Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [ 18 F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [ 18 F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [ 18 F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUV peak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [ 18 F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm 3 ), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [ 18 F]NaF uptake, with SUV peak ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [ 18 F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.
Original languageEnglish
Pages (from-to)1-6
JournalBone
Volume124
Early online date8 Mar 2019
DOIs
Publication statusPublished - 1 Jul 2019

Cite this

@article{99958250b4844aafa7fd6608f56ba196,
title = "Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: An [18F]NaF PET/CT study",
abstract = "Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [ 18 F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [ 18 F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [ 18 F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUV peak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [ 18 F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm 3 ), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8{\%}) of identified HO structures and, in all cases, was accompanied by increased [ 18 F]NaF uptake, with SUV peak ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [ 18 F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.",
keywords = "18Fluoride, Chronic course, Fibrodyplasia ossificans progressiva, Heterotopic ossification (HO), Imaging, PET (positron emission tomography), Progression, Volume",
author = "Esm{\'e}e Botman and Raijmakers, {Pieter G. H. M.} and Maqsood Yaqub and Bernd Teunissen and Coen Netelenbos and Wouter Lubbers and Schwarte, {Lothar A.} and Dimitra Micha and Nathalie Bravenboer and Ton Schoenmaker and {de Vries}, {Teun J.} and Gerard Pals and Smit, {Jan Maerten} and Pieter Koolwijk and Trotter, {Dinko Gonz{\'a}lez} and Lammertsma, {Adriaan A.} and Eekhoff, {E. Marelise W.}",
note = "Copyright {\circledC} 2018. Published by Elsevier Inc.",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.bone.2019.03.009",
language = "English",
volume = "124",
pages = "1--6",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Evolution of heterotopic bone in fibrodysplasia ossificans progressiva

T2 - An [18F]NaF PET/CT study

AU - Botman, Esmée

AU - Raijmakers, Pieter G. H. M.

AU - Yaqub, Maqsood

AU - Teunissen, Bernd

AU - Netelenbos, Coen

AU - Lubbers, Wouter

AU - Schwarte, Lothar A.

AU - Micha, Dimitra

AU - Bravenboer, Nathalie

AU - Schoenmaker, Ton

AU - de Vries, Teun J.

AU - Pals, Gerard

AU - Smit, Jan Maerten

AU - Koolwijk, Pieter

AU - Trotter, Dinko González

AU - Lammertsma, Adriaan A.

AU - Eekhoff, E. Marelise W.

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [ 18 F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [ 18 F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [ 18 F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUV peak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [ 18 F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm 3 ), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [ 18 F]NaF uptake, with SUV peak ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [ 18 F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.

AB - Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [ 18 F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [ 18 F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [ 18 F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUV peak values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [ 18 F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm 3 ), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [ 18 F]NaF uptake, with SUV peak ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [ 18 F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.

KW - 18Fluoride

KW - Chronic course

KW - Fibrodyplasia ossificans progressiva

KW - Heterotopic ossification (HO)

KW - Imaging

KW - PET (positron emission tomography)

KW - Progression

KW - Volume

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064262971&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30858149

U2 - 10.1016/j.bone.2019.03.009

DO - 10.1016/j.bone.2019.03.009

M3 - Article

VL - 124

SP - 1

EP - 6

JO - Bone

JF - Bone

SN - 8756-3282

ER -