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Fibrous Dysplasia

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Copyright 1991, 1996, 1998, 1999, 2002, 2014

NORD is very grateful to Frederick Singer, MD, Director, Endocrine/Bone Disease Program, John Wayne Cancer Institute, for assistance in the preparation of this report.

Synonyms of Fibrous Dysplasia

Disorder Subdivisions

General Discussion

Fibrous dysplasia (FD) is a rare bone disorder. Bone affected by this disorder is replaced by abnormal scar-like (fibrous) connective tissue. This abnormal fibrous tissue weakens the bone, making it abnormally fragile and prone to fracture. Pain may occur in the affected areas. As children grow, affected bone may become misshapen (dysplastic). FD may only affect one solitary bone (monostotic disease) or the disorder can be widespread, affecting multiple bones throughout the body (polyostotic disease). The severity of the disorder can vary greatly from one person to another. Any part of the skeleton can be affected, but the long bones of the legs, the bones of the face and skull (craniofacial area), and the ribs are most often affected. FD is usually diagnosed in children or young adults, but mild cases may go undiagnosed until adulthood. In some cases, FD may not require treatment; in other cases, certain medications and surgical procedures may be recommended.

FD was first described in the medical literature in 1938 by Dr. Lichtenstein and in 1942 by Drs. Lichtenstein and Jaffe. Fibrous dysplasia can occur as part of a larger disorder such as McCune-Albright syndrome (fibrous dysplasia-café au lait spots-endocrine dysfunction) or Mazabraud syndrome (fibrous dysplasia-myxomas). The term Jaffe-Lichtenstein syndrome is sometimes used synonymously with monostotic FD or to denote cases of polyostotic FD with café au lait spots, but no endocrine dysfunction. These disorders most likely represent a spectrum of disease associated with activating mutations of the GNAS1 gene.


The severity and specific symptoms of FD can vary greatly from one person to another. Most affected individuals only have one bone involved and often there are no associated symptoms (asymptomatic). Many times, FD is discovered incidentally when x-rays are performed for another reason. Conversely, some affected individuals can have multiple bones affected and develop severe and potentially disabling or disfiguring symptoms. In most cases, onset of symptoms is usually in childhood; it is unusual for the onset of the disorder to occur after 10.

FD is a benign (noncancerous) disorder and does not spread. The bone or bones that are affected by the disorder are usually established early in life and it is very rare for new areas to become affected. The areas affected may be described as lesions. FD lesions may progressively grow and expand until an affected bone finishes growing. These lesions can eventually cause affected bones to become abnormally weakened, misshapen, and prone to facture. Bone pain can also occur and may be severe in some cases.

Specific symptoms associated with FD depend upon the specific bones involved. Any part of the skeleton can potentially be affected, but the long bones of the arms and legs, the bones of the face and skull (craniofacial area), and the ribs are most often affected. Monostotic FD often presents as a painless swelling on the ribs. FD affecting the spine can cause abnormal curvature of the spine (scoliosis). When the long bones of the legs are affected, this can lead to frequent fractures due to weight bearing when walking or standing. Additionally, the long bones can eventually become bowed. In children, their legs may not be of equal length (limb length discrepancy). Eventually, this can affect a person’s ability to walk, causing an abnormal gait (e.g. walking with a limp).

FD of the craniofacial region can cause a variety of symptoms depending on the type and specific location of the lesions(s). Such symptoms can include pain, nasal congestion, misaligned or displaced teeth, uneven jaws, and facial asymmetry, in which one side of the face does not match the other side. FD in the craniofacial region can alter the facial features resulting in an abnormally prominent forehead (frontal bossing), bulging eyes (proptosis), and difference in the vertical positions of the eyes so that the eyes are uneven (vertical dystopia). The degree of facial abnormality can vary greatly from one person to another. The shape of the skull may be altered in certain cases.

FD can potentially cause a variety of neurological symptoms as areas of abnormal tissue development can compress nearby nerves. Specific symptoms are related to the specific nerves involved. For example, vision loss and hearing impairment can occur because of compression of optic and auditory nerves in the skull. However, vision loss and hearing impairment only occur in rare instances.

The abnormal structure of affected bone can lead to degenerative arthritis in adjacent joints.

Women with FD may be at risk of increased pain during pregnancy because of the estrogen receptors found in FD.

Although the term tumor may be used to describe FD lesions, these growths are benign (non-cancerous). Only in extremely rare cases, estimated to be approximately .4-4% of cases, do FD lesions become cancerous (malignant transformation). These malignant tumors developed in individuals who had been radiated for bone pain; a treatment option that has been abandoned.


The underlying cause of FD is not fully understood. Researchers believe that the disorder is caused by a mutation in a gene called GNAS1. This gene mutation occurs after fertilization of the embryo (somatic mutation) and is therefore not inherited, nor will affected individuals pass the mutation on to their children. Affected individuals have some cells with a normal copy of this gene and some cells with the abnormal gene (mosaic pattern). The variability of symptoms of FD is due, in part, to the ratio of healthy cells to abnormal cells. Researchers do not know why these somatic mutations occur; they appear to develop randomly for unknown reasons (sporadically).

The GNAS1 gene is located on the long arm (q) of chromosome 20 (20q13.2) Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 20q13.2” refers to band 13.2 on the long arm of chromosome 20. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

The GNAS1 gene creates (encodes) a protein known as a G-protein. In FD, a gain-of-function mutation in the GNAS1 gene results in the overproduction of this G-protein. In turn, this results in the overproduction of a molecule known as cyclic adenosine monophosphate (cAMP), which is involved in the change (differentiation) of osteoblasts in bone. Osteoblasts are immature bone-forming cells that form new bone. The human skeleton is living tissue that is constantly changing (remodeling). It is believed that FD involves increased bone turnover. Bone turnover is a normal process in which bone gradually breaks down (bone resorption) and then reforms. Bone turnover involves osteoblasts and cells that control bone resorption (osteoclasts). The interaction between osteoclasts and osteoblasts determines how bone reforms. The interaction is a complex process that involves many factors. Improper differentiation of osteoblasts due to mutation of the GNAS1 gene is believed to contribute to the development of FD.

When other cells such as endocrine or skin cells are involved in addition to osteoblasts, McCune-Albright syndrome develops.

Affected Populations

Fibrous dysplasia affects males and females in equal numbers. The disorder is diagnosed earlier in children and young children. The exact incidence and prevalence of the disorder is unknown. Mild cases may go undiagnosed, making it difficult to determine the true frequency of FD in the general population. The monostotic form is more common than the polyostotic form; according to some reports by a ratio of 4:1.

Related Disorders

Symptoms of the following disorders can be similar to those of fibrous dysplasia. Comparisons may be useful for a differential diagnosis.

A variety of benign and malignant bone tumors or disorders associated with such tumors can cause symptoms similar to those seen in FD. Such tumors include ossifying fibromas, osteofibrous dysplasia, osteosarcomas, adamantinomas, eosinophilic granulomas, chondrosarcoma, Ollier disease, multiple exostoses, and neurofibromatosis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

McCune-Albright syndrome (MAS) is an extremely rare disorder characterized by polyostotic fibrous dysplasia that occurs with at least two additional findings - patches of abnormal skin pigmentation (i.e., areas of light-brown skin [cafe-au-lait spots] with jagged borders); abnormalities in the glands that regulate the body's rate of growth, its sexual development, and certain other metabolic functions (multiple endocrine dysfunction). Depending on the number and location of the skeletal abnormalities, mobility may be impaired, as well as vision and/or hearing and the individual may experience substantial pain. Malfunctioning endocrine glands can result in the development of secondary sexual characteristics at an age younger than normal (precocious puberty). MAS is the result of a genetic change (mutation) in the GNAS gene that occurs randomly, for no apparent reason (sporadic). In individuals with the disorder, this sporadic genetic mutation is present in only some of the body's cells (mosaic pattern). The symptoms and physical characteristics associated with the disorder vary greatly from case to case, depending upon the specific body cells and tissues that are affected by the genetic mutation. This mutation occurs after fertilization (postzygotic somatic mutation). It is not inherited from the parents. The range of severity of the disorder is very broad: some children are diagnosed in early infancy with obvious anomalies of bone and increased hormone production by one or more of the endocrine glands; others show no evidence of bone, skin or endocrine malfunction in childhood and may enter puberty at an appropriate age. (For more information on this disorder, choose “McCune-Albright syndrome” as your search term in the Rare Disease Database.)

Mazabraud syndrome is an extremely rare disorder characterized by the association of FD with multiple myxomas, which are benign tumors consisting of connective tissue. Myxomas usually involve large muscle groups. In some cases, affected individuals may only have a solitary myxoma. Most cases of Mazabraud syndrome are associated with polyostotic FD, but monostotic FD has been reported as well. FD lesions usually affect the long bones of the leg. Females are affected more often than males in the cases report so far in the medical literature (which number fewer than 100). The growths associated with Mazabraud syndrome are benign, but malignant transformation has been reported in rare cases. The relationship between myxomas and FD is not fully understood.

Cherubism is a rare disorder characterized by displacement of normal bone tissue with areas of fibrous growth (fibrous dysplasia) within the upper and/or lower jaw bones (maxilla and/or mandible) on both sides of the face (bilateral). This causes abnormal expansion of the jaw bones, unusual chubbiness and swelling of the face, and, in severe cases, “upturning” of the eyes. In some cases, fibrous dysplasia may also occur in other bones of the body, particularly the ribs. Some affected individuals may also exhibit other abnormalities such as multiple, patchy areas of dark pigmentation (cafe-au-lait spots) and/or several warty birthmarks (nevi) on the skin. Symptoms usually become apparent in the third or fourth year of life. Cherubism is thought to be inherited as an autosomal dominant genetic trait with variable expressivity and penetrance. Whereas 100% of affected males with a defective gene for cherubism will exhibit the characteristics typically associated with the disorder (high penetrance), only 50 to 75% of females with the disease gene demonstrate symptoms of the disease (reduced penetrance). Mutations in the SH3BP2 gene are associated with approximately 80% of individuals with cherubism.

Paget’s disease of bone is a chronic, slowly progressive skeletal condition of abnormally rapid bone destruction (osteolytic) and reformation (osteoblastic). The new bone may occur in one or more regions of the body and is structurally abnormal, dense and fragile. This abnormal development may cause bone pain, arthritis, deformities and fractures. The bones most frequently affected are in the spine, skull, pelvis and lower legs. The exact cause of Paget’s disease is controversial, although studies implicate gene abnormalities and chronic viral infections. The disorder is usually not diagnosed until after 50 years of age. (For more information on this disorder, choose “Paget’s” as your search term in the Rare Disease Database.)

Standard Therapies

A diagnosis of fibrous dysplasia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Individuals with mild forms of monostotic FD may be diagnosed incidentally when receiving an x-ray for another reason.

Clinical Testing and Workup
Specialized imaging techniques may be used to evaluate bone. Such imaging techniques include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. The abnormal tissue in FD resembles ground glass when seen on x-ray. These tests may be used to determine how extensively bones are affected.

A bone scan, also known as bone scintigraphy, is used to determine the extent of bone disease and may be used when a solitary FD lesion is found to confirm a diagnosis of monostotic FD or discovered additional affected areas (polyostotic FD). During this test, a harmless radioactive dye is injected into the affected bone. A special camera that can track the dye as it travels through bone is used to create a picture of the skeleton and determine all affected areas.

Bone biopsy is the surgical removal and microscopic examination of a small sample of affected tissue. A bone biopsy can reveal characteristic changes to bone that occur in individuals with FD and may be necessary to distinguish a FD lesion from other types of growths or tumors if it is unclear after an x-ray.

A highly sensitive, specific form of polymerase chain reaction (PCR) has been used to detect somatic mutations of the GNAS1 gene that characterize FD. PCR is a laboratory test that has been described as a form of “photocopying.” It enables researchers to enlarge and repeatedly copy sequences of DNA. As a result, they are able to closely analyze DNA and more easily identify genes and genetic changes (mutations). In FD, a specific form of PCR testing can detect activating mutations of GNAS1 in peripheral blood cells.

The treatment of FD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, general internists, orthopedic surgeons, endocrinologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Psychosocial support for the entire family is essential as well.

Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease progression; size of the lesion(s); the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens, surgical treatments and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors. Being seen by a physician(s) with familiarity in treating individuals with FD is recommended.

In many cases, FD lesions do not cause any symptoms (asymptomatic). In such cases, observation and patient education may be all that is needed. Follow up x-rays every six months are recommended to determine whether the lesion has progressed.

Individuals with FD have been treated with drugs known as bisphosphonates such as pamidronate or alendronate. These drugs reduce bone turnover by inhibiting bone resorption. Calcium and vitamin D may be given along with the drug. Some affected individuals respond favorably to such therapy with the main benefit being decreased bone pain. Other affected individuals do not respond to therapy with bisphosphonates or relapse after an initial period of improvement. Relapse of bone pain is more common in individuals with polyostotic FD. Stronger bisphosphonate medications such as zoledronic acid may be used in such cases and may be most effective in improving bone pain.

Surgery is often used to treat individuals with FD, although most physicians recommend a conservative strategy. Surgery should be undertaken only for lesions that causing difficulty in some way. Surgery may be undertaken to correct disfigurement or deformity, to correct limb length discrepancy, to eradicate symptomatic lesions (e.g. those causing pain and/or compressing a nerve), to treat specific complications such as scoliosis, or to prevent fracture. Standard surgical procedures are effective in most adults with monostotic FD.

Investigational Therapies

The drug tocilizumab is being studied as a potential therapy for FD. Tocilizumab is a drug that works by blocking the activity of interleukin-6 (IL-6), a specialized protein (cytokine) that stimulates bone resorption. Affected bone cells in FD release excess levels of interleukin-6 and researchers believe inhibiting IL-6 will decrease bone resorption.

Additional drugs are being study as potential therapies for FD. Such drugs include denosumab, a monoclonal antibody currently approved to treat osteoporosis and pregabalin, which is effective at treating neuropathic pain. More research is necessary to determine the long-term safety and effectiveness of experimental medications for the treatment of individuals with FD.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, in the main, contact:

For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

Fibrous Dysplasia Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:


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Report last updated: 2014/01/27 00:00:00 GMT+0