Osteomyelitis is an infection of the bone caused by bacteria, fungi, or mycobacteria. The infection can land in the bone via the bloodstream (hematogenous spread), contiguous spread from adjacent soft tissues, or direct inoculation during trauma, or surgery. The disease process is characterized by the progressive destruction of bone at the center of infection and new appositional bone growth around it. Osteomyelitis is found in both adults and children, though its presentation and prognosis are different in the two groups. Pediatric patients, whose bones have open growth plates, are accordingly more susceptible to infection, but this infection is likewise more amenable to antibiotic treatment. By contrast, osteomyelitis in adults often requires surgical debridement and still has poorer outcomes, owing to both host and disease factors. The major risk factors for osteomyelitis include diseases that compromise the immune system, IV drug use, vascular disease, diabetes mellitus, sickle cell anemia, peripheral neuropathy, prior trauma, and retained orthopaedic implants.

Structure and Function

Osteomyelitis in children occurs most commonly in the metaphysis of the femur or tibia due to hematogenous seeding; that is, circulating bacteria in the bloodstream land in the bone. In children over the age of 18 months, the metaphyseal region has straight, narrow capillaries coursing to, but not across, the growth plate. These vessels then turn back at a 180-degree angle to drain into the veins. This “hair pin” turn decelerates the blood and allows any bacteria within the bloodstream to escape and lodge within the bone (Figure 1).

Figure 1: Schematic drawing of the vascularization of long bones in children between 18 months and 16 years of age. Capillaries in the metaphysis do not cross the physis and instead make a “hair pin” turn that allows circulating bacteria to deposit and infect the bone. (Modified from doi: 10.5334/jbr-btr.1300 The Many Faces of Osteomyelitis: A Pictorial Review)

In children under 18 months, the metaphyseal capillaries extend across the physis into the epiphysis. As a result, any circulating bacteria may not only infect the bone but seed the joint and cause septic arthritis as well.

In healthy adults, most cases of osteomyelitis are caused by direct inoculation from trauma. Hematogenous osteomyelitis is more prevalent among IV drug users and typically affects the vertebrae. Contiguous osteomyelitis tends to occur in older patients with sensory neuropathy (often secondary to diabetes mellitus) or vascular insufficiency, leading to skin ulceration and breakdown.

When bacterial seeding occurs, regardless of mechanism, a local immune response leads to increased vascular permeability, edema, and recruitment of polymorphonuclear leukocytes. This purulence increases pressure within the medullary canal and can further obstruct blood flow. Extrusion of purulent fluid through the bone’s surface to the periosteum, resulting in a sub-periosteal abscess, can occur as well. Increased pressure leads to ischemia and bone necrosis. The necrotic and infected bone may become sequestered during the formation of new bone, making the eradication of bacteria difficult or impossible without surgical excision. The new bone is called an “involucrum,” and the infected bone it surrounds is called the “sequestrum” (Figures 2 and 3).

Figure 2: Schematic drawing of the consecutive events of acute osteomyelitis: (a) initial metaphyseal focus, (b) lateral spread to the cortex, (c) cortical penetration and periosteal elevation, (d) formation of a thick involucrum, (e) further expansion of the metaphyseal focus with extensive involucrum. (Courtesy of doi: 10.5334/jbr-btr.1300 The Many Faces of Osteomyelitis: A Pictorial Review)
Figure 3: Plain radiograph of chronic osteomyelitis of the femur. The focal area of increased opacity represents necrotic bone or sequestrum (blue arrow). (Courtesy of doi: 10.5334/jbr-btr.1300 The Many Faces of Osteomyelitis: A Pictorial Review)

Osteomyelitis can be classified according to its duration (e.g.,acute, subacute, chronic) and mode of origin (e.g., hematogenous, contiguous,direct inoculation). The disease can also be categorized by the Cierny-Mader classification to be in one of four anatomic stages. In stage 1, infection isconfined to the medullary cavity of the bone. In stage 2, there is a superficialinfection affecting the cortex of the bone. Stage 3 involves both cortical andmedullary bone but without loss of structural stability; in stage 4, there isloss of stability. This classification further subdivides patients according to the presence or absence of local and systemic factors that affect the health status of the host, such as diabetes mellitus, vascular insufficiency,malnutrition, peripheral neuropathy, smoking, and others.

Patient Presentation

In pediatric patients, acute osteomyelitis typically presents with fever and progressive pain. If the infection involves the lower extremity, pelvis, or spine, the patient may limp or refuse to walk. If the upper extremity is involved, the patient may refuse to use that extremity. On physical exam, the patient usually does not look well. The affected region is typically swollen, warm to the touch, and tender to palpation. The patient may also experience limited range of motion of the nearby joint.

In contrast to acute osteomyelitis, subacute and chronic osteomyelitis in pediatric patients typically presents with pain but no fever or constitutional symptoms. The primary complaint is typically well localized pain in the metaphysis of the long bone; however, this can also occur in the epiphysis or diaphysis. Patients typically report pain that is worse with activity and temporarily improved with rest. On physical exam, the patient may appear well. The affected region is typically tender to palpation with mild swelling and possible limited range of motion of the nearby joint. The patient may also have an antalgic gait.

The signs and symptoms of osteomyelitis in adults can be subtle, so a careful history taking of the risk factors for osteomyelitis is essential. Acute osteomyelitis may present with erythema, swelling, and pain; the presence of fever is variable. In chronic osteomyelitis, there is also erythema, swelling, and pain typically at a site of high risk, such as prior injury, surgery, or ulceration. If an abscess is present in the soft tissues, a fluctuant swelling with overlying redness may be seen. seen.

Objective Evidence

Although osteomyelitis is associated with an elevated white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level, these abnormal lab tests are nonspecific. A normal ESR and CRP level can help exclude a diagnosis of osteomyelitis. Although the white blood cell count can be elevated, a normal value does not exclude a diagnosis of osteomyelitis. CRP levels can also be used to monitor response to treatment.

Blood cultures are helpful in pediatric osteomyelitis; they can identify the infecting organism in 40-50% of cases and allow for targeted antibiotic therapy.

Radiographic assessment includes plain radiographs, magnetic resonance imaging (MRI), and bone scans. A plain radiograph can help rule out other diagnoses such as fracture or metastasis. MRI is both sensitive and specific for detecting osteomyelitis and should be ordered if the diagnosis of osteomyelitis is suspected (Figure 4).

Figure 4: (Left) Plain radiograph of osteomyelitis of the tibia demonstrating a lytic lesion in the metaphysis (red arrow) with periosteal reaction (green arrow). (Right) Coronal T1-weighted MRI demonstrating intramedullary bone edema. (Courtesy of BMC Infectious Diseases volume 18, Article number: 665 (2018))

Three-phase technetium-99 bone scans and tagged WBC scans are commonly used modalities. A bone biopsy is helpful not only for making the diagnosis of osteomyelitis but also for identifying the offending pathogen and its antibiotic susceptibilities.


Osteomyelitis occurs in all age groups. The annual incidence of osteomyelitis in children is about 13 per 100,000 persons, with no significant difference in occurrence rates between males and females. Children with immunodeficiency, diabetes, hemoglobinopathy, and systemic inflammatory conditions are at increased risk. The incidence of adult osteomyelitis in the United States is estimated to be about 21 per 100,000 persons. The incidence is slightly higher in men, perhaps related to a higher prevalence of trauma or risk factors such as comorbid disease.

Most cases of adult osteomyelitis in healthy individuals are due to open fractures or postoperative infection. Direct spread from diabetic ulcers is also common.

Differential Diagnosis

Note the maxim: “What looks like a tumor might be an infection, and vice versa.” Moreover, Ewing's sarcoma, like osteomyelitis, is frequently associated with fever.

Trauma to bone and the ensuing periosteal reaction produced by the healing process can mimic early osteomyelitis as well.

Bone pain from a sickle cell crisis can mirror that of acute osteomyelitis.

Sensory neuropathy leading to skin ulceration can cause both osteomyelitis and Charcot arthropathy, namely the destruction of a joint resulting from lysis and fragmentation of the bone in the setting of neuropathy. The radiographic appearance of a Charcot joint is similar to that of osteomyelitis and ultimate differentiation may require biopsy and microbiological culture (Figure 5).

Figure 5: Radiographic changes in a foot with Charcot arthropathy; the appearance is very similar to that of osteomyelitis. (Courtesy of David E. Oji, M.D. Stanford University School of Medicine)

Scurvy, although rare in developed countries, may be seen inmalnourished populations.

Red Flags

Because osteomyelitis in young children is often seen concurrently with septic arthritis of a nearby joint, the presence of one requires additional workup to rule out the other.

There should be a high index of suspicion for patients with risk factors for osteomyelitis, as initial radiographs can be normal and lab test abnormalities are usually nonspecific.

IV drug users are at increased risk for vertebral osteomyelitis. Sudden, severe back pain in a patient who uses IV drugs should be suspected to have osteomyelitis until proven otherwise.

Treatment Options and Outcomes

Pediatric patients are usually treated empirically with intravenous antibiotics, later tailored to the results of blood cultures. If patients fail to improve from a clinical and laboratory standpoint after 72 hours of antibiotic therapy, repeat imaging and surgical debridement are indicated. Otherwise, antibiotics are typically continued for four to six weeks. The timing of transition from IV to oral antibiotics is controversial, though it is often feasible to make this transition after several days provided that the patient is improving. With appropriate treatment, the patient's clinical exam should normalize over six to twelve weeks. If acute osteomyelitis is not treated, it can develop into chronic osteomyelitis and cause destruction of bone as well as extension into surrounding tissues.

Skeletally immature patients with a history of osteomyelitis near the physis should be monitored long-term for signs of growth arrest.

Osteomyelitis in adults is treated with antibiotics and often surgical debridement as well. Empiric antibiotic therapy is used at first, while culture and sensitivity data are pending. Empiric antibiotic selection guided by patient-specific factors that can point to the etiology of the osteomyelitis. For example, Staphylococcus aureus is the most common offending organism in normal hosts, whereas salmonella is most common in individuals with sickle cell disease. Generally, a broad-spectrum regimen against both Gram-positive and Gram-negative organisms is best.

Acute osteomyelitis in adults can be treated with antibiotics alone, if it is diagnosed within 48 hours after the onset of symptoms and there is no abscess. If there is an abscess or avascular tissue, surgical debridement is needed to clear the infection, as antibiotics reach necrotic bone poorly if at all. All sequestra, necrotic bone, and retained hardware should be removed.

Local antibiotics can also be administered by implanting polymethyl methacrylate (PMMA) or calcium sulfate that contains and elutes antibiotics (Figure 6). Calcium sulfate is biodegradable and does not need to be removed; PMMA cement is not resorbed and thus a subsequent procedure may be needed for its removal. On the other hand, PMMA can provide structural support. Additional procedures such as bone grafting or soft tissue coverage may be required.

Figure 6: Surgical debridement and antibiotic placement. In the panel at left, the area of osteomyelitis is exposed (green arrows). In the center panel, all infected bone is removed, creating a trough (black arrows). In the panel at right, the area is filled with antibiotic-impregnated calcium sulfate (blue arrows). (Modified from Zhou et al, Journal of Orthopaedic Surgery and Research volume 15, Article number: 201 (2020))

If osteomyelitis is caused by infection of a prosthetic joint, that joint must be removed, ideally as part of a two-stage revision (i.e., the infected arthroplasty is removed and not re-implanted until the infection clears).

In extreme cases involving extensive bone damage or irremediable vascular disease, amputation may be needed. Even in less extreme cases, treatment of osteomyelitis is not always successful. Possible complications include failure to eradicate the infection (about 25% of cases of chronic osteomyelitis), bone deformity (malunion), failure of fracture healing (nonunion) (Figure 7), septic arthritis of adjacent joints, systemic or contiguous soft tissue infection, and, in rare instances, sinus tract formation at risk for a resultant squamous cell carcinoma.

Figure 7: Radiographs demonstrating nonunion of a tibia and fibula fracture in the setting chronic osteomyelitis. There is increased lucency around the external fixator’s pin tracts. (Courtesy of https://www.cureus.com/articles/20536-chronic-osteomyelitis-revisited-a-case-report)

Risk Factors and Prevention

The major risk factors for osteomyelitis include diseases that compromise the immune system (either directly or because of their associated medications), IV drug use, vascular disease, diabetes mellitus, sickle cell anemia, peripheral neuropathy, prior trauma (especially open fractures), and retained surgical hardware such as fracture fixation devices or joint replacement prostheses.

Children who are immunodeficient are more likely to suffer from osteomyelitis due to atypical organisms and may benefit from vaccination. For example, individuals with sickle cell anemia can be immunized against salmonella, though the efficacy of this approach still requires confirmation with randomized controlled trials.

Patients with diabetic neuropathy should perform daily foot exams and complete early treatment of minor foot injuries to prevent potentially devastating complications of osteomyelitis.

Key Terms

Bone infection, Joint infection, Osteomyelitis


Recognize risk factors for osteomyelitis. Identify osteomyelitis on plain radiography.

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