Fibrous dysplasia of bone is a rare condition in which healthy bone tissue is replaced by abnormal, scar-like fibrous tissue, leading to weakened bones that are more prone to fractures and deformities. This genetic disorder can affect a single bone or multiple bones throughout the body, and while it cannot be cured, various treatment approaches can help manage symptoms and improve quality of life for those affected.
Understanding Fibrous Dysplasia
Fibrous dysplasia is a rare bone condition where normal bone tissue is replaced by fibrous tissue that resembles scar tissue. This abnormal tissue is not as strong as healthy bone, making affected bones weaker, more brittle, and prone to breaking. The condition is classified as benign, which means it is not cancerous and does not spread from one bone to another.[1]
The abnormal fibrous tissue develops because of a problem in how bone cells form and grow. Instead of creating strong, solid bone through normal bone development processes, the body produces soft, stringy fibrous tissue that cannot provide the same structural support. This makes the bone fragile and susceptible to expansion, deformity, and fracture.[5]
Any bone in the body can be affected by fibrous dysplasia, though certain bones are more commonly involved. The bones most frequently affected include the thigh bone, shin bone, ribs, skull and facial bones, upper arm bone, and pelvis. When the condition affects bones in the face and skull, it is sometimes called craniofacial fibrous dysplasia.[2]
Epidemiology and Disease Patterns
Fibrous dysplasia is considered a rare disorder, accounting for approximately seven percent of all benign bone tumors. The estimated prevalence ranges from one in five thousand to one in thirty thousand individuals, though exact figures vary across different populations.[2][4]
The condition typically manifests during childhood and early adulthood, usually between the ages of three and fifteen years. Individual bone lesions commonly appear during the first few years of life and tend to expand throughout childhood. The vast majority of clinically significant bone lesions become detectable by age ten, with very few new lesions appearing after age fifteen.[4][5]
Males and females are generally affected equally by fibrous dysplasia. However, there is one important exception: McCune-Albright syndrome, a specific type of polyostotic fibrous dysplasia that involves multiple body systems, is more common in girls and women.[5][8]
The condition presents along a broad clinical spectrum. Some individuals have only a single affected bone with minimal symptoms, while others experience severe, disabling disease involving multiple bones throughout the body. This wide variation in presentation means that the impact on daily life can range from negligible to profoundly limiting.[4]
Causes of Fibrous Dysplasia
Fibrous dysplasia is caused by a change in a gene called GNAS1, which occurs after conception while a baby is developing in the womb. This gene mutation affects cells called osteoblasts, which are responsible for building and developing healthy bone tissue. When these cells malfunction due to the genetic change, they produce abnormal fibrous tissue instead of normal bone.[1][3]
The mutation disrupts the normal bone remodeling process. Typically, bone constantly renews itself by breaking down old bone and forming new bone in its place. In fibrous dysplasia, the genetic change causes a problem in the bone formation process, resulting in new bone that is fibrous and scar-like rather than strong and solid.[3]
Scientists do not fully understand what triggers this genetic change to occur. What they do know is that the mutation happens randomly and is not inherited from parents. This means that fibrous dysplasia is not passed down through families, and individuals with the condition cannot pass it on to their biological children. The mutation is described as somatic, meaning it occurs in some but not all cells of the body, creating a mosaic pattern of affected and unaffected tissue.[5][3]
Risk Factors
Because fibrous dysplasia results from a spontaneous genetic mutation that occurs during fetal development, there are no known behavioral, environmental, or lifestyle risk factors that increase the likelihood of developing the condition. The mutation happens randomly and cannot be predicted or prevented.[6]
The condition is not linked to family history, diet, environmental exposures, or any actions taken by parents before or during pregnancy. Unlike some genetic conditions, fibrous dysplasia does not run in families and there are no known genetic markers that would indicate a person is at higher risk of having a child with the condition.[2]
However, individuals who have fibrous dysplasia affecting multiple bones are at increased risk of developing McCune-Albright syndrome, which involves not only bone abnormalities but also skin changes and hormone problems. This syndrome represents a more severe form of the condition with additional complications beyond the skeletal system.[8]
Types of Fibrous Dysplasia
Healthcare providers classify fibrous dysplasia based on the number of bones affected and whether other body systems are involved. Understanding the type helps doctors predict the course of the disease and plan appropriate treatment.[1]
Monostotic fibrous dysplasia affects only a single bone in the body. This is the most common form of the condition, accounting for approximately seventy-five to eighty percent of all cases. People with monostotic disease typically have fewer problems than those with multiple affected bones. The skull is the most commonly affected site in monostotic fibrous dysplasia. In many cases, this form of the condition becomes inactive after puberty, though the abnormal bone does not disappear.[2][5]
Polyostotic fibrous dysplasia affects multiple bones throughout the body. It can involve more than one bone within the same limb or multiple bones in different parts of the skeleton. This form is usually more severe and tends to be discovered earlier in life than monostotic disease. The lesions in polyostotic disease may remain active throughout a person’s life and are more likely to progress rapidly, especially in growing children.[2]
Some individuals with polyostotic fibrous dysplasia also develop McCune-Albright syndrome, a condition characterized by bone disease combined with hormone abnormalities and distinctive skin pigmentation. The skin changes appear as darkened patches with irregular edges, often described as café-au-lait spots. Hormone problems can include early onset of puberty before age ten, overactive thyroid gland, overactive pituitary gland leading to abnormal height, and other endocrine disturbances.[1][8]
Symptoms and Clinical Presentation
The symptoms of fibrous dysplasia vary widely from person to person, and some individuals may have no symptoms at all. Many people discover they have the condition only when an X-ray is taken for an unrelated medical problem. In general, people with fibrous dysplasia affecting one bone experience fewer issues than those with multiple affected bones.[1]
Bone pain is one of the most common symptoms when they do occur. This pain results from the expansion of the abnormal bone tissue or from pressure that the expanding bone places on nearby nerves. The pain can range from mild discomfort to severe, disabling pain that interferes with daily activities.[8]
Bone fractures happen more easily in people with fibrous dysplasia because the abnormal fibrous tissue is weaker than normal bone. These fractures may occur with minimal trauma or sometimes even without any obvious injury. Some individuals experience recurring fractures in the same location, which can be particularly frustrating and limiting.[1][5]
Changes in bone shape and deformities are common, especially when weight-bearing bones like those in the legs and pelvis are affected. The abnormal tissue can cause bones to become enlarged, curved, or misshapen. In the legs, this may result in differences in limb length, leading to an unusual walking pattern such as waddling or limping. When the spine is involved, it can lead to abnormal curvature or scoliosis.[1][6]
When fibrous dysplasia affects the skull and facial bones, it can cause visible facial asymmetry, where one side of the face appears different from the other. This may present as a painless lump or gradual change in facial appearance. Expansion of bone tissue in the skull can lead to nasal congestion, jaw misalignment, and dental problems including crowded, separated, or misaligned teeth. In more severe cases, expansion of skull bones can compress nerves, potentially leading to bulging eyes, vision loss, or hearing loss.[1][3]
Children with fibrous dysplasia in the bones of the arms or legs typically present with limping, pain, or fractures that occur without significant injury. Frequent fractures and progressive deformity may lead to difficulties with walking and reduced mobility, which can significantly impact a child’s ability to participate in normal activities.[4]
When McCune-Albright syndrome is present, additional symptoms beyond the skeleton may occur. These include patches of darkened skin with irregular, jagged edges, early sexual development, excessive sweating and weight loss from an overactive thyroid, weight gain and diabetes development, high calcium levels in the blood, and excessive growth from high levels of growth hormone.[3][6]
Prevention
Because fibrous dysplasia results from a spontaneous genetic mutation that occurs during fetal development, there are currently no known methods to prevent the condition from developing. The genetic change happens randomly and cannot be predicted, avoided, or stopped through any known interventions.[2]
However, for individuals who have been diagnosed with fibrous dysplasia, certain measures may help prevent complications. Regular monitoring through follow-up appointments with healthcare providers allows for early detection of changes in bone health and timely intervention when problems arise.[1]
Maintaining overall bone health through adequate nutrition, including sufficient calcium and vitamin D intake, may support the strongest possible bones given the underlying condition. Some individuals may benefit from medications called bisphosphonates, which are drugs that can strengthen bones and may help reduce pain and the risk of fractures.[1][14]
For children with fibrous dysplasia, wearing braces can support affected bones and help them grow as correctly as possible, potentially preventing deformities from worsening. Activity modifications may be recommended to reduce the risk of fractures, though complete restriction of physical activity is generally not advised as maintaining muscle strength and general fitness remains important.[1]
Regular dental check-ups are important for individuals with craniofacial fibrous dysplasia to monitor and manage potential dental complications such as crowding, misalignment, enamel changes, and increased risk of tooth decay.[3]
Pathophysiology
The underlying problem in fibrous dysplasia involves a malfunction in the normal process of bone formation and maintenance. Healthy bone constantly undergoes a process called remodeling, in which old bone is broken down by specialized cells and new, strong bone is formed to replace it. This balance keeps bones healthy and strong throughout life.[3]
In fibrous dysplasia, the mutation in the GNAS gene disrupts the activity of bone-building cells called osteoblasts. The gene mutation causes these cells to malfunction, leading to persistent, abnormal signaling within the cells. Specifically, the mutation affects a protein called Gsα, which normally helps regulate cell activities. When this protein is permanently activated due to the mutation, it causes excessive production of a signaling molecule called cyclic AMP, which in turn disrupts normal bone formation.[4]
Instead of forming organized, mineralized bone tissue with the normal microscopic structure that provides strength, the affected osteoblasts produce abnormal fibrous connective tissue. This tissue is similar to scar tissue and lacks the organized structure and mineral content that give normal bone its strength and rigidity. Under a microscope, the abnormal bone shows thin, irregular bony structures surrounded by fibrous tissue instead of the thick, organized bone structure seen in healthy bone.[4]
The abnormal bone tissue in fibrous dysplasia also has a greatly increased rate of bone turnover, meaning the processes of bone breakdown and formation are happening much faster than normal. This accelerated turnover contributes to bone weakness and the various complications seen in the condition. The rapid turnover can be detected through blood tests that measure certain enzymes and proteins released during bone metabolism.[13]
Because the genetic mutation affects only some cells in the body (creating a mosaic pattern), the disease can vary greatly in its extent and severity. The more cells that carry the mutation, and the earlier in development the mutation occurred, the more widespread and severe the disease tends to be. This explains why some people have only a single affected bone while others have involvement of multiple bones throughout the body.[3]
In individuals with McCune-Albright syndrome, the same genetic mutation that affects bone cells can also occur in other cell types, particularly in hormone-producing glands and skin cells. When the mutation occurs in gland cells, it causes those cells to become overactive, leading to hormone imbalances. In skin cells, the mutation results in increased pigmentation, creating the characteristic café-au-lait spots.[2]
The fibrous lesions typically do not disappear on their own, though they may stabilize and stop growing, particularly after skeletal maturity is reached. In rare cases (less than one percent of patients), the fibrous tissue can undergo malignant transformation and become cancerous, developing into bone cancers such as osteosarcoma or chondrosarcoma. This risk is slightly higher in individuals with polyostotic disease or McCune-Albright syndrome.[2][4]
Diagnosis
Diagnosing fibrous dysplasia involves several steps and multiple types of tests. A healthcare provider will begin with a thorough physical examination, carefully examining any areas of the body that are painful or appear abnormal. They will ask detailed questions about when symptoms first appeared and how they have changed over time.[1]
For individuals with suspected McCune-Albright syndrome, the doctor will check the skin for café-au-lait spots, which are darkened patches with irregular edges. Blood tests may be performed to evaluate hormone levels and check for endocrine abnormalities.[6]
X-rays are typically the first imaging test ordered and are very useful in diagnosing fibrous dysplasia. They can show characteristic changes in bone structure that suggest the presence of fibrous tissue. The abnormal areas often have a distinctive appearance on X-rays that experienced doctors can recognize.[2][6]
A bone scan, also called scintigraphy, is particularly valuable for determining the full extent of the disease. This nuclear medicine test involves injecting a small amount of radioactive material that is taken up by bone tissue. It can reveal all affected bones throughout the body in a single test, which is crucial for distinguishing monostotic from polyostotic disease and for understanding the overall disease burden. This test should be performed in all patients with suspected fibrous dysplasia.[4][6]
CT scans (computed tomography) and MRI scans (magnetic resonance imaging) provide more detailed images than regular X-rays. These advanced imaging techniques can show the exact location and extent of fibrous tissue within bones, help evaluate how the condition affects nearby structures like nerves and blood vessels, and are particularly useful when planning surgical treatment. MRI is especially helpful for assessing the soft tissues around affected bones.[1][6]
Blood and urine tests may be ordered to check for elevated levels of certain enzymes and proteins that indicate increased bone turnover. High levels of these markers can suggest active disease. These tests can also help monitor the condition over time and assess response to treatment.[1]
In some cases, a biopsy may be necessary to confirm the diagnosis. This involves removing a small sample of the abnormal bone tissue, which is then examined under a microscope. The biopsy can typically be performed using a needle through a small incision while the patient is under anesthesia. The microscopic appearance of the tissue helps confirm the diagnosis and rule out other bone conditions that may look similar on imaging tests.[1][6]
Treatment and Management
Treatment for fibrous dysplasia depends on the severity of symptoms, the location and extent of bone involvement, and how the condition affects daily life. There is no cure for fibrous dysplasia, so treatment focuses on managing symptoms, preventing complications, and improving quality of life.[1]
Many individuals with mild, asymptomatic disease require only observation. This involves regular follow-up appointments with a healthcare provider who monitors bone health and watches for any changes or new symptoms. This approach is often appropriate for people with a single bone lesion that is not causing problems or located in a low-risk area.[1]
Medications play an important role in managing fibrous dysplasia. Bisphosphonates are drugs commonly prescribed to strengthen bones and reduce the risk of fractures. These medications work by slowing down the excessive bone breakdown that occurs in fibrous dysplasia. Studies have shown that bisphosphonates can reduce bone pain in many patients, though they do not eliminate the fibrous tissue or cure the condition. The pain relief can significantly improve quality of life for individuals experiencing chronic discomfort.[14][1]
A newer medication called denosumab has shown promising results in clinical trials. This drug blocks a protein that contributes to excessive bone turnover. Research has found that denosumab significantly reduced abnormal bone turnover in adults with fibrous dysplasia, improved bone quality and strength, and led to improvements in some complications, such as increased lung function in patients with rib lesions and vision improvements in some with skull involvement. However, in most patients, the benefits stopped when the medication was discontinued, and careful monitoring is needed.[13]
Bracing and supportive devices can help stabilize affected bones, particularly in growing children. Wearing braces supports bones and helps them grow as correctly as possible, potentially preventing deformities from worsening. These devices are especially useful for bones in the legs that bear weight.[1]
Surgery may be necessary in several situations. It is commonly performed to repair fractures, correct significant deformities that interfere with function, prevent anticipated fractures in high-risk areas, or address complications such as compression of nerves affecting vision or hearing. Surgical options include removal of abnormal bone tissue followed by bone grafting, where healthy bone from another part of the body or from a donor is used to replace the diseased bone. However, there is a risk that the abnormal tissue may grow back, particularly if the patient’s own bone is used.[1][6]
Other surgical procedures include placement of metal rods down the center of long bones to strengthen them and prevent fractures or deformities, removal of bone wedges to correct deformities, and use of bone substitutes made from calcium-based materials. Because fibrous dysplasia creates bones with a rich blood supply, blood transfusions may be needed during surgery.[6][10]
Pain management is an important aspect of care. This may include over-the-counter or prescription pain medications, bisphosphonates for their pain-relieving effects, and physical therapy to maintain function and reduce discomfort.[10]
For individuals with McCune-Albright syndrome, treatment must address the endocrine abnormalities in addition to bone disease. This typically involves referral to an endocrinologist, a specialist in hormone disorders, who can manage problems such as early puberty, thyroid dysfunction, and other hormonal imbalances.[6]
