Osteomyelitis is an infection of bone. This is a relatively common occurrence in the pediatric age group; the incidence of osteomyelitis in the United States is 1 in 5000 children per year and 1 in 1000 neonates per year.¹ Osteomyelitis most often occurs due to hematogenous inoculation of the bone with bacteria. Organisms can also be introduced via a puncture wound or by way of spread from an adjacent structure (e.g., skin or paranasal sinuses). Organisms other than bacteria are occasionally involved, including viruses, fungi, and spirochetes. Classification schemes for osteomyelitis involve the nature of the infecting organism (e.g., pyogenic, fungal, tuberculous, or viral), the mechanism of bone inoculation (e.g., hematogenous or direct implantation), and the chronicity of the infection (i.e., acute, subacute, and chronic osteomyelitis).^2–7

Acute Osteomyelitis

Acute bacterial osteomyelitis is the most common type of bone infection in children. This most frequently occurs by way of hematogenous spread from a remote source. The metaphyseal region is the most susceptible osseous site for hematogenous infection, due to the presence of slowly flowing blood within sinusoidal networks that lack active phagocytes. In at least 50% of instances of epiphyseal osteomyelitis, there is a contiguous focus of infection in the metaphysis. Transphyseal spread of infection from the metaphysis to the epiphysis is most common during the first year of life, when cartilaginous channels span the growth plate and serve as conduits for passage of microorganisms between these structures.

The typical pathophysiology of hematogenous osteomyelitis involves the transport of organisms into the bone via the nutrient arteries. The terminal arteriole branches of the nutrient arteries form loops (loop capillaries) along the metaphyseal margin of the growth plate. Blood then passes into the venous sinusoids in the intramedullary portion of the metaphysis. Slow turbulent flow of blood within these venous sinusoids facilitates implantation of the infecting organisms. Bacteria proliferate and cause an exudative process within the intramedullary portion of the involved metaphysis. The resultant edema causes elevation of intraosseous pressure, which thereby diminishes local perfusion. The sinusoids and adjacent arterioles and venules may thrombose, leading to bone necrosis.

The elevated interosseous pressure that occurs as part of a bone infection contributes to the dissemination of organisms through the interstices of endosteal bone. Longitudinal spread occurs through the medullary cavity of the metaphysis and, potentially, into the diaphysis. Lateral extension may result in penetration through the cortex and into the subperiosteal space, where an exudate may form. If penetration occurs through the periosteum, secondary infection of the adjacent deep soft tissue structures occurs. Because cortical penetration most often is at the level of the metaphysis, those joints with capsules that encompass the metaphysis are at greatest risk for secondary septic arthritis; the hip and the shoulder are the most important of these joints.

The physis serves as a barrier to the extension of a metaphyseal infection into the epiphysis, as the growth plate is relatively avascular. A separate epiphyseal artery supplies the epiphysis. However, persistent transphyseal vascular communications are usually present in infants younger than 12 months of age, making young infants susceptible to spread of metaphyseal infection into the epiphysis and joint. After growth plate closure, metaphyseal vessels progressively penetrate the epiphysis; therefore, epiphyseal infection can occur in adolescents as well.

At least three-quarters of cases of acute hematogenous osteomyelitis involve the long bones. In general, the most rapidly growing bones and those with the largest metaphyses are most commonly affected. The most common sites of osteomyelitis are the metaphyses of the femur, tibia, and humerus. Non-long bone sites of osteomyelitis (about one-quarter of cases) include, in decreasing order of frequency, the ilium, vertebral column, calcaneus, femur adjacent to the greater trochanter, ischium, tibia adjacent to the tubercle, scapula, talus, pubis, patella, tarsal bones, navicular bone, and sternum. Infections at these sites tend to involve metaphyseal-equivalent regions, such as the apophyses of the iliac wings.

The classic clinical manifestations of osteomyelitis include pain, fever, and leukocytosis. However, up to one-third of children with osteomyelitis are afebrile and have a normal white blood cell (WBC) count at the time of initial presentation. The erythrocyte sedimentation rate is elevated in approximately 95% of these children. A positive blood culture is obtained in less than half of children with osteomyelitis. Percutaneous or operative sampling also fails to establish a bacteriological diagnosis in many instances. Staphylococcus aureus is the causative agent of acute hematogenous osteomyelitis in 85% to 90% of pediatric patients. Group B β-hemolytic Streptococcus species constitute the second most common group of organisms, particularly in neonates and young infants. Gram-negative enteric organisms are occasional pathogens in the skeleton. Kingella kingae is a gram-negative coccobacillus that can cause osteomyelitis, but typically requires specimen collection with a blood culture vial in order to establish the diagnosis. Salmonella osteomyelitis can occur in children with sickle cell disease. Pseudomonas aeruginosa infection is a potential complication of a penetrating foot injury.

In infants with hematogenous osteomyelitis, the clinical manifestations are often nonspecific. Common findings include pain, soft tissue swelling, and diminished use of the affected extremity (“pseudoparalysis”). Hematogenous spread of infection from an umbilical catheter is a relatively common mechanism of bone inoculation in neonates. Neonatal osteomyelitis is multifocal in 45% to 75% of cases. The most common sites are the femur, humerus, and tibia. Extension of infection into an adjacent joint occurs in up to three-fourths of cases.

Older children with acute osteomyelitis frequently have local signs of inflammation. Limping is a frequent presenting complaint in children with osteomyelitis involving the lower extremity. There is sometimes a history of recent trauma, possibly predisposing the bone to infection in the presence of bacteremia. There is often tenderness to palpation in the region of the involved bone. The pain may increase with motion. Muscle spasm may cause flexion of the joint. Some children with acute osteomyelitis have systemic signs and symptoms such as fever, chills, malaise, and dehydration. The adult form of hematogenous osteomyelitis that occurs in adolescents often has a more insidious onset.

Although radiographically demonstrable osseous manifestations of acute osteomyelitis do not usually develop until at least 7 days after the onset of infection, helpful clues to the diagnosis are usually present earlier in the course of the infection. Within a few days of onset, radiographic evidence of local soft tissue swelling is sometimes present. Muscles adjacent to the infected bone may become enlarged. With the prompt institution of appropriate antibiotic therapy, radiographic findings of bone destruction may never develop. Other patients have focal radiolucencies within the affected bone beginning 10 to 14 days after the onset of infection. These localized metaphyseal radiolucencies may progress to a pattern of irregular destruction, sometimes with extension into the metaphyseal cortex and subperiosteal region. Periosteal new bone formation occurs. The severity of bone destruction tends to be greater in neonates with acute osteomyelitis than in other age groups.^2,8

Bone scintigraphy is quite sensitive for the early detection of acute osteomyelitis; skeletal scintigraphy is generally positive within 24 to 72 hours of the onset of symptoms. The classic appearance is that of a well-defined region of avid uptake on both blood pool and delayed images. Metaphyseal osteomyelitis often has a flame shape on scintigraphy (Figure 62-1). Occasionally, hyperemia causes a somewhat larger region of diffuse moderately increased uptake surrounding the more intense region of actual infection. In the appropriate clinical situation, scintigraphy is often the only imaging study required for the diagnosis of osteomyelitis.

Uncommonly, regional ischemia or bone infarction in a patient with acute osteomyelitis results in diminished tracer accumulation with scintigraphy (Figure 62-2). This is termed cold or infarctive osteomyelitis. There is usually surrounding intense tracer accumulation in the viable portion of the bone. Infarctive osteomyelitis generally represents a somewhat advanced and severe infection. Neonates are more prone to infarctive osteomyelitis than are older children.

Observation of the imaging pattern during the blood pool and delayed phases of skeletal scintigraphy is helpful for the differentiation between osteomyelitis, cellulitis, and septic arthritis. With osteomyelitis, there is avid tracer accumulation during both phases of the examination. Cellulitis usually results in prominent tracer accumulation in the involved soft tissues on blood pool images due to hyperemia, but normal or only mildly increased uptake in the adjacent osseous structures on delayed images. With septic arthritis, blood pool images show prominent periarticular activity due to synovial hyperemia. Delayed images with septic arthritis show normal osseous uptake or subtle periarticular increased activity. Septic arthritis of the hip frequently is accompanied by diminished activity in the femoral head and physis due to tamponade.

[₁₈F]-Fluorodeoxyglucose positron emission tomography shows increased accumulation of radiotracer in areas of bone infection. This is due to increased glucose metabolism in the granulocytes and macrophages at the site of infection in response to inflammatory mediators.⁹

The sensitivity of MR for the diagnosis of acute osteomyelitis is equal to or greater than that of scintigraphy. Manifestations of the infection are nearly always present on MR by the time of clinical presentation. The initial finding is due to marrow edema, with diminished signal intensity on T1-weighted images and hyperintensity on T2-weighted (fat-suppressed) images; short tau inversion recovery (STIR) images are frequently helpful. When present, cortical destruction results in elevated signal intensity in the normally hypointense peripheral strip of cortex. Fluid in the subperiosteal space is hyperintense on T2-weighted images and hypointense on T1-weighted sequences. Subperiosteal fluid does not enhance on images obtained with IV gadolinium, whereas the elevated periosteum enhances prominently. Reactive bone formation is hypointense on all sequences. T2-weighted images often show increased signal intensity in adjacent soft tissue structures, due to either reactive edema or associated cellulitis (Figure 62-2).^10,11

The earliest sonographic manifestations of acute osteomyelitis are deep soft tissue thickening and increased echogenicity due to edema adjacent to the involved bone. Doppler imaging may show hyperemia in the adjacent soft tissues. Sonography is quite sensitive for the detection of an associated joint effusion. In some cases, subperiosteal fluid is visible. The wall on a subperiosteal abscess is hyperemic on color Doppler imaging. With a large focus of cortical disruption, there may be irregularity of the hyperechoic cortical surface.^12,13

CT is somewhat less sensitive than scintigraphy and MR for the detection of acute osteomyelitis, and therefore is usually not selected as the imaging technique early in the course of the disease. An early CT finding of acute osteomyelitis is increased attenuation of the marrow space due to edema, hemorrhage, or purulent material. Soft tissue swelling in the periosseous tissues is an additional early finding. A subperiosteal abscess is demonstrated as a fluid collection with enhancing walls. CT is the most sensitive imaging technique for the detection of cortical destruction.

For most children with suspected acute osteomyelitis, the typical imaging approach consists of standard radiographs followed by bone scintigraphy or MR. Unless there is a concern for multifocal disease, MR is usually the most efficacious technique. MR is highly sensitive for the marrow edema that is the indicator of infection. It allows detection of associated complications such as septic arthritis or soft tissue abscess. MR also avoids patient radiation exposure. Percutaneous imaging-guided aspiration of the infected bone marrow and any focus of subperiosteal fluid is usually indicated. Because most patients with osteomyelitis are treated with IV antibiotics, peripherally inserted central line placement at the time of the bone aspiration can be helpful.

In most patients with osteomyelitis, the diagnosis and initiation of effective treatment occur in the early phase of the infection. Cortical disruption tends to be minimal and there is prompt reconstitution of destroyed trabeculae in the metaphysis. With more severe infections or those in which there is a delay in treatment, extensive periosteal new bone formation in the healing phase may form an involucrum around fragments of devitalized bone. A focus of dead bone is termed a sequestrum. A sequestrum appears sclerotic relative to adjacent viable bone on radiographs and CT, and is hypointense on MR; surgical removal is sometimes indicated. Other potential complications of acute osteomyelitis that may be identified on imaging studies include intraosseous or soft tissue abscess formation, pathological fracture, sinus tract or fistula, and premature closure or other deformity of a growth plate.

Fungal organisms that can cause osteomyelitis include Blastomyces, Candida, and Histoplasma. These infections usually occur in association with a predisposing factor such as broad-spectrum antibiotic therapy, immunosup pression, prematurity, or hyperalimentation. Neonatal Candida osteomyelitis can occur in association with maternal vaginal candidiasis. Joint involvement in these infants often precedes osseous infection. Multifocal osteomyelitis is an uncommon complication of disseminated histoplasmosis. In Africa, bone and joint infections due to Histoplasma duboisii are relatively common. Paracoccidioides brasiliensis is a potential bone pathogen in Latin American children.¹⁴

Aspergillus osteomyelitis is most often due to direct spread of infection from the lung; there appears to be a predilection for this complication in patients with chronic granulomatous disease. Imaging studies typically show local bone destruction in association with a large, contiguous soft tissue mass of the lung and chest wall. Hematogenous inoculation can also occur, usually producing imaging findings similar to those of other fungal bone infections.

Brucella osteomyelitis results in osteolytic foci with minimal periosteal new bone formation. There is a predilection for involvement of the vertebrae. Joint infections can also occur in patients with brucellosis.¹⁵

Subacute Osteomyelitis

Subacute osteomyelitis refers to a form of bone infection that is clinically and radiographically distinct from classic acute osteomyelitis. The pathophysiology may involve infection with an organism of low virulence (i.e., primary subacute osteomyelitis) or antibiotic blunting of an acute infection without eradication. Subacute osteomyelitis has an insidious onset, with symptoms usually present for at least 2 weeks prior to diagnosis. The major complaint often is pain or limping. Swelling of the overlying soft tissues is usually minimal. The involved limb typically functions normally. Systemic manifestations of the bone infection are absent or minimal. The WBC count is usually normal and blood cultures are negative. The erythrocyte sedimentation rate is often elevated. Occasionally, an organism can be cultured from the involved bone; S. aureus is the most commonly isolated bacteria in these patients.^16–19

The most important pathological and radiological feature of subacute osteomyelitis is a type of localized bone abscess that is termed a Brodie abscess. This is a relatively small osseous cavity that is usually surrounded by a sclerotic rim of reactive bone. The cavity contains fluid and/or granulation tissue. Imaging studies show a Brodie abscess as a round, oval, or serpiginous osseous defect, usually located in the metaphysis of a long bone. The abscess may cross the growth plate into the epiphysis. CT sometimes shows a small dense sequestrum within the abscess cavity. Adjacent periosteal reaction is usually present; in some patients, sclerosis and periosteal new bone formation are the only radiographic manifestations of subacute osteomyelitis.

A Brodie abscess has a relatively characteristic target appearance when viewed in cross-section on MR. The central cavity has low signal intensity on T1-weighted images. There is an adjacent inner ring of granulation tissue that is hyperintense on all sequences. An outer dense fibrotic ring is hypointense on all sequences. There may also be a peripheral halo that is hypointense on T1-weighted images and hyperintense on T2-weighted images, due to edema. The surrounding rim of active inflammation enhances with contrast, but the central area of necrosis within the abscess does not enhance.^20,21

Chronic Osteomyelitis

Chronic osteomyelitis refers to long-term infection of the bone that is results in extensive sclerosis and, in many patients, an abscess or sinus tract. Some cases are associated with a prior fracture, surgical procedure, or penetrating trauma. Imaging studies show thickened, irregular, sclerotic bone at the site of involvement, usually in conjunction with irregular radiolucent areas. There is usually a relatively long segment of bone that is involved; periosteal bone formation is extensive. CT and MR show varying signal intensity/attenuation of the involved segment of bone due to the presence of reactive new bone formation, granulation tissue, and fibrosis.^22,23

CT and MR are useful in patients with chronic osteomyelitis for the detection of a bone abscess, sequestrum, or complication in the adjacent soft tissues. A bone abscess produces relatively low attenuation on CT and, unless there is granulation tissue, does not enhance with contrast. An abscess has high signal intensity on T2-weighted MR images. A central sequestrum is sometimes present; this is hyperattenuating on CT and hypointense on MR (Figure 62-3).

Sclerosing osteomyelitis of Garré refers to a sclerosing form of chronic osteomyelitis that apparently is due to a low-grade infection. There is an insidious clinical onset; patients report pain, but systemic signs and symptoms of infection are mild or absent. The diaphysis of a long bone is the most common site. Radiographs and CT show diffuse new bone formation in the involved segment, and minimal or no bone destruction. Abscess and sequestrum formation are not features of this type of chronic osteomyelitis. The involved bone may be somewhat bowed. The clinical and radiographic features of sclerosing osteomyelitis of Garré can mimic those of osteoid osteoma; CT and skeletal scintigraphy are helpful in these patients to help exclude the presence of the nidus of an osteoid osteoma.^24,25

Yaws is caused by infection with the spirochete Treponema pertenue. These patients frequently report bone pain. Radiographs show active periosteal bone formation, which is sometimes massive. In the later stages of the disease, findings of chronic osteomyelitis may be present, with bone destruction, fistula formation, and sequestration.

Chronic recurrent multifocal osteomyelitis (CRMO; plasma cell osteomyelitis) is an idiopathic multifocal inflammatory disorder of bone. Biopsy of involved bone shows nonspecific chronic inflammatory changes, with plasma cell, lymphocytic, and histiocytic infiltration. No organisms are isolated with culture, and antibiotics do not alter the course of the disease. CRMO is apparently an autoinflammatory disease. The typical age range at diagnosis is 5 to 15 years. Common skeletal sites of involvement include the metaphyses of the knees (the tibia is the single most common site), the clavicles, the spine, and the facial bones. The lesions are sometimes bilateral and symmetric.^26–28

The clinical onset of CRMO is insidious. The most common clinical manifestations are localized pain and soft tissue swelling. Systemic manifestations are absent or minimal. Some radiographically visible lesions are asymptomatic. In some patients with CRMO, there are associated cutaneous lesions, such as a pustular rash of the palms and plantar aspects of the feet (see the SAPHO Syndrome section). CRMO usually has a benign, self-limited course, although resolution may take several years. There is considerable variability between patients with respect to the course. Periods of remission are sometimes followed by unexplained exacerbation.

The early radiographic manifestation of CRMO is lytic bone destruction. Later in the course, sclerosis results in a mixed character (Figure 62-4). Periosteal reaction is common. Vertebral body involvement may lead to collapse, with disc space preservation. The osseous lesions of CRMO avidly accumulate bone-seeking radiopharmaceuticals. Scintigraphic abnormalities sometimes precede clinically or radiographically demonstrable lesions. In the early phase, MR shows marrow edema, often in conjunction with periostitis, soft tissue inflammation. Chronic or recurrent lesions have a mixed character, due to the presence of sclerosis or hyperostosis.^29,30

SAPHO syndrome refers to the combination of cellulitis, acne, pustulosis, hyperostosis, and osteitis. This syndrome shares some features with CRMO and spondyloarthropathy. The major cutaneous manifestations are palmoplantar pustulosis, acne conglobata, and hidradenitis suppurativa. Potential musculoskeletal manifestations include aseptic osteitis, hyperostosis, and bone hypertrophy. The most common sites of skeletal involvement are the anterior chest wall and the spine. Imaging findings of vertebral involvement include vertebral body osteosclerosis, paravertebral ossifcations, and vertebral collapse. Cortical erosion at the corner (typically anterior) of 1 or more vertebral bodies is a relatively characteristic finding on MR evaluation. There is often concomitant involvement of the vertebral end plate or anterior vertebral body cortex.^31–34

The skeletal system accounts for 10% to 20% of all extrapulmonary tuberculosis. The most common skeletal sites are the spine and the synovial joints.³⁵ In children, skeletal tuberculosis typically occurs by way of hematogenous spread from a primary source; extension from tuberculous arthritis is an additional potential mechanism. The primary site, however, may not be clinically or radiographically demonstrated; evidence of concurrent pulmonary tuberculosis is present in less than half of these patients.^36–38

The initial osseous manifestation of osseous tuberculous infection is a granulomatous lesion that develops at the site of deposition of the mycobacterium. There is subsequent caseation that results in trabecular destruction. If there is progression, cortical destruction may occur, leading to periosteal reaction and an extraosseous inflammatory mass. The imaging features of bone tuberculosis are often similar to those of chronic pyogenic osteomyelitis. Any portion of bone can be involved; tuberculosis is an important consideration in the differential diagnosis of a radiolucent epiphyseal lesion. Reactive sclerosis is sometimes minimal, resulting in the appearance of a well-defined “cystic” defect in the epiphysis or metaphysis of a long bone. Bone abscess and sinus formation are relatively common with tuberculosis. Tuberculous dactylitis (spina ventosa) may cause bone expansion in conjunction with lytic areas.³⁸

Tuberculous involvement of a joint is usually the result of hematogenous inoculation of the synovium. Tuberculous arthritis may have an insidious onset. Involvement is often monoarticular; the hip and knee are the most frequent sites. Joint effusion and contracture may occur. The diagnosis can be established with a needle biopsy of the synovium; this procedure is particularly helpful for the child with monoarticular arthritis and a positive tuberculin skin test. The joint space is usually preserved in the early phases of tuberculous arthritis, due to a lack of destructive proteolytic enzymes.³⁹