Lesion Expansion in Craniofacial Fibrous Dysplasia: Natural History and Indicators of Progression in the Frontal, Zygomatic, and Sphenoid Bones

Fibrous dysplasia (FD) is characterized by expansile fibro-osseous lesions that may occur in association with endocrinopathies as part of McCune-Albright syndrome (MAS). Craniofacial FD may result in substantial morbidity, including facial asymmetry and compression of vital neurovascular structures. There is a critical need to understand the natural history and risk factors for craniofacial lesion expansion to develop preventative trials and identify candidates for intervention. The purpose of this study was to evaluate expansion rates in periorbital bones (frontal, zygomatic, and sphenoid). Patients with craniofacial FD and serial CT imaging were evaluated. Volumetric analyses were performed and generalized mixed model analysis was used to investigate risk factors associated with expansion. Age, MAS-associated endocrinopathies, sex, Skeletal Burden Score, and history of bisphosphonate treatment were evaluated. A previous dataset for the gnathic region was included in statistical analyses to expand upon prior findings. 238 lesions (46 frontal, 43 zygomatic, 45 sphenoid, 41 mandible, 63 maxilla) in 70 patients were evaluated. Frontal, zygomatic, and sphenoid lesion volume increased with age (p<0.001), however expansion rates decreased over time (p<0.001). Both age-related expansion and lesion growth deceleration were highly location dependent, with frontal lesions experiencing the most rapid changes compared to other regions. Patients with growth hormone excess demonstrated greater lesion expansion rates (p=0.0173). There were no associations between sex and other MAS-associated endocrinopathies, or bisphosphonate treatment. Craniofacial lesion expansion rates are most rapid in younger children (generally below age 10) and decline as patients approach adulthood. FD lesions involving the frontal bone expand at a greater rate than sphenoid, zygomatic, and previously- reported gnathic lesions. These differences in growth rates indicate that location-specific analyses are critical to assess FD progression. The availability of quantitative natural history data will guide clinicians in identifying candidates for interventions, and will inform the development of clinical trials for preventative therapies.