Flare‐Up After Maxillofacial Surgery in a Patient With Fibrodysplasia Ossificans Progressiva: An [¹⁸F]‐NaF PET/CT Study and a Systematic Review

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder leading to progressive heterotopic ossifications (HO) of muscles, tendons, and ligaments, which can be induced by trauma or by surgery. Despite strong medical advice to the contrary, an FOP patient insisted on surgery to alleviate her complete trismus, which caused an unbearable impact on her quality of life (QOL). The entire trismus history of this FOP patient is presented. [18F]‐NaF position emission tomography/computed tomography (PET/CT) scans were introduced as an imaging method for heterotopic bone formation activity. To place our findings into context, a systematic review on jaw surgery in FOP was performed. After falling down the stairs, a 9‐year‐old patient developed mobility impairment of her left‐sided jaw. During the following 13 years bone scintigraphy showed persistent activity of the disease leading to progressive left‐sided zygomatico‐mandibular fusion by HO, resulting in complete trismus. Within 1 month after HO removal on the left side and a matching right coronoidectomy, [18F]‐NaF PET/CT demonstrated a substantial flare‐up activity followed by new HO in both masseter and temporalis muscles. Despite recurrent HO and trismus her QOL increased due to a stable increased interincisal opening of 5.5 mm. Although systematic review reveals a 100% risk of HO recurrence after jaw surgery, information on improved QOL is scarce. In conclusion, surgery in FOP may be beneficial for QOL despite new HO formation. Assessment of disease activity using [18F]‐NaF PET/CT is possible before HO is evident on CT and may serve as a new and quantitative marker of the disease. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Longitudinal Evaluation of Pain, Flare‐Up, and Emotional Health in Fibrodysplasia Ossificans Progressiva: Analyses of the International FOP Registry

“…FOP patients may experience multiple flare‐ups and HO lesions across time and, in some instances, within the same anatomical location . Apart from the direct trauma flare‐ups can have on nervous system pain pathways and the peripheral structures they innervate, the occurrence of multiple flare‐ups likely alters the functionality of pain systems both in the periphery and central nervous system (CNS).…”

“…FOP patients may experience multiple flare-ups and HO lesions across time and, in some instances, within the same anatomical location. (21)(22)(23) Apart from the direct trauma flare-ups can have on nervous system pain pathways and the peripheral structures they innervate, the occurrence of multiple flare-ups likely alters the functionality of pain systems both in the periphery and central nervous system (CNS). Taken together, the effect of flare-up episodes is likely cumulative; potential outcomes of these pathologic events include a facilitation of a chronic pain background or flare-ups become more painful as they occur in later years of life.…”

Special considerations for clinical trials in fibrodysplasia ossificans progressiva (FOP)

“…This will also allow quantitation of bone formation. Other related assessments, such as 18 F sodium fluoride positron emission tomography (PET)/CT can also be considered ; however, availability may be limited in some institutions. Where alternate scores or measures are used, these need to be demonstrated to be at least equivalent in performance to the recommended measures, and ideally have known and close correlation with the recommended measures.…”

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

“…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).…”