From the Guidelines
Fibrodysplasia Ossificans Progressiva (FOP), also known as Fibrous Dysplasia, is a severely disabling heritable disorder of connective tissue characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) that forms qualitatively normal bone in characteristic extra-skeletal sites. This condition is estimated to have a worldwide prevalence of 1/1 300 000 to 1/2 000 000 1. The diagnosis of FOP can be made by clinical evaluation, with confirmatory genetic testing available, and is caused by a recurrent activating mutation in the gene encoding Activin A receptor type I/Activin-like kinase 2 (ACVR1/ALK2) 1.
Key Characteristics of FOP
- Congenital malformations of the great toes
- Progressive HO that forms qualitatively normal bone in characteristic extra-skeletal sites
- Sporadic episodes of painful soft tissue swellings (‘flare-ups’) that transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bone
- No ethnic, racial, gender, or geographic predilections
Management and Treatment
- At present, there are no definitive treatments for FOP, but a brief, 4-day course of high-dose corticosteroids combined with nonsteroidal anti-inflammatory drugs (NSAIDs) may help to reduce the intense inflammation and tissue edema seen in the early stages of the disease 1
- Preventative management is based on prophylactic measures against falls, respiratory decline, and viral infections
- The median estimated lifespan is 56 years, with most patients being wheelchair-bound by the end of the second decade of life and commonly dying of complications of thoracic insufficiency syndrome 1
Important Considerations
- Delayed diagnosis can still occur despite the hallmark changes in great toes
- Differential diagnoses include progressive osseous heteroplasia (POH), osteosarcoma, lymphoedema, soft tissue sarcoma, desmoid tumours, aggressive juvenile fibromatosis, calcinosis of skin and muscles, infection, and non-hereditary (acquired) heterotopic ossification 1
From the Research
Definition and Characteristics of Fibrous Dysplasia
- Fibrous dysplasia (FD) is a benign skeletal disorder that can affect one or multiple bones, often involving long bones, ribs, and craniofacial bones 2, 3, 4, 5.
- It is characterized by bone deformities, pain, and iterative fractures, and can also present with endocrine dysfunction and cutaneous café-au-lait spots 3.
- The disease can be monostotic (affecting one bone) or polyostotic (affecting multiple bones) 4, 5.
Etiology and Pathophysiology
- Fibrous dysplasia is caused by a somatic activating mutation of the Gs alpha subunit of protein G, resulting in an increased cAMP concentration and abnormalities of osteoblast differentiation 3.
- This leads to the production of abnormal bone and an increase in interleukin-6-induced osteoclastic bone resorption 3.
Diagnosis and Treatment
- Diagnosis relies on X-ray examination and pathology 3.
- Treatment options include bisphosphonate therapy, which can help improve function, decrease pain, and lower fracture risk in selected patients 2, 3, 5, 6.
- Surgery is indicated for confirmatory biopsy, correction of deformity, prevention of pathologic fracture, and/or eradication of symptomatic lesions 5.
- Calcium, vitamin D, and phosphorus supplements may be useful in patients with deficiency 6.