Osteomyelitis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

Pathophysiology

Entry of the organism into bone is the first step in osteomyelitis and occurs by three main mechanisms:

1. Hematogenous seeding
2. Contiguous spread of infection to bone from adjacent soft tissue
3. Direct inoculation from trauma or orthopedic surgery (including prosthetics).

Pathogenesis

Several factors contributing to pathogenesis of osteomyelitis include,

Microbial factors

• Etiologic pathogen possesses numerous cell-wall associated adhesins mediating specific attachment to a wide variety of extracellular matrix proteins found in bone including, fibronectin, laminin, osteopontin, bone matrix sialoprotein and collagen.
• After attachment to the bone matrix, direct toxin effect of pathogen may lead to tissue necrosis.
• Adherent bacterial growth leads to the formation of a biofilm (an adherent consortium of micro-organisms enmeshed in an exocellular polysaccharide).
• Biofilmed pathogens are more resistant to host defense and are able to survive longer than usual.

Host factors

Hematogenous spread

• The pathogen most commonly localizes to the metaphysis of a large long bone just beneath the growth plate.
• In adults, after closure of the growth plate, the metaphyseal and epiphyseal vessels establish reconnections so bacteria entering the nutrient artery are directed to the vascular loops beneath the articular cartilage.
• Accordingly, acute hematogenous osteomyelitis in infants and adults often affects the epiphysis.
• In children the growth plate acts as an barrier and the infection is limited to the metaphysis.
• Extension across the growth plate is impeded in children but after closure of growth palate, joint involvement becomes possible.
• In the spine, blood-borne pathogens usually localize to the subchondral regions of the vertebral body.

contiguous spread

• In contiguous spread, bone adjacent to a cutaneous or mucosal ulcer or soft tissue abscess are affected.
• It is more commonly seen in the setting of periodontal and sinus disease, cellulitis of diabetic feet, epidural abscess, decubitus ulcer, or septic arthritis.
• In this setting the inflammatory process must first destroy the periosteum or articular surface before it accesses the bone.
• Unlike hematogenous osteomyelitis, the cortex instead of the medullary cavity is initially infected, and the site at which this occurs influences the rapidity of spread and extent of disease.
• Pathogens triggers inflammation and due to this inflammatory process, intraoseous pressure inside the tight bone matrix increases and may lead to thrombosis of bone vasculature that finally results in bone death.
• If infection progresses, pus may track to other areas of the bone along the medullary canal or through the Haversian systems in cortical bone from the medulla to the outer surface of the cortex and form a subperiosteal abscess.
• This may contribute to a bacteremia or it may track out into the soft tissues and eventually form abscesses or a sinus tract draining to the outside.
• Dead bone accelerates biofilm formation.
• Both the inflammatory cytokines and mediators released during infection, and in some cases bacterial products themselves, can trigger bone resorption either by osteoclast activation or by stimulating phagocytic cells to take on a bone-resorbing phenotype.
• Bone loss starts from around the dead area and will cause separating it from the surrounding living bone and ultimately, to form the sequestrum.
• At the same time, where periosteal stripping has occurred, the resulting periosteal reaction produces a shell of new bone, the involucrum, around the dead bone.

Mechanism of disease: Generally, microorganisms may infect bone through one or more of three basic methods: via the bloodstream, contiguously from local areas of infection (as in cellulitis), or penetrating trauma, including iatrogenic causes such as joint replacements or internal fixation of fractures or root-canaled teeth. Once the bone is infected, leukocytes enter the infected area, and in their attempt to engulf the infectious organisms, release enzymes that lyse the bone. Pus spreads into the bone's blood vessels, impairing their flow, and areas of devitalized infected bone, known as sequestra, form the basis of a chronic infection. Often, the body will try to create new bone around the area of necrosis. The resulting new bone is often called an involucrum. On histologic examination, these areas of necrotic bone are the basis for distinguishing between acute osteomyelitis and chronic osteomyelitis. Osteomyelitis is an infective process which encompasses all of the bone (osseous) components, including the bone marrow. When it is chronic it can lead to bone sclerosis and deformity.

In infants, the infection can spread to the joint and cause arthritis. In children, large subperiosteal abscesses can form because the periosteum is loosely attached to the surface of the bone.

Because of the particulars of their blood supply, the tibia, femur, humerus, vertebra, the maxilla, and the mandibular bodies are especially susceptible to osteomyelitis. However, abscesses of any bone may be precipitated by trauma to the affected area. Many infections are caused by Staphylococcus aureus, a member of the normal flora found on the skin and mucous membranes.

Staphylococcus aureus is the organism most commonly isolated from all forms of osteomyelitis.

Bloodstream-sourced osteomyelitis is seen most frequently in children, and nearly 90% of cases are caused by Staphylococcus aureus. In infants, S. aureus, Group B streptococci (most common) and Escherichia coli are commonly isolated; in children from 1 to 16 years of age, S. aureus, Streptococcus pyogenes, and Haemophilus influenzae are common. In some subpopulations, including intravenous drug users and splenectomized patients, Gram-negative bacteria, including enteric bacteria, are significant pathogens.

The most common form of the disease in adults is caused by injury exposing the bone to local infection. Staphylococcus aureus is again the most common organism seen in osteomyelitis seeded from areas of contiguous infection, but anaerobes and Gram-negative organisms, including Pseudomonas aeruginosa, E. coli, and Serratia marcescens, are also common, and mixed infections are the rule rather than the exception.

Systemic mycotic (fungal) infections may also cause osteomyelitis. The two most common pathogens involved in such infections are Blastomyces dermatitidis and Coccidioides immitis.

In osteomyelitis involving the vertebral bodies, about half the cases are due to Staphylococcus aureus, and the other half are due to tuberculosis (spread hematogenously from the lungs). Tubercular osteomyelitis of the spine was so common before the initiation of effective antitubercular therapy that it acquired a special name, Pott's disease, by which it is sometimes still known. The Burkholderia cepacia complex have been implicated in vertebral osteomyelitis in intravenous drug abusers.

Factors that may commonly complicate osteomyelitis are fractures of the bone, amyloidosis, endocarditis, or sepsis.

In children, the long bones are usually affected. In adults, the vertebrae and the pelvis are most commonly affected.

Acute osteomyelitis almost invariably occurs in children. When adults are affected, it may be because of compromised host resistance due to debilitation, intravenous drug abuse, infectious root-canaled teeth, or other disease or drugs (e.g. immunosuppressive therapy).

Osteomyelitis is a secondary complication in 1-3% of patients with pulmonary tuberculosis. In this case, the bacteria generally spread to the bone through the circulatory system, first infecting the synovium (due to its higher oxygen concentration) before spreading to the adjacent bone. In tubercular osteomyelitis, the long bones and vertebrae are the ones which tend to be affected.

Gross Pathology

Osteomyelitis in cancer.
Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology.

Microscopic Pathology

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