Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: An [18F]NaF PET/CT study

Botman, Esmée; Raijmakers, Pieter; Yaqub, Maqsood; Teunissen, Bernd P.; Netelenbos, Coen; Lubbers, Wouter D.; Schwarte, Lothar A.; Micha, Dimitra; Bravenboer, Nathalie; Schoenmaker, Ton; Vries, Teun J. de; Pals, Gerard; Smit, Jan Maerten; Koolwijk, Pieter; Trotter, Dinko González; Lammertsma, Adriaan A.; Eekhoff, Elisabeth M. W.

doi:10.1016/j.bone.2019.03.009

Cited by 18 publications

(19 citation statements)

References 21 publications

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“…Interestingly, despite low doses of radiation, they reported nonprogression of calcification for periods of up to 10 years, and they did not report having to treat previously treated areas again. In the future, it would be interesting to assess disease activity before and after treatment with [ 18 F]NaF PET/CT, as this could objectively assess effects of radiotherapy on disease activity (4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

“…Whether radiotherapy can cause sufficient trauma to trigger a flare-up, leading to HO, is unclear. Previously, we have demonstrated that [ 18 F]NaF PET can be used to detect activity of disease just prior to the formation or progression of HO (4)(5)(6). Intravenously administered labeled sodium fluoride ([ 18 F]NaF) binds to newly formed hydroxyapatite and, therefore, can be used to detect osteoblastic activity (7).…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy in Fibrodysplasia Ossificans Progressiva: A Case Report and Systematic Review of the Literature

et al. 2020

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Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disease, characterized by the formation of heterotopic ossification (HO) in muscles, ligaments, and tendons. Flare-ups, an inflammatory process that often precedes the formation of HO, can occur spontaneously, but trauma is also a common trigger. It is not known whether radiotherapy, especially in higher doses, might cause sufficient trauma or inflammation to trigger a flare-up and subsequent HO in FOP patients. We report the case of a patient undergoing radiotherapy for the treatment of a 1-cm-wide basal cell carcinoma (BCC) of the lower lip. In addition, we present a systematic review of the available literature. Our patient received 54 Gy in 18 fractions with orthovoltage therapy, resulting in a clinical complete response of the tumor. Six months after treatment, there were no signs of HO either clinically or on [ 18 F]NaF PET/CT. The systematic review identified 11 publications describing either radiation treatment in FOP or radiation therapy as a cause of HO in non-FOP patients. Six case reports described the use of radiation in FOP patients for various reasons, including one with a high-dose treatment of a lip BCC using superficial X-ray therapy. The remaining five studies described the use of low-dose radiotherapy to prevent or treat either an FOP flare-up or HO formation. None of these cases showed worsening of disease that could be attributed to the use of radiation therapy. Radiation induced HO in non-FOP patients was rare and occurred in five studies. The largest of these studies suggested that HO was induced after treatment with high doses, resulting in more widespread evidence of tissue damage, potentially being the end result of this damage. In conclusion, available reports suggest no contraindication to radiotherapy in FOP patients; although the number of cases was small, systematic toxicity reports often were not available, and none of the reports described high-dose, high-energy radiation treatment at locations such as muscle and joint regions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Radiotherapy in Fibrodysplasia Ossificans Progressiva: A Case Report and Systematic Review of the Literature

et al. 2020

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“…In this animal model, the MRI T2‐signal was in accordance with the [ 18 F]NaF PET signal . For human FOP patients, however, it is not known whether edema on MRI can distinguish between ossifying and nonossifying flare‐ups, as well as between active and asymptomatic chronic FOP disease, as in the case for [ 18 F]NaF PET/CT . Therefore, the aim of this study was to assess whether MRI can identify different stages of FOP.…”

Section: Introductionmentioning

confidence: 89%

“…The [ 18 F]NaF dose was adjusted to weight (eg, 83 MBq [ 18 F]NaF for a 70‐ to 79‐kg patient) and a scan time of 2 min per bed position was used. Uptake of [ 18 F]NaF was considered increased for chronic lesions when SUV peak exceeded 8.4 . The method used to analyze [ 18 F]NaF PET/CT has been previously described .…”

Section: Methodsmentioning

confidence: 99%

“…[ 18 F] Sodium fluorde (NaF) Positron Emision Tomography (PET) / Computed Tomography (CT), however, it has become possible to identify which of these flare‐ups will lead to HO . Recently, it was shown that [ 18 F]NaF PET/CT can also identify asymptomatic chronic progression of existing HO based on relatively lower, but still increased [ 18 F]NaF uptake . Using this new marker of active and chronic FOP disease, it has become possible to investigate the diagnostic role of other, more widely available imaging modalities such as Magnetic Resonance Imaging (MRI).…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic Value of Magnetic Resonance Imaging in Fibrodysplasia Ossificans Progressiva

et al. 2020

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Using [18F] Sodium Fuoride (NaF) Positron Emission Tomography (PET) it is not only possible to identify the ossifying potency of a flare‐up, but also to identify an asymptomatic chronic stage of fibrodysplasia ossificans progressiva (FOP). The purpose of this study was to investigate the diagnostic role of a more widely available imaging modality, Magnetic Resonance Imaging (MRI), which is of special interest for studies in pediatric FOP patients. MRI and [18F]NaF PET/CT images at time of inclusion and subsequent follow‐up CT scans of 4 patients were analyzed retrospectively. Presence, location, and intensity of edema identified by MRI were compared with activity on [18F]NaF PET. Occurrence or progression of heterotopic ossification (HO) was examined on the follow‐up CT images. Thirteen different lesions in various muscle groups were identified: five lesions with only edema, five lesions with both edema and increased [18F]NaF uptake, one lesion with only increased [18F]NaF uptake, and two lesions with neither edema nor uptake of [18F]NaF. Mild edema, found in three lesions, was present at asymptomatic sites, which did not show increased [18F] NaF uptake or progression of HO on consecutive CT images. Moderate edema was found in three symptomatic lesions, with increased [18F]NaF on PET and progression of HO on CT. Severe edema was identified in four lesions. Interestingly, two of these lesions did not develop HO during follow‐up; one of these two even gave obvious symptoms of a flare‐up. MRI can identify whether symptoms are the result of an acute flare‐up by the presence of moderate to severe edema. The occurrence of severe edema on MRI was not always related to an ossifying lesion. The additional diagnostic value of MRI requires further investigation, but MRI does not seem to fully replace the diagnostic characteristics of [18F]NaF PET/CT in FOP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Whole-body Computed Tomography Versus Dual Energy X‑ray Absorptiometry for Assessing Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva

et al. 2021

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Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder that leads to heterotopic ossification (HO), resulting in progressive restriction of physical function. In this study, low-dose, whole-body computed tomography (WBCT) and dual energy X-ray absorptiometry (DXA) were evaluated to determine the preferred method for assessing total body burden of HO in patients with FOP. This was a non-interventional, two-part natural history study in patients with FOP (NCT02322255; date of registration: December 2014). In Part A (described here), WBCT and DXA scans were individually assessed for HO presence and severity across 15 anatomical regions. All images were independently reviewed by an expert imaging panel. Ten adult patients were enrolled across four sites. The sensitivity to HO presence and severity varied considerably between the two imaging modalities, with WBCT demonstrating HO in more body regions than DXA (76/138 [55%] versus 47/113 [42%]) evaluable regions). Inability to evaluate HO presence, due to overlapping body regions (positional ambiguity), occurred less frequently by WBCT than by DXA (mean number of non-evaluable regions per scan 1.2 [standard deviation: 1.5] versus 2.4 [1.4]). Based on the increased sensitivity and decreased positional ambiguity of low-dose WBCT versus DXA in measuring HO in patients with FOP, low-dose WBCT was chosen as the preferred imaging for measuring HO. Therefore, low-dose WBCT was carried forward to Part B of the natural history study, which evaluated disease progression over 36 months in a larger population of patients with FOP.

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Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: An [18F]NaF PET/CT study

Cited by 18 publications

References 21 publications

Radiotherapy in Fibrodysplasia Ossificans Progressiva: A Case Report and Systematic Review of the Literature

Radiotherapy in Fibrodysplasia Ossificans Progressiva: A Case Report and Systematic Review of the Literature

Diagnostic Value of Magnetic Resonance Imaging in Fibrodysplasia Ossificans Progressiva

Whole-body Computed Tomography Versus Dual Energy X‑ray Absorptiometry for Assessing Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva

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