- Credits
- Section Writer: Dr. Om J Lakhani
- Section Editor: Dr. Om J Lakhani
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Q. What is Fibrous dysplasia?
- This is a condition in which a part of the bone is replaced by fibrous tissue. There is poorly formed trabecular bone.
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Q. What causes this condition?
- It is mainly due to postzygotic mutation in GNAS1 gene. Hence it is a part of McCune Albright syndrome.
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Q. What are the clinical presentation of Fibrous dysplasia?
- May present with severe disabling disease in early life to incidentally detect bone lesion to in later life.
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Q. What are subtypes of FD based on number of bones involved?
- Monostotic FD
- Polyostotic FD
- Panostotic FD all bones involved.
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Q. Which mineral disorder is associated with polyostotic FD?
- Hypophosphatemic rickets.
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Q. What is the pathogenesis of FD?
- Missense mutation in GNAS1 which encodes Gsalpha.
- Loss of intrinsic GTPase activity of Gs alpha.
- Continued action of adenylate cyclase.
- Continued production of cAMP.
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Q. When does the mutation in the GNAS generally take place?
- Generally post zygotic in inner cell mass stage.
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Q. What is the pathophysiology in the bone in FD?
- Normal bone is replaced by fibrous tissue. This tissue does not have any marrow and is obviously weaker than normal bone.
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Q. So what has GNAS to do with FD?
- Abnormal function of Gs alpha abnormal differentiation of mesenchymal stem cell and abnormal function of mutated osteoblasts which are formed from it.
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Q. What is the reason for osteomalacia seen along with it?
- Mutated osteocytes excess FGF23 hypophosphetemic rickets.
Clinical features
Pearl: Most of the bone involvement is present before the age of 5 years.
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Q. When are the patient most symptomatic?
- Fractures are most likely to occur during the rapid phase of development ie during adolescence.
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Q. What are the common symptoms?
- Recurrent fracture Limp Pain.
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Q. Which are common sites for pain?
- Ribs Long bones Craniofacial bones Spine Pelvis.
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Q. What produced long bone deformities?
- Improper healing and improper treatment of fractures.
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Q. What produces the craniofacial abnormalities?
- Overgrowth of the sites of lesion.
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Q. Which are the 2 most common sites of involvement?
- Base of the skull Proximal metaphysis of femur.
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Q. How does the femoral disease commonly present?
- Limp Pain Fracture Deformity Shepard's crook deformity.
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Q. What is the common lesion seen in Xray?
- Expansile lytic bone lesion In the medullary space With thinning of the overlying cortex. This is the typical ground glass apperance.
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Q. What is the importance of sclerosis in this lesion?
- Some lesion can be sclerotic. Presence of sclerosis suggests active lesions.
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Q. What are the facial deformities that occur?
- Facial asymettry or bump on the face Malar prominence.
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Q. Does the skull base involvement produce cranial nerve palsies?
- It is very rare. Sometime vessels in the FD can bleed forming an aneursymal bone cyst which can expand the lesion and cause cranial nerve involvement.
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Q. Why is it importnt to examine the spine in these patients?
- FD can involve the spine. This can lead to scoloiosis. It can progress to a degree where it is lethal.
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Q. Is malignancy seen in FD?
- Rarely osteosarcoma can occur in the FD lesions. Q What is the role of surgery in FD It is indicated for pain or deformity or when there is fracture It is not indicated for cosmetic reasons
- It is very rare for Osteosarcoma to occur. It mainly occurs in those exposed to high dose external beam radiation.
Management
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Q. What is the role of bone scintigraphy in FD?
-It can help predict the extent of the disease and functional outcome.
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Q. What is done when there is fracture of the femur?
-Insertion of intramedullary nails.
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Q. What is the role of bisphosphonates in FD?
- Reduces pain.
- Improves radiographic apperance
- Reduces fracture risk.
- However, in trials only reduction of pain is seen.
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Q. Which two drugs based on pathogenesis of the disease have been used in FD?
-Toclizumab - it is an anti-IL6 drug developed mainly for Rheumatoid arthritis, since IL6 is involved in pathogenesis of FD, it can be used for this indication.
Denusomab - it is an anti-RANKL antibody, again based on pathogenesis, it can be tried in FD. -
Q. What is the new method for monitoring patients with Fibrous dysplasia?
- Na-18F PET CT.
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Q. What is the role of Denosumab in this condition?
- Denosumab is thought to reduce pain like Bisphosphonates. However, the recent articles have also shown regression and stabilisation of the lesions. These case reports have used Denosumab every 3 monthly instead of 6 monthly.
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Q. What is Mazabraud syndrome?
-This is intramuscular myxoma with Fibrous dysplasia or McCune-Albright syndrome.
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Q. What is the role of surgery in FD?
-It is indicated for pain or deformity or when there is fracture. It is not indicated for cosmetic reasons.