OVERVIEW

What is polyostotic fibrous dysplasia?

Polyostotic fibrous dysplasia, classified as a G-protein disease, is a rare disorder caused by somatic mutations, also known as polyostotic fibrous dysplasia or McCune-Albright syndrome. The condition was first described by McCune (1936) and Albright (1937), hence the eponymous naming.

The classic manifestations of this disease include three major features: polyostotic fibrous dysplasia (such as bone pain, deformities, and fractures), café-au-lait skin pigmentation, and precocious puberty. It may also be accompanied by various endocrine hyperfunctions (e.g., obesity, hyperthyroidism, Cushing's syndrome, acromegaly, hyperparathyroidism, and hyperprolactinemia) as well as non-endocrine manifestations (e.g., liver abnormalities such as abnormal liver enzymes, neonatal jaundice, and cholestasis; cardiac issues such as cardiomegaly, myocardial hypertrophy, persistent tachycardia, and sudden death; renal disorders such as hyperphosphaturia, hypophosphatemic rickets, and osteomalacia).

Currently, there is no cure for this disease, and treatment is limited to symptomatic management.

Is polyostotic fibrous dysplasia common?

No.

Polyostotic fibrous dysplasia is uncommon, classified as a rare disease, and currently lacks comprehensive epidemiological data on its incidence.

SYMPTOMS

What are the common symptoms and manifestations of polyostotic fibrous dysplasia?

The typical triad of polyostotic fibrous dysplasia includes: polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty.

• Polyostotic fibrous dysplasia: Lesions may involve bones throughout the body, where normal bone tissue and marrow are replaced by abnormal fibrous tissue, leading to bone pain, limb movement disorders, facial and limb deformities, fractures, and even skull lesions affecting nerves, potentially causing blindness and deafness.

• Café-au-lait skin pigmentation: This is often the first sign of the disease. The lesions have irregular borders (described as "coast of Maine" borders) and typically appear as small patches, usually unilateral and not crossing the midline. They are commonly found on the back but may also appear on the lips, neck, lower back, buttocks, and thighs. The pigmentation may be faint at birth but darkens and spreads with age or sun exposure. Some patients may develop oral mucosal freckle-like nevi as they grow older.

• Precocious puberty: In females, normal sexual development follows a sequence after puberty onset: body shape changes → pelvic widening → breast development → pubic and axillary hair growth → menstruation → ovulation. Normally, breast development precedes menarche by 1.5–3 years. In this condition, precocious puberty is characterized by menarche occurring before breast development or with an interval of less than 1.5 years, while pubic and axillary hair growth is delayed. In males, precocious puberty manifests as early sperm production, testicular enlargement, and secondary sexual characteristics; bilateral or unilateral macroorchidism is common.

What are the manifestations of endocrine hyperfunction associated with polyostotic fibrous dysplasia?

• Obesity;

• Hyperthyroidism: Often presents as thyroid enlargement and multiple thyroid nodules (usually benign), but classic hyperthyroidism symptoms like heat intolerance, sweating, palpitations, and weight loss are uncommon;

• Cushing syndrome: Bilateral nodular adrenal cortical hyperplasia may occur in early infancy, preceding precocious puberty. Clinical manifestations are atypical, lacking obvious moon face or striae. In children, Cushing syndrome mainly presents as growth retardation;

• Acromegaly;

• Hyperprolactinemia;

• Hyperparathyroidism.

What non-endocrine manifestations can polyostotic fibrous dysplasia present?

Polyostotic fibrous dysplasia may adversely affect cardiac, renal, and hepatic functions, as follows:

• Kidneys: Hyperphosphaturia, hypophosphatemic rickets, or osteomalacia.

• Liver: Abnormal liver enzymes, neonatal jaundice, biliary abnormalities, cholestasis.

• Heart: Cardiomegaly, myocardial hypertrophy, persistent tachycardia, and sudden death.

CAUSES

What is the cause of polyostotic fibrous dysplasia?

Polyostotic fibrous dysplasia is not hereditary. The disease occurs due to acquired mutations in the Gsα (stimulatory G protein α-subunit) gene. Cells with these mutations proliferate and differentiate uncontrollably, leading to excessive growth of abnormal fibrous tissue, which results in bone lesions. Overproduction of skin melanin causes café-au-lait spots, while hyperplasia and hypertrophy of endocrine gland cells lead to corresponding endocrine disorders.

Who is more likely to develop polyostotic fibrous dysplasia?

Polyostotic fibrous dysplasia can occur at any age, but most cases develop before the age of 30, with an average onset age of 8. It affects both males and females, but is more common in women, with a male-to-female ratio of 1:3 to 1:6.

Is polyostotic fibrous dysplasia contagious?

No.

Polyostotic fibrous dysplasia is not contagious. It is caused by acquired genetic mutations.

Is polyostotic fibrous dysplasia hereditary?

No.

Polyostotic fibrous dysplasia is not hereditary. It is caused by acquired somatic (not germline) gene mutations and is considered a rare disease.

DIAGNOSIS

How is polyostotic fibrous dysplasia diagnosed?

When diagnosing polyostotic fibrous dysplasia, doctors primarily rely on the triad of bone lesions, skin pigmentation (café-au-lait spots), and precocious puberty, along with accompanying endocrine disorders or abnormalities outside the endocrine system, as well as features such as Gsα gene mutations.

What tests are needed for polyostotic fibrous dysplasia?

Generally, biochemical tests, endocrine function tests, imaging studies, pathological examinations, and genetic testing are required.

• Biochemical tests: Primarily used to assist in diagnosis, including liver function, kidney function, blood glucose, blood calcium, blood phosphorus, alkaline phosphatase, 24-hour urine calcium, and urine phosphorus.

• Endocrine function tests: Primarily used to assist in diagnosis, including sex hormones, cortisol, adrenocorticotropic hormone, thyroid function, growth hormone, and parathyroid hormone.

• Imaging studies: Primarily used to assist in diagnosis, including X-rays, CT scans, MRI, bone density tests, and isotope bone scans.

• Pathological examinations: Primarily used to assist in diagnosis, involving bone biopsy.

• Genetic testing: Primarily used to assist in diagnosis, detecting Gsα gene mutations.

TREATMENT

Which department should I visit for polyostotic fibrous dysplasia?

Endocrinology.

Can polyostotic fibrous dysplasia heal on its own?

No.

Polyostotic fibrous dysplasia cannot heal on its own and requires lifelong treatment.

How is polyostotic fibrous dysplasia treated?

The treatment of polyostotic fibrous dysplasia is primarily symptomatic, meaning it addresses the patient's specific and prominent issues with targeted therapies.

• Treatment for bone lesions:

  • Bisphosphonates are effective in inhibiting bone disease. Etidronate is the preferred choice, administered orally at 20 mg per kilogram of body weight daily for 6 months to 1 year.

  • For severe cases, pamidronate may be used intravenously at 1 mg per kilogram of body weight daily for 3 days, repeated every 3 months. The interval between treatments can be gradually extended as symptoms improve.

  • For patients with severe limb deformities, osteotomy and correction surgery may be performed, or the affected bone may be curetted and treated with bone grafting and internal fixation.

• Treatment for precocious puberty and delayed epiphyseal closure: Medications such as hydroxyprogesterone, medroxyprogesterone, megestrol, testolactone, or tamoxifen may be used as needed.

• Treatment for hyperpigmented patches: Currently, there is no effective treatment for the hyperpigmented patches associated with polyostotic fibrous dysplasia.

• Treatment for other associated conditions: Such as Cushing's syndrome or acromegaly, which should be managed according to the relevant disease guidelines.

Can polyostotic fibrous dysplasia be completely cured?

No.

Polyostotic fibrous dysplasia cannot be cured. Current treatments only address the patient's specific symptoms.

DIET & LIFESTYLE

Does polyostotic fibrous dysplasia affect fertility?

Patients with polyostotic fibrous dysplasia have reproductive function and it generally does not affect fertility.

What should patients with polyostotic fibrous dysplasia pay attention to in daily life?

• This is a rare disease. Once diagnosed, in addition to active treatment, patients should focus on nutritional supplementation and maintain a healthy diet, avoiding overeating. For obese patients, dietary control may be necessary.

• For those with limb disabilities, appropriate exercise should be performed under family supervision to prevent falls.

• Family members should closely monitor changes in the patient's condition and ensure strict adherence to medical instructions regarding medication.

PREVENTION

Can Polyostotic Fibrous Dysplasia Be Prevented?

Currently, there are no clear and effective measures to prevent the occurrence of polyostotic fibrous dysplasia.