Fibrous dysplasia (FD) is a rare, non-cancerous bone disorder where normal bone structure is progressively replaced by abnormal, scar-like fibrous tissue. This replacement, known as fibro-osseous proliferation, weakens the bones, making them prone to fracture and deformity. FD can affect any bone, but most commonly involves the long bones of the legs, the pelvis, and the skull. The disorder varies widely, ranging from a single, asymptomatic lesion to severe, widespread disease causing significant impairment.
The Biological Basis of Fibrous Dysplasia
Fibrous dysplasia arises from a sporadic, non-inherited genetic change that occurs after conception, known as a post-zygotic mutation. This mutation affects the GNAS gene, which provides instructions for making the alpha subunit of a G-protein (Gαs). The change causes the Gαs protein to become constantly active, leading to overstimulation of a signaling pathway inside affected cells.
This inappropriate signaling primarily affects skeletal progenitor cells, the precursors to bone-forming cells called osteoblasts. Instead of maturing into healthy osteoblasts that produce strong bone, the mutated progenitor cells proliferate excessively. They produce disorganized, immature bone tissue and fibrous material, resulting in the characteristic fibro-osseous lesions. Because the mutation is present only in certain cells, the disease creates a “mosaic” pattern.
Clinical Forms and Classification
Fibrous dysplasia is classified based on the number of bones affected and the presence of additional symptoms outside the skeleton. The most common form is Monostotic FD, accounting for 70% to 85% of cases, which involves only a single bone. These lesions are often discovered incidentally and may remain asymptomatic throughout life.
When the disease affects multiple bones, it is termed Polyostotic FD, occurring in 15% to 30% of patients. This form tends to be more severe, appears earlier in childhood, and often affects bones on one side of the body. The long bones of the legs and the pelvis are frequently involved, leading to a higher risk of complications and functional impairment.
The most extensive form is McCune-Albright Syndrome (MAS), which combines Polyostotic FD with extra-skeletal manifestations. These features commonly include café-au-lait skin macules (light brown patches with jagged borders) and hyperfunctioning endocrinopathies. The most frequent endocrine issue is gonadotropin-independent precocious puberty in girls, but it can also include thyroid overactivity or growth hormone excess. The clinical presentation of MAS is highly variable, depending on which tissues harbor the GNAS mutation.
Recognizing the Signs and Symptoms
The manifestations of fibrous dysplasia are directly related to the weakened state of the affected bones. Bone pain is a frequent complaint, especially in weight-bearing bones like the legs and pelvis. This discomfort presents as a dull ache that intensifies with activity and may worsen over time.
The replacement of normal bone with fibrous tissue can lead to significant bone deformities. In the legs, repeated microfractures can cause the thigh bone (femur) to bow, sometimes resulting in a characteristic “shepherd’s crook” curvature. Involvement of the skull and facial bones can cause asymmetry, potentially leading to vision or hearing loss if nerves are compressed.
Patients with FD lesions are susceptible to pathological fractures—breaks that occur with little or no trauma. These fractures are often the first sign of the disease and are particularly common in the polyostotic form. In McCune-Albright Syndrome, non-skeletal signs include the distinctive, irregularly bordered café-au-lait skin patches. Endocrine symptoms like early puberty or rapid growth are also part of the clinical picture in MAS.
Diagnostic Process and Treatment Strategies
Diagnosing fibrous dysplasia begins with a physical examination and standard X-rays, which may reveal the characteristic appearance of the lesion. The affected bone area often has a hazy or smoky look, described as a “ground-glass” appearance, due to the disorganized bone tissue. Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI) provide more detailed information on the extent of the lesion and its proximity to surrounding structures.
In some instances, particularly for Monostotic FD, a bone biopsy may be necessary to confirm the diagnosis by examining a small tissue sample. Management focuses on controlling symptoms and preventing complications, as there is currently no cure. Monitoring is the approach for asymptomatic lesions without signs of progression.
Pain management often involves bisphosphonates, medications that reduce bone turnover and alleviate pain in many patients. Surgical interventions correct deformities and prevent or treat fractures. Procedures may include curettage (scraping out the abnormal tissue) followed by bone grafting, or the placement of metal rods and plates to stabilize weakened bones, especially the long bones. Patients with McCune-Albright Syndrome require additional treatment for specific endocrine issues, often involving specialists to manage conditions like precocious puberty or thyroid problems.