6/19/22, 6:16 PM 6067

Official reprint from UpToDate®

www.uptodate.com © 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Hematogenous osteomyelitis in children: Evaluation and

diagnosis
Author: Paul A Krogstad, MD
Section Editors: Sheldon L Kaplan, MD, William A Phillips, MD
Deputy Editor: Mary M Torchia, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2022. | This topic last updated: Jul 13, 2020.

INTRODUCTION

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 osteomyelitis 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".)

DEFINITION AND PATHOGENESIS

Osteomyelitis is an infection localized to bone. It is usually caused by microorganisms

(predominantly bacteria) that enter the bone via the bloodstream (hematogenously).

Osteomyelitis also may result from direct inoculation of bone with bacteria in association with
an open fracture or as a complication of puncture wounds or the placement of orthopedic
hardware (such as pins or screws). (See "Infectious complications of puncture wounds".)

Less commonly, osteomyelitis may arise as an extension of a contiguous infection (eg,

decubitus ulcer, deep wound infection, sinusitis, periodontal disease).

https://www.uptodate.com/contents/6067/print 1/46
6/19/22, 6:16 PM 6067

DIAGNOSTIC APPROACH

Overview — The diagnosis of osteomyelitis is supported by a combination of [1]:

● Clinical features suggestive of bone infection (constitutional symptoms, focal symptoms

and signs of bone inflammation including limitation of function) associated with elevated
erythrocyte sedimentation rate (ESR), and/or C-reactive protein (CRP) (see 'Clinical
suspicion' below and 'Blood tests' below)

● An imaging study with abnormalities characteristic of osteomyelitis ( table 1) (see

'Radiographs' below and 'Advanced imaging' below)

● A positive microbiologic or histopathologic specimen (see 'Microbiology' below and

'Histopathology' below)

● A response to empiric antimicrobial therapy (see 'Response to empiric therapy' below)

The diagnosis often is unclear at the initial evaluation. The initial presentation may be delayed,
and signs and symptoms nonspecific. A high index of suspicion and monitoring of the clinical
course are essential to establishing the diagnosis. We suggest that an orthopedic surgeon or
interventional radiologist be consulted as early as possible to assist in obtaining specimens
from the site of infection and assessing the need for surgical intervention. (See 'Microbiology'
below and "Hematogenous osteomyelitis in children: Management", section on 'Indications for
surgery'.)

The diagnosis is confirmed by histopathologic evidence of inflammation in a surgical specimen

of bone ( picture 1A-C) (if obtained) or identification of a pathogen by culture or Gram stain in
an aspirate or biopsy of bone or a periosteal fluid collection [2].

The diagnosis is probable in a child with compatible clinical, laboratory, and/or radiologic
findings ( table 1) in whom a pathogen is isolated from blood or joint fluid or, if cultures are
negative, detection of S. aureus, S. pneumoniae, or K. kingae by polymerase chain reaction (PCR)
in bone aspirates, subperiosteal collections, or synovial fluid. We also consider the diagnosis to
be probable in a child with compatible clinical, laboratory, and radiologic findings and negative
cultures and PCR if he or she responds as expected to empiric antimicrobial therapy.

The diagnosis is unlikely if advanced imaging studies (particularly magnetic resonance imaging
[MRI]) are normal throughout the evaluation.

https://www.uptodate.com/contents/6067/print 2/46
6/19/22, 6:16 PM 6067

Clinical suspicion — Based upon the history and physical examination, acute hematogenous
osteomyelitis should be suspected in infants and children with findings suggestive of bone
infection, including:

● Constitutional symptoms (irritability, decreased appetite or activity), with or without fever

● Focal symptoms and signs of bone inflammation (eg, warmth, swelling, point tenderness)
that typically progress over several days to a week; symptoms and signs in infants and
small children may be poorly localized

● 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 also should also be considered in children who are found to have bacteremia or
an abnormal imaging study of bone in the evaluation of trauma or nonspecific signs or
symptoms (eg, irritability, fever without a source).

Risk factors that may raise suspicion for osteomyelitis include (see "Hematogenous
osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Risk
factors'):

● Bacteremia or sepsis
● Immune deficiency (eg, sickle cell disease, chronic granulomatous disease)
● Recent or current indwelling vascular catheter, including hemodialysis catheter
● For neonates – Prematurity, skin infection, complicated delivery, urinary tract anomalies,
late onset neonatal sepsis

Initial evaluation — The initial evaluation for children with suspected osteomyelitis includes
blood tests and radiographs of the affected area(s).

Blood tests — Initial blood tests for children with suspected osteomyelitis include a complete
blood count (CBC) with differential, ESR, and/or CRP [3]. To avoid multiple venipunctures, at
least one blood culture should be obtained at the same time as these studies. Blood cultures
are discussed below. (See 'Microbiology' below.)

At the time of presentation, elevation of ESR (>20 mm/h) and/or CRP (>10 to 20 mg/L [1 to 2
mg/dL]) is sensitive (approximately 95 percent) in cases of culture-proven osteomyelitis in

https://www.uptodate.com/contents/6067/print 3/46
6/19/22, 6:16 PM 6067

children, but ESR and CRP are nonspecific [4-6]. Elevated ESR and/or CRP support the diagnosis
of osteomyelitis but do not exclude other conditions in the differential diagnosis. ESR and CRP
may be normal early in the infection in some patients, and repeat testing may be warranted
within 24 hours in children in whom osteomyelitis is strongly suspected. CRP and, to a lesser
extent, ESR also are important markers for evaluating the response to therapy. (See
"Hematogenous osteomyelitis in children: Management", section on 'Response to therapy'.)

Elevation of the white blood cell (WBC) count is neither a sensitive nor a specific indicator of
osteomyelitis. In a 2012 systematic review of >12,000 patients, the WBC was elevated in only 36
percent [5]. However, the CBC and differential are helpful in evaluating other considerations in
the differential diagnosis of children with bone pain (eg, vaso-occlusive crisis in sickle cell
disease, leukemia). (See 'Differential diagnosis' below.)

Radiographs — Radiograph(s) of the affected region(s) should be performed as the initial

imaging study to exclude other causes of pain (eg, bone tumors and fractures) [3,7,8].
Radiographs are usually normal or inconclusive early in the course of osteomyelitis. Newborn
infants are an exception to this general rule; radiographs are abnormal at the time of evaluation
in most newborn and young infants who are ultimately found to have osteomyelitis [9,10]. For
older children with suspected osteomyelitis and normal or inconclusive radiographs, MRI is
usually indicated. (See 'Advanced imaging' below and 'Differential diagnosis' below.)

Characteristic findings — Children with suspected osteomyelitis and characteristic

abnormalities on initial radiographs are likely to have osteomyelitis ( table 1). They should
receive empiric antibiotic therapy pending further evaluation (microbiology and possibly
additional imaging studies). (See "Hematogenous osteomyelitis in children: Management",
section on 'Empiric parenteral therapy' and 'Microbiology' below and 'Advanced imaging'
below.)

Radiographic findings that are compatible with osteomyelitis include:

● 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

However, these findings generally are not apparent at the onset of symptoms. The timing and
typical sequence of radiographic changes of osteomyelitis varies depending on which bones are
affected and the age of the patient.

● Long bones – The typical sequence of radiographic changes in long bones of children is as
follows [11,12]:
https://www.uptodate.com/contents/6067/print 4/46
6/19/22, 6:16 PM 6067

• Approximately three days after symptom onset – Small area of localized, deep, soft-
tissue swelling in the region of the metaphysis ( image 2)

• Three to seven days after symptom onset – Obliteration of the translucent fat planes
interposed within muscle by edema fluid

• Ten to 21 days after symptom onset (7 to 10 days in neonates) – Evidence of bone

destruction (osteopenia, osteolytic lesions), periosteal reaction, cortical thickening,
periosteal elevation (due to subcortical purulence ( image 1A-D)); these lesions may
require surgical debridement or drainage (see "Hematogenous osteomyelitis in
children: Management", section on 'Indications for surgery')

• One month or longer – Lytic sclerosis

● Membranous, irregular bones – Bone destruction and periosteal elevation generally are
apparent two to three weeks later than in long bones.

● Pelvic bones – Radiographs usually are not useful in the diagnostic evaluation of
osteomyelitis of the pelvis; in one large series, they were abnormal in only 25 percent of
patients [13].

● Vertebral osteomyelitis – In children with vertebral osteomyelitis, radiographs are

normal at initial presentation in more than 50 percent of cases [14]. Initial abnormalities
may include localized rarefaction of one vertebral plateau, followed by involvement of
adjacent vertebrae. Marked destruction of bone, usually anteriorly, can occur, followed by
anterior osteophytic reactions with bridging and bone sclerosis.

● Discitis – The radiographic changes of discitis are first noted several weeks after the onset
of symptoms, with the following sequence:

• Narrowing of the disc space two to four weeks after the onset of symptoms

• Destruction of the adjacent cartilaginous vertebral end-plates

• Herniation of the disc into the vertebral body

In older children, anterior spontaneous fusion is common. Rarely, vertebral body

compression or wedging is noted.

Despite the delay in radiographic changes, findings suggestive of discitis often are
apparent at the time of presentation (because of the indolent course). In one series, as an

https://www.uptodate.com/contents/6067/print 5/46
6/19/22, 6:16 PM 6067

example, radiographic changes were present on initial evaluation in more than 70 percent
of cases [14].

Normal radiographs — A normal radiograph early in the course (eg, within seven days of
symptom onset) does not exclude osteomyelitis. Children with suspected osteomyelitis (eg,
localized bone pain, limited function, elevated ESR or CRP) and normal initial radiographs
generally should receive empiric antibiotic therapy pending additional imaging and the results
of microbiologic studies. However, school-age children who are afebrile and have equivocal
physical examination findings, and normal radiographs may occasionally be followed closely
without antimicrobial therapy pending additional evaluation. (See "Hematogenous
osteomyelitis in children: Management", section on 'Empiric parenteral therapy' and 'Advanced
imaging' below and 'Microbiology' below.)

Further imaging, usually with MRI or scintigraphy, should be performed as soon as possible in
any child with suspected osteomyelitis whose initial radiographs are normal, regardless of
whether antibiotic therapy is initiated ( image 3). (See 'Advanced imaging' below.)

Advanced imaging — Most children with suspected osteomyelitis undergo additional imaging
with MRI, scintigraphy, computed tomography (CT), and/or ultrasonography ( table 2).
Indications for these imaging studies may include:

● Confirmation of the diagnosis 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)

Magnetic resonance imaging — If it is available, MRI is the imaging modality of choice when
imaging other than radiography is needed to establish the diagnosis of osteomyelitis (eg, early
in the course) or to delineate the location and extent of bone and soft tissue involvement (
table 2) [3,7,8]. Intravenous contrast is not generally required but may help define
intramedullary abscess or intramuscular abscesses [15]. Osteomyelitis is unlikely if MRI is
negative.

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) [16]

https://www.uptodate.com/contents/6067/print 6/46
6/19/22, 6:16 PM 6067

● Pelvic osteomyelitis [17-19]

● Involvement of the vertebral body and the adjacent disc in children with vertebral
osteomyelitis

● Areas that may require surgical drainage (eg, sinus tracts, intraosseous abscesses,
subperiosteal or soft-tissue collections of pus) ( image 4) (see "Hematogenous
osteomyelitis in children: Management", section on 'Indications for surgery')

● Involvement of the growth plate ( image 3) [20-22]

● Contiguous septic arthritis (especially in the evaluation of young children with possible
septic arthritis of the hip or femoral osteomyelitis)

● Associated pyomyositis

● Evidence of venous thrombosis

The major advantages of MRI compared with other imaging modalities include accurate
identification of subperiosteal or soft-tissue collections of pus and avoidance of exposure to
ionizing radiation [23]. In addition, the efficacy of MRI does not appear to be affected by
diagnostic or surgical intervention. However, repeat MRI may be of limited value after surgical
drainage because it can be difficult to distinguish between postsurgical changes and recurrent
or persisting infection. Repeat MRI seldom leads to management changes in patients with
clinical improvement. In a retrospective review of 60 cases of acute osteomyelitis, only 11 of 104
repeat MRIs resulted in a change in treatment; in all 11 cases, the CRP was persistently elevated
or rising [24].

Disadvantages of MRI include a longer scanning time than CT and the need for sedation or
general anesthesia for an adequate study in most young children, which may be a limiting
factor in some institutions. MRI is less useful when multiple sites of involvement are suspected
or there are no localized clinical findings. Finally, MRI is not always readily available.

MRI demonstrates excellent anatomic detail and differentiation among soft tissue, bone
marrow, and bone ( image 5).

● Areas of active inflammation show a decreased signal in T1-weighted images and an

increased signal in T2-weighted images [25]. 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.

https://www.uptodate.com/contents/6067/print 7/46
6/19/22, 6:16 PM 6067

● The penumbra sign (high-intensity-signal transition zone between abscess and sclerotic
bone marrow in T1-weighted images ( image 6)) is characteristic of subacute
osteomyelitis and in one study was helpful in differentiating between indolent infections
and neoplasms [26].

● The signal from infected bone marrow can be enhanced with intravenous gadolinium
contrast [27], but this is seldom necessary for diagnostic purposes [15,28]. Because of the
risk of nephrogenic systemic fibrosis, imaging with gadolinium should be avoided, if
possible, in patients with moderate or advanced renal failure. (See "Nephrogenic systemic
fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease".)

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 [14,16].

The sensitivity and specificity for the detection of bone involvement in children with suspected
osteomyelitis with MRI are high (80 to 100 percent and 70 to 100 percent, respectively, in a 2012
systematic review) [5]. Given the high sensitivity, osteomyelitis is unlikely if the MRI is negative
[7], although rare patients lack MRI abnormalities at the time of presentation. False-positive
results may occur in patients with adjacent soft tissue infection; adjacent soft tissue infection
can cause edema of the bone that may be interpreted as "consistent with osteomyelitis" but
represents sympathetic inflammation rather than bone infection. False-positive MRI results also
may occur in children with vitamin C deficiency [29-32]. (See 'Other noninfectious conditions'
below.)

Scintigraphy — We suggest scintigraphy (also known as radionuclide scanning or bone scan)

when MRI is not available and imaging other than radiography is needed to establish the
diagnosis of osteomyelitis ( table 2). Scintigraphy also may be useful when the area of
suspected infection cannot be localized or multiple areas of involvement are suspected.

Scintigraphy is helpful early in the course, readily available, relatively inexpensive, and requires
sedation less frequently than MRI in young children. However, it does not provide information
about the extent of purulent collections that may require drainage (eg, intramedullary abscess,
muscular phlegmon) [7]. Scintigraphy may be falsely negative if the blood supply to the
periosteum is disrupted (eg, subperiosteal abscess) and during the transition between
decreased and increased activity [33,34]. In addition, scintigraphy involves exposure to ionizing
radiation [35].

The three-phase bone scan utilizing technetium 99m (99mTc) usually is performed as the initial
nuclear medicine procedure in the evaluation of osteomyelitis. It consists of:

https://www.uptodate.com/contents/6067/print 8/46
6/19/22, 6:16 PM 6067

● 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

Increased uptake of tracer in the first two phases can be caused by anything that increases
blood flow and is accompanied by inflammation. Osteomyelitis causes focal uptake in the third
phase; the intensity of the signal reflects the level of osteoblastic activity. Localization of a lesion
near a growth plate can complicate interpretation.

The sensitivity and specificity for the detection of bone involvement in children with suspected
osteomyelitis with scintigraphy generally are high, but the range is wider than MRI (53 to 100
percent and 50 to 100 percent, respectively in a 2012 systematic review) [5]. Sensitivity is
variable in neonates but appears to be lower than in older children [9,36,37]. Scintigraphy has
been shown to have poor sensitivity (53 percent) in cases of osteomyelitis caused by methicillin-
resistant Staphylococcus aureus (MRSA) [7].

MRI generally is preferred if the results of the three-phase 99mTc bone scan are equivocal.
Scintigraphy with inflammation imaging tracers (eg, gallium or indium) may be helpful but
involve additional exposure to radiation.

Computed tomography — MRI usually is preferred to CT in the evaluation of suspected

osteomyelitis. However, CT better delineates changes in bone and may be preferred when
significant bone destruction is identified on radiographs [16]. CT findings of osteomyelitis
include increased density of bone marrow, periosteal new bone formation, and periosteal
purulence.

Other potential indications for CT may include:

● Delineation of the extent of bone injury in chronic osteomyelitis or planning the surgical
approach to debridement of devitalized bone (sequestra) ( image 7)

● Lack of availability of MRI or contraindications to MRI

CT is less time consuming than MRI, and young children usually do not require sedation.
However, CT exposes children to ionizing radiation.

Ultrasonography — Ultrasonography usually is not helpful in the diagnosis of osteomyelitis.

However, it can identify fluid collections associated with bone infections and may improve the
success of percutaneous diagnostic and therapeutic drainage procedures [8,38,39].

https://www.uptodate.com/contents/6067/print 9/46
6/19/22, 6:16 PM 6067

Ultrasonography findings consistent with osteomyelitis include fluid collection adjacent to the
bone without intervening soft tissue, elevation of the periosteum by more than 2 mm, and
thickening of the periosteum. (See "Approach to imaging modalities in the setting of suspected
nonvertebral osteomyelitis", section on 'Ultrasonography'.)

Microbiology

General principles — Isolation of a pathogen from bone, subperiosteal fluid collection, joint
fluid, or blood or PCR detection of pathogens in bone, subperiosteal fluid collection, or joint
fluid establishes a diagnosis of confirmed or probable osteomyelitis in children with compatible
clinical and/or radiologic findings and speciation and susceptibility testing are essential for
planning treatment. (See "Hematogenous osteomyelitis in children: Management", section on
'Antimicrobial therapy'.)

With an increasing proportion of cases caused by antibiotic-resistant organisms (eg,

community-associated MRSA) and previously unusual species (eg, Kingella kingae in young
children), it is particularly important to collect specimens for culture from as many sites of
infection as possible.

It is preferable to obtain microbiologic specimens before administration of antibiotics, but this

must be weighed against the potential for additional complications of ongoing bacteremia by S.
aureus or other pathogens. If bone culture cannot be obtained immediately, decisions
regarding immediate or delayed administration of antibiotics generally are made in
consultation with the orthopedic surgeon. For children with signs of systemic illness (eg, fever,
tachycardia), we provide antibiotic therapy immediately following blood culture. In a
retrospective review of 250 cases of osteomyelitis, the rates of culture positivity were similar
(approximately 74 percent) whether or not patients received antibiotics before cultures were
obtained, although there was a tendency for cultures obtained by interventional radiology to
more likely be positive if obtained within 24 hours of initiating antibiotic treatment [40]. In
another retrospective study, operative cultures were positive in 42 of 50 children (84 percent)
with osteomyelitis who received preoperative antibiotics [41].

Sites to culture — Specimens for culture should be obtained from blood and as many
potential sites of infection as possible. An orthopedic surgeon and/or interventional radiologist
should be consulted as early as possible in the evaluation of children with suspected
osteomyelitis to assist in obtaining specimens for histopathology and/or culture and assessing
the need for surgical intervention. In a retrospective review of 250 cases of osteomyelitis from a
single institution, blood cultures were positive in 46 percent of cases in which they were
obtained, cultures obtained in the operating room (OR, bone, subperiosteal abscess, adjacent

https://www.uptodate.com/contents/6067/print 10/46
6/19/22, 6:16 PM 6067

septic arthritis) were positive in 82 percent, and cultures obtained in interventional radiology
(IR) were positive in 52 percent [40]. OR/IR cultures were positive in 80 patients who had
negative blood cultures; among these cases, results of OR/IR cultures prompted a change in
antibiotic therapy in 68 (85 percent).

It is important to inform the microbiology laboratory if less common or fastidious organisms

(eg, K. kingae) are suspected because they may require specific media, growth conditions, or
prolonged culture time ( table 3) [42].

● Blood cultures – We recommend at least one, and preferably two, blood cultures be
obtained before administration of antibiotics to children with osteomyelitis. Although less
frequently positive than cultures from bone or adjacent abscesses, blood cultures may be
the only positive source of identification of the pathogen [5,40,42,43].

● Bone culture – Bone samples for culture, Gram stain, and histopathology should be
obtained whenever possible [40,43]. Culture specimens may be obtained by percutaneous
needle aspiration (which may be guided by ultrasonography, fluoroscopy, or other
imaging modality) or open biopsy (particularly if surgery is required for therapeutic
drainage and debridement). (See "Hematogenous osteomyelitis in children:
Management", section on 'Indications for surgery'.)

● Other cultures – Subperiosteal exudate, joint fluid, and pus from adjoining sites of
infection should be obtained and sent for Gram stain and culture whenever possible, as
directed by imaging studies [40]. Specimens may be obtained by percutaneous needle
aspiration (which may be guided by ultrasonography, fluoroscopy, or other imaging
modality). Injection of bone aspirates or periosteal collections into blood culture bottles is
recommended to enhance recovery of K. kingae [44,45]. (See "Hematogenous
osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on
'Kingella kingae'.)

Percutaneous needle aspiration is often successful in neonates with extensive soft-tissue

and periosteal involvement and 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.

As reported in a 2012 systematic review of observational studies of osteomyelitis (during or

after 2000), a pathogen is isolated from any culture (blood, tissue, pus) in approximately 50
https://www.uptodate.com/contents/6067/print 11/46
6/19/22, 6:16 PM 6067

percent of cases [5]. The yield of cultures of bone tissue or pus is greater than that from blood
cultures (70 versus 40 percent).

Other microbiologic studies — Other microbiologic studies may be helpful in the detection of
specific pathogens. PCR (if available) can be particularly helpful for detecting K. kingae in
purulent materials or bone specimens, particularly when Kingella-specific methods are used
[46-48].

Histopathology — The diagnosis of osteomyelitis is confirmed in children who have

histopathologic evidence of inflammation in a surgical specimen of bone ( picture 1A-C). An
orthopedic surgeon and/or interventional radiologist should be consulted as early as possible
in the evaluation of children with suspected osteomyelitis to assist in obtaining specimens for
histopathology and/or culture and assessing the need for surgical intervention.

Histopathologic specimens may be obtained by percutaneous needle aspiration (which may be

guided by ultrasonography, fluoroscopy, or other imaging modality) or open biopsy (particularly
if surgery is required for therapeutic drainage and debridement). (See "Hematogenous
osteomyelitis in children: Management", section on 'Indications for surgery'.)

Response to empiric therapy — Improvement in constitutional symptoms and localized

inflammation (eg, erythema, point tenderness) with empiric antimicrobial therapy helps to
support the diagnosis of osteomyelitis, particularly in children in whom no pathogen is isolated.
(See "Hematogenous osteomyelitis in children: Management", section on 'Response to therapy'
and 'Probable osteomyelitis' below.)

In children with normal MRI and/or scintigraphy, a lack of clinical response to empiric therapy
and the results of blood cultures help to direct additional evaluation for other conditions in the
differential diagnosis. (See 'Osteomyelitis unlikely (advanced imaging studies normal)' below
and 'Differential diagnosis' below.)

DIAGNOSTIC INTERPRETATION

Confirmed osteomyelitis — The diagnosis of osteomyelitis is confirmed by histopathologic

evidence of inflammation in a surgical specimen of bone ( picture 1A-C) (if obtained) or
identification of a pathogen by culture or Gram stain in an aspirate or biopsy of bone or
periosteal fluid collection [2].

Probable osteomyelitis — The diagnosis of osteomyelitis is probable in a child with compatible

clinical, laboratory, and/or radiologic findings ( table 2) in whom a pathogen is isolated from

https://www.uptodate.com/contents/6067/print 12/46
6/19/22, 6:16 PM 6067

blood or joint fluid, or if cultures are negative, detection of S. aureus, S. pneumoniae, or K. kingae
by polymerase chain reaction (PCR) in bone aspirates, subperiosteal collections, or synovial
fluid. We also consider the diagnosis to be probable in a child with compatible clinical,
laboratory, and radiologic findings and negative cultures and PCR if he or she responds as
expected to empiric antimicrobial therapy.

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 by isolation
of an organism from bone or blood [49]. (See "Hematogenous osteomyelitis in children: Clinical
features and complications", section on 'Complications' and "Hematogenous osteomyelitis in
children: Management", section on 'Empiric parenteral therapy'.)

The response to empiric antimicrobial therapy in children with culture-negative osteomyelitis

directs the need for additional evaluation. (See "Hematogenous osteomyelitis in children:
Management", section on 'Culture-negative osteomyelitis'.)

Osteomyelitis unlikely (advanced imaging studies normal) — Osteomyelitis is unlikely if

advanced imaging studies (usually magnetic resonance imaging or scintigraphy) are normal
throughout the evaluation. The major considerations in the differential diagnosis and approach
to continued evaluation and management depend upon the results of the blood culture and
response to antimicrobial therapy:

● Positive blood culture, improvement with empiric therapy – A source of infection other
than osteomyelitis must be sought (see 'Other infections' 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 warranted (see 'Other infections' below)

● Negative blood culture, no improvement with appropriate therapy – A bacterial infection is

unlikely; fungal and noninfectious causes of musculoskeletal pain should be sought;
discontinuation of empiric antimicrobial therapy may be warranted (see 'Noninfectious
conditions' below)

DIFFERENTIAL DIAGNOSIS

https://www.uptodate.com/contents/6067/print 13/46
6/19/22, 6:16 PM 6067

The differential diagnosis of osteomyelitis includes infectious conditions, noninfectious

conditions, and radiographic mimics ( table 4).

Other infections — Infections that do not involve bone may cause fever, pain, and tenderness
overlying bone, mimicking hematogenous osteomyelitis. These infections usually are
distinguished from osteomyelitis by imaging studies that lack the characteristic features of
osteomyelitis ( table 1). (See 'Advanced imaging' above.)

Other infections that may share features of osteomyelitis (and may complicate or be
complicated by osteomyelitis) include:

● Septicemia (see "Clinical features, evaluation, and diagnosis of sepsis in term and late
preterm infants", section on 'Clinical manifestations' and "Systemic inflammatory response
syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations,
and diagnosis", section on 'Clinical manifestations')

● Cellulitis (see "Cellulitis and skin abscess: Epidemiology, microbiology, clinical

manifestations, and diagnosis", section on 'Cellulitis and erysipelas')

● Septic arthritis; approximately one-third of cases of osteomyelitis extend to the contiguous

joint (as many as 75 percent in neonates) [50-53] (see "Bacterial arthritis: Clinical features
and diagnosis in infants and children", section on 'Clinical features')

● Deep abscesses (eg, psoas abscess) (see "Psoas abscess", section on 'Clinical
manifestations')

● Pyomyositis (see "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 [54]. It has been reported at all ages [51]. Garré sclerosing osteomyelitis is
thought to be triggered by odontogenic infection [55-57], but noninfectious causes of
inflammation also may play a role.

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 osteomyelitis. Imaging may localize the areas of bony
involvement and indicate the absence of features suggestive of chronic osteomyelitis, such as

https://www.uptodate.com/contents/6067/print 14/46
6/19/22, 6:16 PM 6067

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)".)

Other noninfectious conditions — Several noninfectious conditions have clinical features

that overlap with osteomyelitis. These include:

● Malignancy – Tumor growth can cause bone pain, and some children with malignancies
(particularly leukemia and Ewing sarcoma) have fever as part of their initial presentation.
Unlike those 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 with 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 the Ewing sarcoma family of tumors", section on 'Signs
and symptoms' and "Bone tumors: Diagnosis and biopsy techniques".)

● Bone infarction – Bone infarction secondary to hemoglobinopathy, especially in infants

with dactylitis, can be particularly difficult to distinguish from osteomyelitis.

Radiographs, scintigraphy, and MRI all show similar results in both conditions. Unlike bone
disease with hemoglobinopathy, osteomyelitis does not respond to hydration and other
supportive measures. (See "Acute and chronic bone complications of sickle cell disease".)

● Vitamin C deficiency – Vitamin C deficiency (scurvy) may cause musculoskeletal pain and
refusal to bear weight, particularly in children with autism spectrum disorder (the
prevalence of which has increased since the early 2000s), intellectual disability, food
aversion, or limited food preferences [29,30,32]. 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: Terminology, epidemiology, and pathogenesis", section on 'Prevalence'.)

● Gaucher disease – Children with Gaucher disease can have painful bone crises similar to
those that occur in patients with sickle cell disease. 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
https://www.uptodate.com/contents/6067/print 15/46
6/19/22, 6:16 PM 6067

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'.)

● Complex regional pain syndrome – Complex regional pain syndrome (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 ESR/CRP. (See "Complex regional
pain syndrome in children", section on 'Diagnosis'.)

● 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 [58] and is difficult to distinguish from osteomyelitis on initial
presentation. Caffey disease can be distinguished from infectious osteomyelitis by bone
biopsy and genetic testing. (See "Differential diagnosis of the orthopedic manifestations of
child abuse", section on 'Infantile cortical hyperostosis (Caffey disease)'.)

Radiographic mimics — Benign and malignant bone tumors and tumors involving bone can
have radiographic appearance similar to osteomyelitis. The acute clinical features and response
to antibiotics in children with osteomyelitis usually distinguish osteomyelitis from these
conditions. However, bone biopsy can be performed if necessary for histopathologic
differentiation.

Bone lesions that can have radiographic appearance 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 histiocytosis

● Osteosarcoma (see "Osteosarcoma: Epidemiology, pathology, clinical presentation, and

diagnosis", section on 'Clinical presentation')
https://www.uptodate.com/contents/6067/print 16/46
6/19/22, 6:16 PM 6067

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

● The diagnosis of osteomyelitis is supported by a combination of clinical features

suggestive of bone infection, an imaging study with abnormalities characteristic of
osteomyelitis ( table 1), a positive microbiologic or histopathologic specimen, and/or a
response to empiric antimicrobial therapy.

The diagnosis often is unclear at the initial evaluation. A high index of suspicion and
monitoring of the clinical course are essential to establishing the diagnosis. An orthopedic
surgeon and/or interventional radiologist should be consulted as early as possible in the
evaluation to assist in obtaining specimens for culture and/or histopathology. (See
'Overview' above.)

● Acute hematogenous osteomyelitis should be suspected in infants and children with

findings suggestive of bone infection, including:

• Constitutional symptoms (irritability, decreased appetite or activity), with or without

fever

• Focal findings of bone inflammation (eg, warmth, swelling, point tenderness) that
typically progress over several days to a week

• Limitation of function (eg, limited use of an extremity; limp; refusal to walk, crawl, sit,
or bear weight)

Osteomyelitis should also be suspected in children who are found to have bacteremia or
an imaging study with characteristic findings during the evaluation of other conditions
(eg, fever, trauma). (See 'Clinical suspicion' above.)

● The initial evaluation of children with suspected osteomyelitis includes complete blood
count with differential, erythrocyte sedimentation rate, C-reactive protein, blood culture,
and radiographs. (See 'Initial evaluation' above.)

https://www.uptodate.com/contents/6067/print 17/46
6/19/22, 6:16 PM 6067

● Radiographs may be sufficient to confirm a diagnosis of osteomyelitis. If needed,

additional evaluation generally includes advanced imaging with magnetic resonance
imaging (MRI) or scintigraphy. If it is available, MRI is preferred to scintigraphy in view of
its higher degree of sensitivity and spatial resolution; however, scintigraphy may be better
if symptoms are poorly localized or multiple areas of involvement are suspected, and can
often be performed without the need for sedation ( table 1 and table 2). (See
'Advanced imaging' above.)

● Specimens for Gram stain and culture should be obtained from as many sites of infection
as possible. Isolation of a pathogen from bone, periosteal collection, joint fluid, or blood is
necessary for diagnosis and speciation and susceptibility testing are essential for planning
for the prolonged treatment required for osteomyelitis. (See 'Microbiology' above.)

● The diagnosis of osteomyelitis is confirmed by histopathologic evidence of inflammation

in a surgical specimen of bone ( picture 1A-C) (if obtained) or identification of a
pathogen by culture or Gram stain in an aspirate or biopsy of bone or a periosteal fluid
collection. (See 'Confirmed osteomyelitis' above.)

The diagnosis is probable in a child with compatible clinical, laboratory, and/or radiologic
findings ( table 1) in whom a pathogen is isolated from blood or joint fluid, or if cultures
are negative, detection of S. aureus, S. pneumoniae, or K. kingae by polymerase chain
reaction (PCR) in bone aspirates, subperiosteal collections, or synovial fluid. We also
consider the diagnosis to be probable in a child with compatible clinical, laboratory, and
radiologic findings and negative cultures and PCR if he or she responds as expected to
empiric antimicrobial therapy. (See 'Probable osteomyelitis' above.)

Osteomyelitis is unlikely if advanced imaging studies (usually MRI or scintigraphy) are

normal throughout the evaluation. (See 'Osteomyelitis unlikely (advanced imaging studies
normal)' above.)

● The differential diagnosis of osteomyelitis includes other infections, noninfectious

conditions, and radiographic mimics ( table 4). (See 'Differential diagnosis' above.)

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch
Dis Child 2012; 97:545.

https://www.uptodate.com/contents/6067/print 18/46
6/19/22, 6:16 PM 6067

2. Krogstad P. Osteomyelitis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases,
8th ed, Cherry JD, Harrison G, Kaplan SL, et al (Eds), Elsevier, Philadelphia 2018. p.516.
3. Saavedra-Lozano J, Falup-Pecurariu O, Faust SN, et al. Bone and Joint Infections. Pediatr
Infect Dis J 2017; 36:788.

4. Harris JC, Caesar DH, Davison C, et al. How useful are laboratory investigations in the
emergency department evaluation of possible osteomyelitis? Emerg Med Australas 2011;
23:317.

5. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute

paediatric osteomyelitis: a systematic review of the literature. J Bone Joint Surg Br 2012;
94:584.

6. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Sensitivity of erythrocyte sedimentation rate
and C-reactive protein in childhood bone and joint infections. Clin Orthop Relat Res 2010;
468:861.

7. Browne LP, Mason EO, Kaplan SL, et al. Optimal imaging strategy for community-acquired
Staphylococcus aureus musculoskeletal infections in children. Pediatr Radiol 2008; 38:841.
8. Jaramillo D, Dormans JP, Delgado J, et al. Hematogenous Osteomyelitis in Infants and
Children: Imaging of a Changing Disease. Radiology 2017; 283:629.
9. Wong M, Isaacs D, Howman-Giles R, Uren R. Clinical and diagnostic features of
osteomyelitis occurring in the first three months of life. Pediatr Infect Dis J 1995; 14:1047.
10. Knudsen CJ, Hoffman EB. Neonatal osteomyelitis. J Bone Joint Surg Br 1990; 72:846.

11. Capitanio MA, Kirkpatrick JA. Early roentgen observations in acute osteomyelitis. Am J
Roentgenol Radium Ther Nucl Med 1970; 108:488.
12. Overturf GD. Bacterial infections of the bones and joints. In: Infectious diseases of the fetus
and newborn infant, 7th, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, P
hiladelphia Vol 2011, p.296.
13. Mustafa MM, Sáez-Llorens X, McCracken GH Jr, Nelson JD. Acute hematogenous pelvic
osteomyelitis in infants and children. Pediatr Infect Dis J 1990; 9:416.
14. Fernandez M, Carrol CL, Baker CJ. Discitis and vertebral osteomyelitis in children: an 18-
year review. Pediatrics 2000; 105:1299.

15. Averill LW, Hernandez A, Gonzalez L, et al. Diagnosis of osteomyelitis in children: utility of
fat-suppressed contrast-enhanced MRI. AJR Am J Roentgenol 2009; 192:1232.
16. Saigal G, Azouz EM, Abdenour G. Imaging of osteomyelitis with special reference to
children. Semin Musculoskelet Radiol 2004; 8:255.

https://www.uptodate.com/contents/6067/print 19/46
6/19/22, 6:16 PM 6067

17. Connolly LP, Connolly SA, Drubach LA, et al. Acute hematogenous osteomyelitis of children:
assessment of skeletal scintigraphy-based diagnosis in the era of MRI. J Nucl Med 2002;
43:1310.

18. Weber-Chrysochoou C, Corti N, Goetschel P, et al. Pelvic osteomyelitis: a diagnostic

challenge in children. J Pediatr Surg 2007; 42:553.
19. McPhee E, Eskander JP, Eskander MS, et al. Imaging in pelvic osteomyelitis: support for
early magnetic resonance imaging. J Pediatr Orthop 2007; 27:903.

20. Mazur JM, Ross G, Cummings J, et al. Usefulness of magnetic resonance imaging for the
diagnosis of acute musculoskeletal infections in children. J Pediatr Orthop 1995; 15:144.

21. Pöyhiä T, Azouz EM. MR imaging evaluation of subacute and chronic bone abscesses in
children. Pediatr Radiol 2000; 30:763.
22. Jaramillo D, Hoffer FA. Cartilaginous epiphysis and growth plate: normal and abnormal MR
imaging findings. AJR Am J Roentgenol 1992; 158:1105.
23. Kan JH, Hilmes MA, Martus JE, et al. Value of MRI after recent diagnostic or surgical
intervention in children with suspected osteomyelitis. AJR Am J Roentgenol 2008; 191:1595.
24. Courtney PM, Flynn JM, Jaramillo D, et al. Clinical indications for repeat MRI in children with
acute hematogenous osteomyelitis. J Pediatr Orthop 2010; 30:883.
25. Guillerman RP. Osteomyelitis and beyond. Pediatr Radiol 2013; 43 Suppl 1:S193.
26. Shih HN, Shih LY, Wong YC. Diagnosis and treatment of subacute osteomyelitis. J Trauma
2005; 58:83.

27. Schmit P, Glorion C. Osteomyelitis in infants and children. Eur Radiol 2004; 14 Suppl 4:L44.
28. Kan JH, Young RS, Yu C, Hernanz-Schulman M. Clinical impact of gadolinium in the MRI
diagnosis of musculoskeletal infection in children. Pediatr Radiol 2010; 40:1197.

29. Kinlin LM, Blanchard AC, Silver S, Morris SK. Scurvy as a mimicker of osteomyelitis in a child
with autism spectrum disorder. Int J Infect Dis 2018; 69:99.
30. Harknett KM, Hussain SK, Rogers MK, Patel NC. Scurvy mimicking osteomyelitis: case
report and review of the literature. Clin Pediatr (Phila) 2014; 53:995.
31. Gulko E, Collins LK, Murphy RC, et al. MRI findings in pediatric patients with scurvy. Skeletal
Radiol 2015; 44:291.
32. Duggan CP, Westra SJ, Rosenberg AE. Case records of the Massachusetts General Hospital.
Case 23-2007. A 9-year-old boy with bone pain, rash, and gingival hypertrophy. N Engl J
Med 2007; 357:392.

https://www.uptodate.com/contents/6067/print 20/46
6/19/22, 6:16 PM 6067

33. Allwright SJ, Miller JH, Gilsanz V. Subperiosteal abscess in children: scintigraphic
appearance. Radiology 1991; 179:725.

34. Tuson CE, Hoffman EB, Mann MD. Isotope bone scanning for acute osteomyelitis and septic
arthritis in children. J Bone Joint Surg Br 1994; 76:306.
35. The Alliance for Radiation Safety in Pediatric Imaging. www.imagegently.org (Accessed on S
eptember 03, 2016).
36. Mok PM, Reilly BJ, Ash JM. Osteomyelitis in the neonate. Clinical aspects and the role of
radiography and scintigraphy in diagnosis and management. Radiology 1982; 145:677.
37. Bressler EL, Conway JJ, Weiss SC. Neonatal osteomyelitis examined by bone scintigraphy.
Radiology 1984; 152:685.
38. Hoffer FA, Emans J. Percutaneous drainage of subperiosteal abscess: a potential treatment
for osteomyelitis. Pediatr Radiol 1996; 26:879.

39. Llewellyn A, Jones-Diette J, Kraft J, et al. Imaging tests for the detection of osteomyelitis: a
systematic review. Health Technol Assess 2019; 23:1.
40. McNeil JC, Forbes AR, Vallejo JG, et al. Role of Operative or Interventional Radiology-Guided
Cultures for Osteomyelitis. Pediatrics 2016; 137.
41. Ratnayake K, Davis AJ, Brown L, Young TP. Pediatric acute osteomyelitis in the postvaccine,
methicillin-resistant Staphylococcus aureus era. Am J Emerg Med 2015; 33:1420.
42. Yeo A, Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ 2014;
348:g66.

43. Zhorne DJ, Altobelli ME, Cruz AT. Impact of antibiotic pretreatment on bone biopsy yield for
children with acute hematogenous osteomyelitis. Hosp Pediatr 2015; 5:337.
44. Yagupsky P. Kingella kingae: from medical rarity to an emerging paediatric pathogen.
Lancet Infect Dis 2004; 4:358.
45. Centers for Disease Control and Prevention (CDC). Osteomyelitis/septic arthritis caused by
Kingella kingae among day care attendees--Minnesota, 2003. MMWR Morb Mortal Wkly
Rep 2004; 53:241.
46. Chometon S, Benito Y, Chaker M, et al. Specific real-time polymerase chain reaction places
Kingella kingae as the most common cause of osteoarticular infections in young children.
Pediatr Infect Dis J 2007; 26:377.
47. Verdier I, Gayet-Ageron A, Ploton C, et al. Contribution of a broad range polymerase chain
reaction to the diagnosis of osteoarticular infections caused by Kingella kingae: description
of twenty-four recent pediatric diagnoses. Pediatr Infect Dis J 2005; 24:692.

https://www.uptodate.com/contents/6067/print 21/46
6/19/22, 6:16 PM 6067

48. El Houmami N, Minodier P, Dubourg G, et al. Patterns of Kingella kingae Disease

Outbreaks. Pediatr Infect Dis J 2016; 35:340.
49. Lyon RM, Evanich JD. Culture-negative septic arthritis in children. J Pediatr Orthop 1999;
19:655.
50. Yagupsky P, Bar-Ziv Y, Howard CB, Dagan R. Epidemiology, etiology, and clinical features of
septic arthritis in children younger than 24 months. Arch Pediatr Adolesc Med 1995;
149:537.

51. Perlman MH, Patzakis MJ, Kumar PJ, Holtom P. The incidence of joint involvement with
adjacent osteomyelitis in pediatric patients. J Pediatr Orthop 2000; 20:40.
52. Pääkkönen M, Kallio MJ, Kallio PE, Peltola H. Shortened hospital stay for childhood bone
and joint infections: analysis of 265 prospectively collected culture-positive cases in 1983-
2005. Scand J Infect Dis 2012; 44:683.
53. Fox L, Sprunt K. Neonatal osteomyelitis. Pediatrics 1978; 62:535.
54. Panders AK, Hadders HN. Chronic sclerosing inflammations of the jaw. Osteomyelitis sicca
(Garré), chronic sclerosing osteomyelitis with fine-meshed trabecular structure, and very
dense sclerosing osteomyelitis. Oral Surg Oral Med Oral Pathol 1970; 30:396.
55. Tong AC, Ng IO, Yeung KM. Osteomyelitis with proliferative periostitis: an unusual case.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 102:e14.
56. Kannan SK, Sandhya G, Selvarani R. Periostitis ossificans (Garrè's osteomyelitis)
radiographic study of two cases. Int J Paediatr Dent 2006; 16:59.

57. Padwa BL, Dentino K, Robson CD, et al. Pediatric Chronic Nonbacterial Osteomyelitis of the
Jaw: Clinical, Radiographic, and Histopathologic Features. J Oral Maxillofac Surg 2016;
74:2393.

58. Gensure RC, Mäkitie O, Barclay C, et al. A novel COL1A1 mutation in infantile cortical
hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. J Clin
Invest 2005; 115:1250.
Topic 6067 Version 30.0

https://www.uptodate.com/contents/6067/print 22/46
6/19/22, 6:16 PM 6067

GRAPHICS

Imaging abnormalities in osteomyelitis

Imaging
Abnormal findings
modality

Plain radiograph* Deep soft tissue swelling (3 days after onset)

Periosteal reaction or elevation (10 to 21 days after onset)

Lytic sclerosis (≥1 month after onset)

Magnetic Bone marrow inflammation (decreased signal in T1-weighted images; increased

resonance signal in T2-weighted images)
imaging
Edema in marrow and soft tissues

Penumbra sign (high-intensity-signal transition zone between abscess and

sclerotic bone marrow in T1-weighted images)

With gadolinium enhancement: absent blood flow, suggestive of necrosis or

abscess

Three-phase bone Focal uptake of tracer in the third phase (delayed phase)
scan

Computed Increased density of bone marrow

tomography
Cortex destruction

Periosteal reaction (new bone formation) formation

Periosteal purulence

Sequestra (devitalized, sclerotic bone)

Ultrasonography Fluid collection adjacent to bone without intervening soft tissue

Thickening of periosteum

Periosteal elevation

* The timing and typical sequence of radiographic changes may vary with the site of infection and
age of the patient.

References:

1. Browne LP, Mason EO, Kaplan SL, et al. Optimal imaging strategy for community-acquired Staphylococcus aureus
musculoskeletal infections in children. Pediatr Radiol 2008; 38:841.
2. Jaramillo D, Treves ST, Kasser JR, et al. Osteomyelitis and septic arthritis in children: Appropriate use of imaging to
guide treatment. AJR Am J Roentgenol 1995; 165:399.
3. Saigal G, Azouz EM, Abdenour G. Imaging of osteomyelitis with special reference to children. Semin Musculoskelet
Radiol 2004; 8:255.
4. Schmit P, Glorion C. Osteomyelitis in infants and children. Eur Radiol 2004; 14 Suppl 4:L44.

https://www.uptodate.com/contents/6067/print 23/46
6/19/22, 6:16 PM 6067

Graphic 96767 Version 3.0

https://www.uptodate.com/contents/6067/print 24/46
6/19/22, 6:16 PM 6067

Acute osteomyelitis

Light micrograph of acute osteomyelitis of the tibia shows many

disconnected bony trabeculae in a sea of inflammatory cells (red
arrow) and a single multinucleated giant cell (black arrow). The
surfaces of the trabeculae (white arrows) have a few
undifferentiated, spindle-shaped connective tissue elements. There
is little evidence of active bone formation or bone resorption.

Courtesy of Jon Mader, MD.

Graphic 72714 Version 3.0

https://www.uptodate.com/contents/6067/print 25/46
6/19/22, 6:16 PM 6067

Early repair in acute osteomyelitis

Light micrograph in acute osteomyelitis of the tibial articular

apparatus. The presence of whorls of chondrocytes (arrows)
indicates early tissue repair in which multinucleated osteoclasts
(dashed arrows) are actively remodeling the subchondral region.
Bone (arrowhead) has replaced the mature lamellar structure, and
the medullary spaces are largely filled with inflammatory cells and
fibrin.

Courtesy of Jon Mader, MD.

Graphic 62981 Version 3.0

https://www.uptodate.com/contents/6067/print 26/46
6/19/22, 6:16 PM 6067

Chronic osteomyelitis

Light micrograph of chronic osteomyelitis of the tibia. Against a

background of inflammatory cells (arrow), there are thickened bony
trabeculae (arrowhead) lined by plump osteoblasts, which are
actively forming bone. The accumulation of small dark cells
(lymphocytes; dashed arrows) represent sites of perivascular
inflammation.

Courtesy of Jon Mader, MD.

Graphic 53767 Version 4.0

https://www.uptodate.com/contents/6067/print 27/46
6/19/22, 6:16 PM 6067

Brodie abscess radiograph

Lateral (A) and frontal (B) radiographs of the right lower extremity demonstrate an
ovoid lucent lesion in the medullary cavity of the proximal metadiaphysis of the tibia
(arrows) with associated periosteal reaction (arrowheads). The lateral radiograph (A)
also demonstrates irregular cortical lucency anteriorly suggesting an area of focal
cortical disruption (dashed arrow).

Reproduced with permission from: Abdulhadi MA, White AM, Pollock AN. Brodie abscess. Pediatr Emerg
Care 2012; 28:1249. Copyright © 2012 Lippincott Williams & Wilkins.

Graphic 87102 Version 5.0

https://www.uptodate.com/contents/6067/print 28/46
6/19/22, 6:16 PM 6067

Progression of radiographic findings in a six-year-old

boy with osteomyelitis of the fibula

(A) Plain radiographs (after one week of swelling and pain in the calf)
were initially interpreted as normal.

(B) A plain radiograph obtained four days after the initial films
demonstrates periosteal reaction and cortical thickening.

(C) T1 weighted magnetic resonance image with gadolinium

demonstrates enhancement of the fibula marrow space and
surrounding soft tissues.

Courtesy of Marvin B Harper, MD.

Graphic 50259 Version 4.0

https://www.uptodate.com/contents/6067/print 29/46
6/19/22, 6:16 PM 6067

Osteomyelitis with subperiosteal abscess

Radiograph of the femur demonstrates periosteal elevation due to a

subperiosteal abscess as the result of osteomyelitis.

Courtesy of Marvin B Harper, MD.

Graphic 71349 Version 4.0

https://www.uptodate.com/contents/6067/print 30/46
6/19/22, 6:16 PM 6067

Lytic lucency in osteomyelitis

(A) Radiograph at the initial evaluation of a nine-year-old with fever and limp
demonstrates a lytic lucency in the distal femoral metaphysis.

(B, C) Axial and coronal magnetic resonance (MR) images delineate the area
of osteomyelitis and adjacent marrow edema.

Reproduced with permission from Jeanne Chow, MD. Children's Hospital-Boston, Copyright ©
Jeanne Chow, MD.

Graphic 51834 Version 5.0

https://www.uptodate.com/contents/6067/print 31/46
6/19/22, 6:16 PM 6067

Early osteomyelitis in a six-year-old with fever and

ankle pain

Radiographs of the ankle (A) demonstrate deep soft tissue swelling

(arrow) inferior to the medial malleolus. A technetium 99m bone
scan shows increased uptake in the distal tibia in the blood flow (B)
and bone uptake (C; four hour) phases.

Courtesy of Marvin B Harper, MD.

Graphic 77957 Version 4.0

https://www.uptodate.com/contents/6067/print 32/46
6/19/22, 6:16 PM 6067

Osteomyelitis in a nine-year-old girl with knee pain

and fever

(A) Plain radiographs of the knee are unremarkable.

(B) T1 weighted MRI demonstrates marked decrease in signal intensity

in the medial metaphysis and epiphysis of the distal femur. There is
some involvement of the soft tissue.

(C) These findings are more pronounced in a T1 weighted MRI with

gadolinium.

MRI: magnetic resonance imaging.

Courtesy of Marvin B Harper, MD.

Graphic 66132 Version 4.0

https://www.uptodate.com/contents/6067/print 33/46
6/19/22, 6:16 PM 6067

Comparison of imaging modalities in children with osteomyelitis

Modality Indications Advantages Disadvantages Comments*

Plain Baseline Inexpensive Abnormal Sensitivity: 16

radiographs Excluding other Easy to obtain findings to 20 percent
conditions in usually not Specificity: 80
differential present at to 100
diagnosis onset of percent
Monitoring symptoms, Normal
disease except in radiograph at
progression newborns onset does
not exclude
osteomyelitis

MRI¶ Identify location No radiation Costly Sensitivity: 80

and extent of risk Less useful in to 100
disease Demonstrates multifocal or percent
Evaluation of early changes poorly Specificity: 70
adjacent in the marrow localized to 100
structures for cavity disease percent
extension of Improved Requires more Osteomyelitis
infection (soft demonstration time than CT unlikely if
tissues, growth of Young children MRI is
plate, epiphysis, subperiosteal may require normal
joint) abscess sedation or Repeat MRI
Evaluation of Demonstration anesthesia seldom leads
difficult sites (eg, of concomitant Not always to
pelvis, vertebral septic arthritis, available management
bodies, venous changes in
intervertebral thrombosis, or patients with
discs) pyomyositis clinical
Planning surgical improvement
intervention

Scintigraphy Poorly localized More useful Radiation Sensitivity: 53

symptoms (eg, than MRI in exposure to 100
young children multifocal or Does not percent
who cannot poorly provide Specificity: 50
verbalize) localized information to 100
Multifocal disease about extent percent
disease Demonstrates of purulent Osteomyelitis
early changes collections that unlikely if
Readily may require scintigraphy
available drainage is normal
https://www.uptodate.com/contents/6067/print 34/46
6/19/22, 6:16 PM 6067

May require May be

less sedation falsely
than MRI negative if
blood supply
to
periosteum is
interrupted
(eg,
subperiosteal
abscess)

CT Evaluation of Less time- Expensive Sensitivity: 67

cortical consuming Increased percent
destruction, than MRI radiation Specificity: 50
bone gas, and Does not exposure percent
sequestrum require Poor soft Generally
Delineating sedation tissue contrast used only if
extent of bone other studies
injury in are not
subacute/chronic possible or
osteomyelitis inconclusive
Planning surgical
interventions
Evaluation of
complications if
MRI not available
or
contraindicated

Ultrasonography Evaluate fluid Inexpensive Does not Sensitivity: 55

collections in No radiation penetrate percent
adjacent burden bone cortex Specificity: 47
structures (eg, Noninvasive percent
joint,
Portable
periosteum)
Monitor abscess
resolution or
progression

MRI: magnetic resonance imaging; CT: computed tomography.

* Values for sensitivity and specificity are from: Dartnell J, Ramachandran M, Katchburian M.
Haematogenous acute and subacute paediatric osteomyelitis: A systematic review of the literature. J
Bone Joint Surg Br 2012; 94:584.

¶ Preferred imaging study when imaging other than plain radiographs are necessary to establish
the diagnosis of osteomyelitis.

https://www.uptodate.com/contents/6067/print 35/46
6/19/22, 6:16 PM 6067

References:

1. Dartnell J, Ramachandran M, Katchburian M. Haematogenous acute and subacute paediatric osteomyelitis: A

systematic review of the literature. J Bone Joint Surg Br 2012; 94:584.
2. Faust SN, Clark J, Pallett A, Clarke NM. Managing bone and joint infection in children. Arch Dis Child 2012; 97:545.
3. Peltola H, Pääkkönen M. Acute osteomyelitis in children. N Engl J Med 2014; 370:352.
4. Yeo A, Ramachandran M. Acute haematogenous osteomyelitis in children. BMJ 2014; 348:g66.

Graphic 96521 Version 5.0

https://www.uptodate.com/contents/6067/print 36/46
6/19/22, 6:16 PM 6067

Magnetic resonance image distal femoral

osteomyelitis and subperiosteal abscess

Axial (A) and coronal (B) magnetic resonance images (post

gadolinium infusion) of a seven-year-old with distal femoral
osteomyelitis and subperiosteal abscess. The abscess is posterior on
the axial view (arrow) and medial to the distal femur on the coronal
view (arrow). The pus is dark and surrounded by an enhancing rim.

Courtesy of William Phillips, MD, Texas Children's Hospital.

Graphic 81461 Version 2.0

https://www.uptodate.com/contents/6067/print 37/46
6/19/22, 6:16 PM 6067

Magnetic resonance image demonstrating

osteomyelitis

(A) The proximal shaft and metaphysis of the left tibia show an
abnormal mottled appearance.

(B) The marrow signal from the left tibia is abnormal. In addition,
there is soft tissue inflammation surrounding the left tibia.

Courtesy of Sheldon L Kaplan, MD. Texas Children's Hospital.

Graphic 59602 Version 3.0

https://www.uptodate.com/contents/6067/print 38/46
6/19/22, 6:16 PM 6067

Penumbra sign in osteomyelitis

Magnetic resonance imaging (MRI) scan shows the penumbra sign

(a transitional zone with relatively high signal intensity between
abscess and sclerotic bone marrow on T1-weighted MRI).

Reproduced with permission from: Shih HN, Shih LY, Wong YC. Diagnosis and
treatment of subacute osteomyelitis. J Trauma 2005; 58:83. Copyright © 2005
Lippincott Williams & Wilkins.

Graphic 56913 Version 11.0

https://www.uptodate.com/contents/6067/print 39/46
6/19/22, 6:16 PM 6067

Devitalized bone (sequestra) in a child with osteomyelitis and septic

arthritis

Radiographic appearance of devitalized bone (sequestra) in anteroposterior and lateral

radiographs (panels A and B, respectively) and computed tomography (panel C) in a 13-year-old
boy who developed femoral osteomyelitis and septic arthritis of the knee as complications of
methicillin-resistant Staphylococcus aureus septic shock.

Courtesy of William A Phillips, MD.

Graphic 128969 Version 1.0

https://www.uptodate.com/contents/6067/print 40/46
6/19/22, 6:16 PM 6067

Clinical features associated with bacterial pathogens that cause acute

hematogenous osteomyelitis in children

Clinical features

Gram-positive bacteria

Staphylococcus aureus All ages; possible associated skin or soft tissue infection; MRSA may
be associated with venous thromboembolism and pulmonary disease

Coagulase-negative Neonates in intensive care unit; children with indwelling vascular

staphylococci catheters (eg, for chronic hemodialysis)

Group A Streptococcus More common in children younger than 4 years; may occur as a
complication of concurrent varicella-zoster virus infection

Group B Streptococcus Infants younger than 3 months (usually 2 to 4 weeks)

Streptococcus pneumoniae Children younger than 2 years who are incompletely immunized;
children older than 2 years with underlying medical conditions (eg,
sickle cell disease, asplenia, splenic dysfunction, immunodeficiency,
chronic heart disease, chronic lung disease, diabetes mellitus)

Actinomyces May affect the facial bones, the pelvis, or vertebral bodies

Gram-negative bacteria

Kingella kingae Children 6 to 36 months; indolent onset; oral ulcers preceding

musculoskeletal findings; may affect nontubular bones

Nonsalmonella gram- Birth to 3 months; children with sickle cell disease; instrumentation of
negative bacilli (eg, the gastrointestinal or urinary tract; immunocompromised host (eg,
Escherichia coli, Serratia) CGD)

Haemophilus influenzae Incompletely immunized children in areas with low Hib immunization
type b rates

Bartonella henselae Children with cat exposure; may affect the vertebral column and
pelvic girdle; may cause multifocal infection

Pseudomonas aeruginosa Injectable drug use

Brucella Travel to or living in an endemic area; ingestion of unpasteurized

dairy products

Mycobacterium Birth in, travel to, or contact with a visitor from, a region endemic for
tuberculosis M. tuberculosis

Nontuberculous Surgery or penetrating injury; CGD; other underlying

mycobacteria immunodeficiency; HIV infection

Salmonella species Children with sickle cell disease or related hemoglobinopathies;

exposure to reptiles or amphibians; children with gastrointestinal
symptoms; children in resource-limited countries

https://www.uptodate.com/contents/6067/print 41/46
6/19/22, 6:16 PM 6067

Polymicrobial infection

More likely with direct inoculation (eg, penetrating trauma) or

contiguous spread (eg, from skull, face, hands, feet)

MRSA: methicillin-resistant S. aureus; CGD: chronic granulomatous disease; Hib: H. influenzae type b.

Graphic 96510 Version 9.0

https://www.uptodate.com/contents/6067/print 42/46
6/19/22, 6:16 PM 6067

Differential diagnosis of osteomyelitis in children and adolescents

Condition Features that distinguish from osteomyelitis

Other infections

Septicemia MRI or scintigraphy studies lack abnormalities

characteristic of osteomyelitis
Cellulitis

Septic arthritis

Deep abscess

Pyomyositis

Garré sclerosing osteomyelitis

Noninfectious conditions

Chronic nonbacterial osteomyelitis Multifocal lesions on imaging studies

(eg, CRMO) Lack of response to antimicrobial therapy

Malignancy (eg, primary bone Intermittent symptoms

tumor, leukemia) Lack of response to antimicrobial therapy
Characteristic histopathology

Bone infarction in patients with Improvement with hydration and other supportive
hemoglobinopathy measures

Vitamin C deficiency (scurvy) Dietary history of limited vitamin C intake (eg, restricted
feeding behavior in children with autism spectrum
disorder)
Petechiae, ecchymoses, bleeding gums, coiled hair,
hyperkeratosis

Gaucher disease Characteristic radiographic features

Dysmorphic features on examination

Complex regional pain syndrome Autonomic dysfunction

Normal erythrocyte sedimentation rate, C-reactive
protein

Caffey disease (infantile cortical Characteristic histopathology

hyperostosis)

Radiographic mimics*

Benign bone tumors:

Fibrous dysplasia Absence of acute symptoms

Osteoid osteoma Lack of response to antimicrobial therapy

https://www.uptodate.com/contents/6067/print 43/46
6/19/22, 6:16 PM 6067

Osteoblastoma Characteristic histopathology

Chondroblastoma
Chondromyxoid fibroma

Langerhans cell histiocytosis Characteristic histopathology

Malignant bone tumors:

Osteosarcoma Intermittent symptoms

Lack of response to antimicrobial therapy
Characteristic histopathology

MRI: magnetic resonance imaging; CRMO: chronic recurrent multifocal osteomyelitis.

* Refer to UpToDate topics on benign bone tumors, Langerhans cell histiocytosis, and malignant
bone tumors for additional information about the radiographic appearance of these conditions.

Graphic 96520 Version 4.0

https://www.uptodate.com/contents/6067/print 44/46
6/19/22, 6:16 PM 6067

Perifollicular abnormalities in scurvy

In this example, the perifollicular hyperkeratotic papules are quite

prominent, with surrounding hemorrhage. These lesions have been
misinterpreted as "palpable purpura," leading to the mistaken
clinical diagnosis of vasculitis.

Reproduced with permission from: Hirschmann JV, Raugi GJ. Adult scurvy. J Am Acad
Dermatol 1999; 41:895. Copyright © 1999 Elsevier.

Graphic 64172 Version 2.0

https://www.uptodate.com/contents/6067/print 45/46
6/19/22, 6:16 PM 6067

Contributor Disclosures
Paul A Krogstad, MD No relevant financial relationship(s) with ineligible companies to disclose. Sheldon
L Kaplan, MD Grant/Research/Clinical Trial Support: MeMed Diagnostics [Bacterial and viral
infections];Merck [Staphylococcus aureus];Pfizer [Streptococcus pneumoniae]. Consultant/Advisory
Boards: MeMed Advisory Board [Diagnostics bacterial and viral infections]. Other Financial Interest:
Elsevier [Pediatric infectious diseases];Pfizer [PCV13]. All of the relevant financial relationships listed have
been mitigated. William A Phillips, MD No relevant financial relationship(s) with ineligible companies to
disclose. Mary M Torchia, MD No relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

https://www.uptodate.com/contents/6067/print 46/46