Mandible / maxilla
Osteomyelitis
Osteoradionecrosis (ORN)



Topic Completed: 1 December 2014

Revised: 8 February 2019

Copyright: 2004-2018, PathologyOutlines.com, Inc.

PubMed Search: Osteoradionecrosis [title] mandible maxilla


Annie S. Morrison, M.D.
Kelly Magliocca, D.D.S., M.P.H.
Page views in 2018: 1,114
Page views in 2019 to date: 672
Cite this page: Morrison A. Osteomyelitis: osteoradionecrosis (ORN). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/mandiblemaxillaORN.html. Accessed June 25th, 2019.
Definition / general
  • Exposed, devitalized bone in radiated field with no healing for 3 months and no evidence of tumor recurrence
  • Osteoradionecrosis (ORN) is considered a late effect of a radiation induced fibroatrophic process, but is not considered as primary osteomyelitis
  • Is more similar to aseptic / avascular necrosis of bone than primary infection of bone, although infection or bacterial colonization can occur
Terminology
  • Synonyms: Radiation osteitis, radio-osteonecrosis, radiation osteomyelitis, osteomyelitis of irradiated bone, osteonecrosis, radio-osteomyelitis, postradiotherapy osteonecrosis

  • Acute suppurative osteomyelitis:
    • Early phase of osteomyelitis, and usually a suppurative (pus forming) condition
    • Exists when an acute inflammatory process moves away from the site of initial infection and spreads through the medullary space of the bone and in most cases, insufficient time has passed for the body to react to the presence of the inflammatory infiltrate
    • Acute phase may lead to the chronic phase which has been arbitrarily defined as an osseous infection lasting at least 1 month
  • Chronic osteomyelitis:
    • May be classified as primary or secondary, and as suppurative or non-suppurative
      • Secondary chronic osteomyelitis (SCO)
      • Primary chronic osteomyelitis (PCO)
      • Chronic tendoperiostitis
  • Chronic recurrent multifocal osteomyelitis (CRMO)
    • CRMO is a relapsing inflammatory disease and is considered a type of seronegative spondyloarthropathy characterized by periods of exacerbations and remissions over many years
    • Characterized by an inflammatory process presenting with findings similar to infectious osteomyelitis; however, no infectious source is identifiable
    • Characterized by insidious onset of low grade fever, local swelling and bone pain
    • Radiologic findings may suggest osteomyelitis, and bone seeking isotopes reveal other asymptomatic sites of involvement
    • Lesions occur mainly in metaphyses of long tubular bones, as well as clavicles, spine, and pelvis; lesions are sometimes symmetrically distributed
    • Precise relationship between primary chronic osteomyelitis, diffuse sclerosing osteomyelitis, CRMO and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is highly debated and not clear at this time
    • Some consider CRMO and SAPHO as primary chronic osteomyelitis with additional extragnathic manifestations
  • Chronic sclerosing osteomyelitis / diffuse sclerosing osteomyelitis:
    • Although the term is usually used synonymously with primary chronic osteomyelitis, it represents a description of a strictly radiological appearance that can be caused by several similar processes, including:
      • Primary and secondary chronic osteomyelitis
      • Chronic tendoperiostitis
      • Ossifying periostitis or Garrè osteomyelitis
      • Medullary osseous infection, probably bacterial, which induces the complete sclerosis
        • Favors young women, is painful and appears radiographically as medullary sclerosis
        • Therapy includes antibiotics and surgical debridement and hyperbaric oxygen therapy in refractory cases
  • Cortical bone:
    • Cortical bone, synonymous with compact bone, is one of the two types of osseous tissue that forms bone
    • As its name implies, cortical bone forms the cortex, or outer shell, of most bones
    • Compact bone, as its name implies, is much denser than cancellous bone, which is the other type of osseous tissue
    • Furthermore, it is harder, stronger and stiffer than cancellous bone
  • Garrè sclerosing osteomyelitis:
    • In 1893, a Swiss physician, Carl Garrè, reported on patterns of acute osteomyelitis
    • Garrè did not have any pathologic specimens for microscopic examination, nor radiographs to augment his descriptions
    • Nonetheless, his name is often associated with the condition in which periosteal duplication, or an "onion-skinning" pattern of periostitis, leads to enlargement of the jaw, usually mandible
  • Involucrum:
  • Medullary bone / medullary cavity / marrow cavity:
    • The medullary cavity (medulla, innermost part) of bone is the central cavity where red bone marrow or yellow bone marrow (adipose tissue) is stored; hence, the medullary cavity is also known as the marrow cavity
    • The medullary cavity has walls composed of spongy bone (cancellous bone) and is lined by endosteum, which are osteoprogenitor cells
  • Osteochemonecrosis of Jaws:
    • Synonyms: bisphosphonate related osteonecrosis of the jaws, bisphosphonate induced osteonecrosis of the jaw, osteonecrosis of jaw, bisphosphonate osteonecrosis, bis-phossy jaw
    • Necrosis of bone related to long term use of antiresorptive medications such as bisphosphonate medications and altered bone metabolism
    • Osteoclasts are thought to be qualitatively impaired, particularly with intravenous forms of bisphosphonate medication, which leads to inadequate remodeling of bone, necrosis
  • SAPHO syndrome:
    • SAPHO syndrome is an acronym for a complex clinical presentation that includes synovitis, acne, pustulosis, hyperostosis and osteitis
    • The osseous lesions mirror primary chronic osteomyelitis and CRMO
    • Unknown cause but thought to arise in genetically predisposed individuals who develop an autoimmune disturbance secondary to exposure to dermatologic bacteria
    • Increased prevalence of HLA-27
    • SAPHO and CRMO are distinguished from other forms of osteitis / osteomyelitis, as these two diseases may have extragnathic skeletal involvement
  • Sequestrum:
Incidence
  • Develops in ~5% (range 5 - 15%, depending on risk factors) treated by radiation therapy to jaws, usually for oral cavity squamous cell carcinoma
  • Rare when exposed to radiation doses less than 60Gy or with use of intensity modulated radiotherapy
  • Risk increases when chemotherapy or brachytherapy also used
  • Onset usually within 2 years of radiotherapy
    • May occur later if associated with a defined traumatic event
    • If onset > 8 years after radiation, must exclude postradiation sarcoma
  • Risk of ORN continues for life of patient
Sites
  • In jaws, predominantly involves the posterior mandible
Pathophysiology
  • Direct or indirect radiation damage to tissues impairs bone's ability to remodel and cope with insult
  • Causes hypoxia, hypovascularity, and hypocellularity; also generation of free oxygen radicals and cytokine release, dysregulation of fibroblasts
Etiology
  • In the setting of radiation therapy, bone has greater density than soft tissue, absorbs more photons with higher energy deposition
  • Mandible bone is higher density than other bones within the facial radiation field
  • Risk factors for the development of ORN:
    • Site and size of primary tumor treated
    • Dose of radiation
    • Large size radiation field
    • Short treatment time
    • Trauma, including type of surgery on mandible
    • Preoperative dental extractions
    • Presence of infection
    • Immune deficiencies
    • Malnutrition
    • Stage III / IV primary carcinoma
Clinical features
  • Foul odor, exposed bone
  • Cutaneous or mucosal wound
  • Pain, which can be intractable
  • Ulceration of mucosa
  • Trismus
  • Local infection with intraoral or extraoral fistula formation
  • Pathologic fracture
  • Food impaction into exposed wounds
  • Nutritional deficiencies, loss of time from work, decreased quality of life
Diagnosis
  • Diagnosis involves the detection of exposed, devitalized bone in a radiated field with no healing for 3 months and no evidence of tumor recurrence
  • Diagnosis is both clinically and radiographically based but a universal staging system is lacking
    • Biopsy may be necessary to differentiate recurrent malignant disease and ORN
    • Cultures are important in cases with superimposed infection
  • Initial correct diagnosis of secondary chronic osteomyelitis must be established prior to any successful treatment
  • Staging Systems:
    • Marx et al:
      • Stage I: exposed bone greater than 6 months
      • Stage II: failure of treatment of Stage I
      • Stage III: poor prognostic factors present (pathologic fracture, orocutaneous fistula, osteolytic involvement of inferior border)
    • Schwartz et al:
      • Stage I:small area of limited exposed cortical bone
      • Stage II: exposed cortical and underlying medullary bone necrotic
      • Stage III: full thickness necrosis, +/- pathologic fracture
    • Store and Boysen Staging:
      • Stage 0: mucosal defects only
      • Stage I: radiologic evidence of ORN + intact mucosa
      • Stage II: radiologic evidence of ORN + denuded bone
      • Stage III: exposed radionecrotic bone + orocutaneous fistulae
Radiology description
  • Radiographic work-up often involves multiple imaging modalities:
  • Plain films:
    • Often panoramic radiographs
    • Good for screening but tends to underestimate extent of disease
    • Lytic areas, with ill defined, non-sclerotic borders
    • May have alternating radiopaque areas
  • Computed Tomography:
    • Best diagnostic modality
    • Cortical bone disruption with mixed lysis and sclerosis
    • Loss of bone results in lytic appearance
    • Pathologic fracture may be present
  • PET/CT:
    • Markedly FDG-avid lesions, may represent inflammation
  • Magnetic resonance imaging:
    • Helpful to look at bone marrow and surrounding soft tissue
    • Low signal intensity on T1 weighted images, postcontrast shows enhancement
    • High T2 signal and contrast enhancement present in setting of infection
Radiology images

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Osteoradionecrosis

Treatment
  • Prevention most important
  • Multiple approaches predicated on clinical presentation and symptoms, size of clinical lesion, response to prior therapies, staging systems
  • Conservative management: oral care, local irrigation, antibiotics, gentle debridement
  • Surgical resection for advanced disease: common indications are pathologic fracture, severe intractable pain
  • Antibiotics
  • Hyperbaric oxygen to promote angiogenesis
Clinical images

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Mandibular osteonecrosis

Gross description
  • Biopsies to confirm diagnosis of osteomyelitis and rule out neoplasia are often minute
  • If segmental mandibulectomy is performed, must sample margins of resection, soft tissue to exclude recurrent disease, pathologic fracture sites to exclude recurrent disease, multiple full thickness cross sections of mandible to document possible disease heterogeneity
Microscopic (histologic) description
  • Microscopic features may overlap with osteomyelitis, particularly in cases with superinfection
  • Three phases:
    1. Prefibrotic phase: chronic inflammation
    2. Organized fibrosis phase: abnormal fibroblastic activity predominates, poorly organized matrix
      • These areas are adjacent to regions of aging fibroblasts in a poorly cellular, fibrotic, and dense sclerotic matrix
    3. Fibroatrophic phase: dense hyalinization and fibrosis with loss of marrow cells
  • Reactive squamous mucosa may line a fistulous tract
  • Secondary infection possible
  • May have necrotic or sclerotic bone with empty osteocyte lacunae
  • Marrow fibrosis, irregular bony trabeculae may lack osteocytes within lacuna
  • Marrow necrosis may evolve through an edematous fibromyxoid nature in the earlier stage of disease
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