Skip to main content

Advertisement

Log in

Current approach to fibrous dysplasia of bone and McCune–Albright syndrome

  • Current Concept Review
  • Published:
Journal of Children's Orthopaedics

Abstract

Fibrous dysplasia (FD) of bone is an uncommon disease caused by sporadic, congenital mutations in the cAMP regulating protein, Gsα. It is an example of somatic mosaicism in which a wide spectrum of disease is possible. Widespread skeletal involvement is often associated with varying combinations of café-au-lait skin spots, and/or endocrine dysfunction (precocious puberty, renal phosphate wasting, hyperthyroidism, and/or growth hormone excess). Unrecognized and untreated endocrine dysfunction can exacerbate the skeletal disease. The diagnosis is usually established on clinical grounds on the basis of physical examination and typical radiographic appearance. Occasionally, gene testing of affected tissue may be helpful. The skeletal sites involved with disease are established at an early age, and the complications of fracture deformity are most pronounced in childhood. Bone pain in the absence of a fracture is more common in adults, but can also be present in children. Treatment with bisphosphonates is usually effective at relieving pain, but probably has no effect on the natural history of the disease. Scoliosis, which was previously thought to be an uncommon occurrence, has been shown to be common and progressive, and as such, warrants investigation and, when necessary, surgical treatment. The surgical management of FD remains challenging. Timing and technique remain controversial, but some consensus exists in that grafting materials (of any type) usually fail and should not be a central aspect of the surgical approach. Intramedullary devices are in general superior to side plates and screws. In extremely widespread disease with very early fracture and deformity, no surgical approach will affect final functional outcome. Efforts should be made for the initiation of international collaborative studies to better define optimal surgical approaches to the treatment of this challenging disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. McCune DJ (1936) 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 52:743–744

    Google Scholar 

  2. Albright F, Butler AM, Hampton AO, Smith P (1937) Syndrome characterized by osteitis fibrosa disseminata, areas, of pigmentation, and endocrine dysfunction, with precocious puberty in females: report of 5 cases. N Engl J Med 216:727–746

    Article  Google Scholar 

  3. Lichtenstein L (1938) Polyostotic fibrous dysplasia. Arch Surg 36:874–898

    Article  Google Scholar 

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

    Google Scholar 

  5. Dorfman HD, Czerniak B (1998) Fibroosseous lesions. In: Dorfman HD, Czerniak B (eds) Bone tumors. Mosby, St. Louis, pp 441–491

  6. Collins MT, Bianco P (2003) Fibrous dysplasia. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 5th edn. American Society for Bone and Mineral Research, Washington D.C., pp 466–470

  7. Bianco P, Robey PG, Wientroub S (2003) Fibrous dysplasia. In: Glorieux FH, Pettifor J, Juppner H (eds) Pediatric bone: biology and disease. Academic Press/Elsevier, New York, pp 509–539

  8. Henschen F, Fallvon H (1926) Osteitis fibosa with multiple tumors in the musculature. Verh Dtsch Ges Pathol 21:93–97

    Google Scholar 

  9. Mazabraud A, Girard J (1957) A peculiar case of fibrous dysplasia with osseous and tendinous localizations. Rev Rhum Mal Osteoartic 24:652–659

    CAS  Google Scholar 

  10. Campanacci M (1999) Bone and soft tissue tumors: clinical features, imaging, pathology, and treatment, 2nd edn. Springer, Berlin Heidelberg New York

  11. Bianco P, Kuznetsov SA, Riminucci M, Fisher LW, Spiegel AM, Robey PG (1998) Reproduction of human fibrous dysplasia of bone in immunocompromised mice by transplanted mosaics of normal and Gsalpha-mutated skeletal progenitor cells. J Clin Invest 101:1737–1744

    Article  CAS  Google Scholar 

  12. Bianco P, Robey P (1999) Diseases of bone and the stromal cell lineage. J Bone Miner Res 14:336–41

    Article  CAS  Google Scholar 

  13. Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192

    Article  CAS  Google Scholar 

  14. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM (1991) Activating mutations of the stimulatory G protein in the McCune–Albright syndrome (see comments). N Engl J Med 325:1688–1695

    Article  CAS  Google Scholar 

  15. Schwindinger WF, Francomano CA, Levine MA (1992) Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune–Albright syndrome. Proc Natl Acad Sci USA 89:5152–5156

    Article  CAS  Google Scholar 

  16. Alman BA, Greel DA, Wolfe HJ (1996) Activating mutations of Gs protein in monostotic fibrous lesions of bone. J Orthop Res 14:311–315

    Article  CAS  Google Scholar 

  17. Riminucci M, Fisher LW, Shenker A, Spiegel AM, Bianco P, Gehron Robey P (1997) Fibrous dysplasia of bone in the McCune–Albright syndrome: abnormalities in bone formation (see comments). Am J Pathol 151:1587–1600

    CAS  Google Scholar 

  18. Riminucci M, Liu B, Corsi A, Shenker A, Spiegel AM, Robey PG, Bianco P (1999) The histopathology of fibrous dysplasia of bone in patients with activating mutations of the Gs alpha gene: site-specific patterns and recurrent histological hallmarks. J Pathol 187:249–258

    Article  CAS  Google Scholar 

  19. Corsi A, De Maio F, Ippolito E, Cherman N, Gehron Robey P, Riminucci M, Bianco P (2006) Monostotic fibrous dysplasia of the proximal femur and liposclerosing myxofibrous tumor: which one is which? J Bone Miner Res 21:1955–1958

    Article  Google Scholar 

  20. Akintoye SO, Chebli C, Booher S, Feuillan P, Kushner H, Leroith D, Cherman N, Bianco P, Wientroub S, Robey PG, Collins MT (2002) Characterization of gsp-mediated growth hormone excess in the context of McCune–Albright syndrome. J Clin Endocrinol Metab 87:5104–5112

    Article  CAS  Google Scholar 

  21. Lee JS, FitzGibbon E, Butman JA, Dufresne CR, Kushner H, Wientroub S, Robey PG, Collins MT (2002) Normal vision despite narrowing of the optic canal in fibrous dysplasia. N Engl J Med 347:1670–1676

    Article  Google Scholar 

  22. Cutler CM, Lee JS, Butman JA, FitzGibbon E, Kelly MH, Brillante B, Feuillan P, Robey P, Dufresne CR, Collins MT (2006) Long term outcome of optic nerve encasement and optic nerve decompression in patients with fibrous dysplasia: risk factors for blindness and safety of observation. Neurosurgery (in press)

  23. Leet AI, Magur E, Lee JS, Wientroub S, Robey PG, Collins MT (2004) Fibrous dysplasia in the spine: prevalence of lesions and association with scoliosis. J Bone Joint Surg Am 86A:531–537

    Google Scholar 

  24. Ruggieri P, Sim FH, Bond JR, Unni KK (1994) Malignancies in fibrous dysplasia. Cancer 73:1411–1424

    Article  CAS  Google Scholar 

  25. Schwartz DT, Alpert M (1964) The malignant transformation of fibrous dysplasia. Am J Med Sci 247:1–20

    Article  CAS  Google Scholar 

  26. Yabut SM Jr, Kenan S, Sissons HA, Lewis MM (1988) Malignant transformation of fibrous dysplasia: a case report and review of the literature. Clin Orthop 228:281–289

    Google Scholar 

  27. Lopez-Ben R, Pitt MJ, Jaffe KA, Siegal GP (1999) Osteosarcoma in a patient with McCune–Albright syndrome and Mazabraud’s syndrome. Skeletal Radiol 28:522–526

    Article  CAS  Google Scholar 

  28. Jhala DN, Eltoum I, Carroll AJ, Lopez-Ben R, Lopez-Terrada D, Rao PH, Pettenati MJ, Siegal GP (2003) Osteosarcoma in a patient with McCune–Albright syndrome and Mazabraud’s syndrome: a case report emphasizing the cytological and cytogenetic findings. Hum Pathol 34:1354–1357

    Article  Google Scholar 

  29. Collins MT, Sarlis NJ, Merino MJ, Monroe J, Crawford SE, Krakoff JA, Guthrie LC, Bonat S, Robey PG, Shenker A (2003) Thyroid carcinoma in the McCune–Albright syndrome: contributory role of activating Gs alpha mutations. J Clin Endocrinol Metab 88:4413–4417

    Article  CAS  Google Scholar 

  30. Scanlon EF, Burkett FE, Sener SF, Green OC, Traisman HS, Marr TJ, Victor TA, Crist ML (1980) Breast carcinoma in a 11-year-old girl with Albright’s syndrome. Breast 6:6–9

    Google Scholar 

  31. Tanabeu Y, Nakahara S, Mitsuyama S, Ono M, Toyoshima S (1998) Breast cancer in a patient with McCune–Albright syndrome. Breast Cancer 5:175–178

    Article  Google Scholar 

  32. Huston TL, Simmons RM (2004) Ductal carcinoma in situ in a 27-year-old woman with McCune–Albright syndrome. Breast J 10:440–442

    Article  Google Scholar 

  33. Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, Waguespack S, Gupta A, Hannon T, Econs MJ, Bianco P, Gehron Robey P (2003) FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112:683–692

    Article  CAS  Google Scholar 

  34. Leet AI, Chebli C, Kushner H, Chen CC, Kelly MH, Brillante BA, Robey PG, Bianco P, Wientroub S, Collins MT (2004) Fracture incidence in polyostotic fibrous dysplasia and the McCune–Albright syndrome. J Bone Miner Res 19:571–577

    Article  Google Scholar 

  35. Bianco P, Riminucci M, Majolagbe A, Kuznetsov SA, Collins MT, Mankani MH, Corsi A, Bone HG, Wientroub S, Spiegel AM, Fisher LW, Robey PG (2000) Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune–Albright fibrous dysplasia of bone. J Bone Miner Res 15:120–128

    Article  CAS  Google Scholar 

  36. Corsi A, Collins MT, Riminucci M, Howell PG, Boyde A, Robey PG, Bianco P (2003) Osteomalacic and hyperparathyroid changes in fibrous dysplasia of bone: core biopsy studies and clinical correlations. J Bone Miner Res 18:1235–1246

    Article  Google Scholar 

  37. Ippolito E, Bray EW, Corsi A, De Maio F, Exner UG, Robey PG, Grill F, Lala R, Massobrio M, Pinggera O, Riminucci M, Snela S, Zambakidis C, Bianco P (2003) Natural history and treatment of fibrous dysplasia of bone: a multicenter clinicopathologic study promoted by the European Pediatric Orthopaedic Society. J Pediatr Orthop B 12:155–177

    Google Scholar 

  38. Hart ES, Kelly MH, Chen CC, Ziran N, Lee JS, Feuillan P, Kushner H, Robey P, Collins MT (2006) Onset and progression of fibrous dysplasia lesions, and relationship to functional outcome. J Bone Miner Res (in press)

  39. Collins MT, Chebli C, Jones J, Kushner H, Consugar M, Rinaldo P, Wientroub S, Bianco P, Robey PG (2001) Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia. J Bone Miner Res 16:806–813

    Article  CAS  Google Scholar 

  40. Collins MT (2004) McCune–Albright syndrome. In: Filetti S (ed) Orphanet Encyclopedia, Paris. http://www.orpha.net/data/patho/GB/uk-McCune-Albright-Syndrome.pdf

  41. Candeliere GA, Roughley PJ, Glorieux FH (1997) Polymerase chain reaction-based technique for the selective enrichment and analysis of mosaic arg201 mutations in G alpha s from patients with fibrous dysplasia of bone. Bone 21:201–206

    Article  CAS  Google Scholar 

  42. Karadag A, Riminucci M, Bianco P, Cherman N, Kuznetsov SA, Nguyen N, Collins MT, Robey PG, Fisher LW (2004) A novel technique based on a PNA hybridization probe and FRET principle for quantification of mutant genotype in fibrous dysplasia/McCune–Albright syndrome. Nucleic Acids Res 32(7):E63

    Article  Google Scholar 

  43. Lumbroso S, Paris F, Sultan C (2004) Activating Gsalpha mutations: analysis of 113 patients with signs of McCune–Albright syndrome—a European Collaborative Study. J Clin Endocrinol Metab 89:2107–2113

    Article  CAS  Google Scholar 

  44. Hannon TS, Noonan K, Steinmetz R, Eugster EA, Levine MA, Pescovitz OH (2003) Is McCune–Albright syndrome overlooked in subjects with fibrous dysplasia of bone? J Pediatr 142:532–538

    Article  Google Scholar 

  45. Collins MT, Kushner H, Reynolds JC, Chebli C, Kelly MH, Gupta A, Brillante B, Leet AI, Riminucci M, Robey PG, Bianco P, Wientroub S, Chen CC (2005) An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia of bone. J Bone Miner Res 20:219–226

    Article  Google Scholar 

  46. Kelly MH, Brillante B, Kushner H, Gehron Robey P, Collins MT (2005) Physical function is impaired but quality of life preserved in patients with fibrous dysplasia of bone. Bone 37:388–394

    Article  Google Scholar 

  47. Leet AI, Wientroub S, Kushner H, Brillante B, Kelly MH, Robey PG, Collins MT (2006) The correlation of specific orthopaedic features of polyostotic fibrous dysplasia with functional outcome scores in children. J Bone Joint Surg Am 88:818–823

    Article  Google Scholar 

  48. O’Sullivan M, Zacharin M (2002) Intramedullary rodding and bisphosphonate treatment of polyostotic fibrous dysplasia associated with the McCune–Albright syndrome. J Pediatr Orthop 22:255–260

    Google Scholar 

  49. Ippolito E, Caterini R, Farsetti P, Potenza V (2002) Surgical treatment of fibrous dysplasia of bone in McCune–Albright syndrome. J Pediatr Endocrinol Metab 15 Suppl 3:939–944

    Google Scholar 

  50. Jung ST, Chung JY, Seo HY, Bae BH, Lim KY (2006) Multiple osteotomies and intramedullary nailing with neck cross-pinning for shepherd’s crook deformity in polyostotic fibrous dysplasia: 7 femurs with a minimum of 2-years follow-up. Acta Orthop 77:469–473

    Article  Google Scholar 

  51. Guille JT, Kumar SJ, MacEwen GD (1998) 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 80:648–658

    CAS  Google Scholar 

  52. Enneking WF, Gearen PF (1986) Fibrous dysplasia of the femoral neck. Treatment by cortical bone-grafting. J Bone Joint Surg Am 68:1415–1422

    CAS  Google Scholar 

  53. Shih HN, Su JY, Hsu KY, Hsu RW (1997) Allogeneic cortical strut for benign lesions of the humerus in adolescents. J Pediatr Orthop 17:433–436

    CAS  Google Scholar 

  54. Segev E, Kollender Y, Bickels J, Flusser G, Issakov J, Wientroub S, Meller I (2002) Cryosurgery in fibrous dysplasia: good result of a multimodality protocol in 16 patients. Acta Orthop Scand 73:483–486

    Article  Google Scholar 

  55. Stanton RP, Montgomery BE (1996) Fibrous dysplasia. Orthopedics 19:679–685

    CAS  Google Scholar 

  56. Di Figlia SE 1951 Cortisone in polyostotic fibrous dysplasia. NY State J Med 51:2665

    CAS  Google Scholar 

  57. Bell NH, Avery S, Johnston CC Jr (1970) Effects of calcitonin in Paget’s disease and polyostotic fibrous dysplasia. J Clin Endocrinol Metab 31:283–290

    Article  CAS  Google Scholar 

  58. Tanner HC Jr, Dahlin DC, Childs DS Jr (1961) Sarcoma complicating fibrous dysplasia. Probable role of radiation therapy. Oral Surg Oral Med Oral Pathol 14:837–846

    Article  Google Scholar 

  59. Riminucci M, Kuznetsov SA, Cherman N, Corsi A, Bianco P, Gehron Robey P (2003) Osteoclastogenesis in fibrous dysplasia of bone: in situ and in vitro analysis of IL-6 expression. Bone 33:434–442

    Article  CAS  Google Scholar 

  60. Liens D, Delmas PD, Meunier PJ (1994) Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet 343:953–954

    Article  CAS  Google Scholar 

  61. Chapurlat RD, Delmas PD, Liens D, Meunier PJ (1997) Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res 12:1746–1752

    Article  CAS  Google Scholar 

  62. Chapurlat R, Delmas PD, Liens D, Meunier PJ (2002) Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res 10:1746–1752

    Google Scholar 

  63. Pfeilschifter J, Ziegler R (1998) Effect of pamidronate on clinical symptoms and bone metabolism in fibrous dysplasia and McCune–Albright syndrome. Med Klin (Munich) 93:352–359

    Article  CAS  Google Scholar 

  64. Lala R, Matarazzo P, Bertelloni S, Buzi F, Rigon F, de Sanctis C (2000) Pamidronate treatment of bone fibrous dysplasia in nine children with McCune–Albright syndrome. Acta Paediatr 89:188–193

    Article  CAS  Google Scholar 

  65. Zacharin M, O’Sullivan M (2000) Intravenous pamidronate treatment of polyostotic fibrous dysplasia associated with the McCune Albright syndrome. J Pediatr 137:403–409

    Article  CAS  Google Scholar 

  66. Parisi MS, Oliveri MB, Gomez Acotto C, Mautalen C (2001) Intravenous pamidronate increases bone mineral density and reduces bone remodeling markers in fibrous dysplasia. Bone 29:300–301

    Article  Google Scholar 

  67. Weinstein RS (1997) Long-term aminobisphosphonate treatment of fibrous dysplasia: spectacular increase in bone density (see comments). J Bone Miner Res 12:1314–1315

    Article  CAS  Google Scholar 

  68. Lane JM, Khan SN, O’Connor WJ, Nydick M, Hommen JP, Schneider R, Tomin E, Brand J, Curtin J (2001) Bisphosphonate therapy in fibrous dysplasia. Clin Orthop 382:6–12

    Article  Google Scholar 

  69. Plotkin H, Rauch F, Zeitlin L, Munns C, Travers R, Glorieux FH (2003) Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone. J Clin Endocrinol Metab 88:4569–4575

    Article  CAS  Google Scholar 

  70. Chapurlat R (2005) Current pharmacological treatment for fibrous dysplasia and perspectives for the future. Joint Bone Spine 72:196–198

    Article  Google Scholar 

  71. Woo SB, Hellstein JW et al (2006) Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144(10):753–761

    Article  CAS  Google Scholar 

  72. Bianco P, Riminucci M, Kuznetsov S, Robey PG (1999) Multipotential cells in the bone marrow stroma: regulation in the context of organ physiology. Crit Rev Eukaryot Gene Expr 9:159–173

    Article  CAS  Google Scholar 

  73. Bianco P, Robey PG (2001) Stem cells in tissue engineering. Nature 414:118–121

    Article  CAS  Google Scholar 

  74. Mankani MH, Kuznetsov SA, Shannon B, Nalla RK, Ritchie RO, Qin Y, Robey PG (2006) Canine cranial reconstruction using autologous bone marrow stromal cells. Am J Pathol 168:542–550

    Article  Google Scholar 

  75. Devauchelle B, Badet L, Lengele B, Morelon E, Testelin S, Michallet M, D’Hauthuille C, Dubernard JM (2006) First human face allograft: early report. Lancet 368:203–209

    Article  Google Scholar 

Download references

Acknowledgment

This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research of the Intramural Research Program, National Institutes of Health, Department of Health and Human Services.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael T. Collins.

About this article

Cite this article

Leet, A.I., Collins, M.T. Current approach to fibrous dysplasia of bone and McCune–Albright syndrome. J Child Orthop 1, 3–17 (2007). https://doi.org/10.1007/s11832-007-0006-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11832-007-0006-8

Keywords

Navigation