Version July 2025
INTRODUCTION —
Osteomyelitis is an infection localized to bone [1]. In children, osteomyelitis is usually caused by microorganisms (predominantly bacteria) that enter the bone via the bloodstream (hematogenously).
Osteomyelitis may also develop following direct inoculation of bone with bacteria in association with an open fracture or as a complication of a puncture wound. (See "Infectious complications of puncture wounds".)
Less commonly, osteomyelitis may develop as an extension of a contiguous infection (eg, decubitus ulcer, deep wound infection, sinusitis, periodontal disease).
Osteomyelitis is acute when the infection is diagnosed within two to four weeks of symptom onset and involves previously uninfected bone [1].
Chronic osteomyelitis is a more protracted and generally indolent disease that usually develops in incompletely treated or previously untreated infections of bone, often accompanied by one or more sequestra (areas of dead bone) that require surgical debridement. It may present as a relapse occurring weeks to years after seemingly successful treatment of the initial infection [2].
The evaluation and diagnosis of hematogenous osteomyelitis in children will be discussed here. The epidemiology, pathogenesis, microbiology, clinical features, complications, and management of osteomyelitis in children are discussed separately:
●(See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology".)
●(See "Hematogenous osteomyelitis in children: Clinical features and complications".)
●(See "Hematogenous osteomyelitis in children: Management".)
CLINICAL FEATURES —
A high index of suspicion is essential to establish the diagnosis of osteomyelitis. Signs and symptoms may be nonspecific, and there may be a delay in the patient's presentation for medical evaluation.
Infants ≤3 months of age — Acute hematogenous osteomyelitis is rare in neonates and infants ≤3 months of age. The majority of these patients are afebrile with mild vomiting or fussiness [3-5]. However, a minority of patients present with signs of sepsis, meningitis, or other serious infection. Acute hematogenous osteomyelitis should be suspected in a young infant with:
●Localized swelling, erythema, and tenderness to palpation of a limb and
●Reduced movement of the limb or inability to move it (functio laesa) secondary to pain
Infants and children >3 months of age — Acute hematogenous osteomyelitis should be suspected in infants and children older than three months of age with any of the following findings [6]:
●Constitutional symptoms (irritability, decreased appetite or activity) and fever (in approximately 80 percent of cases)
●Focal symptoms and signs of bone inflammation (eg, warmth, swelling, point tenderness) that typically progress over several days to a week
●Limitation of function (limited use of an extremity; limp; refusal to walk, crawl, sit, or bear weight)
Additional clinical features of osteomyelitis in children are discussed separately. (See "Hematogenous osteomyelitis in children: Clinical features and complications", section on 'Clinical features'.)
Osteomyelitis should also be considered if an abnormal bone imaging study is discovered during an evaluation of a presumed musculoskeletal injury.
Risk factors — Risk factors that increase suspicion for osteomyelitis include (see "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Risk factors'):
●Bacteremia or sepsis
●Recent or current indwelling vascular catheter, including hemodialysis catheter
●Inborn errors of immunity or acquired immune deficiency (eg, sickle cell disease [SCD], chronic granulomatous disease)
Risk factors specific to neonates include skin infection; complicated pregnancy, labor, or delivery; urinary tract anomalies; and late-onset neonatal sepsis.
INITIAL EVALUATION
Physical examination — The components of the musculoskeletal examination include the following:
●Observation – The musculoskeletal examination begins with observation of the affected and contralateral extremity looking for asymmetry in bulk. Inspect the overlying skin for erythema. Evaluate for restricted movements of the extremity and refusal to bear weight. Assess the gait for signs of antalgia.
●Palpation – Palpate the overlying skin to assess for increased warmth and fluctuance. Based on the location of symptoms, apply gentle pressure to bones that are adjacent to or in the vicinity of the child's symptoms.
Applied pressure over the medial and lateral aspects of the calcaneus often identifies inflammation near the two ossification centers. Palpation of the iliac crests, symphysis pubis, and lateral buttocks is used to identify/evaluate for pelvic osteomyelitis [7].
●Percussion – Percuss the vertebral bodies to assess for vertebral osteomyelitis.
●Range of motion – Conduct the Flexion, Abduction, and External Rotation (FABER) maneuver, which consists of simultaneous flexion, abduction, and external rotation at the hip to further assess for pelvic osteomyelitis.
Laboratory evaluation — The initial laboratory evaluation of children with suspected osteomyelitis includes a complete blood count (CBC) with differential and a C-reactive protein (CRP) [1,8].
●White blood cell count – Elevation of the white blood cell count is neither a sensitive nor specific indicator of osteomyelitis [9]. However, the results of a CBC and differential may identify other etiologies of bone pain in children (eg, vaso-occlusive crisis in sickle cell disease [SCD], leukemia). (See 'Differential diagnosis' below.)
●Inflammatory markers – Inflammation is a hallmark of osteomyelitis. Although both CRP and erythrocyte sedimentation rate (ESR) are nonspecific markers of inflammation, elevated levels of either test support the diagnosis of osteomyelitis in a child with the clinical features described above. This is particularly relevant when the initial radiograph is normal. (See 'Clinical features' above.)
Nonetheless, inflammatory markers may be normal or minimally elevated at the time of presentation, especially in cases of Kingella kingae infection [10]. When osteomyelitis is strongly suspected and the CRP is normal, a repeat CRP should be drawn within 24 to 48 hours.
Of note, the 2021 Infectious Diseases Society of America and Pediatric Infectious Diseases Society clinical practice guideline does not recommend measuring ESR due to its poor specificity and sensitivity in cases of acute osteomyelitis and because the ESR remains elevated long after the effectiveness of therapy has been established [1].
High-quality data on the sensitivity of CRP for the diagnosis of hematogenous osteomyelitis are lacking. Additionally, a numerical value above which a CRP is considered positive has not been established. In a retrospective study based largely in the United States, a CRP >2 mg/dL was one of four factors that correlated with a diagnosis of osteomyelitis [6]. In systematic reviews of observational studies, the pooled sensitivity of CRP was 72 to 89 percent [9,11]. In view of the unsatisfactory sensitivity and specificity of a CRP, it should not be used as an independent diagnostic predictor.
A baseline CRP should still be obtained at the time of an initial evaluation of suspected hematogenous osteomyelitis because it can be useful for monitoring the response to treatment if the diagnosis is probable or confirmed [1]. (See "Hematogenous osteomyelitis in children: Management", section on 'Response to therapy'.)
Blood cultures — To avoid multiple venipunctures, at least one blood culture should be obtained at the same time as the CBC and CRP. Although blood cultures are less frequently positive than cultures from bone or adjacent areas of purulence, they may be the only source of pathogen identification and may prevent the need for bone aspiration that is pursued solely for microbiologic studies [1,9,12-14].
Radiographs — Radiographs of the affected region(s) should be obtained as part of the initial evaluation. Although radiographs may not demonstrate any characteristic findings of osteomyelitis early in the disease process, they may identify other causes of pain (eg, bone tumors, fractures) [1,8,15-17].
In infants ≤3 months of age, we obtain a skeletal survey to evaluate for polyostotic disease, which is common in this age group [3,18].
General findings — Osteomyelitis is likely when radiographs demonstrate characteristic findings (table 1) [17] including:
●Deep soft-tissue swelling
●Evidence of periosteal new bone formation (periosteal reaction) (image 1A-B)
●Periosteal elevation (suggestive of periosteal abscess) (image 1D)
●Lytic lesions (image 1C) or sclerosis, indicating subacute/chronic infection
Findings specific to affected bony regions — The timing and typical sequence of radiographic changes of osteomyelitis vary depending on which bone is affected.
●Long bones – Radiographic changes in long bones appear in a sequence. The typical timing from symptom onset to each radiographic finding is as follows [19,20]:
•At three days, a small area of localized, deep soft-tissue swelling may be seen in the region of the metaphysis (image 2).
•At three to seven days, edema fluid obliterates the translucent fat planes within muscle.
•At 10 to 21 days (7 to 10 days in neonates), evidence of bone destruction (osteopenia, osteolytic lesions), periosteal reaction, cortical thickening, and periosteal elevation (due to subcortical purulence (image 1A-D)) are visible.
•At one month (or longer), lytic sclerosis becomes evident.
●Membranous, irregular bones – Bone destruction and periosteal elevation appear three to six weeks after symptom onset (three to four weeks in neonates).
●Pelvic bones – Plain radiographs have poor sensitivity for osteomyelitis of the pelvis (20 to 38 percent) and should not be done as part of the diagnostic evaluation [21,22]. Magnetic resonance imaging (MRI) should be obtained instead. (See 'MRI preferred modality' below.)
●Vertebral osteomyelitis – Initial findings may include localized rarefaction of one vertebral plateau followed by involvement of adjacent vertebrae. However, radiographs are abnormal in only approximately half of cases [23].
●Discitis – The radiographic changes of discitis are first noted two to four weeks after the onset of symptoms in the following sequence:
•Narrowing of the disc space
•Destruction of the adjacent cartilaginous vertebral endplates
•Herniation of the disc into the vertebral body
Several studies indicate that most children will have disc space narrowing (70 to 100 percent) at the time of presentation [23-25].
Significance of normal radiographs — A normal radiograph within 7 to 10 days of symptom onset does not exclude osteomyelitis. Radiographs in infants and children >3 months of age are usually normal or inconclusive at this stage. In systematic reviews, the sensitivity of radiographs at initial presentation ranged from 16 to 37 percent [1,9].
By contrast, radiographs are abnormal at the initial presentation of most newborns and infants with osteomyelitis who are ≤3 months old [3-5]. (See "Hematogenous osteomyelitis in children: Clinical features and complications", section on 'Birth to three months'.)
Children with suspected osteomyelitis (eg, localized bone pain, limited function, elevated CRP) and normal initial radiographs (image 3) should have advanced imaging as soon as possible. (See 'Advanced imaging' below.)
ROLE OF EMPIRIC ANTIBIOTIC THERAPY —
Empiric antibiotics are often started (after obtaining blood cultures) if there will be a delay in obtaining advanced imaging and/or invasive specimens. The indications for and timing of empiric antibiotic therapy are determined by the severity of the child's illness, as discussed separately. (See "Hematogenous osteomyelitis in children: Management", section on 'Indications'.)
SUBSEQUENT EVALUATION
Advanced imaging — Most children with suspected osteomyelitis undergo advanced imaging (table 2). The objectives of advanced imaging studies include:
●Further diagnostic evaluation of osteomyelitis in children with normal initial radiographs
●Further evaluation of abnormalities identified on radiographs (eg, bone destruction)
●Evaluation of extension of infection (eg, growth plate, epiphysis, joint, adjacent soft tissues)
●Guidance for percutaneous diagnostic and therapeutic drainage procedures (eg, needle aspiration, abscess drainage)
MRI preferred modality — MRI, when available, is the preferred imaging modality for identifying the location and extent of bone and soft tissue involvement (table 2) [1,8,15,16,26]. Intravenous contrast is not generally required but may help define intramedullary or intramuscular abscesses [27].
MRI is particularly useful in identifying and/or distinguishing:
●Early changes in the bone marrow cavity (before changes in cortical bone are apparent on radiographs) [28]
●Pelvic osteomyelitis [7,29-31]
●Involvement of the vertebral body and the adjacent disc in children with vertebral osteomyelitis [32]
●Areas that may require surgical drainage (eg, intraosseous abscesses, subperiosteal or soft-tissue collections of pus (image 4); sinus tracts in cases of chronic osteomyelitis) (see "Hematogenous osteomyelitis in children: Management", section on 'Indications for surgery')
●Involvement of the growth plate (image 3) [33-35]
●Contiguous septic arthritis (especially in the evaluation of young children with possible septic arthritis of the hip or femoral osteomyelitis) (see "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Other infections')
●Associated pyomyositis
●Evidence of venous thrombosis associated with osteomyelitis [15]
The major advantages of MRI compared with other imaging modalities include accurate identification of subperiosteal and soft-tissue collections of pus and avoidance of exposure to ionizing radiation [36]. MRI demonstrates excellent anatomic detail and differentiation among soft tissue, bone marrow, and bone (image 5). Additionally, the diagnostic accuracy of MRI does not appear to be affected by prior diagnostic or surgical intervention.
Disadvantages of MRI include a longer scanning time than computed tomography (CT) and the need for sedation or general anesthesia to obtain an adequate study in many young children. It is less useful when multiple sites of involvement are suspected or there are no localized clinical findings.
Findings characteristic of osteomyelitis on MRI include:
●Areas of active inflammation show a decreased signal in T1-weighted images and an increased signal in T2-weighted images [37]. Fat-suppression sequences, including short tau inversion recovery (STIR), decrease the signal from fat and are more sensitive for the detection of bone marrow edema.
●The penumbra sign (high-intensity-signal transition zone between abscess and sclerotic bone marrow in T1-weighted images (image 6)) is characteristic of Brodie abscesses; in one study, it was helpful in differentiating between indolent infections and neoplasms [38].
●The signal from infected bone marrow can be enhanced with intravenous gadolinium contrast [39], but this is seldom necessary for diagnostic purposes [27,40]. Gadolinium contrast clarifies the anatomy of complex cases (eg, chronic osteomyelitis with a sinus tract identified on examination, sequestrum identified on plain radiographs). Because of the risk of nephrogenic systemic fibrosis, imaging with gadolinium should be avoided, if possible, in patients with moderate or advanced kidney failure.
●MRI abnormalities in discitis include reduction of disc space, increased T2 signal in the adjacent vertebral end plates, and signal intensity changes in the intervening discs [23,28].
False-positive MRI results may occur in patients with adjacent soft tissue infection. These infections may cause bone edema that is interpreted as "consistent with osteomyelitis" but actually represents sympathetic inflammation rather than bone infection. False-positive MRI results also may occur in children with vitamin C deficiency [41-44]. (See 'Differential diagnosis' below.)
Alternatives to MRI
●Scintigraphy – Scintigraphy (also known as radionuclide scanning or bone scan) (table 2) is useful for further evaluation of children with characteristic findings of osteomyelitis on plain radiographs. It is also useful when the area of suspected infection cannot be localized or multiple areas of involvement are suspected.
Scintigraphy is readily available, relatively inexpensive, and requires less frequent sedation for young children than MRI. However, it does not provide information about the extent of purulent collections that may require drainage [15], and it requires exposure to ionizing radiation [45].
The procedure is a three-phase bone scan utilizing technetium-99m (99mTc) that consists of:
•A nuclear angiogram (the flow phase), obtained two to five seconds after injection
•The blood pool phase, obtained 5 to 10 minutes after injection
•The delayed phase, specific for bone uptake, obtained two to four hours after injection
Positive results during the first two phases are nonspecific and can be caused by any condition that increases blood flow and is accompanied by inflammation.
Focal uptake during the third phase signals likely osteomyelitis. However, positive findings on scintigraphy may indicate diagnoses other than osteomyelitis, such as fracture, bone tumor, cellulitis, and pyogenic arthritis [1]. A false-negative study may occur when there is a large subperiosteal abscess or other process that disrupts blood supply to the periosteum [16,46,47].
A systematic review identified four studies that evaluated the predictive value of scintigraphy for the diagnosis of osteomyelitis [1]. The sensitivities ranged from 53 to 91 percent and specificities from 47 to 84 percent. The sensitivity of scintigraphy in neonates appears to be lower than in older infants and children [3,15,48,49]. Scintigraphy has been shown to have poor sensitivity (53 percent) in cases of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) [15]. Consequently, scintigraphy should not be used when evaluating a patient with a known MRSA infection.
If findings of the three-phase bone scan are equivocal, further study with an MRI is generally preferred. If MRI is unavailable, scintigraphy with other isotopes used to identify areas of inflammation (eg, gallium or indium) have been used but involve additional exposure to radiation.
●Ultrasonography – Ultrasonography is seldom employed in the diagnosis of osteomyelitis. However, it can identify fluid collections associated with bone infections and is often used to guide percutaneous diagnostic and therapeutic drainage procedures [16,26,50]. Other findings that are consistent with osteomyelitis include elevation of the periosteum by more than 2 mm and thickening of the periosteum.
●CT – CT is seldom used in the evaluation of suspected osteomyelitis. While CT will identify changes in the density of bone marrow, periosteal new bone formation, and periosteal purulence, it lacks the sensitivity and specificity of MRI in the diagnosis of acute osteomyelitis and involves exposure to ionizing radiation. Estimates of the sensitivity and specificity of CT are derived from three small studies in which sensitivity ranged from 62 to 100 percent and specificity from 50 to 75 percent [51-53].
CT scanning may be useful in determining the extent of bony abnormalities in chronic osteomyelitis when significant bone destruction (including the presence of sequestra) is identified on radiographs [1,28]. It may be particularly useful in planning the surgical approach to debridement of devitalized bone (image 7).
Advanced imaging normal — Osteomyelitis is unlikely if advanced imaging studies, especially MRI, are normal. In a systematic review, the sensitivity of MRI was 81 to 100 percent and the specificity was 67 to 94 percent for the detection of bone involvement in children with suspected osteomyelitis [1]. In rare cases, when no other cause for focal pain has been identified and osteomyelitis continues to be the most likely etiology, a repeat MRI (usually within five to seven days) may identify abnormalities that confirm a diagnosis of osteomyelitis.
Decisions regarding next steps depend upon the results of the blood culture and response to empiric antimicrobial therapy:
●Positive blood culture, improvement with empiric therapy – A source of infection other than osteomyelitis must be sought (see 'Other infectious conditions' below)
●Positive blood culture, no improvement with appropriate therapy – Other sources of bacteremia and noninfectious conditions that may have predisposed the patient to bacteremia must be sought aggressively (see 'Differential diagnosis' below)
●Negative blood culture, improvement with empiric therapy – The child may have a more superficial source of infection (eg, cellulitis); a shorter course of antimicrobial therapy may be appropriate (see 'Other infectious conditions' below)
●Negative blood culture, no improvement with appropriate therapy – A bacterial infection is unlikely; fungal and noninfectious causes of musculoskeletal pain should be sought; empiric antimicrobial therapy should be discontinued (see 'Noninfectious conditions' below)
Invasive procedures — Invasive sampling is performed in all areas identified as likely foci of infection by physical examination, plain radiography, or advanced imaging. (See 'Physical examination' above and 'Radiographs' above and 'Advanced imaging' above.)
If MRI findings suggest that any areas require drainage, we consult with an orthopedic surgeon to determine if surgery and drainage are indicated rather than nonsurgical invasive sampling.
Identification of the pathogen and its antibiotic susceptibility profile is fundamental for developing the management plan. Blood cultures may also provide this information; however, their sensitivity is low for the detection of bacterial pathogens that cause osteomyelitis in children.
In a meta-analysis of 17 observational studies including 962 children with confirmed osteomyelitis, the average combined positivity rate of bone and tissue specimen cultures was 65 percent (95% CI 56-75) [1]. In comparison, among 1422 children, the average positivity rate of blood culture was 31 percent (95% CI 26-36) [1].
We consult with an orthopedic surgeon and/or interventional radiologist to determine the best sampling strategy for a given patient and to assist in obtaining specimens from the site(s) of infection.
●Bone sampling – Bone samples or bone marrow aspirates should be obtained whenever possible for aerobic culture, Gram stain, and histopathology [12,14]. Bone culture specimens may be obtained by percutaneous needle aspiration (which may be guided by ultrasonography, fluoroscopy, or other imaging modality [54]) or open biopsy (particularly if surgery is required for therapeutic drainage and debridement). (See "Hematogenous osteomyelitis in children: Management", section on 'Indications for surgery'.)
It is important to notify the microbiology laboratory if less common or fastidious organisms (eg, K. kingae) are suspected because cultures may require specific media or growth conditions or prolonged culture time (table 3) [13]. Injection of bone aspirates or periosteal collections into blood culture bottles is recommended to enhance recovery of K. kingae. (See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Kingella kingae'.)
Nucleic acid amplification tests (NAATs) are useful for detecting specific pathogens, especially in the pretreated patient with negative cultures [1,55]. NAATs are particularly helpful for detecting K. kingae in purulent materials or bone specimens [56-58].
Cultures for rare pathogens (eg, anaerobic bacterial, fungi, mycobacteria) are usually reserved for children with clinical suspicion or epidemiologic risk factors (eg, penetrating inoculation, immunocompromise (table 3)) [1,59].
●Other specimens – Subcutaneous abscesses, subperiosteal exudates, joint fluid, and pus from other sites of infection near the suspected foci of osteomyelitis should be obtained and sent for Gram stain and culture whenever possible, as directed by imaging studies [12].
Percutaneous needle aspiration is often successful in neonates with extensive soft-tissue and periosteal involvement and in infants and young children with subperiosteal collections. Percutaneous techniques are less successful in older children and adolescents, who may require bone aspiration or drilling to obtain culture specimens. In such cases, the risk of epiphyseal damage and further destruction of bone must be weighed against the benefit of obtaining a specimen.
Culturing specimens from multiple sites increases the likelihood of identifying a pathogen and determining antibiotic susceptibility [1,12], which allows for therapy using an antibiotic with a narrow spectrum of activity. This is particularly important in areas in which antibiotic-resistant organisms such as community-associated MRSA are relatively common [1]. (See "Hematogenous osteomyelitis in children: Management".)
DIAGNOSTIC INTERPRETATION
Synthesis of data — The diagnosis of osteomyelitis may be supported by a combination of [60]:
●Clinical features suggestive of bone infection (eg, constitutional symptoms, focal symptoms and signs of bone inflammation, limitation of function) coupled with elevated C-reactive protein (CRP) (see 'Clinical features' above and 'Laboratory evaluation' above)
●An imaging study with abnormalities characteristic of osteomyelitis (table 1) (see 'Radiographs' above and 'Advanced imaging' above)
●A positive microbiologic or histopathologic specimen (see 'Invasive procedures' above)
●Clinical improvement with empiric antimicrobial therapy (see "Hematogenous osteomyelitis in children: Management", section on 'Empiric parenteral therapy')
Diagnostic certainty — Depending on the clinical features or combination of features, the diagnosis of hematogenous osteomyelitis is either confirmed, probable, or unlikely.
●Osteomyelitis confirmed – The diagnosis of osteomyelitis is confirmed by either of the following:
•Evidence of inflammation found on histopathologic examination of a surgical bone specimen (picture 1A-C)
•Identification of a pathogen by culture or Gram stain of a bone aspirate, bone biopsy or surgical specimen, or aspirate of a periosteal fluid collection [61]
●Osteomyelitis probable – The diagnosis of osteomyelitis is probable in a child with compatible clinical and radiologic findings (table 1) plus either of the following (see 'Physical examination' above):
•Identification of a typical pathogen (eg, S. aureus, beta-hemolytic streptococci, K. kingae, Streptococcus pneumoniae) from blood or joint fluid by culture, Gram stain, or nucleic acid amplification test (NAAT)
•Improvement with empiric antimicrobial therapy
The next steps in evaluating children who have clinical and radiologic findings compatible with osteomyelitis but do not meet any of the additional two criteria are discussed separately. (See "Hematogenous osteomyelitis in children: Management", section on 'Culture-negative osteomyelitis'.)
Given the potential morbidity of delayed treatment, children with probable osteomyelitis should be managed in the same manner as children in whom infection has been confirmed [62]. (See "Hematogenous osteomyelitis in children: Management", section on 'Empiric parenteral therapy'.)
●Osteomyelitis unlikely – Osteomyelitis is unlikely if MRI or bone scanning studies are normal. The next steps in the evaluation depend upon the results of the blood culture and response to antimicrobial therapy. (See 'Advanced imaging normal' above.)
DIFFERENTIAL DIAGNOSIS —
The differential diagnosis of osteomyelitis includes other infectious conditions, noninfectious conditions, and radiographic mimics (table 4).
Other infectious conditions — The signs and symptoms that lead to suspicion of osteomyelitis (eg, constitutional, inflammatory, functional) may be caused by an infectious condition that mimics hematogenous osteomyelitis but does not involve bone. These infections are often distinguishable from osteomyelitis by their MRI findings (table 1). (See 'Findings specific to affected bony regions' above and 'Advanced imaging' above.)
These infections, which may also complicate or be complicated by osteomyelitis, include:
●Sepsis – In a minority of infants ≤3 months, sepsis may be the only sign of osteomyelitis. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at or after 35 weeks gestation", section on 'Clinical manifestations' and "Sepsis in children: Definitions, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
●Cellulitis – Soft tissue infections cause localized swelling, erythema, and tenderness to palpation of a limb and may be falsely interpreted as 'consistent with osteomyelitis' on MRI when sympathetic inflammation causes bone edema. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Cellulitis and erysipelas'.)
●Septic arthritis – The pathogenesis of septic arthritis and many of its signs and symptoms are similar to osteomyelitis, and the two conditions may coexist. Approximately one-third of cases of osteomyelitis extend to the contiguous joint (as many as 75 percent in neonates) [18,63-66]. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Clinical features' and "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children", section on 'Pathogenesis'.)
●Deep abscesses (eg, psoas abscess or obturator internus abscess [67]) – Deep abscesses are usually identified by advanced imaging during the evaluation of a child in whom osteomyelitis is suspected because of fever and pain with movement. (See "Psoas abscess", section on 'Clinical manifestations'.)
●Pyomyositis – Localized swelling and dull muscle pain may be the only indications of pyomyositis in the first week of illness. (See "Primary pyomyositis", section on 'Clinical manifestations'.)
●Garré sclerosing osteomyelitis – Garré sclerosing osteomyelitis is characterized by rigid bony swelling at the periphery of the mandible and nonsuppurative sclerotic bone inflammation [68]. It has been reported at all ages [64]. Garré sclerosing osteomyelitis is thought to be triggered by odontogenic infection [69-71], but noninfectious causes of inflammation also may play a role.
●Congenital syphilis – Long bone abnormalities related to congenital syphilis may be associated with pain and limited movement of the involved extremity. (See "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis", section on 'Clinical manifestations'.)
Noninfectious conditions
Chronic nonbacterial osteomyelitis — Chronic nonbacterial osteomyelitis (CNO; also called chronic recurrent multifocal osteomyelitis [CRMO]) is a chronic inflammatory bone disorder that primarily affects children. It is characterized by bone pain with insidious onset. The initial presentation is similar to that of infectious osteomyelitis. Imaging may localize the areas of bony involvement and indicate the absence of features suggestive of chronic osteomyelitis, such as an abscess or sinus tract. Microbiologic and pathologic studies from bone biopsy specimens are generally necessary to differentiate CNO from infectious osteomyelitis. The evaluation and treatment of CNO are discussed in detail separately. (See "Chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO) in children".)
Other noninfectious conditions — Several noninfectious conditions have clinical features that overlap with osteomyelitis and include:
●Malignancy – Tumor growth may be associated with bone pain, and some children with malignancies (particularly leukemia and Ewing sarcoma) have fever as part of their initial presentation. Unlike with osteomyelitis, symptoms can be intermittent in children with cancer. Affected children also fail to respond to empiric antibiotic therapy. Osteomyelitis and cancer involving bone are usually differentiated by bone biopsy. (See "Overview of common presenting signs and symptoms of childhood cancer", section on 'Bone and joint pain' and "Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children", section on 'Presentation' and "Clinical presentation, staging, and prognostic factors of Ewing sarcoma", section on 'Signs and symptoms' and "Bone tumors: Diagnosis and biopsy techniques".)
●Bone infarction – Bone infarction secondary to sickle cell disease (SCD), especially in infants with dactylitis, can be particularly difficult to distinguish from osteomyelitis. Furthermore, osteomyelitis is a common complication of SCD.
An elevated reticulocyte count and/or sickled cells on a peripheral smear are consistent with SCD.
Radiographs, scintigraphy, and MRI findings are similar in both conditions. In contrast to the vaso-occlusive episodes associated with SCD, osteomyelitis does not respond to hydration and other supportive measures. (See "Acute and chronic bone complications of sickle cell disease".)
●Gaucher disease – Children with Gaucher disease can have painful bone crises similar to those that occur in patients with SCD. During bone pain crises, ischemia can be detected by technetium bone scan. Radiographs of the distal femur may demonstrate deformities caused by abnormal modeling of the metaphysis that are characteristic of Gaucher disease. However, the possibility of osteomyelitis should be considered in febrile patients with Gaucher disease who do not improve with hydration and other supportive measures. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis" and "Gaucher disease: Treatment", section on 'Skeletal disease'.)
●Vitamin C deficiency – Vitamin C deficiency (scurvy) may cause musculoskeletal pain and refusal to bear weight, particularly in children with autism spectrum disorder, intellectual disability, food aversion, or limited food preferences [41,42,44].
Additional findings of vitamin C deficiency, which do not always accompany the musculoskeletal findings, include petechiae, ecchymoses, bleeding gums, coiled hairs, and hyperkeratosis (picture 2). (See "Overview of water-soluble vitamins", section on 'Deficiency' and "Autism spectrum disorder (ASD) in children and adolescents: Terminology, epidemiology, and pathogenesis", section on 'Prevalence'.)
●Complex regional pain syndrome (CRPS) – CRPS is an uncommon chronic condition that causes pain, swelling, and limited range of motion in the affected extremity. It frequently begins after an injury, surgery, or vascular event. Vasomotor instability and chronic skin changes also occur. CRPS may be distinguished from osteomyelitis by autonomic dysfunction and normal inflammatory markers (eg, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). (See "Complex regional pain syndrome in children", section on 'Diagnosis'.)
●Neuropathic arthropathy (Charcot foot) – Neuropathic arthropathy is a progressive degeneration of the weightbearing joints of the foot that occurs in people with peripheral neuropathies (eg, related to spinal cord abnormality or injury) [72,73]. Clinical features include localized swelling, erythema, and warmth. Biopsy may be necessary to differentiate neuropathic arthropathy from osteomyelitis, particularly in the early inflammatory stage when there are few or no radiologic abnormalities [74]. (See "Surgical management of neuropathic arthropathy (Charcot foot)", section on 'Anatomy and classification'.)
●Caffey disease – Caffey disease (infantile cortical hyperostosis) is an inherited disease that usually presents in early infancy with fever, subperiosteal bone hyperplasia, and swelling of overlying soft tissues. It is a rare disorder caused by a subset of mutations in the type 1 collagen gene COL191 [75]. Caffey disease is difficult to distinguish from osteomyelitis at initial presentation and may require bone biopsy and genetic testing to make the diagnosis. (See "Differential diagnosis of suspected child physical abuse: Orthopedic manifestations", section on 'Infantile cortical hyperostosis (Caffey disease)'.)
Radiographic mimics — The radiographic appearance of benign and malignant bone tumors can be similar to osteomyelitis. The acute clinical features and response to antibiotics in children with osteomyelitis usually distinguish osteomyelitis from these conditions. However, bone biopsy may be necessary for histopathologic differentiation.
Bone lesions with radiographic appearances similar to osteomyelitis include (table 4):
●Fibrous dysplasia (see "Nonmalignant bone lesions in children and adolescents", section on 'Fibrous dysplasia')
●Osteoid osteoma and osteoblastoma (see "Nonmalignant bone lesions in children and adolescents", section on 'Bone-forming lesions')
●Chondroblastoma and chondromyxoid fibroma (see "Nonmalignant bone lesions in children and adolescents", section on 'Cartilage-forming tumors')
●Eosinophilic granuloma and other forms of Langerhans cell histiocytosis (see "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis", section on 'Lytic bone lesions')
●Osteosarcoma (see "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis", section on 'Clinical presentation')
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Septic arthritis and osteomyelitis in children".)
SUMMARY AND RECOMMENDATIONS
●Clinical suspicion – The diagnosis of osteomyelitis often is uncertain at the initial evaluation. A high index of suspicion is essential to establish the diagnosis.
Findings that raise suspicion for acute hematogenous osteomyelitis include (see 'Clinical features' above):
•Constitutional symptoms, with or without fever
•Localized swelling, erythema, and tenderness to palpation of a limb
•Reduced movement of the limb or inability to move it secondary to pain
•Detection of bacteremia or characteristic imaging findings during evaluation of a presumed musculoskeletal injury
●Initial evaluation – The initial evaluation of children with suspected osteomyelitis includes (see 'Initial evaluation' above):
•Complete blood count (CBC) with differential and C-reactive protein (CRP)
•Blood culture
•Radiograph(s) of the affected region (table 1)
●Subsequent evaluation
•Advanced imaging – Advanced imaging is indicated in most children with osteomyelitis. MRI is the preferred advanced imaging modality; alternatives include scintigraphy, ultrasonography, and CT (table 2). (See 'Advanced imaging' above.)
•Invasive procedures – If advanced imaging is abnormal, invasive procedures are conducted to obtain specimens for Gram stain, histology, culture, and nucleic acid amplification testing (NAAT). Patients whose MRI findings identify areas that require surgery and drainage are taken to the operating room. For all other children, we consult with an orthopedic surgeon and/or interventional radiologist to assist with obtaining nonsurgical specimens from as many sites of infection as possible. (See 'Invasive procedures' above.)
●Diagnostic interpretation – The diagnosis of osteomyelitis may be supported by a combination of clinical features, findings on radiograph or advanced imaging (table 1), culture results or histopathologic findings, and/or response to empiric antimicrobial therapy. (See 'Synthesis of data' above.)
Diagnostic certainty of osteomyelitis is determined as follows (see 'Diagnostic certainty' above):
•Confirmed
-Histopathologic evidence of inflammation on a tissue specimen of bone (picture 1A-C) or
-Identification of a pathogen by culture or Gram stain from an aspirate or biopsy of bone or periosteal fluid
•Probable – Compatible clinical and radiologic findings (table 1) and at least one of the following:
-Identification of a typical pathogen from blood or joint fluid by culture, Gram stain, or NAAT
-Improvement with empiric antimicrobial therapy
•Unlikely – Normal advanced imaging studies, especially MRI (see 'Advanced imaging' above)
●Differential diagnosis – The differential diagnosis of osteomyelitis includes other infectious causes and conditions, noninfectious conditions, and radiographic mimics (table 4). (See 'Differential diagnosis' above.)
