Fracture Nonunion

Fracture nonunion is failure of a fracture to heal, with no progression toward union on serial radiographs and a persistent fracture line, usually defined as no healing at 9 months after injury or no radiographic progress over 3 consecutive months. A fracture that has not united but is still healing is delayed union.

Nonunion complicates 5 to 10% of all fractures, and more often involves the tibia, femoral shaft, scaphoid, clavicle, humerus, femoral neck, fifth metatarsal base and ulna. Risk factors are smoking, diabetes, malnutrition, vitamin D deficiency, NSAID and corticosteroid use, open fractures, infection, bone loss, soft tissue stripping, inadequate fixation (excess movement or excess gap), distraction, and fracture sites with a poor blood supply.

The Weber and Cech classification separates hypertrophic nonunion (good blood supply, abundant callus, inadequate stability: elephant foot or horse hoof), oligotrophic (viable but little callus), and atrophic nonunion (no callus, poor biology, bone ends tapered). Other types are infected nonunion and synovial pseudarthrosis (a fluid filled false joint). Complications are chronic pain, deformity, implant failure, limb shortening, joint stiffness, infection, muscle atrophy and disability.

Pathophysiology.

Union needs mechanical stability, adequate biology (osteogenic cells, osteoconductive scaffold and osteoinductive signals) and blood supply. Hypertrophic nonunion is a mechanical failure: movement at the fracture site produces cartilage and fibrous tissue instead of bone. Atrophic nonunion is biological failure from devascularisation, bone loss, infection or systemic factors.

The diamond concept summarises the necessary elements: osteogenic cells, growth factors, osteoconductive matrix and mechanical stability, with the host environment as the framework.

Persistent pain at the fracture site, especially on loading, movement at the fracture (palpable or visible), deformity, swelling, limb shortening, and implant loosening or breakage. A draining sinus, erythema, warmth or fever suggests infection. Look for risk factors: smoking, diabetes, nutrition, medication (NSAIDs, steroids, anticoagulants, bisphosphonates), alcohol and previous surgery.

Examine alignment, rotation, leg length, range of motion of adjacent joints, neurovascular state, skin and scars, and signs of infection. Check the opposite limb for comparison.

• Radiographs in two planes at regular intervals; the fracture line is visible without bridging callus. Hypertrophic nonunion shows flared callus, atrophic nonunion shows tapered, sclerotic ends. The Radiographic Union Score for Tibia (RUST) quantifies cortical bridging.
• CT with multiplanar and 3D reconstruction is the most accurate method to confirm nonunion and measure bridging, bone loss, gaps and implant position.
• Blood tests: full blood count, C-reactive protein, erythrocyte sedimentation rate, calcium, phosphate, 25-hydroxyvitamin D, parathyroid hormone, thyroid stimulating hormone, HbA1c, albumin, testosterone and cortisol where indicated.
• Exclude infection: white cell count, inflammatory markers, MRI, nuclear imaging, and intraoperative cultures (at least 5 deep tissue samples) and histology.
• Bone scan or MRI shows vascularity; plain films are enough for most.

Differential diagnosis.

• Delayed union and infected nonunion.
• Pathological fracture and stress fracture.
• Malunion with pain and avascular necrosis.
• Synovial pseudarthrosis and Charcot arthropathy.

Correct the host factors.

• Stop smoking (all nicotine products), treat diabetes (HbA1c under 8% or 64 mmol/mol), optimise nutrition, and correct vitamin D deficiency, hypocalcaemia and endocrine causes.
• Stop NSAIDs, systemic corticosteroids, and, where possible, other drugs that impair healing.
• Colecalciferol 50 000 IU orally once weekly for 6 to 8 weeks, then 800 to 2000 IU daily (maximum 4000 IU daily without monitoring). Avoid with hypercalcaemia.
• Dietary calcium to a total of 1000 to 1200 mg daily with the vitamin D; check 25-hydroxyvitamin D and calcium at 8 to 12 weeks.

Hypertrophic nonunion (stability problem). Revise the fixation to increase stability: exchange nailing with a larger reamed nail for the femur and tibia, dynamic or static locking, additional plating (augmentation), or compression plating. Bone graft is usually not needed.

Atrophic or oligotrophic nonunion (biology problem).

• Debride the fibrous tissue, open the medullary canal and decorticate, restore bone contact, and fix rigidly.
• Autologous iliac crest bone graft is the reference method for bone grafting (reamer-irrigator-aspirator from the femur is an alternative). Large defects over 4 to 6 cm: Masquelet induced membrane technique, vascularised fibular graft, or bone transport with a ring fixator.
• Recombinant human bone morphogenetic protein 2 is approved for open tibial fractures and is used off label with lasting evidence of benefit in nonunion; use with caution because of heterotopic bone and swelling.
• Low intensity pulsed ultrasound and electrical stimulation are adjuncts with limited evidence.
• Teriparatide 20 micrograms subcutaneously once daily for up to 24 months (off label for nonunion; avoid with Paget disease, prior skeletal radiotherapy, bone metastases, hypercalcaemia or pregnancy; check calcium) is used in selected patients, with limited evidence.

Infected nonunion. Staged surgical and antibiotic treatment by a bone infection service is needed.

Elderly or unfit patients. Non-operative options are bracing, ultrasound, and accepting a stable fibrous union.

Operative antibiotic prophylaxis. Cefazolin 2 g intravenously (3 g when weight is 120 kg or over) within 60 minutes before incision as a single dose (repeat after 4 hours or blood loss over 1500 mL).

With severe penicillin allergy, use vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose, with levels and creatinine checked in prolonged cases. Withhold prophylactic antibiotics until deep samples are taken when infection is suspected.

Thromboprophylaxis. Enoxaparin 40 mg subcutaneously once daily, started 6 to 12 hours after surgery and continued for 10 to 14 days for upper limb and tibial surgery, and 28 to 35 days for femoral surgery or when mobility is reduced.

Dose adjustments: 20 mg once daily at creatinine clearance under 30 mL/min; adjust by anti-Xa level in obesity and renal impairment. Check the platelet count on days 5 to 14 for heparin induced thrombocytopenia. Use mechanical prophylaxis until then.

Analgesia.

• Paracetamol 1 g orally every 6 hours as needed for up to 5 to 7 days (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• Oral morphine 5 to 10 mg every 4 hours as needed for severe pain for up to 3 days (start 2.5 to 5 mg with age over 75 or eGFR under 30 mL/min/1.73 m2; avoid exceeding 60 mg in 24 hours without senior review). Monitor sedation and respiration and prescribe a laxative.
• Avoid NSAIDs while union is awaited.

Monitoring. Radiographs at 6 weeks, 3 months, 6 months, 9 months and 12 months after surgery, with CT when union is unclear. Wound, implant position, alignment and weight bearing at each visit. Calcium and 25-hydroxyvitamin D at 3 months. Pain and function with a validated score.

Referral and escalation. Refer every nonunion to orthopaedics (or a limb reconstruction or trauma centre for complex cases). Urgent referral for implant failure, infection, nerve injury or an open wound.

Special groups.

• Smokers: nonunion rates are 2 to 3 times higher; cessation support is part of treatment.
• Diabetes: poor control delays union; optimise before elective surgery.
• Children: nonunion is rare, apart from congenital pseudarthrosis of the tibia and lateral humeral condyle.
• Kidney impairment: avoid NSAIDs, reduce morphine doses, and adjust vitamin D and calcium.