Osteomyelitis is an infection of bone, usually caused by bacteria, resulting in inflammation, bone destruction, and necrosis.

Exam domain	One-glance essentials
Definition / diagnosis	Infection of bone (bone marrow inflammation) caused by bacteria; classified by onset: Acute (<2 wk), Subacute (<3 mo), Chronic (>3 mo) ^[1]^[2] *Cierny-Mader classification: Stages I–IV (medullary → superficial → localized → diffuse) combined with Host class A (normal) / B (compromised) / C (treatment worse than disease) ^[3]^[4] Three routes of infection: haematogenous* (most common in children), contiguous spread, and direct inoculation (trauma/surgery) ^[1]^[2]
Epidemiology / risks	*Key risk factors: age >60, recent bacteraemia, diabetes, malignancy on treatment, cirrhosis, renal disease, IV drug abuse, long-term steroids, recent dental procedure ^[5]^[4] S. aureus* is the most common organism at all ages; Salmonella disproportionately common in sickle cell disease; TB always a differential in Hong Kong ^[1]^[6] Age-site predilection: infants → epiphysis (transphyseal vessels); children → metaphysis (growth plate barrier); adults → vertebrae (haematogenous) ^[7]^[2] Diabetic foot → polymicrobial (S. aureus, Strep, anaerobes, Gram-negatives); implant-related → coagulase-negative Staph ^[1]^[4]
Core mechanism	Bacteraemia → seeding in metaphyseal sinusoids (slow turbulent flow, absent phagocytic lining) → suppuration → ↑ intraosseous pressure ^[1]^[2] Pus exits via Volkmann canals → subperiosteal abscess → periosteal stripping → ischaemic necrosis → sequestrum (dead bone), involucrum (reactive new bone), cloacae (draining sinuses) ^[7]^[3] Infants: transphyseal vessels allow spread across growth plate → septic arthritis of adjacent joint (especially intracapsular hip metaphysis) ^[5]^[2]
Clinical picture	Acute: localised bone pain, fever, swelling, limited ROM, tenderness over metaphysis; pseudoparalysis in neonates ^[1]^[6] Chronic: draining sinus tract, recurrent flares, deformity; vertebral osteomyelitis → back pain ± neurological deficit (red flag: epidural abscess → paraplegia) ^[3]^[8] *Pyogenic vs TB spine: pyogenic = acute onset, disc space narrowing, lumbar; TB = insidious, disc relatively spared, thoracic, gibbus deformity ^[9]^[10] Diabetic foot: probe-to-bone test* positive (PPV ~89%) suggests underlying osteomyelitis; Charcot is painless with no cortical erosion or sinus ^[3]^[4]
Investigations	*First-line labs: CBP, ESR, CRP; CRP rises within 6–8 hours (early response marker); ESR for long-term monitoring; blood cultures ×2 (positive in ~50%)* ^[7]^[3] *X-ray always first* but normal in acute (<10–14 days); chronic: osteosclerosis, sequestrum, involucrum, periosteal reaction — *can mimic malignancy* ^[5]^[3] *MRI is gold standard imaging: detects marrow oedema within 24–48 hours; delineates abscess, soft tissue extension, sinus tracts ^[7]^[2] Bone biopsy with culture + histopathology* is the definitive gold standard — sinus tract swab culture is unreliable (do NOT use to guide antibiotics except S. aureus) ^[3]^[4]
Management	**Obtain blood/bone cultures, then start empiric therapy covering likely S. aureus and local MRSA risk; narrow to culture results. Route/duration depend on site, host and chronicity; many cases need about 4–6 weeks ^[5]^[2] Surgery indicated when: failed medical treatment, abscess formation, or sequestrum present; chronic requires thorough debridement + dead space management ^[5]^[3] Surgical approach guided by Cierny-Mader stage: I = unroofing; II = debridement ± coverage; III = debridement + bone graft; IV = stabilisation (Ilizarov) + debridement ± ablation ^[3]^[4] Host optimisation is as important as treating the bone — treat diabetes, nutrition, immunosuppression; amputation indications: 3 D's — Dead, Damage, Danger** ^[3]^[2]
Complications	*Chronic osteomyelitis* (sequestrum → involucrum → cloacae → draining sinus); *septic arthritis* especially with intracapsular metaphysis (hip in infants) ^[5]^[3] *Epidural abscess* from vertebral osteomyelitis → spinal cord compression → paraplegia (surgical emergency); *AVN* from raised intraosseous pressure ^[8]^[3] Chronic: Marjolin's ulcer (SCC in draining sinus after 20–30 years); secondary AA amyloidosis → nephrotic syndrome; growth disturbance in children (physeal damage → LLD) ^[3]^[2] Systemic: septicaemia → multi-organ failure; metastatic infection (endocarditis, multifocal osteomyelitis) — amputation and mortality rates depend on aetiology and host factors ^[3]^[4]
Prevention / follow-up	Perioperative antibiotic prophylaxis and aseptic technique during orthopaedic surgery to prevent direct inoculation osteomyelitis ^[1]^[2] *Monitor ESR, CRP and clinical signs (pain, swelling, ROM)* during and after treatment; CRP for early response, ESR for long-term follow-up to detect recurrence ^[7]^[3] Optimise host factors: glycaemic control in diabetics, smoking cessation, nutrition, immunosuppression review — reduces recurrence and improves surgical outcomes ^[3]^[4]
Exam traps	*Chronic osteomyelitis can mimic bone malignancy on X-ray* (osteosclerosis, periosteal reaction, wide transition zone); sequestrum is pathognomonic of osteomyelitis (not seen in tumours) ^[5]^[3] Ewing sarcoma is the great mimicker in children — both cause fever, bone pain, elevated ESR, aggressive periosteal reaction; biopsy is essential to differentiate ^[3]^[2] Normal X-ray does NOT exclude acute osteomyelitis — changes take 10–14 days to appear; always proceed to MRI if clinical suspicion is high ^[7]^[3] Sinus tract swab cultures are unreliable and should NOT guide antibiotic therapy; always obtain bone biopsy culture for definitive microbiology ^[3]^[4]

References

^[1] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 2, 3, 7, 8, 9, 10, 14, 17) ^[2] Senior notes: maxim.md (sections 566, 567, 572) ^[3] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 10, 14, 15, 28, 44, 46, 52, 54) ^[4] Senior notes: maxim.md (sections 566, 567, 572, 583, 454) ^[5] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 7, 9, 10, 12, 14, 44, 54) ^[6] Senior notes: maxim.md (section 566) ^[7] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 7, 12, 14, 15, 19) ^[8] Lecture slides: GC 110. Paraplegia Spinal cord compression Transverse myelitis Spinal dysraphism Neuroimaging III Spinal Cord.pdf (p. 23) ^[9] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 3, 19, 21, 41) ^[10] Lecture slides: GC 226. Lumbar Spine Pathology_Part E (2).pdf (p. 2)

Osteomyelitis

Osteomyelitis is an infection of bone caused by bacteria ^[1]. The name itself tells you exactly what it is: "osteo" = bone, "myel" = marrow, "itis" = inflammation. So it is fundamentally an inflammatory process of bone and marrow, almost always driven by microbial infection.

It can affect any bone in the body, can occur at any age, and ranges from a rapidly fulminant acute illness to a smouldering chronic condition that persists for years with intermittent flare-ups. The critical concept is that bone, once infected, is notoriously difficult to sterilise because of its rigid structure (limited ability to swell and recruit immune cells), relatively poor blood supply in certain regions, and the propensity for dead bone to harbour organisms beyond the reach of antibiotics and host defences.

Why is bone infection so hard to treat?

Bone is a rigid, semi-closed compartment. When pus forms inside the medullary canal, intraosseous pressure rises sharply, compressing the blood supply from within. Meanwhile, the periosteum can be stripped off from outside, cutting off the periosteal blood supply. Dead bone (sequestrum) acts as a foreign body — avascular, so antibiotics cannot penetrate it and immune cells cannot reach it. This is why prolonged antibiotics (4–6 weeks) and often surgical debridement are needed.

2. Epidemiology

Common in paediatric patients ^[1] — haematogenous osteomyelitis peaks in childhood (particularly boys, M:F ≈ 2:1)
Incidence: approximately 2–13 per 100,000 persons/year in developed countries; higher in low-income settings
In adults, osteomyelitis is more commonly secondary to contiguous spread (e.g., diabetic foot ulcers, post-surgical, open fractures) rather than haematogenous
Vertebral osteomyelitis is the most common form of haematogenous osteomyelitis in adults (peak age > 50 years)
In Hong Kong, with an ageing population and rising prevalence of diabetes mellitus, contiguous osteomyelitis (e.g., diabetic foot osteomyelitis) and post-operative/implant-related osteomyelitis are of particular clinical relevance
Sickle cell disease is an important risk factor globally (Salmonella osteomyelitis) but is rare in the Chinese population

High prevalence of DM → diabetic foot infections/osteomyelitis is a major clinical burden
Tuberculosis (TB) remains relevant — spinal TB (Pott's disease) should always be in the differential, especially in elderly and immigrant populations
Post-operative osteomyelitis following orthopaedic implant surgery (e.g., open reduction internal fixation of fractures)
Neonatal osteomyelitis in NICU settings (Group B Streptococcus, E. coli)

Category	Specific Risk Factors	Mechanism
Age extremes	Neonates, children, elderly	Children: rich metaphyseal blood flow with slow/turbulent sinusoids → bacterial seeding. Elderly: immunosenescence, comorbidities
Diabetes mellitus	Peripheral neuropathy + peripheral vascular disease	Neuropathy → unrecognised trauma → ulcer → contiguous spread to bone. PVD → impaired healing and immune response
Immunosuppression	Long-term steroid use, malignancy on treatment, HIV, biologics ^[1]	Impaired cell-mediated and humoral immunity
Vascular disease	PVD, cirrhosis, renal disease ^[1]	Poor tissue perfusion → impaired immune cell delivery and antibiotic penetration
IV drug abuse	Drug abuse ^[1]	Repeated bacteraemia with unusual organisms (Pseudomonas, MRSA, Candida); direct inoculation
Recent bacteraemia	Any source: endocarditis, UTI, line sepsis ^[1]	Haematogenous seeding to bone
Trauma / Surgery	Open fractures, ORIF, prosthetic joints	Direct inoculation of organisms; implant biofilm formation
Recent dental procedure ^[1]	Oral flora bacteraemia	Transient bacteraemia → haematogenous seeding (particularly vertebral)
Sickle cell disease	HbSS	Functional asplenia + bone infarcts → Salmonella and S. aureus osteomyelitis
Contiguous soft tissue infection	Decubitus ulcers, diabetic foot ulcers	Direct extension of infection to underlying bone

High Yield – Risk Factors from Lecture Slides

The lecture slides list these risk factors for musculoskeletal infection (under septic arthritis but equally applicable): age > 60, recent bacteraemia, diabetes, malignancy on treatment, cirrhosis, renal disease, drug abuse, long-term steroid, recent dental procedure ^[1]. Learn these — they are commonly tested.

4. Anatomy and Function: Why Certain Sites Are Affected

Understanding why osteomyelitis preferentially affects certain anatomical locations requires understanding the bone blood supply at different ages.

Long bones receive blood from three sources:

Nutrient artery → enters the diaphysis through the nutrient foramen → divides into ascending and descending branches in the medullary canal → supplies the inner 2/3 of cortex and marrow
Metaphyseal arteries → periosteal vessels that penetrate near the metaphysis
Periosteal arteries → supply the outer 1/3 of cortex

The critical area is the metaphysis:

Terminal branches of metaphyseal arteries form loops at the growth plate and enter irregular afferent venous sinusoids. Blood flow is slowed and turbulent, predisposing to bacterial seeding. In addition, lining cells have little or no phagocytic activity. This area is a "catch basin" for bacteria, and foci of osteomyelitis may form. ^[1]

This is a beautifully elegant explanation of why the metaphysis is the most common site of haematogenous osteomyelitis in children: slow, turbulent flow + lack of local phagocytic defence = perfect conditions for bacteria to settle and proliferate.

Age Group	Primary Site	Reason	Clinical Consequence
Infants < 1 year	Epiphysis	Transphyseal vessels cross the growth plate in infants → bacteria can reach the epiphysis	→ Septic arthritis possible (because epiphysis is intra-articular) ^[2]
Children (1–16 years)	Metaphysis	Growth plate acts as an avascular barrier — vessels loop and turn back	Growth plate inhibits spread of infection to epiphysis/joint (except hip, shoulder, elbow where metaphysis is intracapsular) ^[2]
Adults	Vertebrae (most common haematogenous site); also diaphysis in contiguous/post-traumatic	Growth plate has closed; vertebral bodies have rich Batson venous plexus blood supply	Vertebral osteomyelitis + discitis

Why does the hip joint get septic arthritis from metaphyseal osteomyelitis in children?

Even though the growth plate normally acts as a barrier, the proximal femoral metaphysis is intracapsular (i.e., it sits within the hip joint capsule). So if infection develops in the proximal femoral metaphysis and breaks through the cortex, it spills directly into the hip joint → septic arthritis. The same applies to the proximal humerus (shoulder joint) and parts of the elbow. This is a classic exam point.

These are horizontal (transverse/oblique) canals connecting the Haversian canals of the cortex to each other and to the periosteal and endosteal surfaces. They are the route by which infection spreads from the medullary cavity through the cortex to reach the subperiosteal space. Understanding this pathway is key to understanding sequestrum, involucrum, and cloacae formation (see Pathophysiology below).

5. Aetiology (with Hong Kong Focus)

There are three main routes: ^[2]

Route	Mechanism	Typical Setting
Haematogenous	Bacteria seed bone via the bloodstream from a distant focus	Children (metaphysis), adults (vertebral bodies), IV drug users
Contiguous spread	Infection spreads from adjacent soft tissue or joint to bone	Diabetic foot ulcers, decubitus ulcers, post-surgical wound infections
Direct inoculation	Organisms introduced directly into bone	Open fractures, surgical procedures (ORIF, joint replacement), penetrating trauma

Organism	Clinical Context	Notes
Staphylococcus aureus	Most common overall — all ages, all types ^[2]	Has adhesins (e.g., fibronectin-binding protein, collagen-binding protein) that bind to bone matrix; produces biofilm on implants
Group A Streptococcus (S. pyogenes)	Second most common in children ^[2]
Salmonella spp.	Sickle cell disease ^[2]	Functional asplenia → encapsulated/enteric organisms; rare in HK
Group B Streptococcus (S. agalactiae)	Neonates	Vertical transmission
Escherichia coli / Gram-negatives	Neonates; UTI-related vertebral osteomyelitis in elderly
Pseudomonas aeruginosa	IV drug users; puncture wounds through footwear	Classic: nail through shoe → Pseudomonas osteomyelitis of foot
Coagulase-negative Staphylococci (e.g., S. epidermidis)	Prosthetic joint / implant-related infections	Biofilm formers
MRSA	Healthcare-associated; IV drug users; community MRSA	Increasingly important — affects antibiotic choice
Mycobacterium tuberculosis	TB spine (Pott's disease) — thoracic spine; also peripheral bones	Relevant in Hong Kong — always consider TB in insidious, atypical presentations
Brucella spp.	Endemic areas (not typical in HK); vertebral involvement
Fungi (Candida, Aspergillus)	Severely immunocompromised
Kingella kingae	Children < 5 years (increasingly recognised)	Often culture-negative; diagnosed by PCR

Organism-Age Association – High Yield

Neonates: Group B Strep, E. coli, S. aureus
Children: S. aureus (most common), Group A Strep, Kingella kingae
Adults: S. aureus; Gram-negatives in vertebral osteomyelitis; coagulase-negative Staph in implant-related
Sickle cell: Salmonella (but S. aureus is still the most common even in sickle cell — Salmonella is just disproportionately common)
IV drug users: S. aureus, Pseudomonas, MRSA
Diabetic foot: Polymicrobial (S. aureus, Strep, anaerobes, Gram-negatives)

This is a classic comparison tested in exams ^[2]:

Feature	Pyogenic	TB Spine (Pott's Disease)
Clinical onset	Acute	Insidious
X-ray disc space	Disc space narrowing (early loss of disc height — bacteria produce proteases that destroy the disc)	Disc space relatively spared (TB granuloma spreads beneath the anterior longitudinal ligament; disc lacks blood supply so TB does not seed there haematogenously)
Most common spinal site	Lumbar (anywhere in spine)	Thoracic (closest to lymph nodes draining lungs via Batson plexus)
Paraspinal abscess	Less common	Cold abscess — classic; may track along the psoas muscle
Vertebral body destruction	Less extensive initially	Can be severe — anterior wedging → gibbus deformity (sharp kyphotic angulation)
Constitutional symptoms	High fever, rigors	Low-grade fever, night sweats, weight loss
Lab findings	High WCC, CRP, ESR	ESR elevated, WCC may be normal, positive tuberculin test/IGRA

Why is the disc space spared in TB? The intervertebral disc is avascular in adults. Pyogenic bacteria reach the disc via the blood supply that anastomoses across the endplate, rapidly destroying the disc. TB, being a granulomatous infection, spreads by subligamentous extension along the anterior longitudinal ligament, "skipping" vertebral levels and sparing the disc until late.

6. Pathophysiology

This is one of the most elegant pathophysiological sequences in orthopaedics. Understanding it step by step explains every clinical and radiological feature.

Term	Definition	Pathophysiology	Clinical Significance
Sequestrum	Necrotic bone that has separated from living bone ^[1]^[2]	Devascularised bone due to ↑ intraosseous pressure + periosteal stripping = no blood supply → bone dies	Acts as a foreign body; harbours bacteria in lacunae; antibiotics cannot penetrate → must be surgically removed for cure
Involucrum	New bone formation surrounding the sequestrum ^[1]^[2]	Periosteum is lifted off by pus but remains alive → its inner cambium layer is a potent osteoblastic surface → lays down new bone around the dead bone	Gives structural support; in children (thick periosteum), involucrum can be extensive and maintain limb integrity
Cloacae	Periosteal openings/sinuses through which pus discharges ^[1]^[2]	Pressure from accumulating pus creates perforations through the involucrum → pus tracks to skin surface	Draining sinus tracts on the skin; chronic discharge is pathognomonic of chronic osteomyelitis

The lecture slide image (p9) beautifully illustrates this sequence: (a) Seeding of infection in metaphyseal vessels → (b) Subperiosteal abscess → (c) Sequestrum formation with involucrum → (d) Cloacae with discharging pus and bone ^[1]

Feature	Children	Adults
Periosteum	Thick, loosely adherent → easily lifted by pus → forms robust involucrum; also means subperiosteal abscesses form easily	Thin, tightly adherent → less involucrum, more intramedullary confinement
Growth plate	Avascular barrier → prevents spread to epiphysis (usually)	Absent (fused) → infection can spread freely through bone
Blood supply	Rich metaphyseal blood supply → high risk of haematogenous seeding	Vertebral bodies have rich blood supply → vertebral osteomyelitis
Recovery potential	Excellent — new bone formation is rapid	Slower healing; more likely to progress to chronic osteomyelitis

Contiguous: Infection in adjacent soft tissue (e.g., diabetic foot ulcer, decubitus ulcer) erodes into bone. The bone cortex is initially involved (superficial osteomyelitis) → progresses inward.
Direct inoculation: Organisms are planted directly into bone (open fracture, surgery). Biofilm formation on implants is a key issue — bacteria form a polysaccharide matrix (glycocalyx) on metal/foreign body surfaces that protects them from antibiotics and immune cells → chronic, indolent infection.

Biofilm — Why Implant Infections Are So Difficult to Treat

Within hours of contamination, bacteria (especially S. aureus and S. epidermidis) adhere to implant surfaces and form a biofilm — a structured community of bacteria encased in an extracellular polysaccharide matrix. Antibiotics penetrate biofilm poorly (up to 1000x higher MIC). Host immune cells cannot phagocytose biofilm-embedded bacteria. This is why implant-related osteomyelitis often requires removal of the implant in addition to antibiotics and debridement.

7. Classification

Classification	Duration	Features
Acute	< 2 weeks	Rapid onset, systemic features (fever, malaise), positive blood cultures more common, X-ray often normal
Subacute	< 3 months	Intermediate; may present as Brodie's abscess (a walled-off intraosseous abscess, often in distal tibia metaphysis of children, with sclerotic rim on X-ray)
Chronic	> 3 months	Sequestrum, involucrum, draining sinuses; systemic features may be absent; X-ray shows sclerosis, periosteal reaction

7.2 By Stage of Infection — Cierny-Mader Classification [1]

This is the most widely used staging system. It combines anatomical type (where in the bone) with physiological host class (how well the patient can fight infection). It directly guides management.

Stage	Name	Description	Aetiology	Treatment Principles
Stage I	Medullary osteomyelitis	Necrosis limited to medullary contents and endosteal surfaces	Haematogenous	Early: Antibiotics/host alteration. Late: Unroofing, intramedullary reaming
Stage II	Superficial osteomyelitis	Necrosis limited to exposed bone surfaces	Contiguous soft tissue infection	Early: Antibiotics/host alteration. Late: Superficial debridement/coverage. Possible ablation
Stage III	Localized osteomyelitis	Well-marginated, stable before and after debridement	Trauma, evolving stages I and II, iatrogenic	Antibiotics/host alteration. Debridement, dead space management. Temporary stabilization, bone graft optional
Stage IV	Diffuse osteomyelitis	Circumferential and/or permeative. Unstable prior to or after debridement	Trauma, evolving stages I, II, and III, iatrogenic	Antibiotics/host alteration. Stabilization – ORIF, external fixation (Ilizarov). Debridement, dead space management. Possible ablation

Class	Description
A	Normal host — good immune function, no systemic compromise
B	Compromised host — local (Bl: scarring, lymphoedema, venous stasis, radiation fibrosis) or systemic (Bs: DM, malnutrition, renal failure, immunosuppression, extremes of age) or both (Bls)
C	Treatment worse than disease — severely compromised; treatment morbidity exceeds disease morbidity; consider suppressive antibiotics only

Cierny-Mader is High Yield

This classification is directly from the lecture slides and guides management decisions. A Stage I-A (medullary osteomyelitis in a normal host) may respond to antibiotics alone, while a Stage IV-B (diffuse osteomyelitis in a compromised host) may require extensive surgery, Ilizarov fixation, and even amputation (ablation). The key principle: treat the bone AND the host.

As discussed in Aetiology:

Haematogenous
Contiguous
Direct inoculation

8. Clinical Features

The clinical presentation depends on whether the osteomyelitis is acute, subacute, or chronic, and on the route of infection and patient age.

Symptom	Pathophysiological Basis
Localised bone pain (most common presenting symptom)	Suppuration within the rigid medullary canal → ↑ intraosseous pressure → stretching of the richly innervated periosteum; inflammatory mediators (PGE2, bradykinin) stimulate nociceptors
Fever, malaise, lethargy (systemic)	Bacteraemia → cytokine release (IL-1, IL-6, TNF-α) → hypothalamic temperature set-point elevation → fever; systemic inflammatory response
Inability to weight-bear / refusal to use limb (especially children)	Pain avoidance; in pre-verbal children, this may be the only clue — "pseudoparalysis"
Pain with movement	Inflammation in adjacent soft tissues and periosteum; if near a joint → may mimic septic arthritis
Chronic: intermittent pain with flare-ups	Persistent low-grade infection with periodic bacterial proliferation overwhelming local defences
Chronic: discharge from sinus tract	Pus tracking from cloacae through involucrum and soft tissues to skin surface

Sign	Pathophysiological Basis
Localised warmth, erythema, swelling (signs of inflammation) ^[2]	Classic inflammatory response: vasodilation (rubor, calor), increased vascular permeability (tumor); cytokine-mediated
Limited range of motion (ROM) ^[2]	Periosteal inflammation and oedema → pain with movement; if adjacent to a joint, effusion and capsular distension further limit ROM
Point tenderness over affected bone	Periosteal stretching and inflammation; the periosteum is the most pain-sensitive structure of bone
Draining sinus tract ^[2]	Chronic osteomyelitis → cloacae through involucrum → sinus tract to skin; indicates sequestrum presence (pus has nowhere else to go)
Soft tissue fluctuance / abscess	Subperiosteal or soft tissue abscess formation from pus tracking out of bone
Inability to weight-bear / antalgic gait	Pain avoidance mechanism; shortened stance phase on affected side
Erythema tracking along limb (in severe cases)	Lymphangitis from spreading infection
Systemic: tachycardia, hypotension (if septic)	Sepsis physiology: systemic vasodilation from inflammatory mediators, myocardial depression

8.3 Special Presentations by Age and Type

Often presents subtly: irritability, pseudoparalysis, poor feeding
May have minimal fever
Epiphyseal involvement (transphyseal vessels present) → can spread to joint → concurrent septic arthritis is common
Multiple bone involvement in up to 40%

Classic presentation: acutely unwell child with localised bone pain, fever, refusal to weight-bear
Long bone metaphyses (distal femur, proximal tibia most common — these are the fastest growing metaphyses in the body, hence the richest blood flow and greatest risk of bacterial seeding)
Important to distinguish from septic arthritis (see Kocher criteria in DDx section later)

Insidious onset of back pain — progressively worsening, unrelenting, worse at night
May have low-grade fever or be afebrile
Localised tenderness over spinous processes
Neurological deficits if epidural abscess develops (emergency!)
Risk factors: recent bacteraemia, diabetes, drug abuse, recent dental procedure ^[1]

Draining sinus tract is the hallmark
Intermittent pain, low-grade inflammation
May flare up with fever and increased drainage
Long-standing sinuses carry a risk of squamous cell carcinoma (Marjolin's ulcer) — rare but important to know
X-ray: sequestrum, involucrum, cloacae, osteosclerosis

Well-defined intraosseous abscess with sclerotic rim
Typically in the tibial metaphysis of an older child/adolescent
Presents with localised pain; often afebrile; ESR mildly elevated
X-ray: well-circumscribed lucent lesion with surrounding sclerosis
Must distinguish from tumour (e.g., osteoid osteoma, Ewing's sarcoma)

Occurs after ORIF, intramedullary nailing, or prosthetic joint replacement
May present early (within weeks — acute, virulent organisms like S. aureus) or late (months to years — indolent organisms like coagulase-negative Staphylococci)
Wound breakdown, persistent discharge, implant loosening are key signs
Biofilm on implant → resistant to antibiotics → often requires implant removal

Exam Pearls – Clinical Features

X-ray in acute osteomyelitis is often NORMAL ^[2] — radiographic changes take 10–14 days to appear (at least 30–50% bone mineral loss needed before lytic changes are visible)
MRI is the best imaging modality for diagnosis ^[2] — high sensitivity and specificity, can detect marrow oedema within 24–48 hours
In chronic osteomyelitis, X-ray can mimic malignancy ^[2] — osteosclerotic lesion, wide zone of transition, periosteal reaction → DDx includes chronic osteomyelitis and bone tumour (e.g., Ewing sarcoma, osteosarcoma)
A draining sinus tract in the context of bone infection = chronic osteomyelitis with sequestrum until proven otherwise

These will be covered in detail in the Complications section later, but briefly — the clinical features of complications include:

Pathological fracture: sudden pain and deformity in a chronically infected bone (weakened by osteolysis)
Growth disturbance (children): if infection damages the growth plate → limb length discrepancy, angular deformity
Septic arthritis: especially from metaphyseal infection in intracapsular locations (hip, shoulder)
Amyloidosis (AA type): chronic inflammatory stimulus → serum amyloid A deposition → nephrotic syndrome, hepatosplenomegaly (rare today with modern treatment)
Squamous cell carcinoma (Marjolin's ulcer) in long-standing draining sinus tracts

To consolidate — the lecture slides show a 4-panel progression:

(a) Seeding of infection in metaphyseal vessels → (b) Subperiosteal abscess formation → (c) Sequestrum (dead necrotic bone) with surrounding involucrum (new bone) → (d) Cloacae: openings through involucrum discharging pus and bone fragments ^[1]

This is the single most important pathophysiological diagram for osteomyelitis. If you can draw and explain this sequence, you understand the disease.

High Yield Summary

Definition: Infection of bone caused by bacteria; "osteo-myel-itis" = bone marrow inflammation ^[1]

Classification by onset: Acute ( < 2 weeks), Subacute ( < 3 months), Chronic ( > 3 months) ^[1]

Classification by stage: Cierny-Mader — Stages I–IV (medullary → superficial → localized → diffuse) combined with Host class A/B/C ^[1]

Routes: Haematogenous, Contiguous, Direct inoculation ^[2]

Most common organism: S. aureus (all ages); Salmonella in sickle cell; TB in Hong Kong always a differential ^[2]

Pathogenesis: Bacteraemia → metaphyseal sinusoid seeding (slow turbulent flow, no phagocytic activity) → suppuration → ↑ intraosseous pressure → pus exits via Volkmann canals → subperiosteal abscess → Sequestrum (dead bone), Involucrum (new bone), Cloacae (draining sinuses) ^[1]^[2]

Age-Site predilection: Infants = epiphysis (transphyseal vessels → septic arthritis risk); Children = metaphysis (growth plate barrier); Adults = vertebrae ^[2]

Clinical features: Localised bone pain, fever, limited ROM, draining sinus tract (chronic); X-ray normal in acute, MRI best for diagnosis ^[2]

Pyogenic vs TB spine: Pyogenic = acute, disc space narrowing, lumbar; TB = insidious, disc relatively spared, thoracic ^[2]

Key risk factors (from slides): Age > 60, recent bacteraemia, diabetes, malignancy on treatment, cirrhosis, renal disease, drug abuse, long-term steroid, recent dental procedure ^[1]

Active Recall - Osteomyelitis (Definition, Epidemiology, Anatomy, Aetiology, Pathophysiology, Classification, Clinical Features)

^[1] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 2, 3, 7, 8, 9, 10, 14, 17) ^[2] Senior notes: maxim.md (sections 566, 567, 572, 583, 454)

Differential Diagnosis of Osteomyelitis

The differential diagnosis of osteomyelitis is one of those clinical exercises where context is everything — the age of the patient, the bone involved, the acuity of presentation, and the radiological appearance all dramatically narrow the list. The challenge is that osteomyelitis is a great mimicker: acutely it can look like cellulitis, septic arthritis, or even a fracture; chronically it can look like a bone tumour. Let's work through this systematically.

Osteomyelitis shares features with many conditions because:

Bone pain + fever = any bone/joint infection, inflammatory arthritis, or malignancy
Radiographic periosteal reaction, osteolysis, and sclerosis = seen in both infection and tumour
Chronic osteomyelitis on X-ray can mimic malignancy — osteosclerotic lesion, wide zone of transition, periosteal reaction ^[2] — these features overlap with aggressive bone tumours (Ewing sarcoma, osteosarcoma)
Conversely, some tumours (particularly Ewing sarcoma) present with fever, elevated ESR/CRP, and a destructive bone lesion → initially misdiagnosed as osteomyelitis

The Golden Rule

Never assume a destructive bone lesion in a child or young adult is "just osteomyelitis" without considering malignancy. Conversely, never biopsy a suspected tumour through an infected field. If in doubt, MRI + biopsy (in a tumour-safe manner) is mandatory. DDx of a bone lesion on X-ray includes chronic osteomyelitis and eosinophilic granuloma ^[2].

Detailed Differential Diagnosis by Clinical Scenario

Differential	Key Distinguishing Features	Why It Mimics Osteomyelitis
Septic arthritis	Pain with movement, monoarthritis ^[2]; joint effusion; inability to weight-bear; joint aspiration is diagnostic (WCC > 50,000, > 75% PMN, positive Gram stain) ^[1]	Both cause fever + limb pain + refusal to use limb. Metaphyseal osteomyelitis can co-exist with septic arthritis (especially hip in infants where metaphysis is intracapsular)
Cellulitis / Soft tissue abscess	Superficial warmth, erythema, swelling; no deep bone tenderness; no periosteal reaction on X-ray; MRI shows soft tissue inflammation without marrow oedema	Overlying soft tissue inflammation in osteomyelitis can look identical clinically
Acute rheumatic fever	Migratory polyarthritis (not fixed to one bone); history of recent streptococcal pharyngitis; elevated ASO titre; Jones criteria	Both present with fever + joint/bone pain in children
Sickle cell vaso-occlusive crisis	Known sickle cell disease; painful bone crisis can mimic osteomyelitis almost perfectly; may have identical imaging. Distinguish by clinical context, blood cultures, bone marrow aspiration	Bone infarcts in sickle cell can cause fever, bone pain, periosteal reaction. Remember: Salmonella osteomyelitis is disproportionately common in sickle cell ^[2] — so both conditions can co-exist
Fracture / Non-accidental injury (NAI)	History of trauma (or inconsistent history suggesting NAI); X-ray shows fracture line; no systemic inflammatory response unless secondary infection	Both cause localised bone pain and refusal to weight-bear
Malignancy (Ewing sarcoma, leukaemia, neuroblastoma metastasis)	Ewing sarcoma: onion-skin periosteal reaction (lamellated) ^[2], diaphyseal, age 5–25; leukaemia: pancytopenia, blast cells on film; neuroblastoma met: age < 5, adrenal mass	Ewing sarcoma classically presents with fever + bone pain + elevated ESR/WCC + aggressive periosteal reaction → can be indistinguishable from osteomyelitis clinically and radiologically
Transient synovitis	Commonest cause of acute hip pain in children (age 3–10); low-grade or no fever; near-normal bloods; joint effusion but non-toxic; resolves spontaneously	Both cause hip pain and limp; differentiate from septic arthritis using Kocher criteria (fever > 38.5°C, non-weight-bearing, ESR > 40, WCC > 12,000)

Ewing Sarcoma vs Osteomyelitis — Exam Favourite

Both can present in a young patient with bone pain, fever, elevated ESR and WCC, and an aggressive-looking bone lesion with periosteal reaction. Lamellated (onion skin) periosteal reaction is seen in both! Spiculated (sunburst) periosteal reaction and Codman's triangle suggest a very aggressive tumour ^[2]. When in doubt, biopsy before antibiotics if tumour is suspected — but never biopsy through potentially infected tissue (seeds tumour/infection along the tract).

Differential	Key Distinguishing Features	Why It Mimics Osteomyelitis
Septic arthritis	Acute hot swollen joint; joint aspiration: WCC > 50,000, > 75% PMN, positive Gram stain ^[1]; most commonly knee or hip; organisms: S. aureus, Neisseria gonorrhoeae (STD) ^[2]	Can co-exist with osteomyelitis; both cause periarticular pain and systemic sepsis
Crystal arthropathy (gout/pseudogout)	Acute monoarthritis; joint aspiration with microscopy to rule out gout ^[2] — negatively birefringent urate crystals (gout) or positively birefringent calcium pyrophosphate (pseudogout); no organisms on culture	Both present as acute hot swollen joint; gout can cause fever and elevated WCC
Cellulitis / Deep soft tissue abscess	No marrow oedema on MRI; responds to antibiotics without bone debridement; superficial process	Can overlie and be secondary to underlying osteomyelitis
Vertebral osteomyelitis DDx: Disc herniation, metastasis, TB spine	Disc herniation: radiculopathy without fever/systemic signs; metastasis: known primary (lung, breast, prostate), lytic/blastic lesions above T5; TB spine: insidious, disc space relatively spared, thoracic level ^[2]	All present with back pain; vertebral osteomyelitis is insidious and can mimic all of these
Diabetic foot: soft tissue infection without bone involvement	Probe-to-bone test negative; MRI shows soft tissue inflammation but no marrow signal changes; no cortical erosion on X-ray	Diabetic foot infections commonly progress to osteomyelitis — the distinction is critical for management (antibiotics alone vs. surgery)
Charcot arthropathy (neuropathic arthropathy)	Painless foot and ankle deformities with warmth, redness, and oedema; DM neuropathy; X-ray: degenerative changes, subluxation ^[3]; joint aspiration to rule out infection	Can look identical to osteomyelitis on MRI (marrow oedema, soft tissue swelling, joint destruction); classically painless (vs. osteomyelitis which is painful) — but neuropathic patients may not feel pain from osteomyelitis either
Avascular necrosis (AVN)	Insidious onset of hip pain; limited ROM (abduction and internal rotation); risk factors: steroid use, alcohol, SLE, osteomyelitis itself ^[4]; MRI: double line sign on T2W ^[4]	Both cause bone pain with limited ROM; AVN can be a complication of osteomyelitis

Charcot vs Osteomyelitis in Diabetic Foot — The Classic Dilemma

Both cause a warm, swollen, deformed foot with abnormal MRI signal. Key differentiators: Charcot is classically painless (neuropathic) whereas osteomyelitis is painful; Charcot shows joint destruction and subluxation without cortical erosion or sinus tract; osteomyelitis shows cortical destruction, marrow oedema crossing the cortex, and often a sinus tract. Probe-to-bone test (if a sterile metal probe can touch bone through a diabetic foot ulcer) has ~90% positive predictive value for osteomyelitis. When in doubt, bone biopsy with culture is the gold standard.

This is where the overlap with malignancy is most problematic. Chronic osteomyelitis on X-ray can mimic cancer ^[2]:

Feature	Chronic Osteomyelitis	Bone Malignancy
Osteosclerosis	Present (involucrum, reactive bone)	Present (osteosarcoma: cloud-like osteoid matrix; osteoblastic metastases)
Wide zone of transition	Can be present	Hallmark of aggressive lesion
Periosteal reaction	Solid or lamellated (onion skin)	Lamellated (Ewing), spiculated/sunburst (osteosarcoma), Codman's triangle (very aggressive) ^[2]
Cortical destruction	Present in advanced cases	Present
Soft tissue mass	Abscess / sinus tract	Tumour mass
Sequestrum	Pathognomonic of osteomyelitis — dead bone within a cavity	Absent (bone fragments in tumour are tumour matrix, not sequestra)
Clinical context	History of previous infection/surgery/trauma; draining sinus	Night pain, weight loss, no infective history

Chronic Bone Lesion DDx	Key Distinguishing Feature
Ewing sarcoma	Age 5–25; diaphyseal; onion skin periosteal reaction; systemic symptoms; biopsy: small round blue cells
Osteosarcoma	Age 10–25; metaphyseal (around the knee); sunburst periosteal reaction, Codman's triangle; elevated ALP; biopsy: malignant osteoid
Eosinophilic granuloma (Langerhans cell histiocytosis) ^[2]	Children/young adults; well-defined lytic "punched out" lesion; skull, femur, pelvis; can have periosteal reaction; biopsy: Birbeck granules, CD1a+ cells
Metastatic bone disease	Age > 40; multiple lesions; known primary (lung, breast, prostate, renal, thyroid); lytic or blastic; above T5 is suspicious
Bone lymphoma	Permeative destruction; can present with soft tissue mass; older adults; biopsy diagnostic
Stress fracture	History of repetitive activity; localised tenderness; X-ray may show periosteal reaction or fracture line; MRI: marrow oedema along fracture plane without abscess
Brodie's abscess (subacute osteomyelitis)	Well-defined lytic lesion with sclerotic rim in the metaphysis; mild inflammatory markers; must distinguish from osteoid osteoma (which also has a lucent nidus with sclerotic rim but has classic nocturnal pain relieved by NSAIDs)

The differential diagnosis of back pain includes ^[5]:

Category	Examples
Mechanical (97%)	Back sprain ( > 70%), lumbar disc degeneration, lumbar disc herniation, spondylolisthesis, fracture (vertebral body, spondylolysis)
Non-mechanical (3%)	Neoplasia, inflammatory arthritis (AS/spondyloarthropathy), infection (osteomyelitis, TB spine, epidural abscess)
Non-spinal diseases	Pelvic inflammatory disease, endometriosis, nephrolithiasis, pyelonephritis, aortic aneurysm

Key points for vertebral osteomyelitis DDx ^[6]:

Spinal metastasis: often above T5 (vs. pyogenic osteomyelitis more common in lumbar); multiple levels; known primary cancer; does not typically cross the disc space early (unlike pyogenic infection which destroys the disc early)
TB spine (Pott's disease): insidious, disc space relatively spared, thoracic level, cold abscess tracking along psoas ^[2]
Epidural abscess: severe back pain + fever + rapidly progressive neurological deficit → surgical emergency
Degenerative disc disease (Modic changes on MRI): Modic type 1 changes (marrow oedema adjacent to endplates) can look very similar to discitis/osteomyelitis on MRI; however, no fever, no elevated inflammatory markers, no enhancement pattern typical of infection

Red Flags for Spinal Infection

In the context of back pain, red flags for infection include ^[6]: fever, immunosuppression (DM, steroid use, HIV), recent bacteraemia, IV drug use, recent spinal procedure, and progressive neurological deficit. These should trigger urgent MRI and blood cultures.

Feature	Osteomyelitis	Septic Arthritis	Bone Tumour	Cellulitis	Charcot
Site of max tenderness	Over bone (metaphysis/diaphysis)	Over joint line	Over bone	Diffuse soft tissue	Over joint/midfoot
ROM	Limited by pain	Markedly limited in all directions	May be preserved early	Preserved	Preserved (painless)
Fever	Usually present (acute)	Usually present	Variable (Ewing: yes)	Usually present	Usually absent
X-ray (acute)	Normal for 10–14 days	Joint effusion, periarticular osteopenia	Lytic/blastic lesion, periosteal reaction	Normal or soft tissue swelling	Degenerative changes
MRI	Marrow oedema, periosteal enhancement, ± abscess	Joint effusion, synovial enhancement	Marrow-replacing mass, soft tissue component	Soft tissue oedema only	Marrow oedema, joint destruction, subluxation
Blood cultures	Positive in ~50% ^[2]	Positive in ~50%	Negative	Usually negative	Negative
Joint aspiration	N/A (unless co-existent septic arthritis)	WCC > 50,000, > 75% PMN, + Gram stain ^[1]	N/A	N/A	Non-inflammatory fluid; rule out infection
Key distinguishing test	MRI + bone biopsy with culture	Joint aspiration	Biopsy (image-guided)	Clinical diagnosis	Probe-to-bone test negative; aspiration sterile

This is a frequently tested framework:

Age	Key Differentials
< 4 years	Transient synovitis, osteomyelitis, septic arthritis, NAI
4–10 years	Transient synovitis, Perthes disease, osteomyelitis/septic arthritis
10–16 years	SCFE, avulsion fracture, osteomyelitis/septic arthritis, malignancy (osteosarcoma, Ewing's)

Why does Perthes disease mimic osteomyelitis? Both cause hip pain and limited ROM (especially internal rotation and abduction) in a child. Perthes is avascular necrosis of the proximal femoral epiphysis — X-ray shows flattening, sclerosis, fragmentation of the femoral head rather than metaphyseal destruction. No fever or elevated inflammatory markers in Perthes.

High Yield Summary – Differential Diagnosis of Osteomyelitis

Acute in children: Septic arthritis (co-exists!), cellulitis, Ewing sarcoma (the great mimicker — both cause fever, bone pain, elevated ESR, aggressive periosteal reaction), transient synovitis, sickle cell crisis, fracture/NAI
Acute in adults: Septic arthritis, crystal arthropathy (gout — always aspirate joint), cellulitis, vertebral: metastasis/TB/disc herniation
Chronic bone lesion: Chronic osteomyelitis can mimic cancer on X-ray ^[2] — osteosclerosis, wide zone of transition, periosteal reaction. DDx: Ewing sarcoma, osteosarcoma, eosinophilic granuloma, metastasis, bone lymphoma. Sequestrum is pathognomonic of chronic osteomyelitis (not seen in tumours)
Vertebral: Pyogenic vs TB spine ^[2] — Pyogenic = acute, disc narrowing, lumbar; TB = insidious, disc spared, thoracic. Also DDx metastasis (above T5, no disc involvement), degenerative Modic changes
Diabetic foot: Osteomyelitis vs Charcot arthropathy — Charcot is painless, no cortical erosion, no sinus. Probe-to-bone test + bone biopsy with culture differentiates
Eosinophilic granuloma ^[2] is a frequently forgotten DDx of a lytic bone lesion with periosteal reaction in children

Active Recall - Differential Diagnosis of Osteomyelitis

References

^[1] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 3, 19, 21, 41) ^[2] Senior notes: maxim.md (sections 566, 567, 572) ^[3] Senior notes: maxim.md (section 550) ^[4] Senior notes: maxim.md (section 522) ^[5] Lecture slides: GC 226. Lumbar Spine Pathology_Part E (2).pdf (p. 2) ^[6] Senior notes: maxim.md (section 464) ^[7] Senior notes: maxim.md (sections 583, 584)

Diagnostic Criteria, Algorithm, and Investigation Modalities for Osteomyelitis

Unlike some conditions (e.g., rheumatic fever with Jones criteria, or septic arthritis with Kocher criteria), osteomyelitis does not have a universally agreed-upon set of formal diagnostic criteria with a scoring system. Instead, the diagnosis is made by integrating clinical suspicion + laboratory markers + imaging + microbiology. The gold standard for definitive diagnosis is bone biopsy with culture and histopathology — this confirms the organism AND the histological presence of infection in bone.

That said, there are well-established diagnostic pillars that, when present in combination, make the diagnosis:

Diagnostic Pillars of Osteomyelitis

Clinical features: Localised bone pain, tenderness, warmth, swelling ± fever ± draining sinus tract
Elevated inflammatory markers: CBP, ESR, CRP ^[1]^[8]
Imaging evidence: X-ray (may be normal acutely); MRI (best for diagnosis — marrow oedema, periosteal reaction, abscess) ^[2]^[8]
Microbiological confirmation: Blood cultures (positive in ~50%) ^[2]; bone aspirate/biopsy culture (gold standard)
Histopathology: Acute inflammatory infiltrate (neutrophils) in bone tissue with necrosis = definitive confirmation

The approach varies depending on the clinical scenario — acute vs. chronic, and the body region involved. Here is a comprehensive algorithm:

Key Points from the Algorithm

X-ray is always the first imaging — it's quick, cheap, and can rule out fractures, show chronic changes, or reveal an alternative diagnosis. But it is insensitive in the first 10–14 days of acute osteomyelitis ^[2]
MRI is the best investigation for diagnosis ^[2] — obtain it whenever clinical suspicion is high, regardless of X-ray findings
Blood cultures are positive in only ~50% of cases ^[2] — a negative blood culture does NOT exclude osteomyelitis
When blood cultures are negative and you need a definitive organism, bone biopsy with culture is the gold standard
Monitor clinical signs such as pain, swelling, range of motion and biochemical markers including ESR, CRP to assess treatment response ^[1]

Investigation Modalities — Detailed Breakdown

Investigation	Key Findings	Interpretation & Pathophysiological Basis
CBP (Complete Blood Picture) ^[1]^[8]	Leukocytosis with neutrophilia (acute); may be normal in chronic or subacute	Acute bacterial infection triggers bone marrow release of neutrophils via G-CSF and IL-6. In chronic osteomyelitis, the WCC may normalise as the infection becomes walled off. A normal WCC does NOT exclude osteomyelitis
ESR (Erythrocyte Sedimentation Rate) ^[1]^[8]^[9]	Typically elevated ( > 40 mm/hr in acute); slow to rise, slow to fall	ESR reflects high blood fibrinogen which causes RBC to stick to each other ^[9] → rouleaux formation → faster sedimentation. Useful for monitoring treatment response because it falls slowly over weeks (half-life ~1 week). If ESR fails to trend down after 2 weeks of treatment → suspect treatment failure or undrained abscess
CRP (C-Reactive Protein) ^[1]^[8]^[9]	Elevated; rises within 6–8 hours after onset of infection ^[9]; peaks at 48 hours	Synthesised by hepatocytes in response to IL-6. More sensitive and specific than ESR for acute infection. Falls rapidly with effective treatment (half-life ~19 hours) → best marker for early treatment response. If CRP initially falls then rises again → suspect complication (abscess, secondary infection, drug fever)
Blood cultures (x2 sets) ^[2]^[8]	Positive in ~50% of haematogenous osteomyelitis ^[2]	Must be drawn before starting antibiotics. Two sets from different venipuncture sites to increase yield and distinguish true bacteraemia from contamination. Positive blood culture + compatible clinical picture = diagnosis without need for bone biopsy
Procalcitonin (PCT)	Elevated in bacterial infection; > 0.5 ng/mL suggests bacterial aetiology	More specific for bacterial infection than CRP (not elevated by viral infection or autoimmune flares). Useful in differentiating osteomyelitis from crystal arthropathy or inflammatory conditions. Not routinely used in all centres
Alkaline Phosphatase (ALP) ^[9]	May be elevated	Reflects osteoblastic activity — new bone formation (involucrum) in osteomyelitis raises ALP. Also elevated in bone tumours, Paget's disease, healing fractures
Globulin level ^[9]	May be elevated in chronic infection	Chronic antigenic stimulation → polyclonal hypergammaglobulinaemia
Serum protein electrophoresis ^[9]	Polyclonal gammopathy in chronic osteomyelitis	Helps distinguish from myeloma (monoclonal spike) which can also cause bone destruction
CaPO₄ ^[9]	Usually normal in osteomyelitis	Helps exclude metabolic bone disease and hyperparathyroidism

CRP vs ESR — Know the Difference for Monitoring

CRP: Rises fast (6–8 hours), falls fast (half-life 19 hours) → best for early detection and early monitoring of treatment response
ESR: Rises slowly, falls slowly (half-life ~1 week) → best for long-term monitoring and detecting relapse
In clinical practice, both are measured at baseline and serially during treatment. Monitor biochemical markers including ESR, CRP ^[1]

2. Imaging Investigations

X-ray is always the first-line imaging investigation — every patient with suspected bone infection gets an X-ray ^[2]^[8]^[9].

Timing	X-ray Findings	Explanation
Acute ( < 10–14 days)	Normal ^[2] — may show only soft tissue swelling	At least 30–50% of bone mineral must be lost before lytic changes are visible on X-ray. In the first 1–2 weeks, the infection is confined to the medullary canal and has not yet caused enough bone destruction to be radiographically apparent
After 10–14 days	Periosteal reaction (earliest bony sign); metaphyseal osteopenia/lucency	Subperiosteal pus lifts the periosteum → new bone forms along the elevated periosteum = periosteal reaction. Inflammatory osteolysis becomes visible
Subacute	Well-defined lucent lesion with sclerotic rim (Brodie's abscess)	Walled-off intraosseous abscess — the sclerotic rim is reactive bone attempting to contain the infection
Chronic	Osteosclerotic lesion, wide zone of transition, periosteal reaction ^[2]; sequestrum (dense dead bone within lucent cavity); involucrum (surrounding new bone); cloacae	Sequestrum appears more radio-dense than surrounding bone because it is avascular → no osteoclastic remodelling → retains its original mineral density while surrounding viable bone undergoes resorption and appears less dense
Chronic — DDx malignancy	Mimic CA: osteosclerotic lesion, wide zone of transition, periosteal reaction ^[2]	DDx: chronic osteomyelitis, eosinophilic granuloma ^[2]. Must obtain MRI ± biopsy to differentiate

Systematic Approach to Describing a Bone Lesion on X-ray ^[2]:

Age of patient
Site — which bone
Location within bone — central, eccentric, within cortex, outside cortex; epiphysis, metaphysis, diaphysis
Morphology — well-defined osteolytic (narrow zone of transition) vs ill-defined osteolytic (wide zone of transition) vs sclerotic ^[2]
Periosteal reaction — Solid (benign), Lamellated/onion skin (aggressive), Spiculated/sunburst (very aggressive), Codman's triangle (very aggressive) ^[2]
Cortical destruction — present or absent
Matrix — chondroid (popcorn) or osteoid (cloud-like) ^[2]
Soft tissue component

For vertebral osteomyelitis on X-ray ^[8]: look for soft-tissue swelling or hip joint capsular distension (with widening of the joint space or even subluxation) and radiographic changes in the proximal femoral metaphysis: osteomyelitis ^[8]. In the spine: endplate irregularity, disc space narrowing (pyogenic) or relative preservation (TB), paravertebral soft tissue shadow widening.

MRI is the best investigation for diagnosis of osteomyelitis ^[2] — it has the highest sensitivity (82–100%) and specificity (75–96%) among all imaging modalities.

MRI Sequence	Findings in Osteomyelitis	Explanation
T1-weighted	Low signal (dark) in bone marrow	Normal fatty marrow is bright on T1W. Infection replaces the fatty marrow with inflammatory exudate and oedema → loss of bright fat signal → dark on T1W
T2-weighted / STIR	High signal (bright) in bone marrow and surrounding soft tissues	Oedema and pus have high water content → bright on T2W/STIR (fluid-sensitive sequences)
T1 with Gadolinium (post-contrast)	Enhancement of bone marrow, periosteum, and surrounding soft tissues; rim-enhancing collections = abscess; non-enhancing area within bone = sequestrum (avascular → no contrast uptake)	Gadolinium highlights areas of increased vascularity and inflammation. A non-enhancing area surrounded by enhancing tissue is the MRI equivalent of a sequestrum — avascular dead bone cannot take up contrast
Diffusion-weighted imaging (DWI)	Restricted diffusion in abscess	Pus is viscous → restricts water molecule movement → bright on DWI. Helps distinguish abscess (restricted) from tumour (variable) and oedema (not restricted)

MRI is useful to detect any co-existent osteomyelitis in the context of septic arthritis ^[1] and may be the most useful test to distinguish proximal femoral osteomyelitis from septic arthritis of the hip ^[8].

Why is MRI Better Than X-ray for Acute Osteomyelitis?

X-ray detects changes in bone mineral density, which requires at least 30–50% mineral loss to be visible — this takes 10–14 days. MRI detects changes in bone marrow signal (fat replacement by oedema/pus), which occurs within 24–48 hours of infection. MRI also shows soft tissue abscesses, subperiosteal collections, joint effusions, and sinus tracts — all crucial for surgical planning.

Caveat: MRI in Diabetic Foot

In the diabetic foot, MRI has reduced specificity because Charcot arthropathy also causes marrow oedema and soft tissue changes. In this context, specific signs of osteomyelitis on MRI include: cortical destruction with marrow signal change contiguous with a skin ulcer, sinus tract extending to bone, and the "ghost sign" (loss of normal marrow signal with enhancement mimicking the shape of the bone). Despite these signs, bone biopsy remains the gold standard in the diabetic foot setting.

Role	Findings	When to Use
Cortical bone detail	Sequestrum, cortical destruction, cloacae — better delineated than on MRI	Chronic osteomyelitis — CT is superior to MRI for detecting sequestra (dense bone is bright on CT, easy to see)
CT-guided biopsy	Allows percutaneous needle biopsy of bone lesion under CT guidance	When blood cultures are negative and a tissue diagnosis is needed; also used when the DDx includes malignancy
Vertebral involvement	Endplate destruction, paravertebral abscess	Used alongside MRI in spinal osteomyelitis

Modality	Findings	Utility
Tc-99m bone scan (triple-phase)	Increased uptake on all three phases (flow, blood pool, delayed) — indicates active bone infection/inflammation	High sensitivity (~95%) but low specificity — also positive in fractures, tumours, Paget's disease, neuropathic joints. Useful when MRI is contraindicated (e.g., pacemaker) or for multifocal disease screening (neonatal osteomyelitis, disseminated infection)
Gallium-67 / Indium-111 labelled WBC scan	Accumulation of radiolabelled leucocytes at the site of infection	Higher specificity for infection than Tc-99m. Useful in chronic osteomyelitis (where Tc-99m may be positive from remodelling alone) and in distinguishing infection from aseptic loosening of prosthetic joints
FDG-PET/CT	Increased FDG uptake at site of infection	Excellent sensitivity; increasingly used for chronic and vertebral osteomyelitis; can differentiate active infection from post-surgical changes. Not first-line due to cost and availability

Role	Utility
Subperiosteal abscess detection	In children, ultrasound can detect subperiosteal fluid collections before X-ray changes appear — quick, non-invasive, no radiation
Joint effusion	If osteomyelitis is near a joint → ultrasound can detect effusion suggesting concurrent septic arthritis
Guided aspiration	Can guide needle aspiration of subperiosteal or soft tissue abscess for culture

Investigation	Method	Key Points
Blood cultures	2 sets from different venipuncture sites, before antibiotics	Positive in ~50% ^[2] — if positive, may avoid need for bone biopsy. Common contaminants (coagulase-negative staph from single bottle) must be distinguished from true pathogen (positive in both sets)
Bone aspirate / biopsy	Percutaneous (CT- or fluoroscopy-guided) or open surgical	Gold standard. Send for: (1) Gram stain, (2) aerobic and anaerobic bacterial culture, (3) AFB smear and culture (to rule out TB — especially important in Hong Kong), (4) fungal culture (if immunocompromised), (5) histopathology. Also send for PCR (16S rRNA) if culture-negative is anticipated
Sinus tract culture	Superficial swab of draining sinus	Unreliable — correlates poorly with deep bone organisms (contaminated by skin flora). Do NOT rely on sinus swab cultures to guide antibiotic therapy. The one exception: if S. aureus is cultured from a sinus tract, it has ~80% correlation with deep bone culture
Joint aspiration (if co-existent septic arthritis suspected)	Gram stain, culture, crystal, glucose ^[1]	Helps differentiate septic arthritis (WCC > 50,000, > 75% PMN, positive Gram stain, low glucose) from gout/pseudogout (crystals present). MRI useful to detect any co-existent osteomyelitis ^[1]
Probe-to-bone test	Sterile metal probe inserted into a diabetic foot ulcer	If the probe can touch bone → positive predictive value ~89% for osteomyelitis. Simple, bedside, no imaging needed. Negative test does not fully exclude osteomyelitis

Sinus Tract Swab Culture — Common Exam Mistake

Students often answer that they would "swab the sinus tract for culture." This is unreliable and does not guide treatment. The sinus tract is colonised by skin flora and superficial contaminants that do not represent the deep bone organisms. The exception is S. aureus isolated from a sinus swab, which has reasonable correlation with the true pathogen. Always aim for deep bone biopsy culture when possible.

Finding	Significance
Acute osteomyelitis	Neutrophilic infiltrate within bone marrow spaces, bone necrosis, microabscess formation, vascular congestion
Chronic osteomyelitis	Lymphocytes, plasma cells, macrophages (chronic inflammatory cells); fibrosis; new bone formation (involucrum); dead bone (sequestrum); granulation tissue
TB osteomyelitis	Caseating granulomas with Langhans giant cells; AFB may be seen on Ziehl-Neelsen stain
Malignancy (exclusion)	Absence of malignant cells — biopsy simultaneously rules out the most important DDx

Special Diagnostic Scenarios

Diagnostic Tool	Interpretation
Probe-to-bone test	Positive if probe touches bone through ulcer (PPV ~89%)
X-ray foot and ankle ^[3]	May show cortical erosion, periosteal reaction, or be normal early
MRI foot	Marrow oedema contiguous with ulcer + cortical disruption = osteomyelitis; distinguish from Charcot (subluxation, no cortical breach from ulcer)
Bone biopsy	Gold standard — culture + histology; guides antibiotic choice
Transcutaneous O₂ pressure (TcPO₂) ^[3]	Assesses wound healing potential ( > 30 mmHg = good); ABPI not useful in DM due to calcification of vessels ^[3] — this affects the decision of whether the limb can heal after debridement

Diagnostic Tool	Interpretation
MRI spine (investigation of choice)	T1 low signal in vertebral body + T2 high signal + disc enhancement + paravertebral soft tissue enhancement; disc involvement = pyogenic (infected disc); disc sparing = TB
Blood cultures	Positive in 30–60% — adequate to guide therapy if positive
CT-guided vertebral biopsy	If blood cultures negative — aspirate disc and adjacent vertebral body for culture + histology
Neurological assessment	Urgent if suspected epidural abscess (back pain + fever + progressive neurological deficit) → emergency MRI → surgical decompression if needed

The lecture slide (p12) shows a classic case: 35-year-old diabetic, 3 months prior had had nailing for closed midshaft tibial fracture, now presents with persistent drainage ^[1]. This is implant-related osteomyelitis.

Diagnostic Tool	Interpretation
X-ray	Periosteal reaction around implant, lucency at bone-implant interface (loosening), progressive osteolysis
CT	Better shows cortical integrity, sequestrum around the implant, sinus tract
MRI	Limited by metal artefact from implant — use metal artefact reduction sequences (MARS/SEMAC/MAVRIC); still useful for soft tissue abscess
Intraoperative deep tissue cultures	Gold standard — multiple deep samples (≥ 3–5) taken at surgery; avoid touching skin/sinus tract; culture for aerobic, anaerobic, AFB, fungi
Sonication of removed implant	Implant placed in sterile container with saline → sonicated to dislodge biofilm → sonication fluid cultured. Increases sensitivity significantly (up to 20% higher than standard tissue culture) for biofilm-embedded organisms

Clinical signs such as pain, swelling, range of motion and biochemical markers including ESR, CRP are used to monitor treatment response ^[1]:

Parameter	Expected Trend with Successful Treatment	Concern if
CRP	Should fall within 48–72 hours of starting effective antibiotics; normalises within 1–2 weeks	Fails to fall or rises again → abscess not drained, wrong antibiotic, drug fever, or new complication
ESR	Falls slowly over weeks; may take 3–6 weeks to normalise	Persistently elevated → ongoing infection; useful for detecting late relapse
Clinical	Pain decreases, swelling subsides, ROM improves, fever resolves	Persistent pain/fever after 48–72 hours → failed medical treatment → consider surgery ^[1]
Imaging (repeat MRI)	Not routinely repeated unless clinical deterioration; MRI changes lag behind clinical improvement	New abscess on imaging or enlarging collection → surgical intervention needed

Change to oral form if showing improvement. Total 6–8 weeks, depends on clinical condition ^[1]. The decision to switch from IV to oral antibiotics is guided by clinical improvement + falling CRP.

High Yield Summary – Diagnosis of Osteomyelitis

No single diagnostic criterion — diagnosis integrates clinical suspicion + labs + imaging + microbiology

First-line labs: CBP, ESR, CRP ^[1]^[8]^[9]; blood cultures x2 (positive in ~50%) ^[2]

First-line imaging: X-ray — always first; normal in acute ( < 10–14 days) ^[2]; chronic: osteosclerosis, sequestrum, involucrum, periosteal reaction → can mimic malignancy ^[2]

Best imaging: MRI — gold standard imaging; detects marrow oedema within 24–48 hours; shows abscess, soft tissue extension, sinus tracts ^[2]^[8]

Gold standard for definitive diagnosis: Bone biopsy with culture + histopathology — especially when blood cultures are negative

Sinus tract swab culture is unreliable — do NOT use to guide antibiotic therapy (except S. aureus)

Probe-to-bone test in diabetic foot: positive PPV ~89%

Monitoring: ESR, CRP, clinical signs (pain, swelling, ROM) ^[1]; CRP for early response, ESR for long-term monitoring

Systematic X-ray description ^[2]: Age, site, location within bone, morphology (zone of transition), periosteal reaction type, cortical destruction, matrix, soft tissue extension

ESR mechanism: high fibrinogen causes RBC to stick → rouleaux → faster sedimentation ^[9]

CRP rises within 6–8 hours of infection onset ^[9]

Active Recall - Diagnosis of Osteomyelitis

References

^[1] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 7, 12, 14, 15, 19) ^[2] Senior notes: maxim.md (sections 566, 567, 572) ^[3] Senior notes: maxim.md (section 550) ^[8] Lecture slides: GC 229. Hip Arthritis (1).pdf (pp. 15, 51, 53) ^[9] Lecture slides: GC 226. Lumbar Spine Pathology_Part C (2).pdf (p. 2)

Management of Osteomyelitis

The management of osteomyelitis rests on two pillars — and you need to understand why both are necessary:

Antibiotics — to kill the bacteria
Surgery — to remove what antibiotics cannot reach (dead bone, abscesses, biofilm on implants)

Why can't antibiotics alone cure all osteomyelitis? Because:

Sequestrum is avascular dead bone → no blood flow → antibiotics delivered intravenously simply cannot reach bacteria hiding in the lacunae of dead bone
Biofilm on implants creates a polysaccharide shield that requires 100–1000x higher antibiotic concentrations to penetrate
Abscesses are walled-off collections of pus → poor antibiotic penetration through the abscess wall; the acidic, anaerobic environment within also inactivates many antibiotics (e.g., aminoglycosides are less effective at low pH)

Therefore: Antibiotics treat the living infected tissue. Surgery removes what is dead. Both together are needed for cure in most cases beyond the earliest acute stages.

Key Management Principle from Lecture Slides

Acute vs Chronic management differs fundamentally ^[1]:

Acute: Antibiotics – broad spectrum. Surgery only when: failed medical treatment or abscess formation
Chronic: Debridement if sequestrum present, abscess formation, failed medical treatment + Antibiotic

In other words: acute osteomyelitis → antibiotics first, surgery if needed. Chronic osteomyelitis → surgery is almost always needed alongside antibiotics.

1. Medical Management — Antibiotics

Principle	Detail	Rationale
Start with IV antibiotics ^[1]	High-dose intravenous route initially	Bone has relatively poor blood supply compared to soft tissues; IV dosing achieves higher peak serum and tissue levels → better bone penetration
Empirical → Targeted	Start empirical broad-spectrum before culture results; narrow once culture and sensitivity (C/ST) are available	You cannot wait 48–72 hours for culture results while the infection progresses; empirical therapy covers the most likely organisms
Monitor clinical signs such as pain, swelling, range of motion ^[1]	Serial clinical assessment	Improving pain, reducing swelling, and improving ROM indicate treatment response
Monitor biochemical markers including ESR, CRP ^[1]	Serial bloods (CRP every 2–3 days initially; ESR weekly)	CRP is the earliest marker to respond to effective treatment (falls within 48–72h). ESR used for long-term monitoring
Change to oral form if showing improvement ^[1]	Switch from IV to oral (PO) when: (1) clinically improving, (2) CRP trending down, (3) tolerating oral intake, (4) reliable patient	Oral antibiotics with good bioavailability (e.g., fluoroquinolones, rifampicin, linezolid, clindamycin) achieve adequate bone concentrations. IV-to-oral switch reduces hospital stay, cost, and IV line complications (thrombophlebitis, line sepsis)
Total 6–8 weeks, depends on clinical condition ^[1]	Total duration of antibiotic therapy	Why so long? Bone turns over slowly. Bacteria within the Haversian and Volkmann canal systems require sustained antibiotic levels for weeks to be eradicated. Short courses → high relapse rates

Duration of Antibiotics — Exam Key Point

Total 6–8 weeks, depends on clinical condition ^[1]. The senior notes state IV cloxacillin x 4–6 weeks ^[2]. In practice:

Acute uncomplicated: 4–6 weeks total (may switch to oral after 1–2 weeks of IV)
Chronic / post-surgical: 6–8 weeks post-debridement (longer if residual infected bone)
Vertebral osteomyelitis: 6–8 weeks (IDSA guidelines support 6 weeks minimum)
Children: often shorter total duration (3–4 weeks) with early switch to oral (after 3–5 days IV) if clinically improving and organism is sensitive — paediatric bone heals faster and children respond better

Clinical Scenario	Most Likely Organism	Empirical Antibiotic	Rationale
Acute haematogenous (child or adult)	S. aureus, Group A Strep	IV cloxacillin ^[2] (or flucloxacillin/nafcillin) = anti-staphylococcal penicillin	"Clox" = cloxacillin; the "cl" reminds you it is resistant to beta-lactamase produced by S. aureus (unlike plain penicillin). First-line for MSSA osteomyelitis
Empirical covering Staphylococcus and Streptococcus species ^[1]	S. aureus, Streptococcus spp.	IV cloxacillin or 1st generation cephalosporin (cefazolin)	Both cover MSSA and Strep effectively; cefazolin has excellent bone penetration
Suspected MRSA	MRSA	IV vancomycin (or teicoplanin)	Vancomycin is the standard anti-MRSA agent; requires therapeutic drug monitoring (trough levels 15–20 mg/L for serious infections)
Immunocompromised patients: should cover gram-negative rods and anaerobes ^[1]	Polymicrobial including Gram-negatives, anaerobes	Add IV ceftriaxone or piperacillin-tazobactam or carbapenem (meropenem) to anti-staphylococcal cover	Immunocompromised patients have broader range of potential organisms; empirical cover must be wider
Sickle cell disease	Salmonella, S. aureus	IV ceftriaxone (covers Salmonella and S. aureus) + cloxacillin	Salmonella is disproportionately common but S. aureus is still the most frequent overall
Post-traumatic / open fracture	S. aureus, Gram-negatives, anaerobes (if soil contamination)	1st gen cephalosporin ± aminoglycoside ± metronidazole (depending on Gustilo-Anderson grade) ^[10]	Grade I: 1st gen cephalosporin; Grade II: add aminoglycoside; Grade III: add metronidazole for anaerobes if farm/soil contamination
Prosthetic joint / implant-related	S. aureus, coagulase-negative Staph (biofilm), Gram-negatives	IV vancomycin + ceftriaxone (or meropenem) empirically; narrow based on deep cultures	Must cover both MRSA and Gram-negatives empirically until cultures guide therapy
Diabetic foot osteomyelitis	Polymicrobial: S. aureus, Strep, enterococci, Gram-negatives, anaerobes	Broad-spectrum: IV piperacillin-tazobactam or amoxicillin-clavulanate + vancomycin (if MRSA risk)	Diabetic foot infections are almost always polymicrobial; bone biopsy culture is the gold standard to guide therapy
TB osteomyelitis	Mycobacterium tuberculosis	Standard anti-TB quadruple therapy: RIPE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) × 2 months, then Rifampicin + Isoniazid × 7–10 months (total 9–12 months)	TB requires prolonged multi-drug therapy because of slow-growing intracellular organisms; single-agent therapy leads to resistance

Organism	Preferred Antibiotic	Notes
MSSA	IV cloxacillin ^[2] (or flucloxacillin) → switch to oral flucloxacillin or ciprofloxacin + rifampicin	Rifampicin has excellent bone penetration and anti-biofilm activity — always use in combination (never monotherapy → rapid resistance)
MRSA	IV vancomycin → switch to oral linezolid, TMP-SMX, or doxycycline (based on sensitivity)	Linezolid: "line-zolid" = oxazolidinone; excellent oral bioavailability and bone penetration; limit to < 4 weeks due to myelosuppression risk
Streptococcus	IV penicillin G or ampicillin	Streptococci remain penicillin-sensitive in the vast majority of cases
Gram-negatives	Based on C/ST: ciprofloxacin, ceftriaxone, meropenem	Fluoroquinolones (e.g., ciprofloxacin) have excellent oral bioavailability and bone penetration — useful for oral switch
Anaerobes	Metronidazole or clindamycin	Metronidazole: "metro-nida-zole" = works by disrupting DNA of anaerobic organisms (requires anaerobic reduction to become active → selective for anaerobes)

Rifampicin — The Anti-Biofilm Agent

Rifampicin has a unique ability to penetrate biofilm and kill sessile (dormant, biofilm-embedded) bacteria. This makes it invaluable in implant-related osteomyelitis. However: (1) Never use as monotherapy — resistance develops within days. (2) Always combine with another active agent. (3) Potent CYP450 inducer — many drug interactions (warfarin, OCP, calcineurin inhibitors).

2. Surgical Management

Acute osteomyelitis — Surgery when: ^[1]

Failed medical treatment (no clinical or biochemical improvement after 48–72h of appropriate IV antibiotics)
Abscess formation (subperiosteal abscess, intraosseous abscess, soft tissue abscess)

Chronic osteomyelitis — Surgery almost always required: ^[1]

Debridement if sequestrum present (sequestrum is avascular → antibiotics cannot reach it → must be physically removed)
Abscess formation
Failed medical treatment
Draining sinus tract (will not resolve without removing the source — the sequestrum)

The Cierny-Mader classification directly guides the surgical approach ^[1]:

Stage	Procedure	Rationale
Stage I — Medullary osteomyelitis	Early: Antibiotics/host alteration. Late: Unroofing, intramedullary reaming ^[1]	Unroofing = creating a cortical window to access the medullary canal and drain pus. Intramedullary reaming = using a reamer to remove infected/necrotic medullary contents, like scooping out the inside of a tube
Stage II — Superficial osteomyelitis	Early: Antibiotics/host alteration. Late: Superficial debridement/coverage. Possible ablation ^[1]	Debridement of the exposed necrotic bone surface + soft tissue coverage (flap) to bring in blood supply. "Ablation" = amputation if the disease is too extensive or the host too compromised
Stage III — Localized osteomyelitis	Antibiotics/host alteration. Debridement, dead space management. Temporary stabilization, bone graft optional ^[1]	After debridement, a dead space (cavity) remains where the infected bone was removed. This must be managed (see below) to prevent re-infection. Bone graft fills the void
Stage IV — Diffuse osteomyelitis	Antibiotics/host alteration. Stabilization – ORIF, external fixation (Ilizarov). Debridement, dead space management. Possible ablation ^[1]	Diffuse disease may render the bone unstable after debridement → requires stabilisation. Ilizarov external fixation allows bone transport (gradually moving a segment of healthy bone to fill the defect) — a remarkable technique for large segmental defects

2c. Key Surgical Concepts

Removal of dead bone (sequestrum) — the fundamental surgical procedure in chronic osteomyelitis
Without sequestrectomy, cure is impossible because the sequestrum acts as a foreign body harbouring bacteria

After debridement/sequestrectomy, a cavity remains within the bone. If left empty, it fills with haematoma → re-infection
Options for dead space management:
- Antibiotic-impregnated PMMA beads (polymethylmethacrylate) — placed in the cavity; elute high local antibiotic concentrations (typically gentamicin or vancomycin); eventually removed and replaced with bone graft at a second stage
- Antibiotic-impregnated calcium sulphate — biodegradable alternative; dissolves over weeks and does not require removal
- Bone graft (autologous cancellous bone from iliac crest) — fills the dead space with osteogenic tissue; typically placed after infection is controlled
- Muscle flap — brings in blood supply to the cavity, which enhances antibiotic delivery and immune cell access. Common flaps: gastrocnemius (proximal tibia), soleus (mid-tibia)
- Masquelet technique (induced membrane technique) — a two-stage approach: (1) cement spacer placed after debridement → induces a biological membrane around it over 6–8 weeks; (2) spacer removed, cavity filled with bone graft contained within the induced membrane (which is rich in growth factors and acts as a biological chamber for osteogenesis)

After extensive debridement, the bone may become structurally unstable (risk of pathological fracture)
Options:
- External fixation (Ilizarov frame) ^[1] — allows bone transport (distraction osteogenesis: cut healthy bone proximally → gradually transport it distally through the defect at ~1mm/day → new bone forms in the gap = regenerate). This is used for large segmental defects
- ORIF ^[1] — plates and screws; used when bone remains relatively stable after debridement
- Intramedullary nail — may be used after thorough debridement; antibiotic-coated nails are available

Particularly important for tibial osteomyelitis (tibia has minimal soft tissue coverage anteriorly — subcutaneous bone)
Local flaps: gastrocnemius (proximal 1/3 tibia), soleus (middle 1/3 tibia)
Free flaps: for distal 1/3 tibia or large defects — microvascular free tissue transfer (e.g., latissimus dorsi, anterolateral thigh flap)

This deserves special discussion because the management depends critically on whether the fracture has healed:

Scenario	Management	Rationale
Fracture healed, implant stable but infected	Remove implant + thorough debridement + prolonged antibiotics	Once the fracture is healed, the implant serves no structural purpose and becomes the source of persistent infection (biofilm). Remove it
Fracture NOT healed, implant infected (early, < 3 weeks)	DAIR protocol: Debridement, Antibiotics, Implant Retention (or exchange to new implant)	Early infection may have immature biofilm that can be disrupted by aggressive debridement + rifampicin-based combination therapy. The implant is still needed for fracture stability
Fracture NOT healed, implant infected (late, > 3 weeks)	Remove implant → external fixation (to maintain alignment) → debridement → staged reconstruction once infection eradicated	Late biofilm is mature and cannot be eradicated with implant in situ. External fixation provides stability without an internal foreign body

Possible ablation is mentioned in the Cierny-Mader classification for Stages II and IV ^[1], and amputation is explicitly an endpoint in severe musculoskeletal infections.

Indications for amputation in osteomyelitis ^[11]^[1]:

Factors favouring amputation over limb salvage ^[1]:

Concurrent medical disease with high anaesthetic risk from multiple operations (e.g., poorly controlled diabetes mellitus, valvular heart disease)
Myonecrosis
Unremitting shock
Concurrent peripheral vascular insufficiency
Rapidly progressive infection
Large area of tissue necrosis (heel pad and sole skin loss)

Factors favouring limb salvage ^[1]:

Good past health
Not life-threatening state
Multiple sites
Responsive to inotropic support

The mnemonic for indications of amputation is the 3 D's ^[11]:

Dead: Ischaemia and unsalvageable
Damage: Trauma/Burns
Danger: Gangrene / Necrotising fasciitis / Osteomyelitis / Ascending sepsis / Malignancy

Levels of amputation ^[11]:

Digital amputation: isolated gangrene or recalcitrant osteomyelitis of a toe
Transmetatarsal: several toes involved
Below knee amputation (BKA): most common type — 90% of patients walk again; energy expenditure ↑40% unilateral
Above knee amputation (AKA): 50% walk again; energy expenditure ↑100% unilateral

Measure	Detail	Rationale
Analgesics ^[2]	Paracetamol, NSAIDs, opioids as needed	Pain from raised intraosseous pressure and periosteal inflammation; adequate analgesia also facilitates rehabilitation
Immobilisation / splinting	Splint or cast for affected limb (especially in children)	Reduces pain, prevents pathological fracture through weakened bone, maintains alignment
Nutritional optimisation	High-protein diet, correct albumin, vitamin C, zinc supplementation	Wound healing and immune function depend critically on nutritional status; malnourished patients have higher failure rates
Host alteration ^[1]	Optimise diabetes control (HbA1c < 8%), smoking cessation, treat immunosuppression, improve nutrition	The Cierny-Mader system emphasises treating the host as much as the bone — a Class B or C host will not heal regardless of how good the surgery is
DVT prophylaxis	LMWH (enoxaparin) if immobilised/post-surgery	Immobilisation + infection → hypercoagulable state → DVT/PE risk
Hyperbaric oxygen therapy (HBOT)	Adjunctive in refractory chronic osteomyelitis	Increases tissue oxygen tension → enhances WBC killing ability (oxidative burst is O₂-dependent), promotes angiogenesis, enhances antibiotic efficacy (aminoglycosides require O₂ for uptake). Evidence is limited but used in select refractory cases

4. Management of Specific Scenarios

First-line: Prolonged IV antibiotics (6–8 weeks) — vertebral osteomyelitis often responds to medical management alone
Immobilisation: brace or external orthosis to reduce pain and prevent deformity
Indications for surgery: neurological deficit (epidural abscess compressing cord/cauda equina), spinal instability, failure of medical therapy, progressive kyphotic deformity
Surgery: anterior debridement + interbody fusion (most common approach) — anterior approach gives direct access to the vertebral body and disc space

Assess vascularity first: TcPO₂ > 30mmHg = adequate healing potential ^[3]; ABPI not useful in DM due to vessel calcification ^[3]
If adequate perfusion: debridement of infected bone + prolonged antibiotics (culture-guided from bone biopsy)
If inadequate perfusion: vascular component: angioplasty ^[3] first to restore blood supply → then reassess
Neuropathic component: customised insole ^[3] to offload pressure and prevent recurrence
Surgical: debridement, below knee amputation ^[3] if the limb is non-salvageable
Multidisciplinary approach: orthopaedics, vascular surgery, endocrinology, podiatry, wound care nurse

Anti-TB chemotherapy: RIPE × 2 months → RI × 7–10 months (total 9–12 months)
Immobilisation/bracing for spinal TB
Surgery: drainage of cold abscess, anterior decompression + fusion if neurological deficit or severe kyphosis (gibbus deformity)
Unlike pyogenic osteomyelitis, TB spine responds well to chemotherapy alone in most cases; surgery is reserved for complications

Intervention	Contraindications / Cautions
Surgical debridement	Cierny-Mader Host Class C — treatment morbidity exceeds disease morbidity; consider suppressive antibiotics only. Also: unacceptable anaesthetic risk, patient refuses surgery
Vancomycin	Renal impairment (nephrotoxic — requires dose adjustment and TDM); "Red man syndrome" if infused too fast (histamine release — not a true allergy)
Rifampicin	Severe hepatic impairment; concurrent warfarin/OCP use (potent CYP450 inducer → reduces drug levels); never use as monotherapy (rapid resistance)
Linezolid	Prolonged use ( > 4 weeks) → myelosuppression (thrombocytopenia, anaemia), peripheral neuropathy, lactic acidosis; serotonin syndrome if combined with SSRIs/MAOIs (linezolid is a weak MAO inhibitor)
Fluoroquinolones	Tendon rupture risk (especially in elderly on steroids); avoid in growing children (theoretical cartilage damage — though increasingly used short-course in paediatric osteomyelitis when benefits outweigh risks); QT prolongation
Aminoglycosides	Nephrotoxicity and ototoxicity with prolonged use; require TDM; less effective in acidic/anaerobic abscess environments
Implant retention (DAIR)	Contraindicated if mature biofilm (infection > 3 weeks), loose implant, sinus tract, difficult-to-treat organisms (MRSA, fungi)
Amputation	Not a contraindication per se, but should be a last resort — consider limb salvage first if the patient is fit enough for multiple operations

High Yield Summary — Management of Osteomyelitis

Acute management ^[1]:

Antibiotics – broad spectrum (empirical, then targeted)
Surgery when: failed medical treatment or abscess formation

Chronic management ^[1]:

Debridement if sequestrum present, abscess formation, failed medical treatment
Antibiotic (6–8 weeks post-debridement)

Antibiotic principles ^[1]:

Start with IV antibiotics
Monitor clinical signs (pain, swelling, ROM) and biochemical markers (ESR, CRP)
Change to oral form if showing improvement
Total 6–8 weeks, depends on clinical condition

First-line antibiotic: IV cloxacillin x 4–6 weeks ^[2] (covers S. aureus — most common organism)

Surgical procedures guided by Cierny-Mader stage ^[1]:

Stage I: Unroofing/reaming
Stage II: Superficial debridement/coverage ± ablation
Stage III: Debridement + dead space management ± bone graft
Stage IV: Stabilisation (ORIF/Ilizarov) + debridement + dead space management ± ablation

Dead space management: antibiotic beads → bone graft → muscle flap → Masquelet technique

Amputation indications (3 D's): Dead, Damage, Danger ^[11]

Host optimisation is as important as treating the bone — antibiotics/host alteration appears in every Cierny-Mader stage ^[1]

Empirical antibiotics and early surgical intervention are necessary in case of life-threatening conditions ^[1]

Active Recall - Management of Osteomyelitis

References

^[1] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 10, 14, 15, 28, 44, 46, 52, 54) ^[2] Senior notes: maxim.md (section 566) ^[3] Senior notes: maxim.md (section 550) ^[10] Senior notes: maxim.md (section 453) ^[11] Senior notes: felixlai.md (section 1381)

Complications of Osteomyelitis

The complications of osteomyelitis can be understood systematically by thinking about what the infection does to bone, to adjacent structures, and to the patient systemically. They also divide logically into complications of the disease itself and complications of the treatment (surgery and prolonged antibiotics). Let's work through each from first principles.

Timing	Local Complications	Systemic Complications
Early / Acute	Subperiosteal abscess, septic arthritis, soft tissue extension, pathological fracture	Sepsis/septicaemia, bacteraemia with metastatic seeding
Late / Chronic	Chronic osteomyelitis, growth disturbance, AVN, deformity, sinus tract, squamous cell carcinoma (Marjolin's ulcer), amyloidosis	Rarely: amyloidosis
Treatment-related	Surgical wound complications, implant failure, recurrence	Antibiotic side effects, amputation complications

A. Complications of the Disease

This is the most common complication of inadequately treated acute osteomyelitis.

Why does it happen? If acute osteomyelitis is not treated early and adequately (or if the organism is resistant), the pathological sequence runs its full course: suppuration → ↑ intraosseous pressure → bone necrosis → sequestrum formation ^[1]^[2]. Once a sequestrum is established, the disease becomes chronic because:
- Sequestrum is avascular → antibiotics cannot reach bacteria within it
- Sequestrum acts as a foreign body → persistent nidus of infection
- Involucrum (new bone) forms around the dead bone but cannot eradicate the infection within it ^[1]
- Cloacae (draining sinuses) develop through the involucrum → chronic discharge to the skin surface ^[1]
Clinical consequence: Draining sinus tract ^[2], intermittent flare-ups of pain and fever, need for prolonged antibiotics + surgical debridement
Chronic osteomyelitis on X-ray mimics malignancy — osteosclerotic lesion, wide zone of transition, periosteal reaction ^[2] → always requires careful differentiation from bone tumour

Key Exam Point

Understand the sequalae of MSS infections if not treated promptly ^[1]. The lecture slides explicitly state this as a learning outcome. Delayed or inadequate treatment of acute osteomyelitis → chronic osteomyelitis → lifelong disease requiring repeated operations.

Why does it happen? Osteomyelitis in the metaphysis can spread to the adjacent joint in two scenarios:
1. In infants < 1 year: transphyseal vessels cross the growth plate → bacteria reach the epiphysis → since the epiphysis is intra-articular, infection spills into the joint ^[2]
2. At any age when the metaphysis is intracapsular: the proximal femur, proximal humerus, and proximal radius/distal lateral humerus have their metaphyses lying within the joint capsule. Infection breaking through the cortex enters the joint directly
Clinical consequence: Acute hot swollen joint with severe pain on movement; joint aspiration: Gram stain, culture, crystal, glucose ^[1]; if untreated → rapid cartilage destruction (cartilage is avascular and exquisitely sensitive to bacterial enzymes and the acidic environment of pus) → secondary osteoarthritis
MRI is useful to detect any co-existent osteomyelitis ^[1] in the setting of septic arthritis — always look for it

Why is septic arthritis a surgical emergency? Articular cartilage has no blood supply — it relies on diffusion from synovial fluid for nutrition. Pus replaces synovial fluid → (1) enzymatic destruction of collagen by bacterial proteases and neutrophil-released MMPs, (2) acidic pH from anaerobic metabolism → chondrocyte death, (3) increased intra-articular pressure → cartilage ischaemia. Irreversible cartilage damage begins within 6–8 hours. This is why empirical antibiotics and early surgical intervention are necessary in case of life-threatening conditions such as septic arthritis ^[1].

Why does it happen? Osteomyelitis causes osteolysis (bone destruction by inflammatory mediators, osteoclast activation by IL-1, TNF-α, RANKL). The cortex is weakened by:
- Intramedullary abscess eroding from within
- Cortical perforation (cloacae)
- Periosteal stripping → loss of periosteal blood supply → cortical devascularisation
When the bone is sufficiently weakened, it can fracture with minimal or no trauma = pathological fracture
Management: Stabilise the fracture (external fixation preferred — avoids introducing more internal hardware into infected bone) + treat the underlying osteomyelitis

Why does it happen? The growth plate (physis) is the engine of longitudinal bone growth. Osteomyelitis can damage the physis in several ways:
- Direct infection of the growth plate (especially in infants where transphyseal vessels carry bacteria to the epiphysis)
- Ischaemia from raised intraosseous pressure and periosteal stripping disrupts the blood supply to the germinal zone of the physis
- Inflammatory mediators directly damage chondrocytes in the proliferative zone
Clinical consequences:
- Limb length discrepancy (LLD): premature physeal closure → shortened limb compared to the contralateral side
- Angular deformity: partial physeal damage → asymmetric growth → varus or valgus deformity
- Joint incongruity: if the epiphysis is damaged → irregular articular surface → early secondary osteoarthritis
More common in younger children (more growth remaining) and in infections involving the physis directly

Why does it happen? Osteomyelitis is listed as a cause of AVN ^[4]:
- Raised intraosseous pressure compresses endosteal vessels
- Periosteal stripping removes the outer cortical blood supply
- Thrombosis of vessels due to septic emboli and inflammation
- Result: complete loss of blood supply to a segment of bone → cellular death of bone components = AVN
Most relevant in the proximal femur (hip) — the femoral head has a precarious blood supply at baseline (retinacular vessels of the medial femoral circumflex artery are the main supply and are easily disrupted)
Clinical features of AVN: insidious onset of hip pain, limited ROM especially abduction and internal rotation ^[4]
Investigations: MRI is the most sensitive — double line sign on T2W ^[4]; X-ray shows crescent sign (subchondral collapse) ^[4]

Why does it happen? Acute osteomyelitis, being a haematogenous infection or at least involving richly vascularised bone, can lead to sustained bacteraemia → systemic inflammatory response → sepsis → septic shock → multi-organ failure
Particular risk in:
- Neonates and infants (immature immune system)
- Immunocompromised patients (DM, steroids, malignancy)
- Delayed diagnosis
Clinical features: High fever, rigors, tachycardia, hypotension, altered mental status, organ dysfunction (AKI, ARDS, DIC)
Severity from mild to life threatening ^[1]; early recognition and high suspicion are important if life-threatening infections ^[1]

Why does it happen? Sustained bacteraemia from the bone focus can seed other organs:
- Endocarditis: bacteria settle on heart valves (especially if pre-existing valvular disease) → S. aureus is the most common cause of acute infective endocarditis
- Septic emboli: from endocarditis or directly from the bone focus → pulmonary septic emboli (lung abscesses), splenic abscess, brain abscess
- Other bones: haematogenous seeding of infection to additional skeletal sites (multifocal osteomyelitis — more common in neonates, up to 40%)
This is why blood cultures are essential — they not only identify the organism but alert you to the risk of metastatic seeding

Why does it happen? Infection in the vertebral body can extend posteriorly into the epidural space → collection of pus compresses the spinal cord or cauda equina
Clinical triad: Back pain + fever + progressive neurological deficit (weakness, sensory loss, bowel/bladder dysfunction)
This is a neurosurgical/orthopaedic emergency — from adjacent foci: osteomyelitis → epidural abscess → IV antibiotics + surgical drainage/debridement ^[12]
Without emergency decompression, irreversible spinal cord damage occurs → paraplegia
The lecture slides on paraplegia list osteomyelitis as an infective cause of spinal cord compression ^[12], specifically through epidural abscess formation

Epidural Abscess — Never Miss This

Any patient with vertebral osteomyelitis who develops new neurological symptoms (leg weakness, urinary retention, saddle anaesthesia) must have emergency MRI spine and urgent surgical decompression. Delay of even hours can mean the difference between recovery and permanent paraplegia. This is a classic exam scenario.

Why does it happen? Long-standing chronic osteomyelitis with a draining sinus tract creates a state of chronic inflammation → chronic tissue repair → repeated epithelial turnover at the sinus opening. Over years to decades, this repeated cellular proliferation increases the risk of malignant transformation
"Marjolin's ulcer" = squamous cell carcinoma arising in a chronically inflamed scar, wound, or sinus tract
Timeframe: typically develops after 20–30 years of chronic draining sinus
Clinical clue: change in the character of the discharge (bloody rather than purulent), increase in pain, new mass at the sinus site, rapidly enlarging ulcer with raised/rolled edges
Management: biopsy of suspicious sinus tract → if SCC confirmed → wide excision ± amputation

Why does it happen? Chronic inflammation (from any cause, including chronic osteomyelitis) → persistent elevation of serum amyloid A (SAA) protein (an acute-phase reactant produced by the liver in response to IL-6) → over months to years, SAA is deposited as insoluble amyloid fibrils in organs
Organs affected: kidneys (nephrotic syndrome — most common presentation), liver (hepatomegaly), spleen
Historical significance: This was a major cause of renal failure before the era of effective antibiotics. Now rare in developed countries due to earlier and more effective treatment of osteomyelitis
Still relevant in settings where chronic osteomyelitis persists for years without adequate treatment

Why does it happen? Prolonged immobilisation (splinting/casting during treatment) + periarticular inflammation → soft tissue fibrosis → adhesions around tendons and joint capsule → reduced ROM
Particularly problematic in children who may develop Volkmann's contracture if the infection causes compartment syndrome (forearm) ^[13]
Prevention: early physiotherapy, judicious immobilisation, early weight-bearing when safe

B. Complications of Treatment

Complication	Mechanism
Wound infection / dehiscence	Operating on already infected tissue → high risk of wound breakdown; poor local blood supply (especially tibia)
Non-union / delayed union	Extensive debridement removes bone stock and periosteum; infection itself impairs osteogenesis
Recurrence of infection	Incomplete debridement leaving residual sequestrum or biofilm; inadequate antibiotic duration
Neurovascular injury	Intraoperative damage during debridement near neurovascular structures
Fracture after debridement	Bone weakened by sequestrectomy → pathological fracture; why stabilisation — ORIF, external fixation (Ilizarov) ^[1] is part of the Cierny-Mader Stage III/IV algorithm

When osteomyelitis necessitates amputation, the complications are:

Timing	Complication	Mechanism
Early	Bleeding and haematoma formation	Surgical site haemorrhage
	Wound infection	Operating through potentially contaminated field
	Phantom limb pain	Central and peripheral nerve reorganisation after limb loss; the brain still "maps" the missing limb
	Skin necrosis	Poor perfusion to the stump (especially in patients with PVD/DM)
Late	Stump ulceration	Pressure from prosthesis on poorly vascularised skin
	Stump neuroma	Cut nerve endings form a disorganised tangle of axons (neuroma) at the stump → painful
	Osteomyelitis (of the stump)	Recurrence of infection in the remaining bone — a devastating irony
	Osteophytes formation in underlying bone	New bone spurs at the cut bone edge → irritation of overlying soft tissue → pain and prosthesis fitting problems
	Fixed flexion deformity	If the joint proximal to the amputation is not kept in extension post-operatively, flexor muscles shorten → flexion contracture → cannot fit prosthesis properly
	Difficult mobilisation	Energy expenditure increases dramatically: BKA unilateral = ↑40%; AKA unilateral = ↑100% ^[11]

HK data: radical debridements (amputations and disarticulations) were performed in 46% of 24 patients with severe MSS infections; mortality ranges from 20 to 75% ^[1] — underscoring the devastating consequences of delayed treatment.

Antibiotic	Complication	Why
Prolonged IV access	Line sepsis, thrombophlebitis	Central or peripheral IV lines in situ for weeks → bacterial colonisation; endothelial inflammation
Vancomycin	Nephrotoxicity, ototoxicity, "Red Man syndrome"	Direct tubular toxicity (nephro); vestibular/cochlear hair cell damage (oto); histamine release if infused too fast (Red Man — not a true allergy)
Cloxacillin/Flucloxacillin	Hepatotoxicity (cholestatic), interstitial nephritis	Idiosyncratic reaction; more common in elderly, prolonged use, pre-existing liver disease
Rifampicin	Hepatotoxicity, drug interactions (CYP450 inducer), orange discoloration of body fluids	Potent CYP450 inducer reduces levels of warfarin, OCP, calcineurin inhibitors
Linezolid	Myelosuppression (thrombocytopenia, anaemia), peripheral neuropathy, lactic acidosis, serotonin syndrome	Mitochondrial toxicity with prolonged use; weak MAO-I activity
Aminoglycosides	Nephrotoxicity, ototoxicity	Accumulation in proximal tubular cells and cochlear/vestibular hair cells; requires TDM
Fluoroquinolones	Tendon rupture, C. difficile colitis, QT prolongation	Disruption of collagen synthesis in tendons; disruption of gut microbiome
C. difficile colitis (any prolonged antibiotic)	Pseudomembranous colitis	Antibiotic-induced disruption of normal gut flora → C. difficile overgrowth → toxin production → mucosal damage

C. Complications by Specific Clinical Setting

Epidural abscess → spinal cord compression → paraplegia (surgical emergency) ^[12]
Spinal instability → kyphotic deformity (especially TB: gibbus deformity)
Psoas abscess (especially TB) → palpable inguinal mass, hip flexion posture

Progressive tissue loss → gangrene → amputation ^[3]
Recurrence — extremely high recurrence rate in diabetic patients due to ongoing neuropathy, vascular disease, and difficulty achieving adequate antibiotic levels in ischaemic tissue

Persistent drainage — as illustrated in the lecture slides: 35-year-old diabetic, 3 months prior had had nailing for closed midshaft tibial fracture, now presents with persistent drainage ^[1]
Implant loosening → fracture instability → non-union
Biofilm persistence → chronic relapsing infection → may ultimately require implant removal ± staged reconstruction

High Yield Summary — Complications of Osteomyelitis

Local complications:

Progression to chronic osteomyelitis (sequestrum → involucrum → cloacae → draining sinus) ^[1]^[2]
Septic arthritis — especially when metaphysis is intracapsular (hip in infants/children) ^[2]
Pathological fracture (bone weakened by osteolysis)
Growth disturbance in children (physeal damage → LLD, angular deformity)
AVN (raised intraosseous pressure → vascular compromise) ^[4]
Epidural abscess from vertebral osteomyelitis → spinal cord compression → paraplegia (emergency) ^[12]
Marjolin's ulcer (SCC in chronic draining sinus — after 20–30 years)
Secondary AA amyloidosis (chronic inflammation → SAA deposition → nephrotic syndrome)

Systemic complications:

Sepsis / septicaemia → multi-organ failure
Metastatic infection (endocarditis, septic emboli, multifocal osteomyelitis)

Treatment complications:

Surgical: recurrence, non-union, wound breakdown, fracture after debridement
Amputation: phantom limb pain, stump neuroma, stump osteomyelitis, fixed flexion deformity ^[11]^[13]
Antibiotics: nephrotoxicity (vancomycin, aminoglycosides), hepatotoxicity (flucloxacillin, rifampicin), myelosuppression (linezolid), C. difficile colitis

HK data: 46% amputation rate in severe cases; mortality 20–75% ^[1]

Early recognition and high suspicion are important if life-threatening infections ^[1]

Active Recall - Complications of Osteomyelitis

References

^[1] Lecture slides: GC 237. Musculoskeletal infection [Updated in 2025] (1).pdf (pp. 7, 9, 10, 12, 14, 44, 54) ^[2] Senior notes: maxim.md (sections 566, 567, 572) ^[3] Senior notes: maxim.md (section 550) ^[4] Senior notes: maxim.md (section 522) ^[11] Senior notes: felixlai.md (section 1381) ^[12] Lecture slides: GC 110. Paraplegia Spinal cord compression Transverse myelitis Spinal dysraphism Neuroimaging III Spinal Cord.pdf (p. 23) ^[13] Senior notes: maxim.md (sections 362, 454)