Polyostotic fibrous dysplasia (PFD) is caused by somatic activating mutations in the GNAS gene in the skeletal stem cells. This leads to the proliferation of immature osteogenic cells and replacement of the normal bone marrow with a fibro-osseous tissue. The lesions can result in deformity of the bones and fractures.

PFD may be mono- or polyostotic. Any part of the skeleton can be affected. The most commonly affected sites are the skull base and proximal parts of the femur. The femoral lesions are responsible for the most functional impairment [1] [2]. The lesions can be isolated or associated with hyperfunctioning endocrinopathies and café-au-lait skin spots called McCune-Albright syndrome [3] [4].

The spectrum of involvement in PFD ranges from two bones to 75% or more of the skeleton. In general, PFD is found in the tibia, femur, pelvic bones and the foot. Other sites may also be affected but less commonly, for example, the skull, ribs, and bones of the upper extremity. The lumbar spine, cervical spine, and clavicle are uncommonly affected.

Typical deformities observed in PFD include leg length discrepancies, rib deformities, and facial asymmetry.

The most common complication of PFD is fracture and it is detected in more than half of the cases with the polyostotic type of the disease [5]. The majority of patients (75%) with PFD have symptoms, including pain, deformities, and pathologic fractures [6].

Malignant transformation can occur but it is rare and the reported prevalence ranges from 0.4% to 4% [5]. The most common malignant tumors are chondrosarcoma, fibrosarcoma, and osteosarcoma. Most of the patients with malignancies are older than thirty years at the time of diagnosis. Generally, the craniofacial region is affected with the femur, tibia, and pelvis following. Polyostotic lesions have a higher rate of malignant transformation than monostotic lesions.

• Precocious Puberty

  Clinical findings Precocious puberty, polyostotic (cystic fibrous dysplasia) spontaneous fractures at young age, café-au-lait spots on skin, ovarian cysts. [medical-dictionary.thefreedictionary.com]

  Puberty — Albright's Syndrome with Precocious Puberty — Albright-Mccune-Sternberg Syndrome — Albright-Sternberg Syndrome — Albright's Syndrome — Syndrome, Albright's — Albright's Disease of Bone [mesh.kib.ki.se]

  Albright's syndrome is characterized by the combination of polyostotic fibrous dysplasia, precocious puberty and café-au-lait spots. [ncbi.nlm.nih.gov]

• Goiter

  A toxic multinodular goiter was also associated, but unique was the spontaneous normalization of the thyroid function. [ncbi.nlm.nih.gov]

  These include sexual precocity, espeCially in females (3, 4), goiter and/or hyperthyroidisr:n (4, 5), growth hormone (GH) hypersecretion (6), Cushing' disease (7) and ac-celerated skeletal growth (8). [docslide.com.br]

  Osteodystrophia fibrosa combined with precocious puberty and exophthalmic goiter. Am. J. Dis. Child. 63: 748, 1942. CrossRef Google Scholar 5. Moldawer M., Rabin E.R. Polyostotic fibrous dysplasia with thyrotoxicosis. Arch. Intern. [link.springer.com]

  The thyroid gland, a butterfly-shaped organ at the base of the neck, may become enlarged (a condition called a goiter) or develop masses called nodules. [ghr.nlm.nih.gov]

  Patients with McCune-Albright Syndrome may have other thyroid abnormalities, including thyroid enlargement (called a goiter), cysts, and nodules. [magicfoundation.org]

• Disability

  Lesions in weight-bearing bones can lead to disabling fractures, while lesions in the skull can lead to compression of vital structures such as cranial nerves. [clinicaltrials.gov]

  Polyostotic fibrous dysplasia leads to progressive and disabling deformity involving the proximal femur. Conventional methods of treatment have been ineffective in controlling this problem. [ncbi.nlm.nih.gov]

  Orthopaedic care may be necessary for disability resulting from pathologic fractures and bony overgrowth. Varying degree of mental retardation. Puberty is usually reached at 5 to 10 years of age. Predominantly in females (3:2). [whonamedit.com]

  Most lesions will be visible on a bone scan by age 5 years, and most functional disability will be present by age 10 years. The bone disease usually progresses during childhood and early adulthood, and becomes less active in later adulthood. [magicfoundation.org]

• Collapse

  More than 30 new chapters are included that reflect advances in the field, such as outcomes and evidence-based medicine, surgical management of nasal valve collapse and choanal atresia, immunology and allergy, allergic and non-allergic rhinitis, complications [books.google.com]

  Review of the radiographs revealed variable degrees of collapse of multiple dorsolumbar vertebrae with evidence of expansion and complete effacement of the trabecular pattern (Figure 6). [ijcasereportsandimages.com]

  Paraspinal soft-tissue extension and vertebral collapse are rare. Kyphotic deformity and spinal cord compression may occur. Degree of confidence Plain radiographs are highly specific when characteristic features are present in a lesion. [emedicine.medscape.com]

  […] the most common reported neurologic complications of fibrous dysplasia. [12] [13] [11] [16] In addition to vision changes and globe displacement, bony thickening of the skull, its bony canals and foramena, and adjacent sinuses may also produce sinus collapse [eyewiki.aao.org]

• Fatigue

  Cushing syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems. In people with McCune-Albright syndrome, Cushing syndrome occurs only before age 2. [ghr.nlm.nih.gov]

  Hyperthyroidism can cause anxiety, fatigue, prominence of the eyes, sweating, heart palpitations, unintended weight loss, and heat intolerance. Osteoporosis may be caused by or worsened by hyperthyroidism. [rarediseases.org]

• Dyspnea

  This report demonstrates that polyostotic dysplasia of the ribs may cause chest pain and dyspnea and present radiographically as a large mass. [dovepress.com]

  Of note, the CTA was performed in the Emergency Department due to the patient’s new onset complaint of dyspnea and anxiety. [healio.com]

• Malocclusion

  Symptoms can include long standing facial asymmetry, proptosis, orbital pain, diffuse headache, double vision, visual loss, hearing loss, malocclusion, cranial nerve palsies, or tearing. [4] Careful attention to facial symmetry, cranial nerve function [eyewiki.aao.org]

• Visual Impairment

  In patients with evidence of visual impairment and optic nerve encasement on imaging, therapeutic optic nerve decompression is advocated in efforts to preserve visual function. [eyewiki.aao.org]

  Neurological examination demonstrated impaired visual acuity and constricted visual field associated with both forehead and right side craniofacial deformity in the general examination. [surgicalneurologyint.com]

• Bone Pain

  RESULTS: All subjects reported marked reduction in bone pain and sustained increased mobility. The fracture rate decreased in most. Orthopedic insertion of intramedullary rods was successful with maintenance of rod position. [ncbi.nlm.nih.gov]

  We evaluated the response to oral Alendronate in a girl with severe MAS FD and observed improved quality of life with reduction of bone pain. Keywords Osteogenesis Imperfecta Bone Pain Pamidronate Fibrous Dysplasia Bisphosphonate Treatment 1. [ijpeonline.biomedcentral.com]

• Osteoporosis

  Osteoporosis International. 2003, 14 (6): 507-514. 10.1007/s00198-003-1399-y. View Article PubMed Google Scholar Solomon DH, Rekedal L, Cadarette SM: Osteoporosis treatments and adverse events. [ijpeonline.biomedcentral.com]

  Primary and secondary osteoporosis, symptomatic Paget disease of bone, osteogenesis imperfecta both in children and adults and fibrous dysplasia are currently the major indications for bisphospho-nates. [indianpediatrics.net]

  Calcium metabolism and 4 7 calcium kinetics before and after long-term thyrocalcitonin treatment in senile osteoporosis. Clin. Sci. 1970: 38, 397–407. Google Scholar 21. Ryan, W. G., Schwartz, T. B. [link.springer.com]

  著者 中島邦晴, 高橋晃, 松本里沙, 福村英信, 齋藤知行 cw 線維性骨形成異常, ｾﾝｲｾｲｺﾂｹｲｾｲｲｼﾞｮｳ, fibrous dysplasia of bone, 054505, *, 多発性疾患, ﾀﾊﾂｾｲｼｯｶﾝ, multiple disease, 057853, 骨粗鬆症治療薬, ｺﾂｿｼｮｳｼｮｳﾁﾘｮｳﾔｸ, drug for treatment of osteoporosis, 055153, 薬物療法, ﾔｸﾌﾞﾂﾘｮｳﾎｳ, drug therapy, 023545 [togodb.dbcls.jp]

• Leg Pain

  […] is a genetic disorder characterized by the association of: endocrinopathy: precocious puberty polyostotic fibrous dysplasia: more severe than in sporadic cases cutaneous pigmentation: coast of Maine ' cafe au lait ' spots Presentation is variable 1 : leg [radiopaedia.org]

  However, individuals with the polyostotic variant are more likely to present with leg pain, limp, or pathologic fractures. 3 On physical examination of the patient in this case, a painless asymmetry of the skull on the left vertex and left proptosis were [healio.com]

  She also had daily bone leg pains which caused frequent school absenteeism. She was in outpatient followup since she was 20 months old when it was noticed café-au-lait spots. [ijpeonline.biomedcentral.com]

• Cafe-Au-Lait Spots

  McCune-Albright syndrome ( MAS ) is a genetic disorder characterized by the association of: endocrinopathy: precocious puberty polyostotic fibrous dysplasia: more severe than in sporadic cases cutaneous pigmentation: coast of Maine ' cafe au lait ' spots [radiopaedia.org]

  When melanotic pigmentation (cafe-au-lait spots) and multiple endocrine hyperfunction are additionally associated it is referred to as albright syndrome ICD-9-CM Volume 2 Index entries containing back-references to 756.54 : [icd9data.com]

  It is characterized by a typical phenotype which includes polyostotic fibrodysplasia, precocious puberty independent from gonadotropins, cafe-au-lait spots and a series of endocrine abnormalities. [bone-abstracts.org]

  Other symptoms include: Bone fractures Deformities of the bones in the face Gigantism Irregular, large patchy cafe-au-lait spots There is no specific treatment for McCune-Albright syndrome. [medlineplus.gov]

  When melanotic pigmentation (CAFE-AU-LAIT SPOTS) and multiple endocrine hyperfunction are additionally associated it is referred to as Albright syndrome Note générale sur le champ d'application : sometimes Jaffe-Lichtenstein (usually monostotic) goes [idref.fr]

• Hyperpigmentation

  It is characterized by deformities and fractures of the bones, endocrine abnormalities including early puberty, and skin hyperpigmentation Fibrous dysplasia of bone affecting several bones. [icd9data.com]

  INTRODUCTION: Fibrous dysplasia (FD) is a disorder involving either one (monostotic) or several bones (polyostotic FD [PFD] and sometimes is associated with cafe- au -lait hyperpigmentation of the skin and one or more hyperfunctioning endocrinopathies [ncbi.nlm.nih.gov]

  THE McCUNE ALBRIGHT SYNDROME: THE McCUNE ALBRIGHT SYNDROME POLYOSTOTIC FIBROUS DYSPLASIA CUTANEOUS HYPERPIGMENTATION ENDOCRINE HYPERFUNCTION The Classic TRIAD ... [slideee.com]

  It is characterized by deformities and fractures of the bones, endocrine abnormalities including early puberty, and skin hyperpigmentation. Fibrous dysplasia of bone affecting several bones. [icd10data.com]

  Introduction McCune-Albright Syndrome (MAS) is a rare disease presenting with the classical triad of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots) and endocrine dysfunction, usually seen as precocious puberty in females [ijpeonline.biomedcentral.com]

• Confusion

  In any event, the amount of cartilage present in the lesion may lead to confusion in diagnosis and the lesion may be mistaken for a chondrosarcoma. [humpath.com]

  FD in the jaw may share several histological features with cemento ossifying fibromas, which can be confused with FD. The cemento ossifying fibroma lesions tend to behave more aggressively than do FD lesions. [ojrd.biomedcentral.com]

The cornerstones of diagnosis in PFD are imaging, and if needed, histological evaluation.

The first line in the workup is a plain radiograph. The diagnosis is straightforward in the presence of typical findings. Computed tomography (CT) scans are necessary to assess complex parts of the skeleton like the pelvis, spine, chest, and facial bones [7] [8] [9] [10].

Bone scintigraphy is of limited use in detecting subtle pathologic fractures. The features of a bone scan in fibrous dysplasia are non-specific. Magnetic resonance imaging (MRI) is required for the assessment of cord compression if the spine is involved [11] [12] [13].

On plain radiography, fibrous dysplasia is observed as a well-defined, intramedullary and expansile lesion in the metaphysis or diaphysis. Lesions can range from completely radiolucent to sclerotic, although, most lesions have the characteristic ground-glass appearance [6]. The underlying histopathology of the lesion correlates directly with the amount of haziness shown radiographically. Radiolucent parts are mainly composed of fibrous elements whereas radiopaque lesions have a larger proportion of woven bone.

These children were treated with a combination of drug treatment (bisphosphonates) and surgical treatment with elongating intramedullary rods (Sheffield) for management of femoral and tibial lesions. [ncbi.nlm.nih.gov]

These data have implications for long-term prognosis, clinical management, and interpretation of therapeutic interventions. [ncbi.nlm.nih.gov]

PROGNOSIS Biological Behavior • Benign tumor • Monostotic lesions have good prognosis • Polyostotic lesions tend to be more active or aggresive • Recurrence following curettage is common particularly when bone grafting the defect with autologous bone [tumorsurgery.org]

- progression of the disease is often erratic; - monostotic lesions : have good prognosis; - polyostotic lesions: - tend to remain more active or aggressive; - are known to occassionally undergo malignant transformation to osteosarcoma or fibrosarcoma [wheelessonline.com]

The prognosis is dependent upon the severity of the disorder Currently, there are no known methods to prevent Fibrous Dysplasia The types of Fibrous Dysplasia include: Monostotic Fibrous Dysplasia: When only a single bone is involved Polyostotic Fibrous [dovemed.com]

Bone is woven rather than lamellar and lacks osteoblastic rimming of trabeculae Treatment Monostotic : curettage and grafting, if symptomatic Polyostotic : symptomatic treatment May require osteotomy for deformity or lengthening / shortening procedures Prognosis [orthopaedicsone.com]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

[…] involve in 10% of the monostotic cases and 50–100% of polyostotic cases.[ 1 ] In the skull, FD can involve any bone but the most common site is the frontal bone followed by sphenoid, parietal, ethmoid, temporal, and occipital bones.[ 1 ] The genetic etiology [surgicalneurologyint.com]

Expanded sections on etiology, treatment, and diagnosis of oral cancer (HPV) describe how subtypes can play an important role in the development and natural history of some head and neck cancers, most notably those arising in the oropharynx. [books.google.com]

Etiology unknown Most common 3-15 years Fundamental abnormality is replacement of medullary bone by fibrous tissue Clinically Deformities Shepherd’s crook deformity of femur Bone pain Most commonly involved bones are pelvis, femora In widespread disease [learningradiology.com]

INTRODUCTION Mc Cune-Albright syndrome is a disease of unknown etiology consisting of polyostotic fibrous dysplasia of bone assoCiate.d with brown pigmented areas of the skin and several endocrine dysfunctions (1,2). [docslide.com.br]

Updated Molecular and Epidemiologic diagrams added to all new chapters. [books.google.com]

Epidemiology This disorder is usually diagnosed in childhood or early adulthood. Usual presentation is in children and adolescents, with a median onset age of 8 years. Fibrous dysplasia makes about 5% of all benign bone tumors. [boneandspine.com]

Metyrapone may also be used for treatment. [12] Epidemiology [ edit ] McCune–Albright syndrome is estimated to occur at a frequency between 1 person in 100,000 to 1 person in 1,000,000 individuals worldwide. [15] Notable cases [ edit ] Mauricio Saravia [en.wikipedia.org]

All cells descended from the mutated cell can manifest features of McCune-Albright syndrome. [ 3 ] Epidemiology McCune-Albright syndrome is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. [ 1 ] Gonadotrophin-independent precocious [patient.info]

Epidemiology Fibrous dysplasia represents about 5% of benign bone lesions [3] ; however, the true incidence is unknown, as many patients are asymptomatic. Monostotic fibrous dysplasia accounts for 75-80% of the cases. [emedicine.medscape.com]

Pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005;87:1848-1864. http://www.ncbi.nlm.nih.gov/pubmed/16085630 Lietman SA, Ding C, Levine MA. [rarediseases.org]

The role of type 1 and type 2 5’-deiodinase in the pathophysiology of the 3,5,3’-triiodothyronine toxicosis of McCune-Albright syndrome. [revista.rmu.org.uy]

Fibrous Dysplasia: Pathophysiology, evaluation and treatment. JB&JS [Internet]. Agust 2015;87-A(8). [revistamedicasinergia.com]

Pathophysiology Fibrous dysplasia is caused by the sporadic mutation of the GNAS1 gene. As a consequence of the mutation, there is a substitution of cysteine or histidine in amino acids of the osteoblastic cells, by arginine. [boneandspine.com]

"The Role of Type 1 and Type 2 5′-Deiodinase in the Pathophysiology of the 3,5,3′-Triiodothyronine Toxicosis of McCune-Albright Syndrome". The Journal of Clinical Endocrinology and Metabolism. 93 (6): 2383–2389. doi : 10.1210/jc.2007-2237. [en.wikipedia.org]

INTERPRETATION: In polyostotic fibrous dysplasia, multiple osteotomies and intramedullary nailing with neck cross-pinning can be used to correct developed or progressing shepherd's crook deformity, and to prevent recurrence and refracture. [ncbi.nlm.nih.gov]

Bisphosphonates are helpful in relieving bone pain, but it is no longer believed that they prevent progression of the disease. [en.wikipedia.org]

Currently, there are no specific methods or guidelines to prevent Fibrous Dysplasia, since it is a genetic condition Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic [dovemed.com]

Alendronate is at present indicated for use in prevention and treatment of osteoporosis and Paget’s disease. It should be used in conjunction with adequate amounts of vitamin D and calcium in the prevention of progressive loss of bone mass. [indianpediatrics.net]

But now, in hopes that her story might call attention to the need for increased resources for the study, treatment and prevention of rare diseases – and community support for children and families suffering from them – Gorbach has decided it’s time to [globalgenes.org]

1. Kelly MH, Brillante B, Kushner H, Gehron RP, Collins MT. Physical function is impaired but quality of life preserved in patients with fibrous dysplasia of bone. Bone. 2005;37(3):388-94.
2. Leet AI, Wientroub S, Kushner H, et al. The correlation of specific orthopaedic features of polyostotic fibrous dysplasia with functional outcome scores in children. J Bone Joint Surg Am. 2006;88(4):818-23.
3. Albright F, Butler AM, Hampton AO, Smith PH. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females, report of five cases. N Engl J Med. 1937;216:727-46.
4. McCune DJ. Osteitis fibrosa cystica; the case of a nine year old girl who also exhibits precocious puberty, multiple pigmentation of the skin and hyperthyroidism. Am J Dis Child. 1936;52:743-4.
5. Shah ZK, Peh WC, Koh WL, Shek TW. Magnetic resonance imaging appearances of fibrous dysplasia. Br J Radiol. 2005;78(936):1104-15.
6. Parekh SG, Donthineni-Rao R, Ricchetti E, Lackman RD. Fibrous dysplasia. J Am Acad Orthop Surg. 2004;12(5):305-13.
7. Bulakbasi N, Bozlar U, Karademir I, Kocaoglu M, Somuncu I. CT and MRI in the evaluation of craniospinal involvement with polyostotic fibrous dysplasia in McCune-Albright syndrome. Diagn Interv Radiol. 2008;14(4):177-81.
8. Unal Erzurumlu Z, Celenk P, Bulut E, Barıs YS. CT Imaging of Craniofacial Fibrous Dysplasia. Case Rep Dent. 2015;134123.
9. Atalar MH, Salk I, Savas R, Uysal IO, Egilmez H. CT and MR Imaging in a Large Series of Patients with Craniofacial Fibrous Dysplasia. Pol J Radiol. 2015;80:232-40.
10. An G, Gui L, Liu J, Niu F, Chen Y, Wang M. Treatment of fibrous dysplasia orbital deformities with digital imaging guidance. J Craniofac Surg. 2015;26(2):449-51.
11. Sood A, Raman R, Jhobta A, Dhiman DS, Seam RK. Normal technetium-99m-MDP uptake in fibrous dysplasia of the hip. Hell J Nucl Med. 2009 Jan-Apr; 12(1):72-3.
12. Bonekamp D, Jacene H, Bartelt D, Aygun N. Conversion of FDG-PET activity of fibrous dysplasia of the skull late in life mimicking metastatic disease. Clin Nucl Med. 2008;33(12):909-11.
13. Qu N, Yao W, Cui X, Zhang H. Malignant transformation in monostotic fibrous dysplasia: clinical features, imaging features, outcomes in 10 patients, and review. Medicine (Baltimore). 2015;94(3):e369.