3 - Article
C2 - 27989444
AN - SCOPUS:85008417790
SN - 1076-6332
VL - 24
SP - 321
EP - 327
JO - Academic radiology
JF - Academic radiology
IS - 3
ER -