Fibrous dysplasia, although a rare condition, is the most common malformation of the bone system in childhood and adolescence. Prognosis and course are generally favorable in fibrous dysplasia resulting from mutative changes.
What is fibrous dysplasia?
Fibrous dysplasia is a rare benign disorder or lesion of the human skeleton that is associated with bone malformations and is attributed to mutative changes. It is caused by a defective synthesis of new bone mass (mainly osteoblast differentiation), resulting in the formation of more fibrous connective tissue with immature non-lamellar bone tubercles (non-fibrous bone trabeculae) instead of healthy bone tissue. The dysregulated bone formation causes irregular bone growth with deformities characterized by structural instability and an increased risk of iterative (recurrent) fractures and exertional pain. In general, the more common monostotic form, in which only one bone is affected, is differentiated from the polyostotic form of fibrous dysplasia involving multiple bones. Increasingly, fibrous dysplasia affects the skull and facial bones, femur, tibia, humerus, and ribs and hip.
Causes
Recent studies suggest a sporadic, postzygotic, or metagamous mutation of the GNAS-1 gene on chromosome 20q13 as the cause of fibrous dysplasia. The affected gene is responsible for the synthesis of certain units (alpha subunits) of G proteins, which play an important role within cellular metabolism for signal transduction. As a result of the mutation, the enzyme adenylate cyclase is excessively activated and there is an overproduction of the cell growth stimulating factors such as cAMP (cyclic adenosine monophosphate), which in turn control the osteoblasts regulating bone formation. The resulting increased production of fibrous connective tissue leads to increased bone growth and bone deformities. Depending on where the mutation is located in the embryonic cell mass, fibrous dysplasia manifests later. In addition, postnatal mutations are thought to be responsible for the monostotic variant of fibrous dysplasia and mutations in later embryonic development are thought to be responsible for the polyostotic variant of fibrous dysplasia, although the triggering factors for these are as yet unknown.
Symptoms, complaints, and signs
Fibrous dysplasia can take a wide variety of courses. The condition does not always cause noticeable symptoms or discomfort. Depending on the severity, and which bones are affected, a number of signs may occur. Typical symptoms include mild pulling bone pain that increases in intensity and duration with exertion. Accompanying this, affected individuals have difficulty walking and limp as a result. There is also an increased risk of so-called fatigue fractures. In this case, the sufferers suffer bone fractures and sprains even during light exertion. Externally, fibrous dysplasia can be recognized, among other things, by the visible bumps that result from the bone changes. In addition, pigmentary disorders, so-called café-au-lait spots, may occur. They can be recognized by their light brown appearance and sharp borders. The spots represent a cosmetic blemish, but are otherwise harmless. They occur when the affected person has the hereditary disease neurofibromatosis type 1 or McCune-Albright syndrome. Children and adolescents suffering from fibrous dysplasia grow faster than healthy people and reach puberty earlier. The condition often occurs together with other hormonal disorders, for example, diabetes, Cushing’s disease, or thyroid dysfunction.
Diagnosis and course
Fibrous dysplasia is diagnosed on the basis of characteristic symptoms. These include, in addition to iterative bone fractures, disturbances of hormonal balance (including growth hormone excess), which cause an accelerated maturation process in affected children and adolescents, possibly pigmentary disorders (“café-au-lait spots”), or pronounced jawbone deformities (cherubism). Radiographically or by computer tomography, the milky glass-like appearance of the affected bone areas, which is typical for fibrous dysplasia, can be made visible.In addition, in active fibrous dysplasia, there is often an elevated concentration of alkaline phosphatase in the serum and of hydroxyproline or deoxypyridinoline in the urine. The diagnosis is confirmed by a biopsy of the affected bone followed by microscopic examination. A bone scintigram may reveal additional foci. Fibrous dysplasia usually has a favorable prognosis and the growth of the corresponding lesion usually stops at the end of puberty. In rare cases (less than 1 percent), malignant degeneration (osteosarcoma) is seen.
Complications
Fibrous dysplasia can cause severe complications if left untreated. First, there is an increased risk of fracture of the affected bone. The disease itself may be associated with dysfunction of the internal organs, leading to heart disease or thyroid dysfunction, for example. If the pancreas is affected, it can lead to hormonal complaints, but also to the development of tumors. The skeletal muscles are more susceptible to so-called myxomas, benign tumors that come to restrict movement, when fibrous dysplasia is present. In addition, the increased bone remodeling process can lead to an increase in alkaline phosphatase in the blood, which in the long term can lead to diseases of the skeletal muscles. As the disease progresses, joint wear and tear may develop. Sometimes porous bones also develop, which in turn can be associated with severe complications. Surgical treatment of fibrous dysplasia also carries some risks. For example, surgery on the axial skeleton can result in internal injuries, infections, and deformities. Surgery on the skull bone may permanently impair its protective function. The accompanying bisphosphonates are associated with typical side effects such as nausea and vomiting, but they can also cause severe bone necrosis and other complications.
When should you see a doctor?
Since there is usually no self-healing in this condition, Fall must be seen by a doctor. This can prevent further discomfort and complications. The doctor should usually be consulted if the affected person suffers from irregular bone growth. This can be manifested by deformities in various parts of the body, although the skull is most affected by the symptoms. Severe pain in the bones also occurs as a result of the disease and can considerably restrict the daily life of the affected person. Especially in children, there is a very rapid growth and maturation. If these complaints also occur, a doctor must also be consulted. The risk of bone fractures is significantly increased by the disease, so that those affected suffer from injuries more often. Diagnosis and treatment of this disease can usually be done either by a pediatrician or by a general practitioner. In some cases, surgical interventions are also necessary to completely limit the symptoms. This can make the affected person’s daily life much easier.
Treatment and therapy
Since the exact etiology of fibrous dysplasia is not yet known, no causal therapy exists. Accordingly, treatment measures are aimed at reducing symptoms and discomfort. In many cases fibrous dysplasia does not require therapeutic measures and is only clinically controlled in its course. Medications are used to reduce pain as part of symptomatic therapy. Although no active substances are yet available that completely stop the increased synthesis of fibrous connective tissue and, accordingly, the characteristic bone deformations, the progression of fibrous dysplasia can be slowed down by inhibiting the so-called osteoclasts (cells that break down bone substance) and the pain on exertion can be reduced with the aid of bisphosphonates (including risedronate, pamidronate, zoledronate). If there is progressive, marked deformity of the affected bones or corresponding clinical symptoms, surgical intervention may be indicated to prevent pathologic fractures and malformations. Resection may involve surgical removal of areas of bone that may restrict mobility or entrap supplying blood vessels and/or nerve pathways.In the facial region in particular, modeling surgery may also be required for cosmetic reconstruction. Radiotherapeutic measures, which are associated with an increased risk of sarcomas (malignant tumors), are now largely avoided in the treatment of fibrous dysplasia.
Outlook and prognosis
If fibrous dysplasia is present, the exact outlook and prognosis are very difficult to predict. The explicit course of the disease depends on many different factors. The biggest factor is medical treatment. If such treatment takes place in the case of fibrous dysplasia, a quick and complication-free cure can be expected. If the patient decides against medical and drug treatment, the disease will most likely worsen within a short period of time. The symptoms that occur will intensify, so that under certain circumstances a life-threatening situation may even arise. The entire course of the disease is different if the affected person decides to undergo medical and drug treatment. In such a case, the prospects and prognosis for a complete cure look much better. With the appropriate medication, the existing fever can be quickly controlled and alleviated. Furthermore, further complications are prevented.
Prevention
In view of the fact that the triggering factors for the underlying mutations are not yet known, fibrous dysplasia cannot be prevented. However, the progression of fibrous dysplasia should be monitored regularly to detect malignant degeneration into osteosarcoma early and to provide appropriate therapy.
Follow-up
The affected person usually has very few options for aftercare with this disease. The affected person is primarily dependent on the rapid measures of an early diagnosis so that no further complications occur. Only early diagnosis can prevent further symptoms or a further worsening of symptoms. It is also not possible for the disease to heal itself, so that a visit to a doctor is definitely necessary in the case of this disease. The sooner the doctor is consulted, the better is the further course of the disease. The treatment of this disease is usually done by taking medication. It is important to ensure that the medication is taken regularly and in the correct dosage. In the case of children, it is above all the parents who should pay attention to the correct dosage. However, surgical interventions are often necessary to alleviate the symptoms. After such an operation, the affected person should in any case rest and take care of his body. Efforts or stressful activities should be avoided. No general prediction can be made about the life expectancy in this disease.
This is what you can do yourself
The treatment of fibrous dysplasia can be supported by some measures. If severe bone pain occurs, pain management with medication can be encouraged by rest and bed rest. Since there is an increased risk of bone fractures with the disease, no high-impact sports such as jogging, climbing or bodybuilding should be performed. If a fracture does occur, a physician must be consulted immediately in any case. The responsible physician should also be informed promptly of any incidents so that the therapy can be adjusted. After a surgical procedure, rest is also indicated. Fibrous dysplasia itself cannot be cured by surgery, so medical check-ups must continue. If the symptoms increase, countermeasures must be taken to compensate for the limited mobility. For example, many sufferers require a walker or wheelchair, and handicapped-accessible furnishings are also necessary for severely ill patients. Together with the physician, these adaptations can be organized and implemented as the disease progresses. In this way, a high quality of life can be maintained even in relatively severe courses.
