eMedicine Specialties > Orthopedic Surgery > Neoplasms

Fibrous Dysplasia

Author: Bernardo Vargas, MD, Consulting Staff, Department of Orthopedic Surgery, Hôpital Universitaire de Geneva, Switzerland
Coauthor(s): 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
Contributor Information and Disclosures

Updated: Aug 13, 2008

Introduction

Fibrous dysplasia of bone is a nonheritable disease in which abnormal tissue develops in place of normal bone. The etiology of this abnormal growth process is related to a mutation in the gene that encodes the subunit of a stimulatory G protein (Gsα) located on chromosome 20.1,2 As a consequence of this mutation, there is a substitution of the cysteine or the histidine—amino acids of the genomic DNA in the osteoblastic cells—by another amino acid, arginine.3 Consequently, the osteoblastic cells will elaborate a fibrous tissue in the bone marrow instead of normal bone.

Abnormalities may involve 1 bone in the monostotic form (70% of cases ) or many bones in the 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).4,5,6,7,8

History of the Procedure

The term fibrous dysplasia was suggested by Lichtenstein and Jaffe in 1942.9

Problem

In 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 risk  of fracture. Incidence of fractures is around  50% of cases.10 This risk of fractures or bone deformity is higher in the long bones, such as the 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.11 The incidence of this risk has been evaluated to be reduced to 1%.11,12 This risk is higher in patients with the polyostotic form, or McCune–Albright syndrome.12

Frequency

Fibrous dysplasia represents about 5% of all benign bone tumors.2 The monostotic form is more common than the polyostotic form. Many patients are asymptomatic, so 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.

Etiology

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.2 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. 

Pathophysiology

As a consequence of the mutation of GNAS1, there is a substitution of cysteine or histidine, amino acids of the genomic DNA in the osteoblastic cells, by another amino acid, arginine.3 Osteoblastic cells expressing this mutation have a higher DNA synthesis than normal bone cells. The growth of these cells is faster, leading to an inappropriate differentiation of mesenchymal cells. At the molecular level, intracellular cAMP levels are increased and osteocalcin is decreased.13 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.

Presentation

Pain is a common sign of fibrous dysplasia in symptomatic patients.14 Most commonly, patients are asymptomatic. Patients usually seek medical care because of either painful swelling and deformity or a pathologic fracture through a weakened bone. Long bones are  commonly affected. The femur is the most common localization. Other sites typically affected are the tibia, maxilla, and skull. Nonskeletal manifestations include abnormal cutaneous pigmentation, precocious puberty, hyperthyroidism, Cushing disease, hyperparathyroidism, and hypophosphatemic rickets. McCune-Albright syndrome is defined as the triad of precocious puberty, polyostotic fibrous dysplasia, and cutaneous pigmentation. Typically, only females are affected by precocious puberty, but the other endocrine abnormalities occur equally in males and females. All of these abnormalities are thought to be due to the same underlying mutation.

Indications

  • Surgical treatment of fibrous dysplasia is indicated in the prevention or treatment of fractures or major deformity.15 The most common surgical indications are fracture of a weight-bearing bone or a progressive disease.
  • Asymptomatic patients do not need treatment.
  • A needle biopsy can be performed if there is doubt about the diagnosis before the initial management.
  • Upper-extremity lesions rarely require surgical management. Nevertheless, vascularized bone grafting has been proposed.16
  • Several studies have shown that bisphosphonates are useful in alleviating chronic pain in patients with fibrous dysplasia,17,18,19,20 but further studies are necessary to confirm these promising results.

Relevant Anatomy

Fibrous dysplasia can affect almost any bone in the body. The relevant anatomy is that of the bone involved.

Contraindications

There are no specific contraindications to surgical intervention in patients with fibrous dysplasia. However, care must be used in the skeletally immature patient. Internal fixation of long bones with intramedullary nails may  be proposed.

More on Fibrous Dysplasia

Overview: Fibrous Dysplasia
Workup: Fibrous Dysplasia
Treatment: Fibrous Dysplasia
Follow-up: Fibrous Dysplasia
Multimedia: Fibrous Dysplasia
References
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References

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

  2. DiCaprio M. R., Enneking W. F. Fibrous Dysplasia. Pathophysiology, Evaluation, and Treatment. J Bone Joint Surg Am. 2005;87:1848-1864. [Medline].

  3. Marie P. Dysplasie fibreuse : aspects tissulaires, cellulaires et moléculaires. Revue du rhumatisme. 2003;7:681–686.

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

  5. Fraser WD, Walsh CA, Birch MA. Parathyroid hormone-related protein in the aetiology of fibrous dysplasia of bone in the McCune Albright syndrome. Clin Endocrinol. 2000;53(5):621-8. [Medline].

  6. Parekh S, Donthineni-Rao R, Ricchetti E. Fibrous dysplasia. J Am Acad Orthop Surg. 2004;12:305-313. [Medline].

  7. 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].

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

  9. 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.

  10. Ippolito E. Bray E. W., Corsic A. et als. Natural history and treatment of fibrous dysplasia of bone:a multicenter clinicopathologic study promoted by the European Pediatric Orthopaedic Society. J of Ped Orthop Part B. 2003,;12:155–177. [Medline].

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

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

  13. Marie PJ, de Pollak C, Chanson P, Lomri A. Increased Proliferation of Osteoblastic CellsExpressing the Activating Gsa Mutation in Monostotic and Polyostotic Fibrous Dysplasia. Am J Pathol. 1997;150:1059-1069. [Medline].

  14. 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. May 1998;80(5):648-58. [Medline].

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

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

  17. 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;Volume 35, Issue 1:235-242. [Medline].

  18. Liens D, Delmas PD, Meunier PJ:. Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet. 1994;343:953-954. [Medline].

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

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

  21. Lietman SA, Ding C, Levine MA. A. 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;87:2489-2494. [Medline].

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

  23. Bridge JA, Rosenthal H, Sanger W. Desmoplastic fibroma arising in fibrous dysplasia. Clin Orthop. 1998;247:272-8. [Medline].

  24. 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.

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Further Reading

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Keywords

fibrous dysplasia, bone dysplasia, osteochondrodysplasia, Albright disease, bone disease, dysplasia, fibrous dysplasia of bone, fibrous dysplasia bone, cherubism, dysplastic disorder, connective tissue, fibroosseous tissue, lamellar bone, monostotic fibrous dysplasia, polyostotic fibrous dysplasia, precocious puberty, skin pigmentation, McCune-Albright syndrome, Mazabraud syndrome, McCune-Albright's syndrome, Mazabraud's syndrome, Albright's disease, Albright syndrome, Albright's syndrome

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Contributor Information and Disclosures

Author

Bernardo Vargas, MD, Consulting Staff, Department of Orthopedic Surgery, Hôpital Universitaire de Geneva, Switzerland
Disclosure: Nothing to disclose.

Coauthor(s)

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 and Australian Orthopaedic Association
Disclosure: Orthopedics hyperguide Honoraria Independent contractor; Stryker Grant/research funds Employment

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Sean P Scully, MD, PhD, Professor, Department of Orthopedics, University of Miami
Sean P Scully, MD, PhD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, International Society on Thrombosis and Haemostasis, and Society of Surgical Oncology
Disclosure: Nothing to disclose.

CME Editor

Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital
Dinesh Patel, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of Physicians of Indian Origin, American College of International Physicians, and American College of Surgeons
Disclosure: Nothing to disclose.

Chief Editor

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 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, and Arkansas Medical Society
Disclosure: Nothing to disclose.

 
 
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