Osteomyelitis - Comprehensive Pathology Notes

1. Definition, Etiology, Pathogenesis, Morphology, and Complications

Definition

Etiology

• Staphylococcus aureus - responsible for 80-90% of culture-positive pyogenic osteomyelitis; staphylococcal cell wall proteins bind bone matrix components (e.g., collagen), facilitating adherence
• Neonates - group B Streptococci and E. coli
• Older children - gram-positive organisms, predominantly S. aureus
• Sickle cell disease - Salmonella and gram-negative organisms (areas of bone infarction serve as a bacterial nidus; loss of splenic function impairs immune response)
• Open fractures / surgical sites - mixed bacterial infections
• Diabetic foot - polymicrobial; gram-negative and anaerobic organisms more common
• Note: No organism is identified in approximately 50% of cases

Pathogenesis

Diagram from Bailey & Love's Surgery: Haematogenous spread - bacteria in arterial blood seed the metaphyseal sinusoidal loops, which thrombose and allow bacterial colonisation

1. Bacteraemia seeds the metaphysis - in children, the looped sinusoidal vessels of the metaphysis have slow blood flow and are susceptible to bacterial trapping, especially after microtrauma
2. Bacteria proliferate and trigger an acute neutrophilic inflammatory response
3. Bone and marrow necrosis occurs within the first 48 hours
4. Bacteria and inflammation spread longitudinally and radially through Haversian (osteon) canals toward the periosteum
5. In children, the periosteum is loosely attached to cortex and can be stripped by the inflammatory exudate, forming a subperiosteal abscess - periosteal lifting further cuts off cortical blood supply and worsens necrosis
6. Periosteal rupture creates a soft tissue abscess that may track to the skin as a draining sinus
7. If infection spreads to the epiphysis or joint space, septic/suppurative arthritis results, with destruction of articular cartilage

Morphology

Acute Phase (first 48 hours)

• Bacteria proliferate in marrow
• Neutrophilic infiltrate - the hallmark of acute inflammation
• Necrosis of osteocytes and marrow fat/hematopoietic elements within 48 hours
• Spread through Haversian canals to the periosteum
• Subperiosteal abscess formation
• Pus may decompress through cortical bone and elevator the periosteum

Subacute/Evolving Phase (after first week)

• Chronic inflammatory cells (lymphocytes, plasma cells, macrophages) are recruited
• Cytokines released → stimulate osteoclastic bone resorption, fibrous tissue ingrowth, and deposition of reactive woven bone at the periphery

Chronic Phase

• Sequestrum: the fragment of dead, necrotic bone entrapped within the infected zone. It is devascularised, often yellow-white, surrounded by pus
• Involucrum: a shell of living reactive (subperiosteal) new bone deposited around the devitalised, infected bone segment by the stripped-up periosteum. It creates the radiographic "bone-within-a-bone" appearance
• Cloaca: openings/perforations in the involucrum through which pus and bone fragments drain to the skin surface via a sinus tract
• Marrow fibrosis and chronic inflammatory infiltrate of lymphocytes and plasma cells

Fig. 19.13 from Robbins Basic Pathology: Resected femur with draining osteomyelitis. Yellow arrow = sequestrum (necrotic original cortex); Red arrow = involucrum (subperiosteal shell of viable new bone)

Complications

2. Acute Pyogenic Osteomyelitis - with Sequestrum and Involucrum

Definition

Clinical Presentation (Acute)

• Systemic illness: malaise, fever, chills, leukocytosis
• Intense throbbing pain over the affected bone
• Local warmth, swelling, and erythema
• Infants: often subtle - unexplained fever, irritability, pseudoparalysis of the limb
• Adults: may present with only localised pain; often post-fracture or post-surgical

Preferred Site

• Metaphysis of long bones (distal femur, proximal tibia, proximal humerus most common in children)
• In neonates: both metaphysis and epiphysis
• In adults: vertebral bodies (haematogenous), foot bones (diabetic)

Pathological Sequence in Acute Stage

1. Bacteria seed the metaphyseal sinusoidal loops during a bacteraemia (often precipitated by microtrauma)
2. Neutrophilic response - pus accumulates in the marrow cavity, raising intramedullary pressure
3. Pus dissects through Haversian and Volkmann's canals to reach the periosteum
4. Subperiosteal abscess forms - periosteal elevation further devascularises the cortex
5. Pus may penetrate the periosteum to form a soft tissue abscess, which may then track to the skin as a sinus tract
6. In children: metaphyseal infection can spread to the joint (septic arthritis)
7. In neonates: the growth plate is not a barrier - epiphyseal and joint infection occur readily

Sequestrum and Involucrum

Sequestrum

• Definition: A fragment of dead, necrotic bone that has become separated from the living bone
• Mechanism: Formed as the devascularised (avascular) cortical bone undergoes necrosis; osteocytes die, the lacunae become empty, and the bone is incapable of repair
• Appearance: Dense, whitish-yellow bone fragment surrounded by pus and granulation tissue
• Significance: Acts as a persistent nidus of infection - antibiotics cannot penetrate avascular bone; this is the main reason acute osteomyelitis becomes chronic
• Histology: Necrotic bone with empty osteocyte lacunae, surrounded by neutrophils

Involucrum

• Definition: A sheath of new reactive bone formed by the elevated periosteum around the sequestrum
• Mechanism: Periosteal stripping is a potent stimulus for osteoblastic new bone formation. The stripped periosteum deposits a cuff of woven bone (the involucrum) around the infected, necrotic segment
• Appearance: Thick, irregular shell of new bone encasing the sequestrum
• Cloaca: Perforations in the involucrum through which pus and sequestrum fragments are extruded via sinus tracts
• Significance: The involucrum represents the body's attempt to wall off infection; together with the sequestrum it creates the classic radiographic "bone-within-a-bone" appearance

Robbins, Cotran & Kumar PBD Fig. 26.16: Resected femur - the drainage tract in the subperiosteal shell of viable new bone (involucrum) reveals the inner native necrotic cortex (sequestrum)

Investigations

• Blood: Leucocytosis, raised ESR and CRP; blood cultures (positive in ~50%)
• Plain X-ray: Often normal in first 10-14 days; later shows lytic destruction, periosteal reaction, reactive sclerosis
• MRI: Most sensitive and specific; detects marrow oedema early; imaging of choice
• CT: Excellent for defining sequestrum, involucrum, and cortical destruction in established disease
• Bone scan (Tc-99m): Sensitive; useful when MRI is unavailable
• Biopsy + culture: Gold standard for identifying the organism

3. Chronic Osteomyelitis - Clinicopathological Features

Definition

Predisposing Factors for Chronicity

• Delayed diagnosis or inadequate initial treatment
• Extensive bone necrosis (large sequestrum)
• Poor host immunity (diabetes, malnutrition, sickle cell disease, immunosuppression)
• Inadequate surgical debridement
• Antibiotic-resistant organisms (e.g., MRSA with Panton-Valentine leukocidin gene)

Clinicopathological Features

Symptoms and Signs

Clinical Course

• Typically punctuated by episodes of acute flare after periods of relative quiescence, sometimes after years of dormancy
• Acute exacerbations triggered by: immunosuppression, trauma, or minor illness

Pathological Features

• Sequestrum: Devitalised bone, may be large or fragmented; surrounded by pus
• Involucrum: Thick shell of new woven/lamellar bone encasing the sequestrum
• Cloaca: Multiple holes in the involucrum
• Sinus tract(s): Chronic, epithelium-lined tracts draining to the skin surface
• Surrounding soft tissue scarring and fibrosis

• Marrow space replaced by fibrosis
• Chronic inflammatory infiltrate: lymphocytes, plasma cells, macrophages
• Necrotic bone (sequestrum) with empty osteocyte lacunae
• Reactive woven bone formation (involucrum)
• Granulation tissue
• Absence of the neutrophilic infiltrate that dominates the acute phase
• Occasionally, Brodie's abscess: a well-circumscribed subacute abscess in the metaphysis, surrounded by sclerotic bone - a contained form seen most often with S. aureus in children

Radiological Features

• Dense, sclerotic bone surrounding the sequestrum
• Cortical thickening (periosteal new bone = involucrum)
• Intraosseous cavity containing sequestrum ("bone within bone")
• Draining sinus tract may be visible on fistulography
• MRI: low signal on T1, high on T2/STIR (oedema and active infection); enhancement with contrast
• CT: superior for quantifying extent of sequestrum

Complications of Chronic Osteomyelitis

1. Pathological fracture - cortical erosion weakens the bone
2. Squamous cell carcinoma (Marjolin's ulcer) - malignant transformation of the sinus tract epithelium after decades of chronic irritation
3. Secondary (AA) amyloidosis - longstanding chronic infection drives sustained amyloid A protein deposition in kidney, liver, spleen; causes nephrotic syndrome and renal failure
4. Sepsis / bacteraemia - haematogenous seeding from the bone focus
5. Endocarditis - seeding of heart valves
6. Sarcoma - very rare osteosarcoma or fibrosarcoma in the infected bone
7. Joint destruction / ankylosis - spread to adjacent joint
8. Growth disturbance in children - physeal damage causing shortening or angular deformity

Quick Reference Summary

• Robbins, Cotran & Kumar Pathologic Basis of Disease (10th ed.), Chapter 26
• Robbins & Kumar Basic Pathology (11th ed.), Chapter 19
• Bailey & Love's Short Practice of Surgery (28th ed.), Chapter 44