Acute Pyogenic Osteomyelitis Imaging

Acute pyogenic osteomyelitis is inflammation of bone caused by an infecting organism. Staphylococcus aureus is the most commonly involved bacterium. ^{[1, 2, 3]}  Acute hematogenous (originating in, or carried by, the blood) osteomyelitis has an incidence of 1 in 5000 children per year in the United States and is the most common musculoskeletal infection in children. About 50% of cases of acute osteomyelitis occur in children younger than 5 years. ^[3]

Various terms had been used to describe infected bone over the years until Nelaton came up with the term “osteomyelitis” in 1844. Before penicillin was introduced in the 1940s, management of osteomyelitis was mainly surgical, consisting of extensive debridement, saucerization, and wound packing, following which the affected area was left to heal by secondary intention, resulting in high mortality from sepsis. Since antibiotics became available, mortality rates from osteomyelitis, including staphylococcal osteomyelitis, have improved significantly. ^[4]

Osteomyelitis usually is clinically diagnosed with support from imaging and laboratory findings. Bone biopsy and microbial cultures offer definitive diagnosis. Plain film radiography should be performed as initial imaging, but sensitivity is low in early stages of the disease. Magnetic resonance imaging (MRI) with and without contrast media has higher sensitivity for identifying areas of bone necrosis at later stages. Staging based on major and minor risk factors can help stratify patients for surgical treatment. Antibiotics are the primary treatment option and should be tailored based on culture results and individual patient factors. Surgical bony debridement is often needed, and further surgical intervention may be warranted for high-risk patients or for those with extensive disease. Diabetes mellitus and cardiovascular disease increase the overall risk of acute and chronic osteomyelitis. ^[5]

Prolonged antibiotic therapy is the cornerstone of treatment for osteomyelitis. Results of culture and sensitivity should guide antibiotic treatment, if possible, but in the absence of these data, it is reasonable to start treatment with empiric antibiotics. A commonly used broad-spectrum empiric antibiotic regimen against both gram-positive and gram-negative organisms, including methicillin-resistant S aureus (MRSA), consists of vancomycin (15 mg/kg intravenously [IV] every 12 hours) plus a third-generation cephalosporin (eg, ceftriaxone 2 g IV daily) or a beta-lactam/beta-lactamase inhibitor combination (eg, piperacillin/tazobactam 3.375 IV every 8 hours). Once sensitivity data become available, antibiotic therapy should be narrowed for targeted coverage of susceptible organisms. ^[4]

Despite advances in health care, osteomyelitis remains a major clinical challenge, with recurrent and persistent infections occurring in approximately 40% of patients. ^[6]

Effective treatment of osteomyelitis involves a collaborative effort among various medical and surgical specialties. The 2 main aspects of therapy are surgical containment of the infection and prolonged antibiotics. Preoperative use of imaging modalities such as MRI allows for delineation of the extent of infection, but intraoperatively it is still difficult for the surgeon to determine whether all necrotic bone and tissue have been successfully removed. Examination of the pathology report helps reveal whether repeat debridement is necessary. ^[4]

Even with these extreme measures, many patients go on to develop chronic infection or sustain disease comorbidities. A better mechanistic understanding of how bacteria invade, survive within, and trigger pathologic remodeling of bone could lead to new therapies aimed at prevention or treatment of osteomyelitis, as well as amelioration of disease morbidity. ^[7]

The disease process involves 5 stages:

1. Inflammation: This stage represents initial inflammation with vascular congestion and increased intraosseous pressure; obstruction to blood flow occurs with intravascular thrombosis.

2. Suppuration: Pus within the bones forces its way through the haversian system and forms a subperiosteal abscess in 2-3 days.

3. Sequestrum: Increased pressure, vascular obstruction, and infective thrombus compromise the periosteal and endosteal blood supply, causing bone necrosis and sequestrum formation in approximately 7 days.

4. Involucrum: This is new bone formation from the stripped surface of the periosteum.

5. Resolution or progression to complications: With antibiotics and surgical treatment early in the course of disease, osteomyelitis resolves without complications.

Imaging modalities

Imaging plays an important role in the diagnosis of acute pyogenic osteomyelitis. Assessment should always start with plain radiographs of the affected area. ^{[1, 8, 9]}  Current imaging recommendations include plain radiography followed by 3-phase bone scanning and/or MRI, if available. ^{[3, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]}

Although osseous changes become apparent on conventional radiographs 5-7 days into the disease process, plain radiographs are useful in ruling out other causes of bone pain, such as stress fracture. Plain radiography and radionuclide bone scanning greatly aid early diagnosis in cases of acute osteomyelitis. Plain radiography is useful for excluding other conditions; radionuclide scanning reveals evidence of inflammation at the site of bone pain.

Nuclear medicine bone scanning is a highly sensitive (>90%) modality in the diagnosis of osteomyelitis. This procedure is performed in 3 stages. Technetium-99m (^99mTc) is used to create images to identify areas of infection and bone remodeling dependent on local blood flow. The sensitivity of bone scanning is often helpful when the exact site and the extent of infection are not known.

Computed tomography (CT) scanning allows for 3-dimensional (3D) examination of bone and surrounding soft tissue. CT scanning is an excellent modality for depicting periosteal new bone formation and cortical bone destruction and for determining whether any sequestration or involucrum is present. Contrast-enhanced CT may reveal a ring-enhancing soft tissue abscess.

Findings on MRI accurately show the extent and structure of the area involved in the pathologic process. Of all the imaging modalities currently in use, MRI has the highest combined sensitivity and specificity (78-90% and 60-90%, respectively) for detecting osteomyelitis. ^[4]  Fat suppression sequences allow better detection of bone marrow edema; however, infection and inflammation cannot be differentiated. MRI may be the imaging modality of choice for infection involving spine, pelvis, or limbs because of its ability to provide fine details of osseous changes and soft tissue extension in these areas.

Additional imaging may be performed with indium-111–labeled leukocytes; gallium (⁶⁷Ga) is used as needed. Ga-67 seems especially valuable in monitoring the efficacy of treatment.

Diagnosing bone infection in the diabetic foot is challenging and often requires several diagnostic procedures, including advanced imaging. Lauri and associates compared the diagnostic performance of MRI, radiolabeled white blood cell (WBC) scintigraphy (with ^99mTc-hexamethylpropyleneamineoxime [HMPAO] or ¹¹¹In-oxine), and fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET)/CT. They reported that various modalities have similar sensitivity but that ¹⁸F-FDG-PET and ^99mTc-HMPAO-labeled WBC scintigraphy offer the highest specificity. ^[20]

In a systematic review and meta-analysis of imaging for detection of osteomyelitis in people with diabetic foot ulcers, Llewellyn and colleagues concluded that both MRI and PET can be used to reliably diagnose this condition and that single-photon emission CT (SPECT) may have good diagnostic accuracy, although evidence is limited. This review confirms current guidelines showing that MRI may be the preferable test in most cases, given its wide availability and the lack of potentially harmful ionizing radiation. ^[21]

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Details of physiology

According to the route of infection, acute osteomyelitis can be classified as hematogenous (originating in, or carried by, the blood) or exogenous (originating outside the body). Hematogenous osteomyelitis is seen predominantly in children and involves the highly vascular long bones, especially those of the lower limb. Hematogenous spread of bacteria usually results in bacteremia with subsequent infection of bone. The pathogen most commonly associated with this type of infection is S aureus; other gram-negative organisms, such as Pseudomonas aeruginosa, are frequently encountered. The microorganism Serratia marcescens is a rare and infrequently encountered cause of this condition known to cause nosocomial infection. This organism can be notoriously difficult to treat, with resistance to many commonly used antibiotics. ^[22]  In adults, hematogenous spread is more common to the lumbar vertebral bodies than elsewhere. In neonatal osteomyelitis, isotopic bone scans are reportedly normal in most patients.

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Before puberty, infection begins in the metaphyseal sinusoidal veins. Because bones are relatively rigid structures, focal edema accumulates under pressure, leading to local tissue necrosis, breakdown of trabecular bone structure, and removal of bone matrix and calcium. Infection spreads along the haversian canals, through the marrow cavity, and beneath the periosteal layer of bone. Subsequent vascular damage causes ischemic death of osteocytes, leading to the formation of a sequestrum (ie, a piece of devitalized bone that has been separated from surrounding bone during the process of necrosis). Periosteal new bone formed on top of the sequestrum is known as the involucrum.

Osteomyelitis may be acute, subacute, or chronic. With acute osteomyelitis, the presenting complaint is usually local pain, swelling, and warmth. These often occur in association with fever and malaise.

Differentiating acute osteomyelitis from bone infarction in patients with sickle cell disease presents a major challenge. These 2 conditions must be differentiated on the basis of clinical findings and imaging studies because both are common in patients with sickle cell disease. These diseases are managed differently.

Fine-needle aspiration (FNA) or needle biopsy under ultrasonographic, fluoroscopic, or CT guidance may be done to obtain samples of pus, tissue, or both, to establish a histologic diagnosis of acute osteomyelitis.

In a retrospective study, Omoke reported that pyogenic osteomyelitis is an important child health problem in developing countries. It is a one-disease state with a spectrum of pathologic features and clinical forms ranging from acute to chronic. Its pattern of presentation varies from and within subregions. In this environment, the chronic pyogenic osteomyelitis sequela to acute hematogenous bone infection in childhood is common. Poverty is a limiting factor in its definitive treatment. These findings call for a policy response aimed at improving care and devising prevention strategies based on observed patterns. ^[23]

Limitations of techniques

Plain radiographs are often normal for at least 1 week following infection; findings are nonspecific.

MRI is contraindicated in patients with certain implant devices and metallic clips, and it is not tolerated by all patients because of claustrophobia or morbid obesity. Young children may require sedation. Use of MRI requires patient cooperation because patient motion may degrade the images.

CT is quick and inexpensive but exposes the patient to ionizing radiation. The risk of a reaction to radioiodinated contrast material is low; detection of bone destruction or a paraspinal mass does not require use of contrast material.

Although radionuclide studies are sensitive, they can be time-consuming, and they offer lower spatial resolution. The incidence of false-negative scans is low among neonates and in elderly patients with osteomyelitis.

The radiographic appearance of osteomyelitis may vary. Radiographs obtained early in the course of the disease may show subtle swelling of deep soft tissue or edematous subcutaneous soft tissue, but radiographs are often normal in the first 7-10 days of infection. By 10-14 days, a focal area of bone opacity develops in the metaphysis. This progresses to lytic destruction with associated focal periosteal reaction. Radiographs typically show a well-defined, longitudinally oriented, ovoid lucency with surrounding sclerotic margin but little to no periosteal new bone formation. ^{[2, 10, 13, 14, 16]}

In the acute phase, radiography has been shown to have low senstitivity for acute osteomyelitis (43-75%), but it is important for ruling out other potential events such as fracture and tumor. ^[2]

(See the images below.)

Radiographs may be normal, particularly early in the disease course. Alternatively, they may reveal soft tissue swelling, periosteal reaction, subperiosteal bone resorption, or erosions and sequestra. Extension of infection through the metaphyseal cortex may lead to periosteal new bone formation. If left untreated, this may completely encircle the bone, becoming an involucrum, which can envelop nonviable infected bone, resulting in a sequestrum.

Degree of confidence

Plain radiography is an inexpensive and noninvasive technique that is readily available worldwide. Radiographic imaging is an essential component in the evaluation of a patient with suspected osteomyelitis. A plain radiograph is usually the initial imaging of choice, but a delay of about 14 days may occur before findings suggestive of osteomyelitis appear. Radiographs are used to rule out other potential causes of symptoms such as metastasis or osteoporotic fracture. Typically seen are soft tissue swelling, osteopenia, osteolysis, bony destruction, and nonspecific periosteal reaction. Lytic lesions are detectable on plain radiographs after approximately 50-75% of the bone matrix has been lost, making this modality inadequate for detection of early bone disease. ^[4]

Radiographs are often normal in the first 7-10 days after the start of infection. Radiographic mimics of osteomyelitis include septic arthritis, Ewing sarcoma, osteosarcoma, juvenile arthritis, sickle cell crisis, Gaucher disease, stress fracture, and other bone lesions that may mimic osteomyelitis clinically.

Computed tomography (CT) is the modality of choice for revealing sequestra and cortical erosions in cases of chronic osteomyelitis. ^{[10, 14, 15, 16]}  In a study by Hald and Sudmann of CT for early diagnosis of acute hematogenous osteomyelitis, results showed that with CT, bone marrow involvement may be detected in patients with osteomyelitis before bony changes appear on routine radiographs. ^[24]

CT scanning allows for 3D examination of bone and surrounding soft tissue. CT scanning is more sensitive than plain radiography for assessing cortical and trabecular integrity, periosteal reaction, intraosseous and soft tissue gas, and the extent of a sinus tract, and it is superior to MRI for detecting necrotic bone fragments. However, although CT is more readily available than MRI, it is more expensive than plain radiography and has a limited role in the diagnosis of osteomyelitis. CT should be used mainly to determine the extent of bony destruction (especially in the spine) to guide biopsies or used in patients with contraindications to MRI. ^[4]

Technologically sophisticated procedures such as CT and MRI should be reserved for situations in which the diagnosis cannot be made with the use of simpler methods, as in cases of osteomyelitis of the spine or pelvis, or when anatomic detail provided by MRI is required for surgical planning. Most children with uncomplicated osteomyelitis probably do not need to undergo CT or MRI. CT diagnosis appears to be particularly useful when osteomyelitis secondary to sinus infection is suspected.

Theoretically, confusion may arise in cases involving other conditions associated with periosteal new bone formation and destructive bone processes such as primary or metastatic bone tumor.

On T1-weighted magnetic resonance imaging (MRI), osteomyelitis typically has low signal intensity; on T2-weighted and short-tau inversion recovery (STIR) imaging, it has high marrow signal intensity. MRI shows marrow edema and the extent of subperiosteal abscess collection. T1-weighted sequences with intravenous gadolinium enhancement allow differentiation of enhancing, hyperemic inflammatory tissue from central pockets of nonenhancing pus. ^{[2, 3, 10, 11, 13, 14, 16]}

MRI offers advantages over other modalities in that it can detect early changes associated with acute osteomyelitis and it can identify extarosseous spread of infection. ^[3]  Of all imaging modalities, MRI has the highest combined sensitivity and specificity (78-90% and 60-90%, respectively) for detecting osteomyelitis. It can detect early bone infection within 3-5 days of disease onset, but its use is limited in the setting of surgical hardware. MRI has a high negative predictive value, so a negative result is sufficient for exclusion of disease if symptoms have been present for at least 1 week. ^[4]  Features of methicillin-resistant S aureus have been shown clearly on MRI. ^[3]

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Osteomyelitis is generally milder in infants than in older children. Among infants, subperiosteal abscess formation is more frequent and rapid, and rupture into soft tissues is more common. In neonates, vascular channels penetrate the cartilaginous epiphysis and allow infection to spread from the metaphysis into the joint, causing adjacent septic arthritis. These changes are visible on sonography or on MRI.

Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). This disease has occurred in patients with moderate to end-stage renal disease after they were given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography (MRA) scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

The physical properties of bone do not usually lend themselves to ultrasonographic investigation because of reflection of sound waves at the soft tissue–bone interface. However, the periosteum, along with early new bone formation and soft tissue changes alongside dense bone, may be imaged. Ultrasonography is useful in the acute phase and shows the presence and extent of any subperiosteal abscess collection (for which aspiration or drainage is required). Thus, it may be helpful for planning surgery. ^{[25, 26]}

Early diagnosis and management of acute osteomyelitis are essential to prevent serious complications. Ultrasonography can play an important role in the early diagnosis of pediatric acute osteomyelitis and should be incorporated into treatment protocols followed in cases of suspected acute osteomyelitis. MRI should be reserved for use as a problem-solving tool. ^[27]

The sensitivity of ultrasonography for acute osteomyelitis has been observed to be 46-74%, and specificity, 63-100%. Ultrasonography is helpful for identifying fluid in joints and soft tissues. ^[2]

Kang and colleagues examined 24 children with clinically suspected acute early-stage hematogenous osteomyelitis by using sonography. ^[28] Subperiosteal abscesses were sonographically detected in all patients at 4-14 days after disease onset. Mean length and anteroposterior distance of subperiosteal abscesses were 86.4 mm and 10.7 mm, respectively. Among 24 cases of subperiosteal abscess, aspiration performed under sonographic guidance revealed purulent fluid in all patients; 23 cases were verified surgically. Results indicate that sonography may be used to diagnose acute hematogenous osteomyelitis at an early stage. The earliest case was diagnosed by means of sonography performed 4 days after disease onset.

Mah and associates studied the sonographic features of acute osteomyelitis in children and found that deep soft tissue swelling was the earliest sign of acute osteomyelitis. The next stage revealed periosteal elevation and a thin layer of subperiosteal fluid; in some cases, this progressed to form a subperiosteal abscess. Later stages were characterized by cortical erosion, which was common among those who had had symptoms longer than 1 week. Concurrent septic arthritis was revealed in 11 patients, most frequently in association with osteomyelitis of the proximal femur or distal humerus. Four weeks after clinical cure, sonography revealed no abnormalities. ^{[29, 30]}

According to Chao and coworkers, who evaluated color Doppler sonography in the diagnosis of acute osteomyelitis in 12 children with clinically suspected acute osteomyelitis, ^[31] color Doppler showed flow within or around the infected periosteum in patients whose symptoms lasted 4 days or longer, whereas no such flow was observed in patients whose symptoms occurred within 4 days. Sonographic follow-up revealed that 6 patients had increased color Doppler vascular flow within and around the affected periosteum, 2 of whom had periosteal abscess. These patients eventually required surgical treatment.

Persistent or increased color Doppler flow during follow-up examination was correlated with elevated serum levels of C-reactive protein (CRP). Color Doppler vascular flow within or around the infected periosteum was correlated with advanced acute osteomyelitis; surgery was required for most patients. Thus, color Doppler sonography allowed detection of advanced osteomyelitis and revealed progression of inflammation during antibiotic therapy. Investigators postulated that color Doppler ultrasonography may be valuable in determining the efficacy of antibiotic therapy and in justifying the need for surgery. ^[31]

In a study of 24 infants with osteomyelitis, Riebel and coworkers ^[32] identified intra-articular fluid collections, subperiosteal abscess formation, or both, as the most frequent early sonographic findings. Such findings preceded radiographic changes by several days in 11 cases. With positive clinical signs of inflammation, sonographic results were usually sufficient for accurate diagnosis. In addition, sonography depicted superficial cortical erosion and even an intramedullary focus in a young patient.

Degree of confidence

Ultrasonography is a noninvasive, simple, and inexpensive technique that uses nonionizing radiation; thus, it is an ideal modality for use in children. Ultrasonography is fairly reliable for differentiating acute hematogenous osteomyelitis from cellulitis, soft tissue abscess, acute septic arthritis, and malignant bone tumor. However, this modality remains operator dependent, and a child with acute tenderness at the site of suspected infection may not be able to tolerate the ultrasonic probe touching the surface.

Larcos and associates found that the sensitivity of ultrasonography was 63% in 16 patients with acute osteomyelitis. ^[33] They prospectively examined 19 patients using high-resolution sonography for subperiosteal fluid or cortical irregularity. The diagnosis was established at surgery (3 cases) or after other testing and at clinical follow-up. Sixteen patients were identified as having osteomyelitis; positive sonographic results were obtained in 10 patients. Two studies yielded false-positive results; diagnostic accuracy was 58%. Thus, ultrasonographic results may be misleading, and investigators emphasized the importance of clinical judgment and additional testing.

Nuclear imaging has high sensitivity for detecting early evidence of bone disease but has very poor specificity. It is especially useful when metal hardware prevents the use of MRI. Three-phase technetium-99 bone scan and tagged white blood cell scans are the modalities commonly used. ^[4]

Technetium-99m (^99mTc) diphosphonate bone scan is usually positive 24 hours after infection; a well-defined focus of tracer activity is apparent 1-2 hours after injection. This finding is correlated with the presence of radiotracer in the same area on dynamic scans. Bone scintigraphy may show focal uptake at the affected site and is particularly valuable in identifying other sites of infection because multifocal osteomyelitis may occur, especially in neonates. ^{[3, 17, 34, 35]}

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Three-phase bone scanning

This technique uses the same radionuclide as is used in static bone scans and consists of the following phases:

• Phase 1: Radionuclide angiography representing the perfusion phase is performed.

• Phase 2: Blood pool images are obtained.

• Phase 3: Static bone scans are obtained.

The sensitivity of the 3-phase bone scan for diagnosis of acute osteomyelitis is higher than that of static bone scans. Sensitivity and specificity of 3-phase bone scans have been reported to be 85-92% and 54-87%, respectively. Uptake on 3-phase bone scans is related to blood flow and osteoblastic activity. In cases of acute osteomyelitis, isotopic activity is increased in all 3 phases.

Gallium scanning

Mechanisms of gallium-67 (⁶⁷Ga) citrate uptake include the following: (1) direct leukocyte and bacterial uptake, (2) lactoferrin and transferring binding, (3) increased vascularity, and (4) increased bone turnover.

Criteria for a positive result on ⁶⁷Ga scanning include uptake exceeding that noted on bone scanning and differences in distribution, as compared to distribution revealed on bone scanning.

If patients who are suspected of having acute osteomyelitis are left untreated and if ^99mTc diphosphonate and ⁶⁷Ga scans show a concordant pattern, scans are interpreted as follows:

• When ^99mTc diphosphonate uptake is less than ⁶⁷Ga uptake, infection is suggested.
• When  ^99mTc diphosphonate is present, reactive bone is suggested;
• When  ^99mTc diphosphonate and ⁶⁷Ga uptake are discordant and when uptake is truly in bone, the likely diagnosis is osteomyelitis.

Johnson and colleagues used ⁶⁷Ga scans to evaluate 22 diabetic patients with osteomyelitis ^[36] ; results revealed sensitivity of 100%, specificity of 40%, and accuracy of 73%.

Schauwecker and colleagues conducted a review of the literature and reported sensitivity of 81% and specificity of 69% with this imaging modality. ^[37]

Indium-111–labeled leukocyte scintigraphy

Indium-111–labeled leukocytes become localized in infectious and inflammatory lesions by means of leukotaxis. Indium-111 is regarded as the best available agent for acute infection. However, Tc-labeled leukocytes have largely replaced indium labeling, especially in studies of suspected osteomyelitis in the extremities.

Images are obtained at 2-4 hours and at 24 hours. Drawbacks of this technique include low count rate, cost of the radiopharmaceutical preparation, complexity of labeling, and lack of bony landmarks. Johnson and coworkers reported sensitivity of 100%, specificity of 70%, and accuracy of 86%. ^[36] When combined with bone scanning, specificity increased to 80% and accuracy increased to 91%.

Neuropathic joint disease and osteomyelitis in diabetes

Diabetes mellitus affects 5% of the US population. Twenty percent of hospitalized adult diabetic patients have foot disorders associated with significant disability. One third have evidence of osteomyelitis. Contributing factors include angiopathy and peripheral neuropathy.

Osteomyelitis in a diabetic setting presents a difficult clinical problem, and differentiating between cellulitis, osteomyelitis, and neuropathic osteoarthropathy may be problematic. These conditions most often affect the feet. Neuropathic osteoarthropathy may cause a warm and swollen extremity even without concomitant infection. Plain radiographs of osteomyelitis may show destructive changes, osteosclerosis, and periosteal new bone formation.

Fracture may occur with minimal trauma in cases of neuropathic osteoarthropathy and may present a complicating factor. Plain radiographs of neuropathic osteoarthropathy may depict joint subluxation, fracture fragmentation, subchondral osteoporosis, sclerosis in adjacent bone, and periosteal new bone formation. Differentiating these changes from infection radiographically may be difficult. Results of bone scintigraphy may be positive in all 3 conditions.

Ga-67 concentrates in inflammatory lesions and may add some diagnostic specificity. An intense concentration of ⁶⁷Ga is thought to indicate osteomyelitis. However, scans may show mildly increased uptake in cases of diabetic neuropathic osteoarthropathy; occasionally, accumulation is substantial, compounding the problem.

Indium-111–labeled white blood cells are specific for acute osteomyelitis and are helpful in differentiating nonseptic from septic osteoarthropathy in diabetic patients. 

According to Schauwecker and associates, ^{[37]  111}In leukocyte imaging had a sensitivity of 100% for acute osteomyelitis and a sensitivity of 60% for chronic osteomyelitis; specificity was 95%. Ga-67 scanning was excellent for ruling out osteomyelitis when findings were normal, or for ruling it in when scans showed hyperintense uptake as compared to bone imaging or a different distribution from bone images. This situation occurred in 28% of patients.

In conclusion, ¹¹¹In-labeled leukocyte imaging may provide further specificity in differentiating septic diabetic osteoarthropathy from nonseptic diabetic osteoarthropathy in patients with increased uptake on bone images, gallium images, or both.

Degree of confidence

Static ^99mTc diphosphonate bone scans have a sensitivity of 83% but a 5-60% false-negative rate in neonates and children because of the masking effect of a normal increase in activity in the epiphyseal plate. Another factor is the unusual spectrum of radioactivity in children with osteomyelitis. Initially, the lesion may appear photon deficient, but it eventually appears as an area of enhanced activity.

The 3-phase bone scan has higher sensitivity and specificity, but it also has several limitations in some patients, including children; those in a posttraumatic or postoperative state; diabetic patients with neuropathic osteoarthropathy; and those with bone tumor, septic arthritis, healed osteomyelitis, Paget disease, or other noninflammatory bone lesions. Confusion may arise in cases of cellulitis, although activity in cellulitis decreases with time.

The sensitivity of ⁶⁷Ga scans is 100%, and increased uptake appears a day earlier than on ^99mTc diphosphonate scans. However, labeled leukocyte scanning has largely replaced ⁶⁷Ga scanning in cases of acute osteomyelitis because of its improved photo flux and dosimetry, which allow faster scanning with better resolution.

False positives/negatives

Bone scintigraphy with ^99mTc diphosphonate is a highly sensitive technique for evaluating bone pathology, but it is not specific. False-positive results may occur with fracture, primary and metastatic neoplasms, heterotopic ossification, arthritis, osteomyelitis, and neuropathic joints. False-negative bone scans may be seen when scanning is performed early in the course of infection or in babies younger than 6 weeks.

On scans, cold lesions may be evident during first hours to first days of infection as a result of increased pressure in the medullary space. Therefore, the lesion can be missed easily.

Osteomyelitis has become a growing concern in modern health care due in no small part to a rise in antibiotic resistance among bacteria, notably Staphylococcus aureus. The current standard of care involves aggressive, prolonged antibiotic therapy combined with surgical debridement of infected tissues. Although this treatment may be sufficient for resolving a portion of cases, recurrence of infection and associated risks, including toxicity, have been reported with long-term antibiotic usage. Therefore, there exists a need to produce safer, more efficacious treatment options for patients with osteomyelitis. ^[38]

In a systematic review and meta-analysis, Huang and coworkers explored the controversial practice of long-term antibiotic use in patients with osteomyelitis. Short antibiotic courses were defined as antibiotics administered for a shorter period than the recommended 4-6 weeks. The overall odds ratio (OR) of treatment failure in patients receiving short-course antibiotics was 1.50 (95% confidence interval [CI], 0.97 to 2.34). Subgroup analysis revealed that short-course antibiotic treatment was associated with increased treatment failure in vertebral osteomyelitis (OR, 2.06; 95% CI, 1.18 to 3.57), while having a similar rate to long-course antibiotic treatment for children with acute osteomyelitis (OR, 1.86; 95% CI, 0.75 to 4.64). Meta-regression revealed that a higher proportion of S aureus infection was related to greater risk of treatment failure in patients with vertebral osteomyelitis. Review authors concluded that short-course antibiotics are safe and effective in children with acute osteomyelitis, and that long-course antibiotics may still be preferred in vertebral osteomyelitis, especially for patients with S aureus infection. ^[39]

A better mechanistic understanding of how bacteria invade, survive within, and trigger pathologic remodeling of bone could lead to new therapies aimed at prevention or treatment of osteomyelitis as well as amelioration of disease morbidity. ^[7]

Early detection of osteomyelitis will likely lead to more favorable outcomes. Diagnosis of osteomyelitis requires a multidisciplinary approach, including clinical examination, recognition and assessment of clinical symptoms, laboratory investigations, and imaging tests. Various imaging modalities have been used in characterization and differential diagnosis of osteomyelitis, such as plain radiography, CT, MRI, bone scintigraphy, positron emission tomography (PET), single-photon emission computed tomography (SPECT), and ultrasonography. The diagnostic accuracy of these imaging tests for diagnosis of osteomyelitis has been systematically reviewed. Although plain radiography has lower sensitivity and specificity than other imaging tests, the American College of Radiology recommends that radiographs should be used as the first-line imaging modality to differentiate osteomyelitis from other clinical conditions such as bone fracture or bone malignancy. Plain radiography, whether with positive or negative results, is usually followed by imaging modalities of higher sensitivity and specificity for diagnosis of osteomyelitis. However, in institutions where the availability of more sophisticated imaging modalities is limited, it is unclear if use of serial radiography (ie, initial assessment with radiographs, followed by subsequent radiographs in 1-3 weeks) could improve diagnostic accuracy for detection of osteomyelitis. ^[40]