Mandible & maxilla

Osteomyelitis and inflammatory conditions

Secondary chronic

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PubMed Search: Secondary chronic osteomyelitis [title]

Annie S. Morrison, M.D.
Kelly Magliocca, D.D.S., M.P.H.
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Cite this page: Morrison A. Secondary chronic. website. Accessed November 29th, 2023.
Definition / general
  • Chronic suppurative osteomyelitis is generally regarded as a secondary, chronic osteomyelitis characterized by a defensive response that leads to production of granulation tissue which subsequently forms dense scar tissue in an attempt to wall off the infected area; the encircled dead space acts as a reservoir for bacteria and antibiotic medications have great difficulty reaching the site
  • Acute and secondary chronic osteomyelitis of the jaws is caused mostly by a bacterial focus (e.g. odontogenic disease, pulpal and periodontal infection, extraction wounds, foreign bodies, infected fractures); they are essentially the same disease separated by the arbitrary time limit of 1 month after disease onset
  • Chronic secondary osteomyelitis: infection is more advanced than in acute cases, by definition, therefore radiographic imaging is usually more conclusive; suppuration, fistula formation and sequestration are characteristic features but are not required for diagnosis
  • Acute suppurative osteomyelitis:
    • Early phase of osteomyelitis, 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; 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, arbitrarily defined as an osseous infection lasting at least 1 month
  • Alveolar osteitis / fibrinolytic alveolitis
    • After tooth extraction, a blood clot is formed at extraction site with eventual organization by granulation tissue and gradual replacement by bone (Oral Maxillofac Surg Clin North Am 2011;23:401)
    • Destruction of the initial clot may delay the steps required for uneventful extraction site healing and leads to alveolar osteitis
    • Clot is lost secondary to transformation of plasminogen to plasmin with subsequent lysis of fibrin and formation of kinins, potent pain mediators
  • Biofilm
    • Collection of microorganisms often embedded in a self produced extracellular polymeric matrix which allows them to adhere to or coat the surface of a living or inanimate structure
  • Chronic osteomyelitis:
    • May be classified as primary chronic osteomyelitis (PCO) or secondary chronic osteomyelitis (SCO) and as suppurative or non-suppurative
  • Chronic recurrent multifocal osteomyelitis (CRMO)
    • Characterized by an inflammatory process presenting with findings similar to infectious osteomyelitis but with no identifiable infectious source
    • Often preteen and teenage patients
    • Disease is often polyostotic and may affect the mandible
    • May represent a widespread variant of primary chronic osteomyelitis
    • CRMO and SAPHO (see below) are distinguished from other forms of osteitis / osteomyelitis as these two diseases may have extragnathic skeletal involvement
  • Chronic sclerosing osteomyelitis / diffuse sclerosing osteomyelitis
    • Primarily descriptive of the radiological appearance of the pathological bone reaction; however, although 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, surgical debridement and hyperbaric oxygen therapy in refractory cases
  • Chronic tendoperiostitis
    • Initially thought to be an obscure infectious process, the clinical presentation is similar to primary chronic osteomyelitis
    • May represent a reactive alteration of bone initiated and exacerbated by chronic overuse of the masticatory muscles, predominantly the masseter and digastric
    • Patients usually present with a history of parafunctional complaints
    • Palpation of the temporal, masseter, medial pterygoid and digastric muscles reveals tenderness in one or more of these locations
    • Radiographically may be similar to primary chronic osteomyelitis with diffuse sclerosing of the marrow and the cortical plate but no pus formation or sequestration
  • Condensing osteitis
    • Localized areas of radiographic bone sclerosis associated with apices of inflamed dead or dying teeth (pulpitis or pulpal necrosis)
    • The association with inflammation, usually a neighboring tooth, is critical, because these lesions can resemble other intrabony processes that produce a somewhat similar pattern
    • Is not considered a true osteomyelitis in the classical sense
  • Cortical bone:
    • Synonymous with compact bone, one of the two types of osseous tissue that forms bone
    • Forms the cortex, or outer shell, of most bones
    • More dense, hard, strong and stiff than cancellous bone (the second type)
  • 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 or radiographs to augment his descriptions
    • Nonetheless, his name is often associated with the condition in which periosteal duplication, or "onion-skinning" pattern of periostitis leads to enlargement of the jaw, usually mandible
  • Involucrum:
  • Medullary bone / medullary cavity / marrow cavity:
    • Medullary cavity (medulla, innermost part) of bone is the central cavity where red bone marrow or yellow bone marrow (adipose tissue) is stored; hence it is also known as the marrow cavity
    • Has walls composed of spongy bone (cancellous bone) and is lined by endosteum, which are osteoprogenitor cells (Wikipedia: Periosteum [Accessed 5 June 2018])
  • Osteochemonecrosis of jaws
    • Synonyms: bisphosphonate related osteonecrosis of jaws, bisphosphonate induced osteonecrosis of jaw, osteonecrosis of jaw, bisphosphonate osteonecrosis, bis-phossy jaw,
    • Necrosis of bone related to long term use of antiresorptive medications such as bisphosphonate and altered bone metabolism
    • Osteoclasts may be qualitatively impaired, particularly with intravenous forms of bisphosphonate, which leads to inadequate remodeling of bone and necrosis
  • Osteoradionecrosis (ORN)
    • Clinically, a chronic non-healing wound of the affected jaw (most commonly mandible), typically with exposure of bone, in a patient with a history of radiation therapy to the head and neck region
    • Radiation injury to jaw that leads to ORN results from chronic hypovascularity, hypocellularity of marrow space and ultimately hypoxemia
    • More similar to avascular necrosis of bone than primary infection of bone, although infection or bacterial colonization can occur
  • Periapical granuloma:
    • Acute or chronic inflammation admixed with fibrous or granulation tissue at the apical or periapical region of a necrotic or partially necrotic tooth root
    • Is devoid of epithelium (i.e. no cyst lining) which distinguishes it from a periapical cyst
  • Proliferative periostitis
    • Represents a periosteal reaction to inflammation
    • The affected periosteum forms several rows of reactive vital bone that parallel each other and expand the surface of altered bone
  • SAPHO syndrome
    • Acronym for a complex clinical presentation that includes synovitis, acne, pustulosis, hyperostosis, 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:
Zurich Classification of Osteomyelitis
  • Primarily based on clinical course and imaging features
  • Histopathology is considered a secondary classification criterion because findings are mostly unspecific and inconclusive by themselves; however, tissue examination is irreplaceable to confirm diagnosis, when clinical and radiological appearance are unclear / atypical, and to exclude possible differential diagnoses
  • The three major classifications are: (Baltensperger, Osteomyelitis of the Jaws: Definition and Classification (Figure 2.2))
    1. Acute Osteomyelitis (AO)
    2. Secondary Chronic Osteomyelitis (SCO)
    3. Primary Chronic Osteomyelitis (PCO)
  • Further subclassification is based on presumed etiology and pathogenesis of disease
  • These criteria are considered tertiary classification criteria and are helpful to determine the necessary therapeutic strategies which may differ somewhat among the subgroups
  • Predominantly involves mandible
  • Chronicity of disease reflects inability of host to eradicate the pathogen, may be due to lack of treatment or inadequate treatment
  • After local blood supply is compromised by acute phase of infection, bone undergoes necrosis and nonviable fragments become sequestra
  • Periosteum still contains osteogenic potential in most cases which contributes to formation of a bony shell (involucrum) covering the sequestra
  • The involucrum may interfere with extrusion of the sequestrum, which may perpetuate the process, in combination with a compromised blood supply and the presence of organisms
  • The role of biofilms in chronic osteomyelitis of the jaws is not well studied
  • Possible polymicrobial bacterial focus: odontogenic disease, pulpal and periodontal infection, extraction wounds, foreign bodies, and infected fractures
  • Specific etiologies:
    • Actinomyces: cervicofacial actinomycosis is a slowly progressive infection with granulomatous and suppurative features
    • Candida albicans: extremely rare, despite being a known commensal of oral cavity
    • Nocardiosis: chronic disease that may resemble actinomycotic infection; primary target is usually lung, then hematogenous spread to other organs, cervicofacial region, occasionally including bone
    • Tuberculosis: osteomyelitis of jaws caused by Mycobacterium tuberculosis; uncommon, usually NOT confined to bone
    • Underlying malignancy and associated osteomyelitis: clinical and radiographic signs of secondary chronic osteomyelitis may be similar to malignant neoplasm complicated by secondary bone infection
    • Underlying additional pathology and associated osteomyelitis: clinical and radiographic signs of secondary chronic osteomyelitis may be difficult or impossible to distinguish from a pre-existing, presently infected pathologic disease in the same anatomic area (example: florid cemento-osseous dysplasia)
Clinical features
  • Clinical presentation of secondary chronic osteomyelitis of jaws may be variable, based on intensity of disease, the host, the organisms and length of time the disease has been in place
  • Clinically and radiographically, ranges from aggressive osteolytic putrefactive phase to a 'dry' osteosclerotic phase
  • Deep pain frequently observed in acute phase, may be less intense or a dull pain in the chronic phase
  • Firm tenderness caused by a periosteal reaction may be seen more often in chronic osteomyelitis rather than the exquisitely painful swelling due to abscess formation in the acute phase
  • Sequestra and fistula formation are more commonly associated with secondary chronic osteomyelitis
  • Initial correct diagnosis of secondary chronic osteomyelitis must be established prior to any successful treatment
  • Adequate diagnosis can usually be achieved based on history, clinical evaluation, imaging studies
  • In special situations when an underlying malignancy is suspected, biopsy prior to the actual surgical intervention is advisable
Radiology description
  • Features:
    • Clinically and radiographically, a spectrum ranging from an aggressive osteolytic putrefactive phase to a 'dry' osteosclerotic phase
    • Early: osteolysis may be predominant feature
    • Advanced: osteolysis and sclerosis, may mimic fibro-osseous lesion of bone
  • Radiographic differential diagnosis (broad since radiologic features are variable)
    • Acute suppurative osteomyelitis
    • Cemento osseous dyplasia (COD) often confused with primary chronic osteomyelitis in literature
      • May be a predisposing factor for bone infection
      • Florid cemento osseous dysplasia appears on radiographs as sclerosing opaque and dense masses
      • The bone changes are often adjacent to apices of teeth and are restricted to alveolar process in either or both jaws
    • Chronic sclerosing osteomyelitis / diffuse sclerosing osteomyelitis
      • Ossifying periostitis and diffuse sclerosing osteomyelitis are descriptive radiological features
      • Both primary and secondary chronic osteomyelitis may demonstrate these patterns with extensive sclerosis, variable amounts of osteolysis and periosteal reaction on diagnostic imaging
    • CRMO
    • Garrè sclerosing osteomyelitis
    • Osteochemonecrosis
    • Osteoradionecrosis
    • Primary chronic osteomyelitis
    • SAPHO syndrome
    • Tendoperiostitis
  • Malignancy or benign aggressive intraosseous neoplasms inducing proliferative periostitis:
    • Ewing sarcoma
    • Langerhans cell histiocytosis
    • Leukemia / lymphoma
    • Metastatic disease to jaws
    • Osteosarcoma
    • Paget disease (deforming ostitis)
      • Due to disturbed bone metabolism, unknown origin
      • Usually occurs in advanced age and affects spine, pelvic skeleton, cranial vault
      • Long bones and facial skeleton are rarely involved
      • If jaws are affected, maxilla is somewhat more often involved than mandible
    • Osteopetrosis (Albers-Schonberg disease)
      • Genetically inherited disease which involves all bones
      • Two major types: autosomal recessive form is "malignant" with anemia, manifests at birth; autosomal dominant form is "benign"
      • Malignant form is more dramatic, with severe impairment and systemic complications, patients rarely living beyond age 10 years
      • Benign form is more likely to be seen in daily practice
      • The jawbone shows massive sclerosis
      • Because of the disturbed physiology of the bone due to insufficient osteoclasts, the osteopetrotic bone cannot be resorbed adequately and sclerosis increases with time jeopardizing bone perfusion; secondary bone infection is common and clinical picture resembles primary or secondary chronic osteomyelitis with predominant sclerosis
      • Because bone physiology is generally disturbed, both jaws may be completely affected, contrary to primary chronic osteomyelitis which generally just affects the mandible
Prognostic factors
  • Often a prolonged course, difficult to predict
  • Risk factors for recurrence: ages 6 - 12 years or > 65 years, pre-admission antibiotic administration, a lesion at the mandibular ramus, concurrent maxillofacial space infection (MSI), and conservation of pathogenic teeth (BMC Infect Dis 2013;13:313)
  • Risk factors for life threatening complications: age > 65 years, admission temperature > 39 degree C, admission white blood cell (WBC) count >15×109/L, pre-admission antibiotic administration, concurrent MSI, pre-existing diabetes, and respiratory difficulty
  • Treatment based on age of patient, presence of underlying additional pathology such as florid cemento osseous dysplasia, presence of systemic disease
  • Surgical debridement: dictated by extent of infection, presence of foreign bodies and nonviable tissues included (J Oral Maxillofac Surg 1993;51:1294)
  • Culture material: tissue samples are favored over surface swabs of necrotic bone
  • Antibiotic therapy: ideally withhold until cultures obtained; initially empiric therapy, often broad spectrum; then Infectious Disease consultation, particularly if considering extended antibiotic regimen
  • Hyperbaric oxygen therapy may be offered
Clinical images

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Extracion of tooth 46

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Mandibular swelling

Gross description
  • In osteomyelitis, surgical therapy intends to remove necrotic bone by "debridement"
  • Macroscopy of specimens removed for osteomyelitis is determined by the type of surgery and depends on the extent and duration of disease
  • Curettage yields small tan to brown hemorrhagic bone fragments and beige inflammatory exudate
  • Small curettage fragments are usually totally embedded in paraffin and normally do not require dissection
  • Larger tissue specimens should be oriented and cut perpendicular to osseous surface
  • Necrotic bone fragments are pale whitish-gray; sequestra usually show an irregular outline
  • Occasionally, a jaw resection is required; on cross section, the bony cortex appears thickened and the cancellous bone sclerosed; osteolytic and osteosclerotic foci may alternate
  • Biopsies to confirm a diagnosis of osteomyelitis and rule out neoplasia may be very small
Microscopic (histologic) description
  • According to Zurich classification, pathology is a secondary classification criterion serving to confirm the diagnosis of osteomyelitis if clinical judgment and diagnostic imaging are inconclusive (J Craniomaxillofac Surg 2004;32:43)
  • Histology of jaw osteomyelitis should always be complemented and interpreted in conjunction with clinical and radiological findings and should NOT be used independently
  • Histology is also essential to exclude differential diagnoses
  • A clear distinction of primary and secondary chronic osteomyelitis solely based on histopathology is not always possible but may be helpful in context with clinical presentation and imaging studies
  • When few clinical signs of suppuration (pus, fistula, sequestra) are evident, histopathology resembles typical appearance of chronic osteomyelitis with no clear distinction of primary and secondary chronic forms
  • An important purpose of histopathological investigation - beyond the confirmation of a clinically and radiologically suspected diagnosis of osteomyelitis - consists of typing and grading of the inflammatory activity; this may help distinguish secondary chronic osteomyelitis from primary chronic osteomyelitis in some cases when clinical course and imaging studies are inconclusive
  • Histopathology in cases of secondary chronic osteomyelitis with significant suppuration demonstrates similar features as acute osteomyelitis with large amounts of polymorphonuclear leucocytes, macrophages, and plasma cells, accompanied by a variable degree of marrow fibrosis and reactive bone formation
  • Cases of secondary chronic osteomyelitis with a less fulminant (e.g., more chronic) course have lymphocytic infiltrate, marrow fibrosis, reactive woven bone formation, minimal marrow adipose
  • Periosteum still contains osteogenic potential in most cases, which contributes to formation of a bony shell (involucrum) covering the sequestra
  • The involucrum may interfere with extrusion of the sequestrum, which may perpetuate the process, in combination with a compromised blood supply and the presence of organisms
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