Nonunion Management

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Nonunion is defined as a fracture that will not heal without intervention (typically no radiographic progress for 3 months and greater than 9 months from injury). The Weber-Cech classification distinguishes hypertrophic (elephant foot/horse hoof with abundant callus - mechanical failure requiring stability) from atrophic (no callus, avascular ends - biological failure requiring bone graft and stability). All nonunions must have infection excluded (CRP, ESR, aspirate/biopsy for culture). The Diamond Concept guides treatment: optimise cells (osteogenic cells), scaffolds (bone graft), growth factors (BMP), and mechanical stability. Key: hypertrophic just needs compression plating; atrophic needs resection of avascular ends plus biological augmentation.

Nonunion is defined as a fracture that will not heal without intervention. Often defined as no radiographic progress for 3 consecutive months and at least 9 months from injury.

Weber-Cech Classification

Viable (Vascular) Nonunion:

• Hypertrophic (Elephant foot): Abundant callus, very vascular. Mechanical failure.
• Slightly Hypertrophic (Horse hoof): Less callus but some biological activity.

Non-viable (Avascular) Nonunion:

• Oligotrophic: Minimal callus, bone ends present but inactive.
• Atrophic: No callus, avascular ends. May be comminuted or with bone loss.

Normal Fracture Healing Process

Normal fracture healing proceeds through overlapping phases:

1. Inflammation (Days 1-7): Hematoma formation, inflammatory cells, cytokines (IL-1, IL-6, TNF-α)
2. Soft callus (Weeks 1-4): Chondrogenesis, fibrous callus formation
3. Hard callus (Weeks 4-12): Woven bone replaces cartilage (endochondral ossification)
4. Remodeling (Months to years): Woven bone replaced by lamellar bone, cortical restoration

Why Nonunion Develops

Nonunion occurs when the normal healing cascade is disrupted by mechanical or biological factors:

Mechanical Factors (Hypertrophic Nonunion):

• Excessive motion at fracture site prevents bridging
• Inadequate fixation (undersized nail, loose screws, plate failure)
• Distraction (gap greater than 2mm impairs bridging)
• Biology is intact (abundant callus visible), but instability prevents consolidation

Biological Factors (Atrophic Nonunion):

• Vascular disruption: Severe soft tissue injury (Gustilo IIIB/C), stripping of periosteum during surgery
• Avascular bone: Scaphoid waist, femoral neck (intracapsular), talus body
• Infection: Low-grade biofilm infection suppresses osteoblast function
• Metabolic: Diabetes, smoking (nicotine vasoconstriction), malnutrition, Vitamin D deficiency
• Medications: NSAIDs (inhibit COX-2 needed for bone healing), corticosteroids (impair osteoblast function)

The Diamond Concept

Giannoudis et al (2007) proposed the "Diamond Concept" - healing requires optimization of all four elements:

1. Osteogenic cells (MSCs, osteoprogenitor cells from periosteum, bone marrow, circulation)
2. Osteoconductive scaffold (bone graft matrix, collagen, HA/TCP ceramics)
3. Osteoinductive signals (BMPs, PDGF, TGF-β, VEGF)
4. Mechanical stability (absolute or relative depending on healing mechanism)

Fifth element (added later): Vascularity - adequate blood supply for oxygen, nutrients, cell delivery

Atrophic nonunion fails on biology (elements 1-3, 5). Hypertrophic nonunion fails on mechanics (element 4).

Infection and Nonunion

Biofilm formation:

• Bacteria (especially Staphylococcus epidermidis, Propionibacterium acnes) form biofilm on implants/bone
• Biofilm protects bacteria from antibiotics and immune system
• Bacterial toxins and inflammatory cytokines inhibit osteoblast function
• Result: Infected nonunion - will not heal without infection eradication

Clinical clue: Any nonunion with persistent pain, elevated CRP/ESR, or sinus drainage should be cultured.

History

Patient presents months to years after initial fracture with:

Pain:

• Persistent pain at fracture site despite "adequate" healing time
• Pain with weight-bearing or activity (mechanical pain suggests instability)
• Constant pain or night pain (suggests infection or severe instability)

Functional Impairment:

• Unable to return to work or activities of daily living
• Ongoing use of walking aids (crutches, walker)
• Reduced range of motion of adjacent joints

Timeline:

• Typically greater than 9 months from injury
• No radiographic progression over 3 consecutive months (FDA definition)
• History of previous failed treatments (may have had bone grafting, revision fixation already)

Risk Factors to Elicit:

• Smoking (2-3x higher nonunion risk - dose dependent)
• NSAIDs (particularly high-dose, prolonged use post-fracture)
• Diabetes mellitus (especially if poorly controlled, HbA1c greater than 8%)
• Malnutrition (low albumin, low Vitamin D)
• Osteoporosis or metabolic bone disease
• Corticosteroid use (chronic, greater than 7.5mg prednisolone daily)
• Severe soft tissue injury at time of original fracture (Gustilo III open fracture)

Examination

Inspection:

• Muscle atrophy of limb (chronic disuse)
• Scars from previous surgeries
• Sinus tract (pathognomonic for infection if present)
• Swelling, erythema (infection)
• Malalignment (varus/valgus deformity, rotational)

Palpation:

• Tenderness at nonunion site
• Palpable gap or instability (if implants failed)
• Warmth (infection)

Movement:

• Abnormal motion at fracture site (should be stable if healed)
• Pain with stress (axial loading, bending, rotation)
• Adjacent joint stiffness (compensatory, prolonged immobilization)

Neurovascular Exam:

• Check for nerve injury from previous surgery or chronic hardware irritation
• Assess vascular status (chronic injury may have vascular compromise)

Red Flags for Infection

• Draining sinus
• Persistent pain despite apparently stable fixation
• Multiple failed surgeries without union
• Elevated inflammatory markers (CRP, ESR) at presentation
• Previous open fracture (Gustilo II/III)

Imaging

Plain Radiographs:

• Orthogonal views (AP and lateral minimum)
• Look for:
  • Callus formation (hypertrophic vs atrophic vs oligotrophic)
  • Fracture line visibility (persistent gap, sclerosis of bone ends)
  • Hardware position (loose screws - lucency around threads, broken plate/screws, nail backing out)
  • Alignment (varus/valgus, angulation, rotation, shortening)
  • Bone stock (comminution, bone loss, osteopenia)

CT Scan:

• Best for assessing bone healing (more sensitive than X-ray for cortical bridging)
• 3D reconstruction helps surgical planning (visualize deformity, bone stock, implant position)
• Identify sequestrum or bone loss in infected cases

MRI:

• Assess for infection (bone marrow edema, fluid collections, sinus tracts, soft tissue abscess)
• Evaluate vascularity of bone ends (signal characteristics)
• Less useful for bony detail than CT

Nuclear Medicine:

• Bone scan (Tc-99m MDP): High sensitivity but low specificity (increased uptake at nonunion regardless of infection)
• White cell scan (In-111 WBC) or FDG-PET: More specific for infection
• Not routinely needed - reserve for difficult cases where infection suspected but cultures negative

Laboratory Investigations

Exclude Infection (Essential):

• CRP (C-reactive protein): Elevated suggests infection (though may be mildly elevated in chronic nonunion without infection)
• ESR (erythrocyte sedimentation rate): Less specific, but persistently elevated concerning
• WBC count: Usually normal in chronic low-grade infection
• Tissue culture: Gold standard
  • CT-guided biopsy or aspiration of nonunion site
  • Minimum 5 tissue specimens (not swabs!)
  • Prolonged culture (14 days) to catch slow-growing organisms (Propionibacterium, Cutibacterium)

Assess Metabolic/Nutritional Status:

• Vitamin D (25-OH Vitamin D): Target greater than 75 nmol/L for optimal bone healing
• Calcium, phosphate, alkaline phosphatase, PTH: Screen for metabolic bone disease
• Albumin, pre-albumin: Markers of nutritional status (low albumin = poor healing)
• HbA1c: If diabetic, target less than 7% for healing
• Thyroid function (TSH, free T4): Hyperthyroidism impairs healing

Specialized Tests (If Indicated):

• DEXA scan: Assess bone mineral density (osteoporosis)
• Bone turnover markers: CTX (resorption), P1NP (formation) - research use
• Genetic testing: Rare cases (osteogenesis imperfecta, hypophosphatasia)

Exclude Infection

Essential in all nonunions.

• Bloods: CRP, ESR, WCC
• Aspiration/biopsy: Culture (prolonged incubation for low-grade organisms)
• Imaging: MRI may show sequestrum, fluid collections

If infected nonunion: Treatment is different (debridement, antibiotic course, then reconstruction).

Address Modifiable Factors

• Smoking cessation (2x higher nonunion risk)
• Optimize nutrition (protein, vitamins)
• Control diabetes (HbA1c)
• Avoid NSAIDs (may impair healing)

Australian Epidemiology and Practice

Nonunion Epidemiology in Australia:

• Tibial shaft fractures have the highest nonunion rate (approximately 5-10%) among long bones
• Australian trauma registries track outcomes including nonunion rates following major trauma
• Indigenous Australians and remote populations may face delayed presentation contributing to higher rates of established nonunion
• Smoking rates remain a significant modifiable risk factor in the Australian population

RACS Orthopaedic Training Relevance:

• Nonunion management is a core FRACS Orthopaedic Surgery examination topic
• Viva scenarios commonly test understanding of Weber-Cech classification, treatment principles for hypertrophic versus atrophic nonunion, and the Diamond Concept
• Key exam focus: Distinguishing mechanical from biological failure, role of infection workup, and indications for Masquelet technique versus bone transport
• Examiners expect knowledge of contemporary evidence including exchange nailing outcomes and bone graft options

PBS (Pharmaceutical Benefits Scheme) Considerations:

• rhBMP-2 (Infuse) is available through Special Access Scheme for specific nonunion indications
• Antibiotic cement spacers (gentamicin-loaded PMMA) are standard of care for infected nonunion staged treatment
• Bisphosphonates should typically be withheld during nonunion treatment to avoid impairment of bone remodeling

eTG (Therapeutic Guidelines) Recommendations:

• Empiric antibiotic selection for infected nonunion follows eTG guidelines for osteomyelitis
• Vancomycin plus piperacillin-tazobactam or meropenem for severe cases pending culture results
• Oral step-down therapy guided by culture and sensitivity results
• Minimum 6 weeks IV antibiotic therapy for infected nonunion before reconstruction

Australian Bone Graft Options:

• Iliac crest autograft remains gold standard for biological augmentation
• RIA (Reamer-Irrigator-Aspirator) graft increasingly used at major Australian trauma centres for large volume autograft harvest
• Allograft bone available through Australian bone banks (Australian Tissue Bank, Symbion)
• Synthetic bone graft substitutes available including tricalcium phosphate and calcium sulphate preparations

Major Trauma Centre Management:

• Complex nonunions with significant bone loss are typically referred to major trauma centres with limb reconstruction expertise
• Multidisciplinary approach involving orthopaedic trauma surgeons, plastic surgeons, infectious diseases specialists, and rehabilitation physicians
• External fixator application and bone transport techniques performed at specialised centres