Orthopedic Surgery for Fibrous Dysplasia 

Fibrous dysplasia of bone is a nonheritable disease in which abnormal tissue develops in place of normal bone. The etiology of this abnormal growth process is related to a mutation in the gene that encodes the subunit of a stimulatory G protein (Gsα) located on chromosome 20.^{[1, 2]} As a consequence of this mutation, there is a substitution of the cysteine or the histidine—amino acids of the genomic DNA in the osteoblastic cells—by another amino acid, arginine.^[3] Consequently, the osteoblastic cells will elaborate a fibrous tissue in the bone marrow instead of normal bone.

Abnormalities may involve 1 bone in the monostotic form (70% of cases) or many bones in the polyostotic form (30% of cases). The polyostotic form is occasionally associated with precocious puberty, fibrous dysplasia, and cafe-au-lait skin lesions (McCune-Albright syndrome, Albright syndrome) or with myxomas of skeletal muscle (Mazabraud syndrome).^{[4, 5, 6, 7, 8]}

An image depicting fibrous dysplasia can be seen below.

The term fibrous dysplasia was suggested by Lichtenstein and Jaffe in 1942.^[9]

In fibrous dysplasia, lesions are characterized by woven ossified tissue and extensive marrow fibrosis. Mechanical quality of bones is decreased. As a consequence of this bone fragility, patients have an increased risk of fracture. Incidence of fractures is around 50% of cases.^[10] This risk of fractures or bone deformity is higher in the long bones, such as the femur, tibia, and humerus, but all the bones can be affected. Pain is a common symptom of patients with fibrous dysplasia. Patients also have an increased risk of malignant tumors such as osteosarcoma, fibrosarcoma, chondrosarcoma, and malignant fibrohistiocytoma.^[11] The incidence of this risk has been evaluated to be reduced to 1%.^{[11, 12]} This risk is higher in patients with the polyostotic form, or McCune–Albright syndrome.^[12]

Frequency

Fibrous dysplasia represents about 5% of all benign bone tumors.^[2] The monostotic form is more common than the polyostotic form. Many patients are asymptomatic, so the true incidence of this disorder is unknown. Usually, fibrous dysplasia presents clinically in children and adolescents, with a median onset age of 8 years. Most cases manifest themselves before the age of 30 years. Males are affected more often than females, except in McCune-Albright syndrome, in which females are affected more often than males.

Fibrous dysplasia is caused by the sporadic mutation of the GNAS1 gene, which encodes the alpha subunit of the stimulatory G protein (G1) located on chromosome 20q13.2-13.3 of the osteoblastic cells.^[2] The consequence of this mutation is an inappropriate cell differentiation resulting in a disorganized fibrotic bone matrix. Cancellous bone maintenance is perturbed, and bone undergoing physiologic remodeling is replaced by an abnormal proliferation of fibrous tissue. The extent and pattern of disease depend on the stage of development and the location at which the mutation occurs. All the bones can be affected.

As a consequence of the mutation of GNAS1, there is a substitution of cysteine or histidine, amino acids of the genomic DNA in the osteoblastic cells, by another amino acid, arginine.^[3] Osteoblastic cells expressing this mutation have a higher DNA synthesis than normal bone cells. The growth of these cells is faster, leading to an inappropriate differentiation of mesenchymal cells. At the molecular level, intracellular cAMP levels are increased and osteocalcin is decreased.^[13] Osteocalcin is a late marker of osteoblast differentiation. Involved bone cells are immature. They fail to produce normal amounts of collagen or to orientate appropriately to the lines of mechanical stress.

Pain is a common sign of fibrous dysplasia in symptomatic patients.^[14] Most commonly, patients are asymptomatic. Patients usually seek medical care because of either painful swelling and deformity or a pathologic fracture through a weakened bone. Long bones are commonly affected. The femur is the most common localization. Other sites typically affected are the tibia, maxilla, and skull. Nonskeletal manifestations include abnormal cutaneous pigmentation, precocious puberty, hyperthyroidism, Cushing disease, hyperparathyroidism, and hypophosphatemic rickets. McCune-Albright syndrome is defined as the triad of precocious puberty, polyostotic fibrous dysplasia, and cutaneous pigmentation. Typically, only females are affected by precocious puberty,^[15] but the other endocrine abnormalities occur equally in males and females. All of these abnormalities are thought to be due to the same underlying mutation.

• Surgical treatment of fibrous dysplasia is indicated in the prevention or treatment of fractures or major deformity.^[16] The most common surgical indications are fracture of a weight-bearing bone or a progressive disease.
• Asymptomatic patients do not need treatment.
• A needle biopsy can be performed if there is doubt about the diagnosis before the initial management.
• Upper-extremity lesions rarely require surgical management. Nevertheless, vascularized bone grafting has been proposed.^[17]
• Several studies have shown that bisphosphonates are useful in alleviating chronic pain in patients with fibrous dysplasia,^{[18, 19, 20, 21]} but further studies are necessary to confirm these promising results.

Fibrous dysplasia can affect almost any bone in the body. The relevant anatomy is that of the bone involved.

There are no specific contraindications to surgical intervention in patients with fibrous dysplasia. However, care must be used in the skeletally immature patient. Internal fixation of long bones with intramedullary nails may be proposed.