Fibrous Dysplasia: Symptoms, Types, Causes and Treatment

Fibrous dysplasia is a rare bone disease that can affect people of any age, causing a unique set of symptoms, challenges, and management decisions. Whether it presents as a single bone lesion or a more complex, widespread condition, fibrous dysplasia can have a profound effect on quality of life. In this article, we’ll explore its symptoms, the different types, what causes it, and the latest evidence-based treatments, all grounded in the latest scientific research.

Symptoms of Fibrous Dysplasia

Fibrous dysplasia often develops insidiously, with symptoms ranging from silent bone changes to visible deformities and even serious complications. Recognizing these symptoms early can guide both patients and clinicians toward timely diagnosis and appropriate management.

Symptom	Description	Prevalence/Significance	Source
Bone Pain	Aching or throbbing pain, often chronic	Common in both monostotic and polyostotic forms; may prompt diagnosis	3 10 12
Deformity	Bowing, asymmetry, or swelling in affected bones	Leads to visible disfigurement, especially craniofacial involvement	1 3 6 7 13
Fractures	Pathological (bone breaks with minimal trauma)	Frequent in weight-bearing bones, especially femur and pelvis	3 10 12
Neurological Symptoms	Visual loss, hearing loss, nerve compression	More common in craniofacial involvement; can be acute or progressive	1 2 6 16
Skin Changes	Café-au-lait spots (pigmented patches)	Prominent in McCune-Albright syndrome (MAS)	5 7 12
Endocrine Dysfunction	Early puberty, thyroid, or other hormonal issues	Seen in polyostotic and MAS forms; can be subtle or severe	4 5 7 12

Table 1: Key Symptoms

Deeper Dive into Symptoms

Bone Pain and Fractures

Fibrous dysplasia often causes chronic bone pain. In some cases, pain is the first or only symptom, especially in the monostotic form. Fractures may occur, sometimes repeatedly, because the abnormal bone is structurally weaker than healthy bone. The risk is higher in weight-bearing bones such as the femur or pelvis, which can lead to limping and mobility issues 3 10 12.

Bone Deformity and Disfigurement

Over time, the replacement of normal bone with fibrous tissue causes bones to expand and deform. In the craniofacial region, this can result in noticeable facial asymmetry or swelling, which may be socially and psychologically distressing 1 6 13. Long bones may develop bowing, particularly in children as their bones grow.

Neurological and Sensory Effects

When fibrous dysplasia affects the skull or facial bones, it may compress nerves, leading to vision loss, hearing loss, or facial pain. Visual loss can be acute, especially if the bones near the optic nerve are involved. Other symptoms may include headaches, vestibular disorders, or sinus issues 1 2 6 16.

Skin and Hormonal Manifestations

In some patients, especially those with McCune-Albright syndrome, skin changes such as café-au-lait spots—irregularly bordered patches of hyperpigmentation—may be seen. These patients can also experience early puberty or other endocrine disturbances, including thyroid, adrenal, or growth hormone abnormalities 5 7 12.

Types of Fibrous Dysplasia

Fibrous dysplasia is not a one-size-fits-all disease. It includes a spectrum of forms, each with its own clinical features, risks, and prognosis.

Type	Main Features	Associated Conditions	Source
Monostotic FD	Single bone involvement	Most common form (~80-90%)	3 4 7 13
Polyostotic FD	Multiple bones, often unilateral	May be associated with endocrine or skin findings	4 5 7 12
Craniofacial FD	Affects skull and facial bones, can be mono/polyostotic	May cause sensory deficits, deformity	1 2 6 13
McCune-Albright Syndrome (MAS)	Polyostotic FD + skin hyperpigmentation + endocrine dysfunction	Severe, multi-system involvement	5 7 12
Mazabraud Syndrome	FD + intramuscular myxomas	Rare, often polyostotic	2 6 7

Table 2: Types of Fibrous Dysplasia

Understanding the Different Types

Monostotic Fibrous Dysplasia

This is the most common form, accounting for up to 90% of cases. It usually involves a single bone—often a rib, femur, tibia, or craniofacial bone. Many people with monostotic FD remain asymptomatic, discovering the disease incidentally during imaging for unrelated issues 3 4 7.

Polyostotic Fibrous Dysplasia

When multiple bones are affected, the disease is termed polyostotic. These cases are less common but tend to be more severe and are often diagnosed in childhood. The lesions are usually unilateral (on one side of the body) and may cause significant deformities, fractures, and functional impairment 4 5 7 12.

Craniofacial Fibrous Dysplasia

Craniofacial involvement is particularly significant, as it can affect vision, hearing, and facial structure. It may present as either monostotic or polyostotic disease but is often the most challenging to treat given the functional and cosmetic implications 1 2 6 13.

McCune-Albright Syndrome (MAS)

MAS is a classic triad: polyostotic fibrous dysplasia, café-au-lait skin spots, and hyperfunctioning endocrinopathies (such as precocious puberty, thyroid disease, or Cushing’s syndrome). It is caused by the same genetic mutation as FD but includes extra-skeletal features 5 7 12.

Mazabraud Syndrome

This rare syndrome combines fibrous dysplasia (typically polyostotic) with soft tissue myxomas (benign muscle tumors). It requires careful monitoring and multidisciplinary care 2 6 7.

Causes of Fibrous Dysplasia

Understanding the cause of fibrous dysplasia helps clarify why the disease behaves as it does and why it can be so variable in presentation.

Cause	Mechanism	Clinical Relevance	Source
GNAS Gene Mutation	Activating mutation (post-zygotic, somatic)	Triggers abnormal bone formation	3 9 11 12 13
Abnormal cAMP Signaling	Constitutive activation of adenylyl cyclase	Disrupts osteoblast differentiation	11 12 13
Increased IL-6	Promotes osteoclastic bone resorption	Worsens bone fragility and pain	10 11
Not Inherited	Occurs sporadically, not passed through families	Explains variable, mosaic distribution	7 11 12

Table 3: Causes of Fibrous Dysplasia

The Science Behind the Disease

Genetics and Molecular Pathways

Fibrous dysplasia is caused by a somatic (post-zygotic) activating mutation in the GNAS gene, which encodes the α-subunit of the stimulatory G protein (Gsα). This mutation leads to constitutive activation of adenylyl cyclase, an enzyme that increases cyclic AMP (cAMP) levels within cells 3 9 11 12 13.

Effects on Bone Cells

Elevated cAMP disrupts the normal maturation of osteoblasts, the cells responsible for forming bone. Instead of creating mature, strong (lamellar) bone, these cells produce immature, disorganized (woven) bone embedded in fibrous tissue. This abnormal bone is weak, prone to deformity and fracture 11 12 13.

Role of Interleukin-6

Mutated cells in FD also secrete more interleukin-6 (IL-6), a cytokine that stimulates osteoclasts—the cells responsible for bone resorption. This increases bone breakdown and further contributes to pain, deformity, and fracture risk 10 11.

Not an Inherited Disorder

Since the mutation occurs after conception, FD is not inherited and does not run in families. The timing and location of the mutation in embryonic development determine how many and which bones are involved, explaining the variability in disease severity and distribution 7 11 12.

Treatment of Fibrous Dysplasia

Managing fibrous dysplasia requires a tailored approach, balancing observation, medical therapy, and surgery depending on the form, symptoms, and risks for each patient.

Treatment Approach	Indication/Goal	Key Facts	Source
Observation	Asymptomatic or mild cases	Most monostotic lesions can be monitored	9 15
Bisphosphonates	Pain, fracture prevention, lesion stabilization	Reduces bone pain, may refill lesions	2 10 14
Surgery	Deformity correction, fracture prevention, nerve compression	Options include curettage, grafting, internal fixation, resection	4 9 15 16 17
Endocrine Management	MAS or polyostotic cases with hormonal issues	Requires multidisciplinary care	5 7 12

Table 4: Treatment Options

Treatment Strategies Explained

Observation and Monitoring

Most people with monostotic, asymptomatic fibrous dysplasia do not need active treatment. Regular check-ups, education about the disease, and imaging to monitor for changes are recommended 9 15.

Medical Therapy

Bisphosphonates (e.g., pamidronate) are anti-resorptive drugs shown to decrease bone pain, reduce fracture risk, and sometimes partially heal bone lesions. They work by inhibiting osteoclast activity, counteracting the increased bone resorption driven by IL-6 2 10 14. Not all patients respond, but many experience significant symptomatic relief.

Hormonal and Metabolic Management is vital for those with MAS or polyostotic disease accompanied by endocrine problems. Treatment may include hormone therapy for precocious puberty, thyroid medications, or other targeted interventions 5 7 12.

Surgical Options

Surgery is reserved for specific situations:

• Deformity Correction: Bowing or angular deformities, especially in weight-bearing bones, may require osteotomy (bone cutting and realignment) and internal fixation 4 9 15.
• Fracture Prevention/Treatment: Pathological fractures that do not heal or recurrent fractures may need surgical stabilization, often with metal rods or plates 9 15.
• Craniofacial Surgery: When facial bones are involved, surgery may address cosmetic or functional problems (e.g., vision or airway compromise). Techniques range from conservative remodeling to radical excision with reconstruction, sometimes using 3D-printed implants or alloplastic materials to restore bone structure 16 17.
• Grafting: Cortical bone grafts are preferred over cancellous grafts, as they are less likely to be resorbed by the abnormal FD tissue 4 9.

The choice between conservative and radical surgery depends on the extent of disease, patient age, location, and symptoms. In craniofacial FD, radical excision is often favored for monostotic cases, while conservative management is preferred in extensive polyostotic or MAS cases 16 17.

Conclusion

Fibrous dysplasia is a complex, variable bone disorder with a range of symptoms and management options. Here’s a summary of the key points covered:

• Symptoms: Include bone pain, deformity, fractures, sensory deficits, skin pigmentation, and hormonal disturbances.
• Types: Range from single-bone (monostotic) to multiple-bone (polyostotic) forms, with special subtypes like craniofacial FD, McCune-Albright, and Mazabraud syndromes.
• Causes: Arise from a post-zygotic activating mutation in the GNAS gene, leading to abnormal bone cell signaling and bone formation.
• Treatment: Is individualized—ranging from observation to medical therapy (especially bisphosphonates), and various surgical interventions, depending on severity and complications.

Fibrous dysplasia requires a multidisciplinary approach and long-term monitoring, but advances in understanding and modern therapies are improving the outlook for patients worldwide.