Orthopedic Surgery for Fibrous Dysplasia

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Fibrous dysplasia (a term first suggested by Lichtenstein and Jaffe in 1942 [1] ) of bone is a nonheritable disease in which abnormal tissue develops in place of normal bone. [2] Abnormalities may involve a single bone (monostotic form; % of cases) or many bones (polyostotic form; 30% of cases). The polyostotic form is occasionally associated with precocious puberty, fibrous dysplasia, and cafe-au-lait skin lesions (McCune-Albright syndrome, Albright syndrome) or with myxomas of skeletal muscle (Mazabraud syndrome). [3, 4, 5, 6, 7]

The etiology of this abnormal process is related to a mutation in the gene that encodes the subunit of a stimulatory G protein (Gsα) located on chromosome 20. [8, 9] As a consequence of this mutation, a substitution occurs in which the cysteine or the histidine—amino acids of the genomic DNA in the osteoblastic cells—is replaced by arginine. [10]  

Fibrous dysplasia lesions are characterized by woven ossified tissue and extensive marrow fibrosis. Mechanical quality of bones is decreased. As a consequence of this bone fragility, patients have an increased (~50%) risk of fracture. [11]  This risk of fractures or bone deformity is higher in the long bones (eg, femur, tibia, and humerus), but all the bones can be affected.

Pain is a common symptom of patients with fibrous dysplasia. Patients also have an increased risk of malignant tumors such as osteosarcoma, fibrosarcoma, chondrosarcoma, and malignant fibrohistiocytoma. [12]  The incidence of this risk has been evaluated to be reduced to 1%. [12, 13]  The risk is higher in patients with the polyostotic form, or McCune-Albright syndrome. [13]

As a consequence of the mutation of GNAS1 (see Etiology), there is a substitution in which cysteine or histidine (amino acids of the genomic DNA in the osteoblastic cells) is replaced by another amino acid, arginine. [10]

Osteoblastic cells expressing this mutation have a higher DNA synthesis than normal bone cells. The of these cells is faster, leading to an inappropriate differentiation of mesenchymal cells. At the molecular level, intracellular cyclic adenosine monophosphate (cAMP) levels are increased and osteocalcin is decreased. [14] Osteocalcin is a late marker of osteoblast differentiation. Involved bone cells are immature. They fail to produce normal amounts of collagen or to orientate appropriately to the lines of mechanical stress.

Fibrous dysplasia is caused by the sporadic mutation of the GNAS1 gene, which encodes the alpha subunit of the stimulatory G protein (G1) located on chromosome 20q13.2-13.3 of the osteoblastic cells. [9]  Although the mutation is known, the actual pathways that lead to abnormal osteoblast differentiation and function are just beginning to be understood.

The consequence of this mutation is an inappropriate cell differentiation resulting in a disorganized fibrotic bone matrix. Cancellous bone maintenance is perturbed, and bone undergoing physiologic remodeling is replaced by an abnormal proliferation of fibrous tissue. 

The extent and pattern of disease depend on the stage of development and the location at which the mutation occurs. All the bones can be affected.

Fibrous dysplasia accounts for about 5% of all benign bone tumors. [9] The monostotic form is more common than the polyostotic form. Because many patients are asymptomatic, the true incidence of this disorder is unknown. Usually, fibrous dysplasia presents clinically in children and adolescents, with a median onset age of 8 years. Most cases manifest themselves before the age of 30 years. Males are affected more often than females, except in McCune-Albright syndrome, in which females are affected more often than males.

Monostotic fibrous dysplasia is active while it is growing but often becomes inactive after puberty. It may reactivate during pregnancy. Polyostotic disease typically remains active throughout life.

Unless malignant transformation develops, fibrous dysplasia is not a life-threatening disease. The lesions tend to stabilize as skeletal maturity is reached. The majority of the monostotic cases have a good evolution regardless of treatment. Polyostotic disease tends to have a poorer prognosis. [15]  Polyostotic lesions are very often associated with one or more fractures. [16]  Malignant transformation develops in a minority of patients (< 0.5%).

The recurrence rate for fibrous dysplasia has been reported to be 21% after curettage and grafting, but if patients are monitored for many years, the rate is probably closer to 100%.

Lichtenstein L, Jaffe HL. Fibrous dysplasia of bone: a condition affecting one, several or many bones, the graver cases of which may present abnormal pigmentation of skin, premature sexual development, hyperthyroidism or still other extraskeletal abnormalities. Arch Pathol. 1942. 33:777-816.

Florez H, Peris P, Guañabens N. Fibrous dysplasia. Clinical review and therapeutic management. Med Clin (Barc). 2016 Dec 16. 147 (12):547-553. [Medline].

Albright F, Butler AM, Hampton AO. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females. N Engl J Med. 1937. 216:727-46.

Fraser WD, Walsh CA, Birch MA, Durham B, Dillon JP, McCreavy D, et al. Parathyroid hormone-related protein in the aetiology of fibrous dysplasia of bone in the McCune Albright syndrome. Clin Endocrinol (Oxf). 2000 Nov. 53 (5):621-8. [Medline].

Parekh SG, Donthineni-Rao R, Ricchetti E, Lackman RD. Fibrous dysplasia. J Am Acad Orthop Surg. 2004 Sep-Oct. 12 (5):305-13. [Medline].

Santos CT, Choo CT, Loh AH. Orbital fibrous dysplasia with soft tissue hamartoma–a variant of Mazabraud’s syndrome. Orbit. 2008. 27 (3):207-9. [Medline].

Chapurlat RD, Orcel P. Fibrous dysplasia of bone and McCune-Albright syndrome. Best Pract Res Clin Rheumatol. 2008 Mar. 22 (1):55-69. [Medline].

Alman BA, Greel DA, Wolfe HJ. Activating mutations of Gs protein in monostotic fibrous lesions of bone. J Orthop Res. 1996 Mar. 14 (2):311-5. [Medline].

DiCaprio MR, Enneking WF. Fibrous dysplasia. Pathophysiology, evaluation, and treatment. J Bone Joint Surg Am. 2005 Aug. 87 (8):1848-64. [Medline].

Marie P. Dysplasie fibreuse: aspects tissulaires, cellulaires et moléculaires. Revue du Rhumatisme. 2003. 7:681-6.

Ippolito E, Bray EW, Corsi A, De Maio F, Exner UG, Robey PG, et al. Natural history and treatment of fibrous dysplasia of bone: a multicenter clinicopathologic study promoted by the European Pediatric Orthopaedic Society. J Pediatr Orthop B. 2003 May. 12 (3):155-77. [Medline].

Ruggieri P, Sim FH, Bond JR, Unni KK. Malignancies in fibrous dysplasia. Cancer. 1994 Mar 1. 73 (5):1411-24. [Medline].

Yabut SM Jr, Kenan S, Sissons HA, Lewis MM. Malignant transformation of fibrous dysplasia. A case report and review of the literature. Clin Orthop Relat Res. 1988 Mar. 228:281-9. [Medline].

Marie PJ, de Pollak C, Chanson P, Lomri A. Increased proliferation of osteoblastic cells expressing the activating Gs alpha mutation in monostotic and polyostotic fibrous dysplasia. Am J Pathol. 1997 Mar. 150 (3):1059-69. [Medline]. [Full Text].

Benhamou J, Gensburger D, Messiaen C, Chapurlat R. Prognostic Factors From an Epidemiologic Evaluation of Fibrous Dysplasia of Bone in a Modern Cohort: The FRANCEDYS Study. J Bone Miner Res. 2016 Dec. 31 (12):2167-2172. [Medline].

Guille JT, Kumar SJ, MacEwen GD. Fibrous dysplasia of the proximal part of the femur. Long-term results of curettage and bone-grafting and mechanical realignment. J Bone Joint Surg Am. 1998 May. 80 (5):648-58. [Medline].

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. 52:743-747.

Bridge JA, Rosenthal H, Sanger WG, Neff JR. Desmoplastic fibroma arising in fibrous dysplasia. Chromosomal analysis and review of the literature. Clin Orthop Relat Res. 1989 Oct. 247:272-8. [Medline].

Lietman SA, Ding C, Levine MA. A highly sensitive polymerase chain reaction method detects activating mutations of the GNAS gene in peripheral blood cells in McCune-Albright syndrome or isolated fibrous dysplasia. J Bone Joint Surg Am. 2005 Nov. 87 (11):2489-94. [Medline].

Liens D, Delmas PD, Meunier PJ. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet. 1994 Apr 16. 343 (8903):953-4. [Medline].

Murray DJ, Edwards G, Mainprize JG, Antonyshyn O. Advanced in the management of fibrous dysplasia. J Plast Reconstr Aesthet Surg. 2008 Aug. 61 (8):906-16. [Medline].

Li P, Zhang ZR, Jiang Y, Xia XD, Wang D, Li XF. MR and CT findings of cyst degeneration of sphenoid bone in McCune-Albright syndrome: a case report. Cases J. 2009 Dec 22. 2:9376. [Medline]. [Full Text].

Zhang L, He Q, Li W, Zhang R. The value of 99mTc-methylene diphosphonate single photon emission computed tomography/computed tomography in diagnosis of fibrous dysplasia. BMC Med Imaging. 2017 Jul 24. 17 (1):46. [Medline]. [Full Text].

Ferreira EC, Brito CC, Domingues RC, Bernardes M, Marchiori E, Gasparetto EL. Whole-body MR imaging for the evaluation of McCune-albright syndrome. J Magn Reson Imaging. 2010 Mar. 31 (3):706-10. [Medline].

Fusconi M, Conte M, Pagliarella M, De Vincentiis C, De Virgilio A, Benincasa AT, et al. Fibrous dysplasia of the maxilla: diagnostic reliability of the study image. Literature review. J Neurol Surg B Skull Base. 2013 Dec. 74 (6):364-8. [Medline]. [Full Text].

Zhang X, Chen C, Duan H, Tu C. Radiographic classification and treatment of fibrous dysplasia of the proximal femur: 227 femurs with a mean follow-up of 6 years. J Orthop Surg Res. 2015 Nov 16. 10:171. [Medline]. [Full Text].

Stanton RP, Diamond L. Surgical management of fibrous dysplasia in McCune-Albright syndrome. Pediatr Endocrinol Rev. 2007 Aug. 4 Suppl 4:446-52. [Medline].

Kumta SM, Leung PC, Griffith JF, Kew J, Chow LT. Vascularised bone grafting for fibrous dysplasia of the upper limb. J Bone Joint Surg Br. 2000 Apr. 82 (3):409-12. [Medline].

Chapurlat RD, Hugueny P, Delmas PD, Meunier PJ. Treatment of fibrous dysplasia of bone with intravenous pamidronate: long-term effectiveness and evaluation of predictors of response to treatment. Bone. 2004 Jul. 35 (1):235-42. [Medline].

Zacharin M, O’Sullivan M. Intravenous pamidronate treatment of polyostotic fibrous dysplasia associated with the McCune Albright syndrome. J Pediatr. 2000 Sep. 137 (3):403-9. [Medline].

DiMeglio LA. Bisphosphonate therapy for fibrous dysplasia. Pediatr Endocrinol Rev. 2007 Aug. 4 Suppl 4:440-5. [Medline].

Majoor BC, Appelman-Dijkstra NM, Fiocco M, van de Sande MA, Dijkstra PS, Hamdy NA. Outcome of Long-Term Bisphosphonate Therapy in McCune-Albright Syndrome and Polyostotic Fibrous Dysplasia. J Bone Miner Res. 2017 Feb. 32 (2):264-276. [Medline].


Kim YH, Song JJ, Choi HG, Lee JH, Oh SH, Chang SO, et al. Role of surgical management in temporal bone fibrous dysplasia. Acta Otolaryngol. 2009 Dec. 129 (12):1374-9. [Medline].

Tomasik P, Spindel J, Miszczyk L, Chrobok A, Koczy B, Widuchowski J, et al. Surgical treatment of dysplasia fibrosa and defectus fibrosus with bone allografts. Ortop Traumatol Rehabil. 2010 Jan-Feb. 12 (1):58-66. [Medline].

Gui H, Zhang S, Shen SG, Wang X, Bautista JS, Voss PJ. Real-time image-guided recontouring in the management of craniofacial fibrous dysplasia. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Dec. 116 (6):680-5. [Medline].

Tham T, Costantino P, Bruni M, Langer D, Boockvar J, Singh P. Multiportal Combined Transorbital and Transnasal Endoscopic Resection of Fibrous Dysplasia. J Neurol Surg Rep. 2015 Nov. 76 (2):e291-6. [Medline]. [Full Text].

Bernardo Vargas, MD Consulting Staff, Department of Orthopedic Surgery, University Hospital of Geneva, Switzerland

Disclosure: Nothing to disclose.

Mark Clayer, MD, MBBS, FRACS, FAOrthA Head of Musculoskeletal Tumor Service, Department of Orthopaedics and Trauma, Queen Elizabeth Hospital; Senior Visiting Medical Specialist, Royal Adelaide Hospital and Women’s and Children’s Hospital, Australia

Mark Clayer, MD, MBBS, FRACS, FAOrthA is a member of the following medical societies: Australian Medical Association, Australian Orthopaedic Association

Disclosure: Received honoraria from Orthopedics hyperguide for independent contractor; Received grant/research funds from Stryker for employment.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug

Disclosure: Received salary from Medscape for employment. for: Medscape.

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine; Clinical Professor of Surgery, Nova Southeastern School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, Arkansas Medical Society, Florida Medical Association, Florida Orthopaedic Society

Disclosure: Nothing to disclose.

Howard A Chansky, MD Associate Professor, Department of Orthopedics and Sports Medicine, University of Washington Medical Center

Howard A Chansky, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Orthopedic Surgery for Fibrous Dysplasia

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