Fibrous dysplasia of bone

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Fibrous dysplasia
Fibrous dysplasia - intermed mag.jpg
Micrograph showing fibrous dysplasia with the characteristic thin, irregular bony trabeculae and fibrotic marrow space. H&E stain.
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg
Symptoms Bone pain, bone deformities, local swelling
Complications Bone fractures
Usual onsetAdolescence or early adulthood (monostotic), before age 10 (polyostotic)
Types Monostotic (75–80% of cases), [1] polyostotic, panostotic
CausesMutations of GNAS locus
Frequency1 in 5,000 to 10,000 [1]

Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment, and pain. [2] Disease occurs along a broad clinical spectrum ranging from asymptomatic, incidental lesions, to severe disabling disease. Disease can affect one bone (monostotic), multiple (polyostotic), or all bones (panostotic) [3] [4] and may occur in isolation or in combination with café au lait skin macules and hyperfunctioning endocrinopathies, termed McCune–Albright syndrome. [2] More rarely, fibrous dysplasia may be associated with intramuscular myxomas, termed Mazabraud's syndrome. [5] Fibrous dysplasia is very rare, and there is no known cure. [6] Fibrous dysplasia is not a form of cancer.

Contents

Presentation

Fibrous dysplasia of the right zygomatic bone (left). Corresponding T2-weighted MRI (left) and CT (right) of the same patient. Dysplasia fibrosa.jpg
Fibrous dysplasia of the right zygomatic bone (left). Corresponding T2-weighted MRI (left) and CT (right) of the same patient.

Fibrous dysplasia is a mosaic disease that can involve any part or combination of the craniofacial, axillary, and/or appendicular skeleton. [7] The type and severity of the complications therefore depend on the location and extent of the affected skeleton. The clinical spectrum is very broad, ranging from an isolated, asymptomatic monostotic lesion discovered incidentally, to severe disabling disease involving practically the entire skeleton and leading to loss of vision, hearing, and/or mobility.[ citation needed ]

Individual bone lesions typically manifest during the first few years of life and expand during childhood. The vast majority of clinically significant bone lesions are detectable by age 10 years, with few new and almost no clinically significant bone lesions appearing after age 15 years. [8] Total body scintigraphy is useful to identify and determine the extent of bone lesions, and should be performed in all patients with suspected fibrous dysplasia. [2]

Children with fibrous dysplasia in the appendicular skeleton typically present with limp, pain, and/or pathologic fractures. Frequent fractures and progressive deformity may lead to difficulties with ambulation and impaired mobility. In the craniofacial skeleton, fibrous dysplasia may present as a painless “lump” or facial asymmetry. Expansion of craniofacial lesions may lead to progressive facial deformity. In rare cases, patients may develop vision and/or hearing loss due to compromise of the optic nerves and/or auditory canals, which is more common in patients with McCune-Albright syndrome associated growth hormone excess. [9] Fibrous dysplasia commonly involves the spine, and may lead to scoliosis, which in rare instances may be severe. [10] Untreated, progressive scoliosis is one of the few features of fibrous dysplasia that can lead to early fatality.

Bone pain is a common complication of fibrous dysplasia. It may present at any age, but most commonly develops during adolescence and progresses into adulthood. [7]

Bone marrow stromal cells in fibrous dysplasia produce excess amounts of the phosphate-regulating hormone fibroblast growth factor-23 (FGF23), leading to loss of phosphate in the urine. [11] Patients with hypophosphatemia may develop rickets/osteomalacia, increased fractures, and bone pain. [12]

Micrograph of fibrous dysplasia (right) juxtaposed with unaffected bone (left). H&E stain. Fibrous dysplasia - very low mag.jpg
Micrograph of fibrous dysplasia (right) juxtaposed with unaffected bone (left). H&E stain.

Pathophysiology

Fibrous dysplasia is a mosaic disease resulting from post-zygotic activating mutations of the GNAS locus at 20q13.2-q13.3, which codes for the α subunit of the Gs G protein-coupled receptor. [13] In bone, constitutive Gsα signaling results in impaired differentiation and proliferation of bone marrow stromal cells. [14] Proliferation of these cells causes replacement of normal bone and marrow with fibrous tissue. The bony trabeculae are abnormally thin and irregular (bony spicules on biopsy).[ citation needed ]

Fibrous dysplasia is not hereditary, and there has never been a case of genetic inheritance from parent to child.[ citation needed ]

Diagnosis

On x-ray, fibrous dysplasia appears as bubbly lytic lesions, or a ground glass appearance. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans may be used to determine how extensively bones are affected. CT can better demonstrate the typical "ground glass" appearance, which is a highly specific radiological finding, while MRI can show cystic areas with fluid contents. [15] A bone scan uses radioactive tracers, which are injected into your bloodstream. The damaged parts of bones take up more of the tracer, which show up more brightly on the scan. A biopsy, which uses a hollow needle to remove a small piece of the affected bone for laboratory analysis, can diagnose fibrous dysplasia definitely.[ citation needed ]

Treatment

Treatment in fibrous dysplasia is mainly palliative, and is focused on managing fractures and preventing deformity. There are no medications capable of altering the disease course. Intravenous bisphosphonates may be helpful for treatment of bone pain, but there is no clear evidence that they strengthen bone lesions or prevent fractures. [16] [17] Surgical techniques that are effective such as bone grafting, curettage, and plates and screws, are frequently ineffective against the Polyostotic version of fibrous dysplasia but often effective against monostotic fibrous dysplasia. [18] [19] Intramedullary rods are generally preferred for management of fractures and deformity in the lower extremities. [19] Progressive scoliosis can generally be managed with standard instrumentation and fusion techniques. [20] Surgical management in the craniofacial skeleton is complicated by frequent post-operative FD regrowth, and should focus on correction of functional deformities. [21] Prophylactic optic nerve decompression increases the risk of vision loss and is contraindicated. [22]

Managing endocrinopathies is a critical component of management in FD. All patients with fibrous dysplasia should be evaluated and treated for endocrine diseases associated with McCune–Albright syndrome. In particular untreated growth hormone excess may worsen craniofacial fibrous dysplasia and increase the risk of blindness. [23] Untreated hypophosphatemia increases bone pain and risk of fractures. [24]

See also

Related Research Articles

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<span class="mw-page-title-main">Café au lait spot</span> Type of birthmark caused by a collection of melanocytes

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<span class="mw-page-title-main">Dysplasia</span> Abnormal development, at macroscopic or microscopical level

Dysplasia is any of various types of abnormal growth or development of cells or organs, and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic scale include epithelial dysplasia and fibrous dysplasia of bone. Dysplasias on a mainly macroscopic scale include hip dysplasia, myelodysplastic syndrome, and multicystic dysplastic kidney.

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Polyostotic fibrous dysplasia is a form of fibrous dysplasia affecting more than one bone. Fibrous dysplasia is a disorder where bone is replaced by fibrous tissue, leading to weak bones, uneven growth, and deformity.

<span class="mw-page-title-main">McCune–Albright syndrome</span> Mosaic genetic disorder affecting the bone, skin and endocrine systems

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Cleidocranial dysostosis (CCD), also called cleidocranial dysplasia, is a birth defect that mostly affects the bones and teeth. The collarbones are typically either poorly developed or absent, which allows the shoulders to be brought close together. The front of the skull often does not close until later, and those affected are often shorter than average. Other symptoms may include a prominent forehead, wide set eyes, abnormal teeth, and a flat nose. Symptoms vary among people; however, intelligence is typically unaffected.

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<span class="mw-page-title-main">Calvarial doughnut lesions-bone fragility syndrome</span> Medical condition

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References

  1. 1 2 Tafti, Dawood; Cecava, Nathan D. (2018-12-18). "Fibrous Dysplasia". NCBI Bookshelf. PMID   30422542 . Retrieved 2019-12-08.
  2. 1 2 3 Boyce, Alison M.; Collins, Michael T. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C. (eds.). Fibrous Dysplasia/McCune-Albright Syndrome. Seattle (WA): University of Washington, Seattle. PMID   25719192.
  3. ↑ Cole DE; Fraser FC; Glorieux FH; Jequier S; Marie PJ; Reade TM; Scriver CR (14 Apr 1983). "Panostotic fibrous dysplasia: a congenital disorder of bone with unusual facial appearance, bone fragility, hyperphosphatasemia, and hypophosphatemia". American Journal of Medical Genetics (4 ed.). 14 (4): 725–35. doi:10.1002/ajmg.1320140414. PMID   6846403.
  4. ↑ Leslie WD; Reinhold C; Rosenthall L; Tau C; Glorieux FH (July 1992). "Panostotic fibrous dysplasia. A new craniotubular dysplasia". Clinical Nuclear Medicine (7 ed.). 17 (7): 556–60. doi:10.1097/00003072-199207000-00005. PMID   1638836. S2CID   43035832.
  5. ↑ Cabral, C. E.; Guedes, P.; Fonseca, T.; Rezende, J. F.; Cruz Júnior, L. C.; Smith, J. (1998-05-01). "Polyostotic fibrous dysplasia associated with intramuscular myxomas: Mazabraud's syndrome". Skeletal Radiology. 27 (5): 278–282. doi:10.1007/s002560050381. ISSN   0364-2348. PMID   9638839. S2CID   6558881.
  6. ↑ "Fibrous Dysplasia - OrthoInfo - AAOS". www.orthoinfo.org. Retrieved 2021-10-13.
  7. 1 2 Kelly, M. H.; Brillante, B.; Collins, M. T. (2008-01-01). "Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions". Osteoporosis International. 19 (1): 57–63. doi:10.1007/s00198-007-0425-x. ISSN   0937-941X. PMID   17622477. S2CID   21276747.
  8. ↑ Hart, Elizabeth S.; Kelly, Marilyn H.; Brillante, Beth; Chen, Clara C.; Ziran, Navid; Lee, Janice S.; Feuillan, Penelope; Leet, Arabella I.; Kushner, Harvey (2007-09-01). "Onset, progression, and plateau of skeletal lesions in fibrous dysplasia and the relationship to functional outcome". Journal of Bone and Mineral Research. 22 (9): 1468–1474. doi: 10.1359/jbmr.070511 . ISSN   0884-0431. PMID   17501668.
  9. ↑ Cutler, Carolee M.; Lee, Janice S.; Butman, John A.; FitzGibbon, Edmond J.; Kelly, Marilyn H.; Brillante, Beth A.; Feuillan, Penelope; Robey, Pamela G.; DuFresne, Craig R. (2006-11-01). "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. 59 (5): 1011–1017, discussion 1017–1018. doi:10.1227/01.NEU.0000254440.02736.E3. ISSN   1524-4040. PMID   17143235. S2CID   19550908.
  10. ↑ Leet, Arabella I.; Magur, Edward; Lee, Janice S.; Wientroub, Shlomo; Robey, Pamela G.; Collins, Michael T. (2004-03-01). "Fibrous dysplasia in the spine: prevalence of lesions and association with scoliosis". The Journal of Bone and Joint Surgery. American Volume. 86-A (3): 531–537. doi:10.2106/00004623-200403000-00011. ISSN   0021-9355. PMID   14996879.
  11. ↑ Riminucci, Mara; Collins, Michael T.; Fedarko, Neal S.; Cherman, Natasha; Corsi, Alessandro; White, Kenneth E.; Waguespack, Steven; Gupta, Anurag; Hannon, Tamara (2003-09-01). "FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting". The Journal of Clinical Investigation. 112 (5): 683–692. doi:10.1172/JCI18399. ISSN   0021-9738. PMC   182207 . PMID   12952917.
  12. ↑ Leet, Arabella I.; Chebli, Caroline; Kushner, Harvey; Chen, Clara C.; Kelly, Marilyn H.; Brillante, Beth A.; Robey, Pamela G.; Bianco, Paolo; Wientroub, Shlomo (2004-04-01). "Fracture incidence in polyostotic fibrous dysplasia and the McCune-Albright syndrome". Journal of Bone and Mineral Research. 19 (4): 571–577. doi: 10.1359/JBMR.0301262 . ISSN   0884-0431. PMID   15005844. S2CID   37760051.
  13. ↑ Weinstein, L. S.; Shenker, A.; Gejman, P. V.; Merino, M. J.; Friedman, E.; Spiegel, A. M. (1991-12-12). "Activating mutations of the stimulatory G protein in the McCune-Albright syndrome". The New England Journal of Medicine. 325 (24): 1688–1695. doi: 10.1056/NEJM199112123252403 . ISSN   0028-4793. PMID   1944469.
  14. ↑ Riminucci, M.; Fisher, L. W.; Shenker, A.; Spiegel, A. M.; Bianco, P.; Gehron Robey, P. (1997-12-01). "Fibrous dysplasia of bone in the McCune-Albright syndrome: abnormalities in bone formation". The American Journal of Pathology. 151 (6): 1587–1600. ISSN   0002-9440. PMC   1858361 . PMID   9403710.
  15. ↑ Pons Escoda, Albert; Naval Baudin, Pablo; Mora, Paloma; Cos, Mònica; Hernandez Gañan, Javier; Narváez, José A.; Aguilera, Carles; Majós, Carles (2020-02-13). "Imaging of skull vault tumors in adults". Insights into Imaging. 11 (1): 23. doi: 10.1186/s13244-019-0820-9 . ISSN   1869-4101. PMC   7018895 . PMID   32056014.
  16. ↑ Plotkin, Horacio; Rauch, Frank; Zeitlin, Leonid; Munns, Craig; Travers, Rose; Glorieux, Francis H. (2003-10-01). "Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone". The Journal of Clinical Endocrinology and Metabolism. 88 (10): 4569–4575. doi: 10.1210/jc.2003-030050 . ISSN   0021-972X. PMID   14557424.
  17. ↑ Boyce, Alison M.; Kelly, Marilyn H.; Brillante, Beth A.; Kushner, Harvey; Wientroub, Shlomo; Riminucci, Mara; Bianco, Paolo; Robey, Pamela G.; Collins, Michael T. (2014-11-01). "A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone". The Journal of Clinical Endocrinology and Metabolism. 99 (11): 4133–4140. doi:10.1210/jc.2014-1371. ISSN   1945-7197. PMC   4223439 . PMID   25033066.
  18. ↑ Leet, Arabella I.; Boyce, Alison M.; Ibrahim, Khalda A.; Wientroub, Shlomo; Kushner, Harvey; Collins, Michael T. (2016-02-03). "Bone-Grafting in Polyostotic Fibrous Dysplasia". The Journal of Bone and Joint Surgery. American Volume. 98 (3): 211–219. doi:10.2106/JBJS.O.00547. ISSN   1535-1386. PMC   4732545 . PMID   26842411.
  19. 1 2 Stanton, Robert P.; Ippolito, Ernesto; Springfield, Dempsey; Lindaman, Lynn; Wientroub, Shlomo; Leet, Arabella (2012-05-24). "The surgical management of fibrous dysplasia of bone". Orphanet Journal of Rare Diseases. 7 (Suppl 1): S1. doi: 10.1186/1750-1172-7-S1-S1 . ISSN   1750-1172. PMC   3359959 . PMID   22640754.
  20. ↑ Leet, Arabella I.; Magur, Edward; Lee, Janice S.; Wientroub, Shlomo; Robey, Pamela G.; Collins, Michael T. (2004-03-01). "Fibrous dysplasia in the spine: prevalence of lesions and association with scoliosis". The Journal of Bone and Joint Surgery. American Volume. 86-A (3): 531–537. doi:10.2106/00004623-200403000-00011. ISSN   0021-9355. PMID   14996879.
  21. ↑ Lee, J. S.; FitzGibbon, E. J.; Chen, Y. R.; Kim, H. J.; Lustig, L. R.; Akintoye, S. O.; Collins, M. T.; Kaban, L. B. (2012-05-24). "Clinical guidelines for the management of craniofacial fibrous dysplasia". Orphanet Journal of Rare Diseases. 7 (Suppl 1): S2. doi: 10.1186/1750-1172-7-S1-S2 . ISSN   1750-1172. PMC   3359960 . PMID   22640797.
  22. ↑ Amit, Moran; Collins, Michael T.; FitzGibbon, Edmond J.; Butman, John A.; Fliss, Dan M.; Gil, Ziv (2011-01-01). "Surgery versus watchful waiting in patients with craniofacial fibrous dysplasia--a meta-analysis". PLOS ONE. 6 (9): e25179. Bibcode:2011PLoSO...625179A. doi: 10.1371/journal.pone.0025179 . ISSN   1932-6203. PMC   3179490 . PMID   21966448.
  23. ↑ Boyce, Alison M.; Glover, McKinley; Kelly, Marilyn H.; Brillante, Beth A.; Butman, John A.; Fitzgibbon, Edmond J.; Brewer, Carmen C.; Zalewski, Christopher K.; Cutler Peck, Carolee M. (2013-01-01). "Optic neuropathy in McCune-Albright syndrome: effects of early diagnosis and treatment of growth hormone excess". The Journal of Clinical Endocrinology and Metabolism. 98 (1): E126–134. doi:10.1210/jc.2012-2111. ISSN   1945-7197. PMC   3537097 . PMID   23093488.
  24. ↑ Leet, Arabella I.; Chebli, Caroline; Kushner, Harvey; Chen, Clara C.; Kelly, Marilyn H.; Brillante, Beth A.; Robey, Pamela G.; Bianco, Paolo; Wientroub, Shlomo (2004-04-01). "Fracture incidence in polyostotic fibrous dysplasia and the McCune-Albright syndrome". Journal of Bone and Mineral Research. 19 (4): 571–577. doi: 10.1359/JBMR.0301262 . ISSN   0884-0431. PMID   15005844. S2CID   37760051.

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