Failure of fracture union most commonly results from inadequate stability/immobilization, avascularity, soft tissue damage or infection.
A fracture gap > 3 mm has been shown to delay union in tibial fractures 12-fold following intramedullary nailing. However, non-union often results from a combination of factors, akin to delayed union (see Table 4.1); these may be broadly classified into fracture instability, poor biological environment and infection.
DIAGNOSIS
Both clinical and radiological assessments are required for the diagnosis of non-union.
Presenting features include pain, abnormal clicking or movement, dysfunction and a possible history of systemic factors such as diabetes mellitus, peripheral vascular disease or smoking. Examination may reveal clinical deformity, limb length discrepancy or gait abnormality. At the fracture site there may be varying degrees of pain and/or abnormal movement, although established pseudarthrosis is often painless and mobile.
Table 4.3 Diaphyseal fracture non-union rates with different treatment modalities
Fracture type Treatment Non-union rate (%)
Closed tibial fracture Non-operative 0–24
Reamed nail 0–4
Unreamed nail 11–27
Plate fixation 0–54
Open tibial fracture Reamed nail 8–36
Unreamed nail 4–48
Plate fixation 0–54
External fixation 6–41
Closed femoral fracture Reamed antegrade nail 0–14
Unreamed antegrade nail 0–39
Reamed retrograde nail 0–8
Unreamed retrograde nail 13–20
Plate fixation 2–7
External fixation 0–12
Closed humeral fracture Non-operative 3–13
Intramedullary nail 0–23
Plate fixation 2–8
Radiographs show a persistent fracture line and features specific to the type of non-union (hypertrophic or atrophic). Images must be obtained in the correct plane of the fracture to avoid giving false reassurance (i.e. oblique radiographs for oblique fractures). Fluoroscopy and stress radiographs can assess stability in all planes. Computed tomography (CT) scanning can be used to confirm non-union if it is not evident on plain radiography.
TREATMENT
The aims of treatment are to restore bone continuity and thus restore functionality of the limb (Table 4.4).
Non-operative treatment
In the absence of pain and other symptoms, a removable splint can be used to provide support at the site of the non-union.
Functional bracing is effective for hypertrophic non-union in particular. Non-invasive
methods to accelerate fracture healing such
as low-intensity pulsed ultrasound (LIPUS), electromagnetic stimulation and shock- wave therapy have shown promising results.
However, despite quoted success rates of >60 per cent, the data are not yet robust enough to warrant routine clinical use.
Operative treatment
Stability and local biology are the two major factors influencing the healing environment;
both must therefore be addressed in all treatment options.
Hypertrophic non-union
Hypertrophic non-union normally occurs against a background of normal biology with adequate local soft tissue and vascular supply.
Stability (or stiffness) is required to facilitate union because instability increases strain (motion) at the fracture site. Perren’s strain theory explains the effect of mechanical factors on the different stages of fracture healing, and the amount of strain dictates the tissue type formed. Each tissue has a different strain tolerance (e.g. lamellar bone 2 per cent, granulation tissue 100 per cent), and bony bridging occurs only if the strain at the fracture site (e.g. after immobilization or fixation) is less than the forming woven bone can tolerate (Table 4.5). High strain levels therefore allow only more strain-tolerant fibrous tissue to form (rather than callus), thus creating a hypertrophic non-union.
Treatment therefore involves alteration of the biomechanical environment by using fixation to create more stable stresses around the fracture. Compression can be achieved by means of intramedullary nailing with dynamic locking or internal fixation (compression or Table 4.4 Treatment options for non-union
Non-operative Operative Functional bracing Bone graft
Autograft (structural and non-structural, vascularized).
Other autograft (bone marrow aspirates, platelet- derived factors).
Allograft (structural and non-structural).
Demineralized bone matrix.
Bone morphogenic proteins.
Calcium-based synthetic substitutes.
Masquelet technique.
Low-intensity pulsed
ultrasound (LIPUS) Exchange nailing Electromagnetic
stimulation
Bone transport
Shock-wave therapy Primary bone shortening and secondary lengthening
Table 4.5 Strain tolerated by different tissues during stages of fracture healing
Tissue type Strain tolerated
Granulation tissue ≤100%
Fibrous connective tissue ≤17%
Fibrocartilage 2–10%
Lamellar bone 2%
bridge plating). External fixation can provide compression while also permitting sufficient strain to allow fibrous tissue to form bone (Fig.
4.3).
In cases of aseptic non-union of femoral fractures, healing rates of 96–100 per cent have been achieved with both internal and external fixation, respectively; similarly successful outcomes are reported at other sites.
• Exchange nailing – Non-unions are common in diaphyseal fractures primarily treated with intramedullary nailing; exchange nailing can be used in these cases. The principle is to remove the existing nail, ream the intramedullary canal by a further 1–2 mm and insert a larger locked intramedullary nail that is appropriately sized. Exchange nailing can also be used in atrophic non-unions, but it may need to be repeated in the tibia in particular. The process primarily stimulates periosteal blood supply with resultant periosteal new bone formation, provides
osteogenic autologous bone graft (reamings) to the fracture and increases the rigidity of fixation. Excellent union rates are reported with exchange nailing:
• 90 per cent following tibial non-union (at average of 10–12 weeks for hypertrophic non-union).
• 70–90 per cent in the femur.
• 40–45 per cent for humeral injuries. The low rate in the humerus may relate to poor vascularity and the high incidence of atrophic non-unions.
Atrophic non-union
Atrophic non-union results from abnormal biology, usually with adequate fracture stability. Further surgical fixation is therefore unlikely to lead to union because of poorly vascularized bone ends and local soft tissue (although some animal and clinical studies have more recently shown that not all atrophic non-unions are inadequately vascularized).
(a) (b)
Figure 4.3. Circular frame distraction treatment for hypertrophic non-union. (a) Anteroposterior radiograph of non-union in the frame used to produce distraction to correct varus deformity with minimal lengthening. (b) Healed fracture.
Initial treatment is directed at altering the biological environment by excision of fibrous tissue and non-viable sclerotic bone ends. The resultant bony defect is managed using bone graft, either inserted directly (Fig. 4.4) or more recently with a combination of induced membranes and autograft (Masquelet technique).
Other options include bone transport (Fig. 4.5) and acute shortening with lengthening (bifocal treatment) (Fig. 4.6).
• Bone graft – Bone graft is used to stimulate osteogenesis by using the properties of osteoconduction and/or osteoinduction (Table 4.6). Osteoconduction involves the differentiation of mesenchymal stem cells into osteoprogenitor cells (graft and host), and osteoinduction helps to bridge the bone defect while providing the necessary
‘scaffolding’ for new bone formation.
Although corticocancellous bone graft is most effective in the management of non- union, there are many other different types:
• Autograft – Bone is transferred from one location to another in the same person.
Autograft may be non-structural or structural, depending on its ability to fill and support bony defects. Examples include the following:
− Cancellous bone is osteogenic and usually non-structural.
− Cortical bone is minimally osteogenic but useful for structural support.
− Vascularized bone uses its own blood supply, which is anastomosed to recipient vessels such as the distal radius (1,2 intercompartmental supraretinacular artery). Combined bone and soft tissue grafts can also be used (e.g.
osteocutaneous from anterior pelvis).
− Bone marrow aspirates are taken from the iliac crest.
− Platelet-derived activators are derived through centrifuged venous blood.
• Allograft – Bone is transferred from one individual (alive or dead) to another of the same species following sterilization to minimize the resultant inflammatory response. Allograft, which can be structural or non-structural, is not as
Table 4.6 Properties of common bone grafts and bone graft substitutes
Immunogenicity Osteogenic Osteoconductive Osteoinductive Structural Vascularized
Autograft
Bone marrow − ++ − + − −
Cancellous − ++ ++ + + −
Cortical − + + + ++ (early) −
Vascularized − ++ +++ + ++ +++
Allograft
Cancellous + − ++ + + +
Cortical + − ++ + ++ ++
Demineralized + − ++ ++ (BMPs) − −
Bone graft substitutes
Calcium phosphates − ++ − + +
BMP, bone morphogenic protein; −, none; +, weak; ++, moderate; +++, strong.
effective as autograft but the two can be mixed together. A common example is a cadaveric femoral head allograft.
• Demineralized bone matrix contains collagen and growth factors and is available as putty, powder or granules.
It is formed following acid extraction of allograft bone and may be less antigenic and more osteoinductive.
• Bone morphogenic proteins (BMPs) – These are multifunctional osteoinductive growth factors. Specifically, BMP-2 and BMP-7 play a key role in osteoblast differentiation. These factors are manufactured using recombinant techniques and are used with a carrier such as allograft or collagen into the site of non-union. The high cost and relative paucity of (albeit encouraging) data have limited widespread use.
• Calcium-based synthetic substitutes – These substitutes, which may be mixed with autograft, are osteoconductive and include calcium triphosphate, calcium sulphate, calcium trisilicate and calcium hydroxyapatite. They are available as granules, chips and putty/paste.
• Masquelet technique – This is a relatively new two-stage technique to reconstruct bone defects. The first stage comprises insertion of a polymethylmethacrylate (PMMA) cement spacer into the defect that induces membrane formation around it. The second involves careful removal of the cement spacer while preserving the surrounding membrane. The bone ends are decorticated and the gap filled with cancellous (and/or cortical strut) autograft surrounded by the membrane. The defect requires stabilization throughout the process (e.g. rigid ring external fixation) until autograft integration and bony union occur.
Bone transport Bone transport techniques are mainly used for managing large bone defects (see Fig. 4.5). This method is based on the principle of tension stress and callotasis, whereby new bone forms in the presence of a gradual increase in tension (distraction osteogenesis), as originally described by Ilizarov in the 1950s. Corticotomy is performed either proximal or distal to the defect; following a latency period of 5–7 days, stable and controlled distraction is undertaken (rate
(a) (b) (c)
Figure 4.4. Excision and shortening treatment with autologous bone grafting for atrophic non-union of the femur.
Radiographs of (a) atrophic non-union;
(b) excision, shortening and bone grafting procedure; and (c) healed fracture.
(a)
Cactus Design and Illustration Ltd
Date: 14.04.2014 Fig No: 4.5g Cat #/Author: K17090 - Dawson-Bowling, Achan, Briggs, Ramachandran Proof Stage: 1
(d)
(e) (b)
Date: 14.04.2014 Fig No: 4.5f Cat #/Author: K17090 - Dawson-Bowling, Achan, Briggs, Ramachandran Proof Stage: 1
(c)
Figure 4.5. Bone defect following excision of a femoral non-union treated with bone transport.
(a) Anteroposterior radiograph of initial non-union following intramedullary nailing; (b) significant bone defect with proximal corticotomy (arrow); (c) and (d) distraction osteogenesis with callotasis (arrow, c) and docking (arrow, d); and (e) healed bone.
of 0.75–1 mm/day, frequency of 0.25 mm 6–8 hourly) using a ring external fixator (e.g. Ilizarov) or monolateral external fixator until it meets and docks with the distal fragment. During this process regenerate bone forms behind the segment and matures into mechanically stable bone. Bone graft may be required at the docking site.
Bifocal treatment Bifocal treatment uses bone transport principles to manage bone defects in a process of ‘compression-distraction’ (see Fig. 4.6). Acute closure of the gap brings
the bone ends together and leads to a leg length discrepancy. Secondary lengthening is undertaken using callotasis, through a corticotomy performed away from the site of non-union. The maximum safe degree of shortening (and therefore lengthening) is approximately 5 cm in the femur and 3 cm in the tibia. This should ideally not exceed 20 per cent of the original bone length because of the risk of neurovascular and soft tissue compromise, with resulting joint instability or stiffness.