title: Fibrous dysplasia.
abstract: Fibrous dysplasia is a developmental abnormality of bone that is characterized by a highly disorganized mixture of immature fibrous tissue and fragments of immature trabecular bone. Fibrous dysplasia may arise as a single, discrete (monostotic) lesion or can occur with a more widespread distribution with multiple lesions that affect many bones (oligo- or polyostotic). Fibrous dysplasia is usually an isolated skeletal finding but can sometimes occur as a component of a multisystem developmental disorder known as McCune-Albright syndrome (MAS) that is also associated with endocrine hyperfunction (e.g. precocious puberty) and caf au lait cutaneous macules. The identification of activating mutations in GNAS in a subset of human GH-secreting pituitary tumors and autonomously functioning human thyroid tumors provided the initial basis for understanding the molecular pathophysiology of McCune-Albright syndrome and fibrous dysplasia. These observations led to the concept that activating mutations of the GNAS gene convert it into a putative oncogene referred to as gsp (Gsa or Gas). The classic radiographic feature of fibrous dysplasia is a hazy, radiolucent, or ground-glass, pattern resulting from the defective mineralization of immature dysplastic bone; it is usually strikingly different from the radiographic appearance of normal bone, calcified cartilage, or soft tissue. The surgical approach to fibrous dysplasia should in general be conservative. Recent research suggests that the WntlB-catenin pathway may play a role in fibrous dysplasia as patients with activating GNAS mutations specifically showed that Gas mutations activated Wnt/B-catenin signaling. Thus inhibition of 8-catenin signaling or silencing GNAS alleles that encode constitutively active Gsa molecules in fibrous dysplasia and McCune-Albright syndrome offer potential therapeutic promise and deserve further study. In summary fibrous dysplasia is a developmental abnormality of bone with a known molecular etiology; Further knowledge about the molecular pathology of fibrous dysplasia may lead to improved conservative therapies in the near future.
authors.affiliation: Musculoskeletal Tumor Center, Cleveland Clinic, Cleveland, OH 44195, USA. LIETMAS@ccf.org
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lietman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
mesh_terms: D005358:Fibrous Dysplasia, Monostotic / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D005359:Fibrous Dysplasia, Polyostotic / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans