Osteomyelitis



Osteomyelitis is an infection of bone 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 apposition of bone around it. Osteomyelitis is found in both adults and children, though the condition is not the same in the two groups: bones with open growth plates are both more susceptible to infection but more amenable to treatment with antibiotic. In adults, osteomyelitis often requires surgical debridement. Unfortunately, osteomyelitis in adults often results in poor outcomes, owing to both biological factors of the disease – it’s hard to clear infections from bone – as well as host factors, such as co-existing vascular disease. 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 about 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 (see Figure 1).

 

Figure 1: Schematic drawing of vascularization of the long bone in children between 18 months and 16 years of age. The need for blood flow in the metaphysis to make a “hair pin” (and not cross the physis) makes it more likely that any circulating bacteria could escape here 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 to the epiphysis. This allows bone infection to possibly seed the joint causing septic arthritis.

 

In healthy adults, most cases of osteomyelitis are related to trauma. Hematogenous osteomyelitis in adults, when it occurs, typically affects the vertebrae; it is more prevalent among IV drug users. Contiguous osteomyelitis in older patients can be seen in the setting of sensory neuropathy (caused by diabetes mellitus, often) 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 might become sequestered by new bone formation, making the eradication of bacteria difficult or impossible without surgical excision. The new bone tissue is called an “involucrum” and the infected bone it surrounds is called the “sequestrum” (see 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 thick involucrum. (e) Further expansion 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 on plain radiograph 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 duration, acute or chronic; and by its mode of origin (e.g., trauma vs hematogenous or contiguous spread). The disease can also be categorized by a clinical (Cierny-Mader) classification to be in one of four stages. In stage 1, infection is confined to the medullary cavity of the bone. In stage 2, there is a focal cortical inoculation. Stage 3 involves both cortical and medullary bone without loss of structural stability; in stage 4, there is loss of stability. This classification is further augmented by noting local and systemic factors that affect the health status of the host, such as diabetes mellitus, vascular insufficiency, malnutrition, peripheral neuropathy, and smoking, to name but a few.

 

 

Patient Presentation

In acute pediatric osteomyelitis, patients typically present with fever and progressive pain. If the lower extremity, pelvis, or spine is involved, it is common for the patient to have a limp or refuse to walk. If the upper extremity is involved, it is common for the patient to refuse to use the 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 have limited motion of the joint adjacent to the region of pain.

 

In subacute and chronic osteomyelitis, pediatric patients typically present with vague discomfort, but no fever or constitutional symptoms. Their 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 by rest. On physical exam, the patient typically does not look sick. The affected region is typically tender to palpation with mild swelling and possible limitations in range of motion of the joint adjacent to the region of pain. The patient may also have an antalgic gait.

 
Diagnosis in adults can be subtle. A history of risk factors for osteomyelitis (see below) should raise suspicion. Acute osteomyelitis may present as erythema/swelling with pain; the presence of fever is variable. In chronic osteomyelitis, there is also erythema, swelling and pain, typically at site at risk: namely, prior injury, surgery, or ulceration. If an abscess has spread out of the bone and into the soft tissues, a fluctuant swelling with overlying redness may be seen.

 

 

Objective Evidence

Abnormalities in laboratory tests are usually nonspecific: elevations of the peripheral white blood cell count, sedimentation rate and C-reactive protein (CRP). A normal sedimentation rate and CRP would tend to exclude the 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 be used to monitor response to treatment.

 

Blood cultures are helpful in pediatric cases; they are able to identify the infecting organism in 40 to 50% of patients and allow targeted antibiotic therapy.

 

Radiographic assessment includes plain radiographs, magnetic resonance imaging (MRI), and bone scanning. A plain radiograph is usually normal initially in acute osteomyelitis, but can 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 (see Figure 4).

 

Figure 4: At left, plain radiographs of a tibia with osteomyelitis, showing a lytic lesion in the metaphysis (red arrow) with periosteal reaction (green arrow). At right, a coronal T1-weighted MRI shows intra-medullary bone edema. (Courtesy of BMC Infectious Diseases volume 18, Article number: 665 (2018))
 

Three-phase technetium-99 bone scans and tagged white blood cell scans are the modalities commonly used. Bone biopsy is helpful not only to make the diagnosis but to identify the pathogen and its susceptibility to antibiotics.

 

 

Epidemiology

Osteomyelitis occurs in all age groups. The annual incidence of acute and subacute osteomyelitis in children is about 13 per 100,000, and there is no significant difference in occurrence rates between males and females. Children with immunodeficiency, diabetes, hemoglobinopathy, and systemic inflammatory conditions are at increased risk. The overall incidence of adult osteomyelitis in the United States is mostly unknown, but is estimated to be about 21 per 100,000. The incidence is slightly higher in men, perhaps related to a propensity for trauma or the higher prevalence of risk factor comorbidities.

 

Most of the cases of adult osteomyelitis in healthy people are due to open fractures or due to infection post-surgery. Direct spread from diabetic ulcers is unfortunately too common.

 

 

Differential Diagnosis

What looks like a tumor might be an infection, and vice versa. Ewing's sarcoma, like osteomyelitis is frequently associated with fever.

 

Trauma to bone and the ensuing periosteal reaction from the healing process may mimic early osteomyelitis.

 

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

 

Sensory neuropathy leading to the formation of skin ulceration can cause osteomyelitis, but also a 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. (Image courtesy pf David E. Oji, M.D. Stanford University School of Medicine)
 

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

 

 

Red Flags

Osteomyelitis in children suggests a possible septic arthritis nearby, and vice versa: the two are often seen simultaneously in one patient.

 

A high index of suspicion is needed for patients with risk factors (see below), as radiographs are normal initially, and lab test abnormalities are usually non-specific.

 

IV drug users have an increased incidence of vertebral osteomyelitis. Sudden, severe back pain in a patient who uses IV drugs should be suspected to have an infection until proven otherwise.

 

 

Treatment Options and Outcomes

Pediatric patients usually can be treated empirically with a trial of empiric intravenous antibiotics, later tailored to the results of blood cultures. If patients fail to improve from a clinical and laboratory standpoint within 72 hours of empiric antibiotic therapy, repeat imaging and surgical debridement are indicated. Antibiotics are typically continued for four to six weeks in total, assuming clinical improvement and resolution of inflammatory markers (CRP). The timing of transition from IV to oral antibiotics is controversial, however it is often feasible to make this transition after several days, provided the patient is clinically improved.

 

If acute osteomyelitis is not treated, it can develop into chronic osteomyelitis and cause destruction of bone as well as extension of the infection to surrounding tissues. With appropriate treatment, the patient's clinical exam should normalize over six to twelve weeks.

 

Skeletally immature patients with a history of osteomyelitis near the ends of long bones should be monitored long term for signs of physeal arrest.

 

Osteomyelitis in the adult is treated with antibiotics, and surgical debridement if necessary. Culture and sensitivity data should guide antibiotic selection, but empiric treatment may be used at first. Empiric treatment can be guided by the etiology of the osteomyelitis and a patient’s specific factors (e.g., staphylococcus aureus is the most common bacteria for normal hosts, whereas salmonella infection is common in sickle cell disease), though a broad-spectrum regimen against both gram-positive and negative organisms is best.

 

Acute osteomyelitis in adults can be treated with antibiotics alone, when it presents within 48 hours and there is no abscess. If there is an abscess and 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 then elutes antibiotics (see 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, e.g., bone grafting or soft tissue coverage, might 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 the 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 case, extensive bone damage or irremediable vascular disease, amputation may be needed. Even in less extreme cases, treatment of osteomyelitis is not always completely successful. Possible complications include failure to eradicate the infection (in about 25% of cases of chronic osteomyelitis); bone deformity and failure of fracture healing, malunion and non-union, respectively (see Figure 7); septic arthritis of adjacent joints; systemic or contiguous soft tissue infection; and, in rare in stances, in the setting of sinus tract formation, squamous cell carcinoma.

 

Figure 7: Radiographs showing a non-union of a fracture of the tibia with chronic osteomyelitis and lucency around the external fixator’s pin tracts. (Image 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 medications); IV drug use; vascular disease; diabetes (likely on the basis of immuno-compromise and vascular disease); sickle cell anemia; peripheral neuropathy; prior trauma, especially open fractures or with retained surgical hardware; and prior total joint replacement.

 

Children who are suffering from immune deficiency syndromes are more likely to suffer from osteomyelitis. Vaccination of individuals at risk or predisposed to atypical organisms might help protect against osteomyelitis. For example, people with sickle cell anemia can be immunized with salmonella vaccines (though there are not randomized controlled trials showing effectiveness of this approach).

 

Patients suffering from diabetic neuropathy should practice daily foot inspection and complete early treatment of minor injuries to the foot, to prevent devastating complications.

 

 

Key Terms

Bone infection, Joint infection, Osteomyelitis

 

 

Skills

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