Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives

Curr Osteoporos Rep. 2016 Oct;14(5):178-86. doi: 10.1007/s11914-016-0317-0.


Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment, and pain. It arises from post-zygotic somatic activating mutations in GNAS, in the cAMP-regulating transcript α-subunit, Gsα. Constitutive Gs signaling results in activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton, this leads to the development of FD lesions with abnormal bone matrix, trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may occur in isolation or in combination with extraskeletal manifestations, including hyperfunctioning endocrinopathies and café-au-lait macules, termed McCune-Albright syndrome (MAS). This review summarizes current clinical and translational perspectives in FD/MAS, with an emphasis on FD pathogenesis, natural history, pre-clinical and clinical investigation, and future directions.

Keywords: FGF23; Fibrous dysplasia; GNAS gene; Gsα; McCune-Albright syndrome.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Density Conservation Agents / therapeutic use
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Chromogranins / genetics*
  • Disease Models, Animal
  • Fibroblast Growth Factor-23
  • Fibrous Dysplasia of Bone / diagnostic imaging
  • Fibrous Dysplasia of Bone / genetics*
  • Fibrous Dysplasia of Bone / pathology
  • Fibrous Dysplasia of Bone / therapy
  • Fibrous Dysplasia, Polyostotic / diagnostic imaging
  • Fibrous Dysplasia, Polyostotic / genetics*
  • Fibrous Dysplasia, Polyostotic / pathology
  • Fibrous Dysplasia, Polyostotic / therapy
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Pain Management
  • Translational Research, Biomedical


  • Bone Density Conservation Agents
  • Chromogranins
  • FGF23 protein, human
  • Fibroblast Growth Factor-23
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs