by Robert C. Mellors, M.D., Ph.D.

III. Bone Infections

1. General Considerations

Osteomyelitis (literally an inflammation of bone and bone marrow) is the generic term for bone infections. Pathogenic microorganisms (pyogenic bacteria, mycobacteria, fungi) can spread to bone by one of three routes: hematogenous spread; direct extension from a contiguous site of infection; and direct introduction. The most serious bone infections are pyogenic osteomyelitis and tuberculosis; also to be noted are rare cases of syphilis and fungus infections. The clinical course of osteomyelitis depends on the characteristics of the causative organism, the route of the infection, and the age of the patient.

2. Hematogenous (Pyogenic) Osteomyelitis

Etiology and Pathogenesis

Acute hematogenous osteomyelitis occurs predominately in children and before the age of epiphysial closure (<21 yrs), typically originates in the metaphysis of long bones in the region of most rapid growth and greatest vascularity, and involves, in order of frequency, the lower end of the femur, the upper end of the tibia and humerus, and the radius. Hematogenous osteomyelitis of children sometimes results from the blood-borne spread to bone of an extraskeletal focus of infection (skin, ear, pharynx) , but most often such a source of infection is not clinically demonstrable. In that event it is generally assumed that transient "trivial" bacteremia arising from "trivial" trauma, such as ordinary cuts and bruises of the skin, is the original source of infection.

Hematogeneous osteomyelitis of children is most often caused by S. aureus which accounts for 60-90% of cases. Osteomyelitis of neonates is also frequently caused by group B streptococci and E. coli. Children with sickle cell disease are prone to acquire Salmonella infections and to develop Salmonella osteomyelitis.

Osteomyelitis of children usually begins in the metaphysis of long bones. The blood-borne bacteria are carried to the marrow space by way of the nutrient artery. The initial site of infection within a particular bone is determined by the vascular anatomy as related to the epiphysial growth plate. In children of more than 1 year of age (who account for most cases, about 80%, of hematogenous osteomyelitis), the metaphysial branches of the nutrient artery do not penetrate the growth plate. The vessels turn back upon themselves just proximal to the plate and enter venous sinusoids in the marrow space of the metaphysis. The venous sinusoids are much larger than the arteries feeding them, have a slower blood flow, and provide a medium favorable for bacterial growth.

Hematogenous osteomyelitis in adults rarely involves the long bones but usually occurs in the vertebrae which are generally highly vascular. The hematogenous spread of infection can occur by way of the nutrient branches of the spinal artery or by flow from the pelvic veins to the lumbar veins and, under conditions of increased abdominal pressure, retrograde flow through the paravertebral venous plexus of Batson. The vertebral infection is usually secondary to a primary bacteremia caused by genitourinary tract infection, soft tissue and respiratory infections, and those contracted by i.v. drug abusers. S. aureus accounts for about 55% of adult bone infections, and Gram-negative bacteria and streptococci for much of the remainder. The complications of vertebral osteomyelitis include extension of the infection to the adjacent disk space and extension to retropharyngeal, mediastinal, peritoneal, and meningeal sites depending on the vertebrae involved.


The bacterial infection causes a fulminant acute inflammation of the marrow space and an exudation of polymorphonuclear leukocytes. The presence of an inflammatory exudate within the rigid limits of the marrow space causes an increase in intramedullary pressure, reduced blood flow, local vascular occlusion, and thrombosis. Local ischemic injury and cell necrosis of marrow and osseous tissue occur, and the bacteria, pus cells, and necrotic debris comprise a septic focus of purulent inflammation. At the early stage of the infection, no specific bone changes are seen by radiography.

The infection may then spread rapidly by way of vascular channels through the medullary cavity and the bone cortex which is thin in the region of the metaphysis and provides easy access to the periosteum. The purulent material may elevate the periosteum and form abscesses beneath it or penetrate the periosteum as sinus tracts which drain into the soft tissue or extend to the skin surface.

646: Skin sinus in chronic pyogenic osteomyelitis, H&E.

The stripping away of the periosteum further impairs the blood supply to the cortical and medullary bone, and larger areas of ischemic bone tissue become necrotic. The areas of bone destruction may be seen in the radiograph as patchy areas of radiolucency. After several days a sizeable portion of the necrotic bone tissue may separate from the viable bone as an avascular bone fragment termed a sequestrum, which may be seen in the radiograph as a radioopaque sequestrum.

648: Chronic osteomyelitis with sequestration of necrotic bone. H&E.

With continuation of the bone infection, chronic inflammatory cells (lymphocytes, histiocytes, plasma cells), proliferating fibroblasts, and reactive new bone formation contribute to the microscopic picture of chronic osteomyelitis.

663: Reactive new bone formation in chronic osteomyelitis. H&E.

The elevated periosteum is stimulated to form new bone which surrounds the underlying infected and inflammed bone with a bony envelope termed an involucrum.

Clinical Course

The onset of hematogenous osteomyelitis is usually sudden in children (but often insidious in adults). The early symptoms of childhood osteomyelitis are those of infection and inflammation: fever, bone pain often throbbing and severe and referred to the metaphysis, tenderness to pressure, limitation of movement which in the extreme may render the limb immobile ("pseudoparalysis"), local erythema, swelling, and heat. Blood cultures are positive in about 50% of pediatric cases . The clinical diagnosis of early osteomyelitis can be supported by a bone scan ( with technicium diphosphonate): increased tracer uptake reflects the inflammatory process in the bone lesion. Plain radiographs usually do not reveal changes until about 10 or more days after the onset of symptoms, because a substantial (30-50%) reduction in bone calcium content is required for the demonstration of an osteolytic destructive lesion.

The course of acute hematogenous osteomyelitis is age-dependent. In neonates (< 3 months of age), bone infections are often fulminant but rarely necrotizing, because the spongy bone and thin cortex adapt to increased intraosseous pressure without compromising the blood supply. In infants (3-12 months) and adults, capillaries extend from the metaphysis to the epiphysis and can spread the infection to the adjacent joint, causing suppurative arthritis and septic joint effusion.

649: Pyogenic osteomyelitis and suppurative arthritis leading to joint destruction. H&E.

In children (>1 yr.) who have an intact epiphysial plate without capillary penetration, a sterile "sympathetic" effusion may occur, indicating a barrier between the infection and the joint space. The pathological picture in hematogenous osteomyelitis may occasionally differ from the spreading and destructive pattern previously described. The initial focus of bone infection may become circumscribed by a fibrous capsule and bone sclerosis to form a localized abscess (Brodie's abscess) which may undergo sterilization or become a chronic focus of infection.

635: Osteomyelitis of tibia with localized (Brodie's) abcess circumscribed by sclerotic bone.

Rarely, in other circumstances, exuberant periosteal new-bone formation dominates the pathological picture, resulting in a non-purulent sclerosing osteomyelitis (Garre's sclerosing osteomyelitis).

A prompt clinical diagnosis and the institution of a potent and protracted regimen of antibiotic therapy have greatly decreased the mortality rate of osteomyelitis which reached as high as 20-40% of cases in the pre-antibiotic era. Nevertheless, even now a sizeable number of bone infections may be undiagnosed or inadequately treated. In chronic osteomyelitis, the avascular dead tissue, pus and bacteria may remain isolated within an area of bone fibrosis and sclerosis and give rise to recurrent episodes of acute osteomyelitis. The treatment of chronic bone infections usually requires , in addition to antimicrobial therapy, surgical intervention to drain abscesses and remove necrotic tissue.

3. Osteomyelitis from a Contiguous Infection

Burns, sinus disease, peridontal infection, soft tissue infection, and skin ulcers caused by peripheral vascular disease (arteriosclerosis, diabetes, vasculitis) are among the adjoining sites of microbial infection that may spread to bone. The onset is often insidious, and the symptoms are those of infection and inflammation of the involved bone. The pathological and radiological changes are similar to those seen in chronic hematogenous osteomyelitis. The treatment usually requires surgical intervention (debridement of necrotic tissue, drainage of abscesses, etc.) combined with bacteriological cultures and appropriate antimicrobial therapy. Blood cultures are positive in about 10% of cases.

4. Osteomyelitis from an Introduced Infection

Penetrating wounds, compound fractures, simple fractures treated surgically with open reduction and internal fixation, prosthetic joint replacements, and other orthopedic appliances (plates, nails, screws, pins) may introduce microbial infection directly into bone. The pathological changes in the involved bone include suppurative inflammation, ischemic necrosis, fibrosis, and reactive new-bone formation as occur in hematogenous osteomyelitis.

5. Bone Tuberculosis

General Considerations

Tuberculous osteomyelitis is almost always caused by the hematogenous spread of organisms from an active focus of tuberculosis elsewhere in the body, usually the lung and occasionally some other site (mediastinal or aortic lymph nodes, kidney, bowel, etc.). The bone infection may occur at any age but is most commonly seen in children. The vertebrae and the long bones of the extremities are most frequently involved. In many cases the infection also spreads to contiguous joints such as the hip, knee, and intervertebral joints.

616: Tuberculosis of knee: the femoral condyles are eroded and destroyed by tuberculosis infection of bone and joint.

The bones and joints of the hands, feet, shoulder, elbow, and ribs are also sometimes involved. In some patients, it may be impossible to determine whether the infection originated within the cancellous bone of the metaphysis or the joint.


The onset of tuberculous osteomyelitis is usually insidious. The infection is unrelenting, necrotizing, and destructive of bone, cartilage, and soft tissue. The tuberculous exudation and the inflammatory necrosis may extend through the medullary and cortical bone, penetrate through the periosteum, and progress through the epiphysial and articular cartilage (radiographic joint space). Tunneling sinuses may extend into the adjoining soft tissue and drain to the skin surface. Sequestration and the formation of an involucrum are uncommon.

Tuberculosis of the spine (Pott's disease) most commonly involves the thoracic and lumbar vertebrae and usually comprises both tuberculous osteomyelitis and tuberculous arthritis.

634: Tuberculosis of spine (Pott's disease) with vertebral collapse and acute kyphotic angulation.

The infection often begins in the anterior part of the vertebral body and extends into the intervertebral disc:

15055: Tuberculosis of spine.

The tuberculous destruction and collapse of the vertebral bodies and discs result in serious deformities (kyphosis and kyphoscoliosis) of the spine. The kyphotic angulation along with the inflammation and edema of the dura caused by vertebral collapse may compress the spinal cord and nerve roots, resulting in pain, muscle spasm and weakness, and paralysis.

The tuberculous exudate emerging from a bone or joint may spread through sinuses in the soft tissue or dissect along fascial planes and muscle sheaths and present at a more remote site as a "cold" abscess, socalled because there is a milder degree of heat compared to a pyogenic abscess and few, if any, acute inflammatory cells. In this way, tuberculous exudation from the thoracolumbar spine may spread along paravertebral muscles and the psoas muscle sheath and localize in the inguinal region (psoas abscess).

Microscopically, tuberculosis of bone and joint is characterized, as are all tuberculous lesions, by the presence of epithelioid granulomas (tubercles) with central caseous necrosis and Langhans' multinucleate giant cells:

651: Tuberculous granuloma of carpal bone. H&E

For a definitive diagnosis, tubercle bacilli must be demonstrated microscopically in the lesions or cultured from bone, joint, or synovial fluid. Tubercle-like (tuberculoid) granulomas may be seen in some other inflammatory diseases of bone such as coccidioidomycosis and Boeck's sarcoid, which is characterized by granulomas that rarely, if ever, caseate or calcify.

6. Bone Syphilis

General Considerations

Syphilitic infection may be acquired in-utero (congenital syphilis) or postnatally (acquired syphilis). Bone syphilis is produced by the hematogenous spread of Treponema pallidum during the secondary or tertiary stages of the disease. In congenital syphilis, the infection is spread to the fetus by way of the placenta. The spirochetes localize at active sites of endochondral ossification in the metaphysis of long tubular bones.


The two chief bone lesions of congenital syphilis are osteochondritis and periostitis. Syphilitic osteochondritis involves the metaphysial-epiphysial junctions of long bones and the costo-chondral junctions. Microscopically, the lesions reveal little evidence of osteoblast activity or endochondral bone formation, the epiphysial zone of provisional calcification is widened (as also shown radiologically), and syphilitic inflammatory granulation tissue extends across the metaphysis. The connection between the metaphysis and epiphysis may be loosened and result in epiphysial separation. The inflammatory granulation tissue permeating the metaphysis contains an abundance of proliferating capillaries and a prominent perivascular infiltrate of mononuclear inflammatory cells, with large numbers of plasma cells. In florid cases, spirochetes may be demonstrated in the lesions by silver stains. Syphilitic periostitis is usually seen in early childhood and is characterized by the infiltration of inflammatory granulation tissue between the periosteum and the bone cortex and by subperiosteal new-bone formation. The tibia is most often affected. The deposition of new bone along the anterior cortical surface produces a forward bowing and sharpening of the tibia, the "saber shin" deformity of congenital syphilis.

Acquired syphilis of bone occurs in the tertiary stage of the disease and involves the long tubular bones, the skull, and the vertebrae. The lesions include syphilitic osteochondritis, periostitis with extensive subperiosteal new-bone formation, and osteomyelitis, usually caused by the formation of gummas in the medullary cavity.

7. Fungus Infections of Bone

Mycotic osteomyelitis is rare and usually occurs from the spread of a contiguous infection of soft tissue or sometimes by hematogenous spread. The fungus diseases most often reported as a cause of skeletal infection are coccidioidomycosis (San Joaquin Valley Fever), actinomycosis, blastomycosis, cryptococcosis, and sporotrichosis.

769: Coccidioidomycosis of bone (vertebra), H&E.

628: Actinomycosis of bone. H&E.