Update on the medical management of fibrous dysplasia of the bone

Abstract

Fibrous dysplasia (FD) is a rare, benign skeletal disorder characterized by expansile, fibrotic bone lesions that replace normal bone, resulting in decreased bone strength, pain, and fractures. The clinical presentation of FD can vary widely, complicating the diagnosis. FD can manifest as monostotic (single bone) or polyostotic (multiple bones) disease and can occur independently or as part of McCune-Albright Syndrome (MAS), a genetic condition that includes café-au-lait skin hyperpigmentation and endocrine abnormalities. FD/MAS arises from activating mutations in the GNAS gene, leading to constitutive activation of the G_sα protein and elevated cAMP levels. Despite understanding the genetic cause of FD, effective treatments remain limited. Current management strategies focus primarily on symptom control following the most recent comprehensive guidelines published in 2019. This review highlights emerging pharmacologic treatments, including denosumab, a monoclonal antibody that has shown promise in reducing lesion size and pain in FD patients, and burosumab, a monoclonal antibody targeting FGF23, which reduces renal phosphate wasting and osteomalacia in FD patients. In addition, we review updates in advanced genetic testing techniques, such as cell-free DNA and direct lesion sampling for next-generation sequencing, which are promising methods for improving the diagnostic accuracy of FD. Finally, multimodal approaches for pain management in FD, including nonsteroidal anti-inflammatory drugs, bisphosphonates, and novel agents like cannabinoids, are being used alongside the traditional approaches with physical therapy and psychological support. Ongoing research aims to enhance our understanding of FD pathogenesis and develop targeted therapies that could potentially reverse disease progression. This review underscores the importance of implementing a multidisciplinary approach in the management of FD/MAS and finding new therapeutic approaches that will help address the diverse manifestations and improve the quality of life for patients.

Keywords: McCune-Albright syndrome; bisphosphonates; fibrous dysplasia; metabolic bone disease; pain management.

Figure 1.

Radiologic imaging of fibrous dysplastic bone. (a) Craniofacial CT scan of a 33-year-old female with FD/MAS, showing extensive fibrous dysplastic bone in the skull (representative lesions, red arrows). Narrowing of the optic canal can be seen in this image (yellow arrow). In addition, this craniofacial lesion shows cystic changes that can be seen in some FD lesions. (b) FD of the right tibia as seen on plain film X-ray, of the same patient at age 29. (c) FD of the craniofacial region in a 16-year-old female, showing the classical ground glass-like lesion. CT, computed tomography; FD, fibrous dysplasia; MAS, McCune-Albright syndrome.

Figure 2.

Hormone signaling in multiple organ systems have been found to impact FD lesion growth. Therapeutic strategies targeting these systems may be helpful in controlling FD. Source: Created with Biorender. Javaid et al. *Investigational use only not FDA approved for FD/MAS. FD, fibrous dysplasia; MAS, McCune–Albright Syndrome.

Figure 3.

The schematic illustration of the pathway of multidisciplinary pain management. Source: Cartoon images were generated by Adobe Illustrator Generate Vector (beta).