Fracture Healing and Complications — Stages, Nonunion, AVN and Fat Embolism

Most fractures heal by secondary (indirect) bone healing, which passes through overlapping stages: haematoma formation → granulation tissue → callus formation → remodelling. Bleeding from torn vessels first forms a clot at the fracture site. Inflammatory cells, platelets and macrophages release cytokines and growth factors — TNF-alpha, bone morphogenetic proteins (BMPs), PDGF, TGF-beta and VEGF — which recruit mesenchymal stem cells and new vessels.

Granulation tissue, made by fibroblasts and inflammatory cells, forms a soft scaffold. Mesenchymal cells differentiate under BMP influence into chondrocytes, producing a cartilaginous soft callus that undergoes endochondral ossification, while osteoprogenitor cells under the periosteum lay down woven bone. The resulting hard callus is then remodelled by coupled osteoclast resorption and osteoblast formation into lamellar bone, guided by mechanical load (Wolff's law) and the piezoelectric effect.

The type of healing is set by mechanical stability, expressed as interfragmentary strain. According to Perren's strain theory, strain below 2% permits primary bone healing, strain between 2% and 10% produces secondary bone healing, and strain above 10% leads to delayed union or nonunion.

Primary (direct) healing follows anatomical reduction with absolute stability — for example compression plating or lag screws. There is no visible callus: bone heals by intramembranous ossification and Haversian remodelling, with cutting cones crossing the fracture line. Secondary (indirect) healing follows relative stability — casts, intramedullary nails, bridging plates and external fixators — and proceeds through callus and endochondral ossification. Callus on an X-ray is therefore expected with a nail but is a warning sign after rigid compression plating.

Healing needs blood supply, stability and healthy biology. Anything that removes one of these can slow union. Smoking impairs healing because nicotine inhibits angiogenesis, producing weak callus. Diabetes mellitus reduces callus cellularity and delays endochondral ossification. Deficient angiogenesis of any cause can lead to delayed union or nonunion.

• Local: high-energy injury with soft-tissue stripping, open fracture, infection, bone loss, interposed soft tissue, poor reduction or fixation.
• Vascular watershed bones: scaphoid, talus and femoral neck.
• Systemic: smoking, diabetes, peripheral vascular disease, vitamin D deficiency, renal insufficiency, poor nutrition.
• Drugs: corticosteroids, NSAIDs and opiates are listed among biological risk factors for poor healing.

Adjuncts used when healing is slow include bone grafts (autograft from the patient or allograft from a donor), BMPs, and bone stimulators (electrical, electromagnetic and low-intensity pulsed ultrasound). The evidence for stimulators remains equivocal, although LIPUS has reported healing rates approaching 80% in delayed unions and nonunions.

Delayed union means the fracture has not united in the time expected for that bone and injury, but healing has not stopped. Nonunion means healing has ceased. The most widely accepted definition, from the US FDA, is a fracture that persists for at least 9 months without signs of healing for 3 consecutive months. Clinically there is pain and movement at the fracture site; radiographs show no bridging bone.

For infected nonunion, inflammatory markers and a bone scan are obtained and intraoperative cultures are the gold standard for guiding antibiotics. A two-stage protocol is standard: remove infected hardware, debride and stabilise (antibiotic beads, cement spacers, external fixation, flap cover), then perform definitive fixation and bone grafting once infection has cleared. For a delayed union, less invasive measures such as dynamisation of a nail or external stimulation can be tried first.

Malunion is union of the fracture in an abnormal position — with angulation, rotation or shortening — that may cause deformity, altered joint loading and later arthritis. Displacement and comminution increase the risk of delayed union, nonunion and malunion, as seen in talar neck fractures, and varus malunion is the commonly reported deformity when medial comminution of the talar neck is missed or poorly reduced.

Classic examination examples: a Colles fracture whose reduction does not hold can unite with the dorsally tilted dinner-fork deformity, and medial column collapse in a supracondylar fracture of the humerus leads to cubitus varus. Some malunions still give satisfactory long-term function, so correction is guided by symptoms; see wrist fractures for distal radius patterns.

Avascular necrosis (osteonecrosis) follows interruption of the blood supply to a segment of bone. The commonest sites overall are the femoral head, knee, talus and humeral head. Bones with retrograde or watershed blood supply — where vessels enter distally and run backwards to the proximal fragment — are the ones at risk after fracture.

After a talar neck fracture, a subchondral lucency (Hawkins sign) on radiographs at 6 to 8 weeks indicates revascularisation; its absence suggests inadequate revascularisation and a higher risk of AVN. Non-traumatic risk factors for osteonecrosis include corticosteroids, alcohol misuse, sickle cell disease, autoimmune disease such as lupus, smoking, chemotherapy and radiotherapy.

Not every AVN follows a fracture. Traumatic causes are femoral neck fracture and hip dislocation (extraosseous arterial interruption) and displaced fractures. Non-traumatic causes include prolonged high-dose corticosteroids (fatty marrow infiltration, osteocyte apoptosis), alcohol misuse, sickle cell disease (intravascular occlusion), Gaucher disease (marrow infiltration), thrombophilias, radiotherapy and chemotherapy, smoking, hyperlipidaemia and lupus. The cause is unknown (idiopathic) in about 25%; Kienbock disease (lunate) and Preiser disease (scaphoid) are examples with an often inexplicable cause.

Fat embolism syndrome (FES) is a potentially life-threatening complication most often linked with long-bone (femur, tibia) and pelvic fractures, and with intramedullary nailing. It typically appears 24 to 72 hours after injury, with an average onset of about 48 hours — this latent interval after the injury is a classic examination clue.

The Gurd and Wilson criteria need 2 major criteria, or 1 major plus 4 minor. Major: petechial rash, respiratory insufficiency and cerebral involvement not explained by head injury. Minor: fever above 38.5 °C, tachycardia above 110/min, retinal changes, jaundice, renal signs, anaemia, thrombocytopenia, raised ESR and fat macroglobulinaemia. Arterial blood gas shows hypoxaemia.

There is no specific treatment: management is supportive, with oxygen and ventilatory support as required. Early open reduction and internal fixation of long-bone fractures is recommended, and the incidence of FES has fallen since early fixation became standard care.

Acute compartment syndrome usually follows a long-bone fracture: tibial fractures are the most common cause, followed by distal radius fractures, and the anterior compartment of the leg is the commonest site. In children, supracondylar fractures of the humerus and forearm fractures are important causes. Rising pressure inside a closed fascial compartment cuts off capillary perfusion to muscle and nerve.

The earliest and most reliable feature is pain out of proportion to the injury, and early on pain may be present only on passive stretching of the muscles in the compartment. The classic five Ps — pain, pallor, paraesthesia, paralysis and pulselessness — are, apart from paraesthesia, late findings; a palpable pulse does not exclude the diagnosis.

An intracompartmental pressure of 30 mmHg or more, or a delta pressure (diastolic BP minus compartment pressure) of 30 mmHg or less, supports the diagnosis and the need for fasciotomy. The ideal window is within 6 hours of injury, which gives almost full recovery of limb function; at 12 hours only about two-thirds regain normal function, and fasciotomy is not recommended after 36 hours. Untreated ischaemia leaves fibrotic muscle — Volkmann's ischaemic contracture in the forearm.