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Osteomyelitis

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 Overview
Introduction

Classifications

Pathophysiology

Clinical manifestations

Role of laboratory tests and radiology in diagnosis and

management
Introduction
- Definition: an inflammation of bone and
bone marrow (usually caused by bacterial
infection)
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Classifications

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Waldvogel system
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- Hematogenous osteomyelitis
- Contiguous focus osteomyelitis: soft tissue
infection, abscess, prosthesis
+ Vascular insufficiency
+ Without vascular insufficiency

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Classifications

- Acute: within 4 weeks

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- Chronic: more protracted, often indolent disease

process with
(1) presence of a sequestrum and/or
(2) relapse of infection in the same site (bone) weeks
to years

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Pathophysiology

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Bacteria contamination
- Acute haematogenous osteomyelitis: most
often in children

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- Inoculation of the metaphyseal vessels

occurs at the transition point from the
arteriolar vessels to the venous sinusoids,
slowing blood flow and increasing vascular
turbulence.

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Bacteria contamination
- Osteomyelitis involving the spine is also most commonly
caused by haematogenous seeding of bacteria into the

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vertebrae

- The venous anatomy of the spine, originally investigated

for its role in cancer metastasis, allows retrograde flow
from the pelvic venous plexus.

- Location: lumbar and thoracic spine, less in cervical spine

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Contiguous infection
- Epidemiology
+ young patients: trauma and related surgery

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+ older patients: decubitus ulcer

- Risk for osteomyelitis in diabetes foot:
+ previous history of foot ulceration prior
+multiple foot wounds
+ wounds that penetrated deep to bone or joint

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Bacteria contamination

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Inflamatory response

- IL-1beta, IL-6, IL-8, TNF-alpha, MIP-1alpha are the

main pro- inflammation cytokines.

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- Matrix metalloproteases, a zinc-dependent group of

endopeptidases, have been proposed as a key element
of bone loss in osteomyelitis.
(secreted by mesenchymal stromal cells and
osteoclasts)

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Abscess formation
- SACs occur when bacteria exploit the host response to
encase themselves in a protective barrier and persist for
prolonged periods of time.

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- The layer of mostly necrotic host immune cells

inadvertently creates an additional protective barrier,
preventing newly recruited host immune cells from
penetrating the abscess and killing the bacteria.

- Within a SAC, bacterial cells are largely devoid of high

amounts of nutrients and oxygen; therefore, to survive in
this environment, S. aureus must tailor its gene expression
according to nutrient availability.

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Sequestrum & implants

- The role of bone necrosis is pivotal to the
establishment of experimental chronic
osteomyelitis: (Norden and Kennedy in 1970) use

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intramedullary sodium morrhuate before direct

inoculation of S aureus in order to obtain
osteomyelitis in rabbits.

- Surgically implanted devices in and around bone

represent a risk factor for the development of
osteomyelitis.

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Biofilm formation
- Structural analyses have shown that these thick
biofilms possess a complex architecture in which
microcolonies can exist in distinct pillar or mushroom-

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shaped structures, through which an intricate channel

network runs. These channels provide access to
environmental nutrients even in the deepest areas of
the biofilm.

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Bacteria contamination
- S. aureus intracellular persistence has been described in a
variety of cell types, including macrophages,
keratinocytes, epithelial cells and endothelial cells.

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- Clinical case studies have described intracellular

colonization of fibroblasts, osteoblasts and osteocytes from
chronically infected bone tissue.

- Direct infection of bone cells is particularly pathogenic as

it has been shown to induce the secretion of
osteoclastogenic cytokines, contributing to pathological
bone loss.

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Osteocyte lacuna-canalicular network

- In contrast to the dogma that S. aureus is a non-
motile cocci organism, recent studies in
experimental models and clinical cases of

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osteomyelitis have revealed that S. aureus can

invade and persist within the OLCN.

- S. aureus deforms to approximately half its native

size to colonize the narrow confines of canaliculi,
which are 100–600nm in size.

- Currently, it is unclear whether antibiotics readily

diffuse into the OLCN of cortical bone at inhibitory
concentrations.

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Symptoms

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Symptoms

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Diagnosis
- Histopathologic examination of bone specimens coupled with bone culture.  
- Biopsy:
+ Empiric antibiotic has failed.
+ Concern for antibiotic-resistant

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+ Presence of a midfoot or hindfoot lesion in diabetic foot infection.

Sensitivity (%) Specificity (%)

CRP 47-72 62-98
PCT 13-43 97-100
XR 16-20 80-100
CT 67-100 1-98
MRI 81-100 67-94
Scintigraphy 53-91 47-84
US 17-60 24-70
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 Diagnosis
 What noninvasive diagnostic laboratory tests should be performed in children with
suspected acute hematogenous osteomyelitis (AHO)?

• In children with suspected AHO, we recommend performing blood culture prior to the
administration of antimicrobial therapy (strong recommendation and moderate certainty
of evidence).
• In children with suspected AHO, we suggest performing a serum C-reactive protein
(CRP) on initial evaluation (conditional recommendation and very low certainty of
evidence).
• In children with suspected AHO, we suggest against using serum procalcitonin (PCT)
(conditional recommendation and low certainty of evidence).
 Diagnosis
 What imaging studies should be performed in children with suspected AHO?

1. In children with suspected AHO, we recommend obtaining plain radiography of

the potentially infected bone(s) rather than not performing plain radiographs.
2. In children with suspected AHO requiring further imaging studies to confirm the
diagnosis, we suggest magnetic resonance imaging (MRI) rather than
scintigraphy (bone scan), computerized tomographic (CT) scan, or ultrasound
(US) (conditional recommendation and very low certainty of evidence). 
 Diagnosis
What is the role of invasive procedures in the diagnosis of children with
suspected AHO?

• In children with suspected AHO, we suggest performing invasive diagnostic

procedures to collect aspirates and/ or biopsy specimens of bone and/or
associated purulent fluid collections for routine microbiological studies (aerobic
bacteriologic culture and Gram stain) rather than only performing noninvasive
diagnostic tests (conditional recommendation and moderate certainty of
evidence). 
 Diagnosis
 For children who require empiric antimicrobial therapy for AHO, should
antibiotics be initiated before invasive diagnostic procedures or can they be
withheld until after these procedures are performed?

• In children with presumed AHO who are ill-appearing or have rapidly progressive
infection, we recommend starting empiric antimicrobial therapy immediately rather
than withholding antibiotics until invasive diagnostic procedures are performed
(strong recommendation and moderate certainty of evidence). 
• In children with presumed AHO who are not clinically ill and for whom an aspirate
or biopsy by invasive diagnostic procedure is being planned prior to initiating
antibiotics, we suggest withholding antibiotics for no more than 48 to 72 hours
(conditional recommendation and very low certainty of evidence). 
 Diagnosis
 In children with AHO, in whom should invasive therapeutic procedures be
performed at the time of diagnosis?

• In children with AHO who present with sepsis or have a rapidly progressive
infection, we recommend debridement of the infected bone and any associated
abscesses as soon as possible after diagnosis, rather than treating with medical
therapy alone (strong recommendation and moderate certainty of evidence).
• In a child with AHO who is clinically stable but is documented to have a
substantial abscess (greater than 2 cm), we suggest debridement rather than
treating with medical therapy alone (conditional recommendation and very low
certainty of evidence).
 Diagnosis

 In children with suspected or confirmed AHO, what clinical and laboratory
criteria should be used to assess the response to treatment?

• In children with suspected or confirmed AHO receiving antimicrobial therapy, we

suggest performing sequential monitoring of CRP in addition to serial clinical
evaluation to assess response to therapy, rather than relying solely on clinical
evaluation (conditional recommendation and low certainty of evidence).
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In children with AHO, should end-of-therapy imaging studies be routinely

obtained?

• In children with uncomplicated AHO that does not involve the physis, we
recommend against obtaining end-of-therapy MRI (strong recommendation and
low certainty of evidence) and suggest against routine end-of-therapy plain
radiographs (conditional recommendation and very low certainty of evidence).
• In children with complicated AHO or with involvement of the physis, we
suggest end-of-therapy imaging studies (plain radiographs and/or MRI)
(conditional recommendation and very low certainty of evidence).
 Diagnosis
For children who have successfully completed antimicrobial therapy for
documented or suspected AHO, in what situations is long-term follow-up required
to address potential sequelae?

• In children with AHO who are determined to be at risk of long-term adverse

outcomes, we suggest a follow-up period of at least 1 year by specialists with
experience treating children with AHO (conditional recommendation and low
certainty of evidence).
 Surgical debridement
- Implant-associated chronic osteomyelitis
- Soft tissue or bone abscess
- Necrotic bone
- Joint infection
 References
 1. Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases
Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous
Osteomyelitis in Pediatrics.
2. Uptodate: Nonvertebral osteomyelitis in adults: Treatment.
3. Pathophysiology and Pathogenesis of Osteomyelitis (Mayank Roy, Jeremy S. Somerson, Kevin G.
Kerr and Jonathan L. Conroy).
4. Pathophysiology of chronic bacterial osteomyelitis. Why do antibiotics fail so often? (J.Ciampolini,
K.G.Harding).
5. Nature review: Skeletal infections: microbial pathogenesis, immunity and clinical management.