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Non-union after plate fixation
S78 Injury, Int. J. Care Injured 49S1 (2018) S78–S82 Volume 49 Supplement 1 June 2018 ISSN 0020-1383
Contents lists available at ScienceDirect
Injury Plating of Fractures: current treatments and complications Guest Editors: Peter Augat and Sune Larsson
j o u r n a l h o m e p a g e : w w w. e l s e v i e r . c o m / l o c a t e / i n j u r y
Non-union after plate fixation A. Hamish R.W. Simpsona,*, S.T. Jerry Tsanga a
Department of Trauma and Orthopaedics, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK
K E Y W O R D S
A B S T R A C T
Non-union Revision surgery Fracture healing
Approximately a third of patients presenting with long-bone non-union have undergone plate fixation as their primary procedure. In the assessment of a potential fracture non-union it is critical to understand the plating technique that the surgeon was intending to achieve at the primary procedure, i.e. whether it was direct or indirect fracture repair. The distinction between delayed union and non-union is a diagnostic dilemma especially in plated fractures, healing by primary bone repair. The distinction is important as nonunions are not necessarily part of the same spectrum as delayed unions. The etiology of a fracture non-union is usually multifactorial and the factors can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. Infection is present in ~40% of fracture non-unions, often after open fractures or impaired wound healing, but in 5% of all non-unions infection is present without any clinical or serological suspicion. Methods to improve the sensitivity of investigation in the search of infection include the use of; sonication of implants, direct inoculation of theatre specimens into broth, and histological examination of non-union site tissue. Awareness should be given to the potential anti-osteogenic effect of bisphosphonates (in primary fracture repair) and certain classes of antibiotics. Early cases of delayed/ non-union with sufficient mechanical stability and biologically active bone can be managed by stimulation of fracture healing. Late presenting non-union typically requires revision of the fixation construct and stimulation of the callus to induce fracture union. © 2018 Elsevier Ltd. All rights reserved.
Introduction
biological or bridge plating is indicated for fixation of comminuted diaphyseal fractures to minimise soft tissue stripping and used as “an internal external-fixator” to induce secondary bone healing [6]. The key to these internal fixators is the locking mechanism of the screw in the implant, which provides angular stability [7].
Fracture non-union is a rare but clinically challenging condition. A population-based analysis found an overall risk of non-union per facture to be 1.9%, rising to 9% in the peak age group of 25–44 years [1]. Approximately a third of patients presenting with long-bone non-union have undergone plate fixation as their primary procedure [2]. In the assessment of a potential fracture non-union it is critical to understand the plating technique that the surgeon was intending to achieve at the primary procedure [2] (i.e. rigid fixation and primary bone healing or biological fixation and secondary bone healing). Primary plate fixation can be achieved using a number of different techniques, depending on the fracture location, morphology, and indication for surgery [3]. The rigid fixation techniques include: 1) tension band plating; 2) Buttress or antiglide, e.g. for AO B-type fractures [4]; 3) neutralisation plates, e.g. for fixation of rotational fractures of the fibula [5]; and 4) compression plating. All of these rigid plating and primary bone healing techniques usually require a certain degree of soft tissue stripping which can have a major bearing on the treatment if the fractures becomes a non-union. In contrast,
* Corresponding author at: Department of Trauma and Orthopaedics, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SA, UK E-mail address: [email protected] (H. Simpson).. 0020-1383/© 2018 Elsevier Ltd. All rights reserved.
Diagnostic dilemma The distinction between delayed union and non-union is a diagnostic dilemma [8], especially after a fracture has been plated. Radiographic techniques are commonly used to infer biological activity at the fracture site and indicate if there is fracture union or non-union. The radiographic grading systems include the Weber and Cech system [9] and the Callus Index [10]. More recently classifications such as the RUST scale have been described and validated for intramedullary fixation of tibia [11,12]. All of these classifications have in common, the detection of callus on plain radiographs as the key diagnostic feature. However, callus formation is not seen in during primary bone healing, i.e. rigid plating and even with ‘biological’ plating, as, unfortunately, plates often obscure both periosteal and endosteal callus. Clinical assessment of mobility at the fracture union has also been described as a surrogate of healing potential [13] but is not useful for determining the progression of healing of a plated fracture. As a consequence of the lack of a robust diagnostic technique, there are many definitions for fracture non-union, which include:
A. Hamish et al. / Injury, Int. J. Care Injured 49S1 (2018) S78–S82
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1. Fracture not healed in the expected time with no progression on plain radiographs, 2. Cessation of fracture healing process 3. Not healed within nine months 4. Need for additional procedures to achieve union. The first three of these criteria rely on radiographic features, such as bridging callus [12] to determine if fracture healing is progressing. Yet, as mentioned above, plated fractures undergoing direct bone healing, often do not have any visible callus. Thus, in plated fractures, the requirement for further surgery (e.g. re-fixation or bone grafting) has been used as a diagnostic criterion for nonunion. However, this can be erroneous, as failure to hold a fracture to union depends on: 1) the fatigue strength of the implant (which is dependent on geometry and type of material of the plate); 2) the rate of healing of the fracture; and 3) the amount of load (both magnitude and number of cycles) taken by the implant and bone fragments, which depends on the technique of fracture fixation. The amount of load on a plate has been measured using implantable telemetric devices fixed onto plates [14] and this may be a method for detecting failure of the fracture repair process. If the fracture has progressed to non-union, the plate will fail eventually, and additional procedures will be needed. If, however the fracture is healing slowly (i.e. a delayed union), the plate may fail before union and would therefore be classified as a non-union even though the healing processed has not ceased (Fig. 1). This would be more likely with a delayed union in a heavy individual with a relatively small plate. From the patient’s perspective, further treatment is needed in both the ‘true’ non-union and the delayed union where the plate has failed, but as the repair process has ceased in the established non-union the patient may benefit from additional stimulation of the fracture. Etiology The etiology of a fracture non-union is usually multifactorial, which can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. It has been shown that a high percentage of fracture non-unions have more than one cause, with infection presence in ~40% of cases. Of note, 5% of all non-unions were found to have the presence of infection despite a lack of clinical or serological suspicion [2]. This is of particular importance in nonunions following plating especially when an open plating procedure has been performed. The diagnostic difficulty of detecting infection clinically, serologically, or through traditional microbiological methods, such as direct culture is related to the presence of the bacterial biofilm. The formation of a biofilm by bacteria is an adaptive state following adherence to host tissue and biomaterials, characterised by the production of an exopolysaccharide matrix, known as a glycocalyx, and transition to a sessile phenotype [15]. These adaptations allow the bacteria to survive in low nutrient environments and evade host immune defenses but present an obstacle in the diagnosis of infected non-unions. The glycocalyx produces a zone of relative immune deficiency as the cellular components of the host immune system are unable to penetrate the extracellular matrix thus minimising any evidence of an immune response to the infection. The bacterial adherence and glycocalyx reduce the yield of swabs and samples obtained for culture, with the sessile phenotype associated with poor growth rates [16]. Methods to circumvent these issues and improve sensitivity of bacterial culture include the use of sonication to liberate a greater proportion of organisms adherent to tissue and implant samples [17] and direct inoculation of theatre specimens into broth to drive the bacteria to a more metabolically active planktonic state [18]. A further diagnostic adjunct is histological examination of non-union site tissue. The presence of >1 neutrophil polymorph seen per high power field on
Fig. 1. Plate failure according to time from fixation and progress of fracture union.
average, after examination of at least ten high power fields has been shown to have 100% positive predictive value for the diagnosis of infected fracture non-unions [19]. Although more recently in the arthroplasty field has been updated to more than 5 neutrophils per high power field [20]. Mechanical factors can influence fracture non-union in a variety of ways depending on the original plating technique. Primary bone healing plating techniques require absolute stability and thus mechanical factors need to be addressed if stability has been lost in order to prevent (or treat) a hypertrophic union. The biological plating techniques require relative stability and so mechanical factors can influence fracture healing in two ways: 1) Excessive motion resulting in a hypertrophic non-union; 2) Excessive rigidity resulting in a lack of stimulus for callus formation. This is primarily dependent on the working length, plate material and plate geometry. Attention to the working length of a plate, when used in a biological fashion, is crucial for allowing the optimal levels of inter-fragmentary motion for fracture union [21,22]; too small a working length will result in non-union and early plate failure. Working lengths of under 30 mm are unlikely to have sufficient micro movement at the fracture site to induce fracture callus with stainless steel plates. Working lengths of 50 mm and 70 mm typically need weight bearing of 200 N and 300 N to provide a good mechanical environment for healing [22]. Loss of screw fixation following plate fixation (all techniques) must always be addressed due to the loss of both axial, angular and rotatory stability; unlike loss of screw fixation with intramedullary devices where only rotatory stability is lost. Biological failure can be a result of both local factors, such as avascular bone with a gap (local), and modifiable and non-modifiable systemic host factors, such as medications and age, respectively [23]. Of particular relevance to plating are bisphosphonates which have been shown to inhibit primary fracture repair and consequently patients on bisphosphonates who sustain a fracture that has been rigidly fixed are prone to non-union [24]. Treatment algorithm (Fig. 2) 1) General considerations when formulating a treatment strategy for fracture non-union following plate fixation a) Host factors Modifiable host risk factors for non-union should be addressed in the pre-operative period [25–27]. Chronic diseases (e.g. diabetes mellitus, chronic renal failure, diabetes mellitus, hypothyroidism, anaemia, peripheral vascular disease) should be optimised before any non-union surgery and the use of medications (Non-steroidal anti-inflammatory medication (NSAIDs) and corticosteroids) alcohol consumption and tobacco should be stopped if at all possible
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Fig. 2. Treatment algorithm for the management of fracture non-union following plate fixation.
[23]. In patients on bisphosphonates, either a biological form of fixation should be used that will use secondary bone repair or the bisphosphonates should be stopped. In vitro and early in vivo work have shown that antibiotics, such as quinolones, rifampicin and aminoglycosides inhibit fracture healing [23]. If possible alternative antibiotics should be used. However, if there are no suitable alternatives, avoiding high levels of the antibiotic may be of benefit.
v) Reconstitution of skeletal integrity
b) Infection Infected non-unions have two interrelated orthopaedic problems: a) deep bone infection, and b) a failure of fracture healing. Various strategies exist [28], which treat:
a) Aseptic non-unions after plating Aseptic non-unions after plating are commonly treated by replating with or without bone grafting, especially in humeral [34] and metaphyseal non-unions [30]. However, if the bone has multiple previous drill holes (‘emmental’ bone) or has been severely damaged by the screws, re-plating may not be possible, and the fracture may need to be stabilised with a nail (diaphyseal) or circular fixator (peri-articular). If the modality is being changed from plating to IM nailing it is essential not to damage the external periosteal supply [35] and medullary blood supply at the same time.
i) the fracture then the infection definitively, (e.g. antibiotic suppression with removal of metalwork following fracture union) ii) the infection definitively then the fracture (e.g. excision of the non-union and secondary bone transport or Masquelet technique) iii) both at the same time, (e.g. acute shortening) iv) neither specifically (e.g. amputation) In order to decide which strategy is best for a given patient that has a failure of healing associated with infection, it is important to determine whether the infection can be suppressed and the fracture healing recommenced with adjunctive treatments until union has occurred. If this is possible then a treatment programme with a shorter rehabilitation time can be offered to the patient. If this is not possible, then it will be necessary to excise the non-union. For all four of the strategies above, deep tissue sampling [29] and the delivery of systemic and/or local antibiotic therapy guided by culture results is routine. The guiding principles for the management of infected non-unions includes: i) Surgical debridement with excision/removal of necrotic and foreign material ii) Dead space management. iii) Bone stabilisation iv) Wound closure (direct or with soft tissue reconstruction)
Current controversy lies in the choice of fixation modality to achieve bone stability [30], optimal delivery of local antibiotics [31,32] and the methods required to reconstitute bone loss [33]. 2) Fixation modalities (Table 1)
b) Septic non-unions after plating In the presence of overt infection, the plate acts as a nidus for biofilm formation and in an established non-union will need to be removed along with any necrotic bone, which may result in a segmental defect. Conventional plates are biomechanically unfavourable in the presence of a defect due to cantilever loading. New designs of plates, such as locking compression plates and minimally invasive systems minimise the soft tissue and biomechanical issues [36,37]. However, even these new designs are seldom the treatment of choice in infected diaphyseal fractures of the lower limb, but they continue to be useful for aseptic or covertly infected non-unions of lower limb metaphyses [30] and humeral [34] fractures. 3) Treatment strategies for aseptic fracture non-unions following plate fixation Consideration of the previous plating technique employed at the time of the original fixation procedure and detection of callus
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Table 1 Skeletal fixation for fracture non-unions following plate fixation: the advantages and disadvantages
Plates
Advantages
Disadvantages
• Versatile method of treating upper/lower limb metaphyseal fractures
• Poor results in tibial and femoral diaphyseal fractures
• Good treatment for humeral diaphyseal non-unions
• Plate failure may occur in situations where prolonged union times are expected
• Standard plating technique requires extensive dissection
• Minimally invasive plate designs now available
• Does not easily allow shortening and lengthening • Difficult to use in conjunction with external fixation • Not suitable alone for defects >6 cm • Nidus for biofilm formation Intramedullary nail
• Stable fixation
• Not applicable for all metaphyseal fractures
• Can bridge long defects
• High complication rate when used in the humerus
• Can be inserted with minimal soft tissue and periosteal disruption
• Not suitable alone for defects >6 cm
• Low rates of malunion
• Nidus for biofilm formation
• Shortening and lengthening can be accomplished relatively easily
• Intramedullary reaming can disseminate infection along the medullary canal
• Can be used in conjunction with external fixation to lengthen bone • Intramedullary nail lengthening devices are available • Allow easy access to soft tissues for bone grafting/flap cover External fixation
• Can be used on upper/lower limb for metaphyseal/diaphyseal fractures
• Cumbersome, poor patient acceptance
• Can be used to shorten or lengthen bone
• Pin-track infection
• Bone transport possible
• Risk of septic arthritis when used close to a joint, especially the knee
• Can be used to compress the fracture site to stimulate healing
• Not ideal on the femur or humerus
• Frame may have to left on for prolonged periods
• Correction of angular or rotational deformity possible • Long defects (>6 cm) can be treated • Smaller nidus for biofilm formation
formation is critical in formulating the optimal treatment strategy. The presence of callus following rigid plating would suggest a mechanical failure with preserved biological healing potential; the absence of callus formation being suggestive of biological failure [38]. If biological plating was performed at the initial fixation surgery, then both biological and mechanical factors must be addressed. a) Biological enhancement of fracture healing Stimulation of callus in primary bone healing can be achieved using: i) osteoinductive/-genic bone grafting [39,40], ii) biologics such as parathyroid hormone [41,42] and novel agents [43], and iii) potentially cells [43–47]. Where secondary bone healing was intended, callus can be stimulated by increasing patient weightbearing or increasing the working length of the plate to allow greater inter-fragmentary motion [48] and axial dynamisation [49] at the non-union site. Potential adjunctive therapies include low-intensity pulsed ultrasound stimulation [50] and pulsed electromagnetic field stimulation [51]. b) Mechanical correction Enhanced mechanical stability in primary bone healing can be achieved with: i) revision +/– double plating in the diaphysis of the upper limb long bones [52], ii) conversion to intramedullary fixation in the diaphysis of the lower limbs however it is essential to avoid simultaneous disruption of the intramedullary and extramedullary blood supply at the same time, iii) conversion to a fixed angle device for metaphyseal fracture non-unions [53] c) Amputation Amputation is seldom regarded as a palatable option by either patient or surgeon, however, it may be a wise choice in some situations in the lower limb but almost never in the upper limb. In particular, when infection is present and the plate has been applied with a large amount of soft tissue stripping, it is likely that
in these cases a large amount of dead bone will be present and a large defect will result after debridement. Some patients may be poor candidates to undergo a prolonged reconstructive procedure involving limb lengthening or bone transport for social or medical reasons and these patients may be best served by a below knee amputation. Various other general factors need to be taken into account [54]. Elderly patients or patients with other risk factors such as smoking, alcohol abuse, steroid treatment, diabetes and occlusive arterial disease, may be better advised to accept amputation rather than risk a prolonged attempt at limb reconstruction with multiple surgical interventions and a high rate of complication. The available evidence suggests that in patients with severe limb injury the functional outcome and the chance of returning to work is no different with below knee amputation or limb salvage [54]. Conclusion Distinguishing between fracture non-union and delayed union, particularly in the early stages, can present a diagnostic conundrum and improved methods for detecting a fracture progressing are needed. It is important to consider all potential causes of fracture non-union. Latent infection is involved in ~5% of cases. Modern microbiological sampling techniques and use of histological assessment can help to reduce false negative results. As with all fractures, host factors need to be carefully considered but certain relatively novel agents such as bisphosphonates are of particular relevance to rigidly fixed fractures, as they inhibit the osteoclasts leading the process of primary bone repair [43]. Mechanical factors often have a role in creating the nonunion either because of excess rigidity (e.g. Locked plates with short working length) or insufficient rigidity (e.g. Failure of plate construct resulting in hypertrophic non-union). If non-unions are identified early whilst there is still sufficient mechanical stability, they can be managed by stimulation of callus. Late presenting non-unions typically require revision of the fixation construct and stimulation of the callus to induce fracture union.
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Disclosure The authors have no conflicts of interest to declare. Acknowledgment The authors of this manuscript express their thanks to the Osteosynthesis and Trauma Care Foundation for the sponsorship of the publication of this Supplement in Injury. References [1] Mills LA, Aitken SA, Simpson AHRW. The risk of non-union per fracture: current myths and revised figures from a population of over 4 million adults. Acta Orthop 2017;88:434–9. [2] Mills LA, Tsang S, Hooper G, Keenan G, Simpson A. The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection. Bone Joint Res 2016;5:512–9. [3] Court-Brown C, McQueen M, Tornetta III P. Trauma. Orthopaedic surgery essentials (1st ed.). Philadelphia: Lippincott Williams and Wilkins; 2006. [4] AO Foundation. 2014. Available from https://www2.aofoundation.org/wps/ portal/surgery [5] Lauge-Hansen N. Fractures of the ankle. Arch Surg 1950;60:957. [6] Rüedi TP, Buckley RE, Moran CG. AO principles of fracture management (2nd ed.). Stuttgart: AO Publishing, Thieme; 2007. [7] Schütz M, Südkamp NP. Revolution in plate osteosynthesis: new internal fixator systems. J Orthop Sci 2003;8:252–8. [8] Corrales LA, Morshed S, Bhandari M, Miclau T. Variability in the assessment of fracture-healing in orthopaedic trauma studies. J Bone Joint Surg Am 2008;90A:1862–8. [9] Weber B, Cech O. Pseudoarthrosis: pathology, biomechanics, therapy, results. Berne: Hans Huber Medical Publisher; 1976. [10] Marsh D. Concepts of fracture union, delayed union, and nonunion. Clin Orthop Relat Res 1998;355(suppl):S22–30. [11] Whelan DB, Bhandari M, Stephen D, Kreder H, Mckee MD, Zdero R, et al. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. J Trauma Inj Infect Crit Care 2010;68:629–32. [12] Leow JM, Clement ND, Tawonsawatruk T, Simpson CJ, Simpson AHRW. The radiographic union scale in tibial (RUST) fractures. Bone Joint Res 2016;5:116–21. [13] Paley D, Catagni MA, Argnani F, Villa A, Benedetti GB, Cattaneo R. Iliazarov treatment of tibial nonunions with bone loss. Clin Orthop Relat Res 1989;241:146–65. [14] Kienast B, Kowald B, Seide K, Aljudaibi M, Faschingbauer M, Juergens C, et al. An electronically instrumented internal fixator for the assessment of bone healing. Bone Joint Res 2016;5:191–7. [15] Gristina AG, Costerton JW. Bacterial adherence and the glycocalyx and their role in musculoskeletal infection. Orthop Clin North Am 1984;15:517–35. [16] Mah TFC, O’Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol 2001;9:34–39. [17] Trampuz A, Piper KE, Hanssen AD, Osmon DR, Cockerill FR, Steckelberg JM, et al. Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint infection is associated with risk of contamination. J Clin Microbiol 2006;44:628–31. [18] Blackmur JP, Tang EYH, Dave J, Simpson AHRW. Use of broth cultures peri-operatively to optimise the microbiological diagnosis of musculoskeletal implant infections. Bone Joint J 2014;96-B. [19] Simpson AHR., Wood M., Athanasou N. Histological assessment of the presence or absence of infection in fracture non-union. Injury 2002;33:151–5. [20] Athanasou NA. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–8. [21] Märdian S, Schaser K-D, Duda GN, Heyland M. Working length of locking plates determines interfragmentary movement in distal femur fractures under physiological loading. Clin Biomech 2015;30:391–6. [22] MacLeod AR, Simpson AHRW, Pankaj P. Age-related optimization of screw placement for reduced loosening risk in locked plating. J Orthop Res 2016;34:1856–64. [23] Gaston MS, Simpson AHRW. Inhibition of fracture healing. J Bone Joint Surg Br 2007;89B:1553–60. [24] Savaridas T, Wallace RJ, Salter DM, Simpson AHRW. Do bisphosphonates inhibit direct fracture healing? A laboratory investigation using an animal model. Bone Joint J 2013;95-B:1263–8. [25] Swanson EA, Garrard EC, O’Connor DP, Brinker MR. Results of a systematic approach to exchange nailing for the treatment of aseptic tibial nonunions. J
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Contents lists available at ScienceDirect
Injury Plating of Fractures: current treatments and complications Guest Editors: Peter Augat and Sune Larsson
j o u r n a l h o m e p a g e : w w w. e l s e v i e r . c o m / l o c a t e / i n j u r y
Non-union after plate fixation A. Hamish R.W. Simpsona,*, S.T. Jerry Tsanga a
Department of Trauma and Orthopaedics, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, UK
K E Y W O R D S
A B S T R A C T
Non-union Revision surgery Fracture healing
Approximately a third of patients presenting with long-bone non-union have undergone plate fixation as their primary procedure. In the assessment of a potential fracture non-union it is critical to understand the plating technique that the surgeon was intending to achieve at the primary procedure, i.e. whether it was direct or indirect fracture repair. The distinction between delayed union and non-union is a diagnostic dilemma especially in plated fractures, healing by primary bone repair. The distinction is important as nonunions are not necessarily part of the same spectrum as delayed unions. The etiology of a fracture non-union is usually multifactorial and the factors can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. Infection is present in ~40% of fracture non-unions, often after open fractures or impaired wound healing, but in 5% of all non-unions infection is present without any clinical or serological suspicion. Methods to improve the sensitivity of investigation in the search of infection include the use of; sonication of implants, direct inoculation of theatre specimens into broth, and histological examination of non-union site tissue. Awareness should be given to the potential anti-osteogenic effect of bisphosphonates (in primary fracture repair) and certain classes of antibiotics. Early cases of delayed/ non-union with sufficient mechanical stability and biologically active bone can be managed by stimulation of fracture healing. Late presenting non-union typically requires revision of the fixation construct and stimulation of the callus to induce fracture union. © 2018 Elsevier Ltd. All rights reserved.
Introduction
biological or bridge plating is indicated for fixation of comminuted diaphyseal fractures to minimise soft tissue stripping and used as “an internal external-fixator” to induce secondary bone healing [6]. The key to these internal fixators is the locking mechanism of the screw in the implant, which provides angular stability [7].
Fracture non-union is a rare but clinically challenging condition. A population-based analysis found an overall risk of non-union per facture to be 1.9%, rising to 9% in the peak age group of 25–44 years [1]. Approximately a third of patients presenting with long-bone non-union have undergone plate fixation as their primary procedure [2]. In the assessment of a potential fracture non-union it is critical to understand the plating technique that the surgeon was intending to achieve at the primary procedure [2] (i.e. rigid fixation and primary bone healing or biological fixation and secondary bone healing). Primary plate fixation can be achieved using a number of different techniques, depending on the fracture location, morphology, and indication for surgery [3]. The rigid fixation techniques include: 1) tension band plating; 2) Buttress or antiglide, e.g. for AO B-type fractures [4]; 3) neutralisation plates, e.g. for fixation of rotational fractures of the fibula [5]; and 4) compression plating. All of these rigid plating and primary bone healing techniques usually require a certain degree of soft tissue stripping which can have a major bearing on the treatment if the fractures becomes a non-union. In contrast,
* Corresponding author at: Department of Trauma and Orthopaedics, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SA, UK E-mail address: [email protected] (H. Simpson).. 0020-1383/© 2018 Elsevier Ltd. All rights reserved.
Diagnostic dilemma The distinction between delayed union and non-union is a diagnostic dilemma [8], especially after a fracture has been plated. Radiographic techniques are commonly used to infer biological activity at the fracture site and indicate if there is fracture union or non-union. The radiographic grading systems include the Weber and Cech system [9] and the Callus Index [10]. More recently classifications such as the RUST scale have been described and validated for intramedullary fixation of tibia [11,12]. All of these classifications have in common, the detection of callus on plain radiographs as the key diagnostic feature. However, callus formation is not seen in during primary bone healing, i.e. rigid plating and even with ‘biological’ plating, as, unfortunately, plates often obscure both periosteal and endosteal callus. Clinical assessment of mobility at the fracture union has also been described as a surrogate of healing potential [13] but is not useful for determining the progression of healing of a plated fracture. As a consequence of the lack of a robust diagnostic technique, there are many definitions for fracture non-union, which include:
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1. Fracture not healed in the expected time with no progression on plain radiographs, 2. Cessation of fracture healing process 3. Not healed within nine months 4. Need for additional procedures to achieve union. The first three of these criteria rely on radiographic features, such as bridging callus [12] to determine if fracture healing is progressing. Yet, as mentioned above, plated fractures undergoing direct bone healing, often do not have any visible callus. Thus, in plated fractures, the requirement for further surgery (e.g. re-fixation or bone grafting) has been used as a diagnostic criterion for nonunion. However, this can be erroneous, as failure to hold a fracture to union depends on: 1) the fatigue strength of the implant (which is dependent on geometry and type of material of the plate); 2) the rate of healing of the fracture; and 3) the amount of load (both magnitude and number of cycles) taken by the implant and bone fragments, which depends on the technique of fracture fixation. The amount of load on a plate has been measured using implantable telemetric devices fixed onto plates [14] and this may be a method for detecting failure of the fracture repair process. If the fracture has progressed to non-union, the plate will fail eventually, and additional procedures will be needed. If, however the fracture is healing slowly (i.e. a delayed union), the plate may fail before union and would therefore be classified as a non-union even though the healing processed has not ceased (Fig. 1). This would be more likely with a delayed union in a heavy individual with a relatively small plate. From the patient’s perspective, further treatment is needed in both the ‘true’ non-union and the delayed union where the plate has failed, but as the repair process has ceased in the established non-union the patient may benefit from additional stimulation of the fracture. Etiology The etiology of a fracture non-union is usually multifactorial, which can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. It has been shown that a high percentage of fracture non-unions have more than one cause, with infection presence in ~40% of cases. Of note, 5% of all non-unions were found to have the presence of infection despite a lack of clinical or serological suspicion [2]. This is of particular importance in nonunions following plating especially when an open plating procedure has been performed. The diagnostic difficulty of detecting infection clinically, serologically, or through traditional microbiological methods, such as direct culture is related to the presence of the bacterial biofilm. The formation of a biofilm by bacteria is an adaptive state following adherence to host tissue and biomaterials, characterised by the production of an exopolysaccharide matrix, known as a glycocalyx, and transition to a sessile phenotype [15]. These adaptations allow the bacteria to survive in low nutrient environments and evade host immune defenses but present an obstacle in the diagnosis of infected non-unions. The glycocalyx produces a zone of relative immune deficiency as the cellular components of the host immune system are unable to penetrate the extracellular matrix thus minimising any evidence of an immune response to the infection. The bacterial adherence and glycocalyx reduce the yield of swabs and samples obtained for culture, with the sessile phenotype associated with poor growth rates [16]. Methods to circumvent these issues and improve sensitivity of bacterial culture include the use of sonication to liberate a greater proportion of organisms adherent to tissue and implant samples [17] and direct inoculation of theatre specimens into broth to drive the bacteria to a more metabolically active planktonic state [18]. A further diagnostic adjunct is histological examination of non-union site tissue. The presence of >1 neutrophil polymorph seen per high power field on
Fig. 1. Plate failure according to time from fixation and progress of fracture union.
average, after examination of at least ten high power fields has been shown to have 100% positive predictive value for the diagnosis of infected fracture non-unions [19]. Although more recently in the arthroplasty field has been updated to more than 5 neutrophils per high power field [20]. Mechanical factors can influence fracture non-union in a variety of ways depending on the original plating technique. Primary bone healing plating techniques require absolute stability and thus mechanical factors need to be addressed if stability has been lost in order to prevent (or treat) a hypertrophic union. The biological plating techniques require relative stability and so mechanical factors can influence fracture healing in two ways: 1) Excessive motion resulting in a hypertrophic non-union; 2) Excessive rigidity resulting in a lack of stimulus for callus formation. This is primarily dependent on the working length, plate material and plate geometry. Attention to the working length of a plate, when used in a biological fashion, is crucial for allowing the optimal levels of inter-fragmentary motion for fracture union [21,22]; too small a working length will result in non-union and early plate failure. Working lengths of under 30 mm are unlikely to have sufficient micro movement at the fracture site to induce fracture callus with stainless steel plates. Working lengths of 50 mm and 70 mm typically need weight bearing of 200 N and 300 N to provide a good mechanical environment for healing [22]. Loss of screw fixation following plate fixation (all techniques) must always be addressed due to the loss of both axial, angular and rotatory stability; unlike loss of screw fixation with intramedullary devices where only rotatory stability is lost. Biological failure can be a result of both local factors, such as avascular bone with a gap (local), and modifiable and non-modifiable systemic host factors, such as medications and age, respectively [23]. Of particular relevance to plating are bisphosphonates which have been shown to inhibit primary fracture repair and consequently patients on bisphosphonates who sustain a fracture that has been rigidly fixed are prone to non-union [24]. Treatment algorithm (Fig. 2) 1) General considerations when formulating a treatment strategy for fracture non-union following plate fixation a) Host factors Modifiable host risk factors for non-union should be addressed in the pre-operative period [25–27]. Chronic diseases (e.g. diabetes mellitus, chronic renal failure, diabetes mellitus, hypothyroidism, anaemia, peripheral vascular disease) should be optimised before any non-union surgery and the use of medications (Non-steroidal anti-inflammatory medication (NSAIDs) and corticosteroids) alcohol consumption and tobacco should be stopped if at all possible
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Fig. 2. Treatment algorithm for the management of fracture non-union following plate fixation.
[23]. In patients on bisphosphonates, either a biological form of fixation should be used that will use secondary bone repair or the bisphosphonates should be stopped. In vitro and early in vivo work have shown that antibiotics, such as quinolones, rifampicin and aminoglycosides inhibit fracture healing [23]. If possible alternative antibiotics should be used. However, if there are no suitable alternatives, avoiding high levels of the antibiotic may be of benefit.
v) Reconstitution of skeletal integrity
b) Infection Infected non-unions have two interrelated orthopaedic problems: a) deep bone infection, and b) a failure of fracture healing. Various strategies exist [28], which treat:
a) Aseptic non-unions after plating Aseptic non-unions after plating are commonly treated by replating with or without bone grafting, especially in humeral [34] and metaphyseal non-unions [30]. However, if the bone has multiple previous drill holes (‘emmental’ bone) or has been severely damaged by the screws, re-plating may not be possible, and the fracture may need to be stabilised with a nail (diaphyseal) or circular fixator (peri-articular). If the modality is being changed from plating to IM nailing it is essential not to damage the external periosteal supply [35] and medullary blood supply at the same time.
i) the fracture then the infection definitively, (e.g. antibiotic suppression with removal of metalwork following fracture union) ii) the infection definitively then the fracture (e.g. excision of the non-union and secondary bone transport or Masquelet technique) iii) both at the same time, (e.g. acute shortening) iv) neither specifically (e.g. amputation) In order to decide which strategy is best for a given patient that has a failure of healing associated with infection, it is important to determine whether the infection can be suppressed and the fracture healing recommenced with adjunctive treatments until union has occurred. If this is possible then a treatment programme with a shorter rehabilitation time can be offered to the patient. If this is not possible, then it will be necessary to excise the non-union. For all four of the strategies above, deep tissue sampling [29] and the delivery of systemic and/or local antibiotic therapy guided by culture results is routine. The guiding principles for the management of infected non-unions includes: i) Surgical debridement with excision/removal of necrotic and foreign material ii) Dead space management. iii) Bone stabilisation iv) Wound closure (direct or with soft tissue reconstruction)
Current controversy lies in the choice of fixation modality to achieve bone stability [30], optimal delivery of local antibiotics [31,32] and the methods required to reconstitute bone loss [33]. 2) Fixation modalities (Table 1)
b) Septic non-unions after plating In the presence of overt infection, the plate acts as a nidus for biofilm formation and in an established non-union will need to be removed along with any necrotic bone, which may result in a segmental defect. Conventional plates are biomechanically unfavourable in the presence of a defect due to cantilever loading. New designs of plates, such as locking compression plates and minimally invasive systems minimise the soft tissue and biomechanical issues [36,37]. However, even these new designs are seldom the treatment of choice in infected diaphyseal fractures of the lower limb, but they continue to be useful for aseptic or covertly infected non-unions of lower limb metaphyses [30] and humeral [34] fractures. 3) Treatment strategies for aseptic fracture non-unions following plate fixation Consideration of the previous plating technique employed at the time of the original fixation procedure and detection of callus
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Table 1 Skeletal fixation for fracture non-unions following plate fixation: the advantages and disadvantages
Plates
Advantages
Disadvantages
• Versatile method of treating upper/lower limb metaphyseal fractures
• Poor results in tibial and femoral diaphyseal fractures
• Good treatment for humeral diaphyseal non-unions
• Plate failure may occur in situations where prolonged union times are expected
• Standard plating technique requires extensive dissection
• Minimally invasive plate designs now available
• Does not easily allow shortening and lengthening • Difficult to use in conjunction with external fixation • Not suitable alone for defects >6 cm • Nidus for biofilm formation Intramedullary nail
• Stable fixation
• Not applicable for all metaphyseal fractures
• Can bridge long defects
• High complication rate when used in the humerus
• Can be inserted with minimal soft tissue and periosteal disruption
• Not suitable alone for defects >6 cm
• Low rates of malunion
• Nidus for biofilm formation
• Shortening and lengthening can be accomplished relatively easily
• Intramedullary reaming can disseminate infection along the medullary canal
• Can be used in conjunction with external fixation to lengthen bone • Intramedullary nail lengthening devices are available • Allow easy access to soft tissues for bone grafting/flap cover External fixation
• Can be used on upper/lower limb for metaphyseal/diaphyseal fractures
• Cumbersome, poor patient acceptance
• Can be used to shorten or lengthen bone
• Pin-track infection
• Bone transport possible
• Risk of septic arthritis when used close to a joint, especially the knee
• Can be used to compress the fracture site to stimulate healing
• Not ideal on the femur or humerus
• Frame may have to left on for prolonged periods
• Correction of angular or rotational deformity possible • Long defects (>6 cm) can be treated • Smaller nidus for biofilm formation
formation is critical in formulating the optimal treatment strategy. The presence of callus following rigid plating would suggest a mechanical failure with preserved biological healing potential; the absence of callus formation being suggestive of biological failure [38]. If biological plating was performed at the initial fixation surgery, then both biological and mechanical factors must be addressed. a) Biological enhancement of fracture healing Stimulation of callus in primary bone healing can be achieved using: i) osteoinductive/-genic bone grafting [39,40], ii) biologics such as parathyroid hormone [41,42] and novel agents [43], and iii) potentially cells [43–47]. Where secondary bone healing was intended, callus can be stimulated by increasing patient weightbearing or increasing the working length of the plate to allow greater inter-fragmentary motion [48] and axial dynamisation [49] at the non-union site. Potential adjunctive therapies include low-intensity pulsed ultrasound stimulation [50] and pulsed electromagnetic field stimulation [51]. b) Mechanical correction Enhanced mechanical stability in primary bone healing can be achieved with: i) revision +/– double plating in the diaphysis of the upper limb long bones [52], ii) conversion to intramedullary fixation in the diaphysis of the lower limbs however it is essential to avoid simultaneous disruption of the intramedullary and extramedullary blood supply at the same time, iii) conversion to a fixed angle device for metaphyseal fracture non-unions [53] c) Amputation Amputation is seldom regarded as a palatable option by either patient or surgeon, however, it may be a wise choice in some situations in the lower limb but almost never in the upper limb. In particular, when infection is present and the plate has been applied with a large amount of soft tissue stripping, it is likely that
in these cases a large amount of dead bone will be present and a large defect will result after debridement. Some patients may be poor candidates to undergo a prolonged reconstructive procedure involving limb lengthening or bone transport for social or medical reasons and these patients may be best served by a below knee amputation. Various other general factors need to be taken into account [54]. Elderly patients or patients with other risk factors such as smoking, alcohol abuse, steroid treatment, diabetes and occlusive arterial disease, may be better advised to accept amputation rather than risk a prolonged attempt at limb reconstruction with multiple surgical interventions and a high rate of complication. The available evidence suggests that in patients with severe limb injury the functional outcome and the chance of returning to work is no different with below knee amputation or limb salvage [54]. Conclusion Distinguishing between fracture non-union and delayed union, particularly in the early stages, can present a diagnostic conundrum and improved methods for detecting a fracture progressing are needed. It is important to consider all potential causes of fracture non-union. Latent infection is involved in ~5% of cases. Modern microbiological sampling techniques and use of histological assessment can help to reduce false negative results. As with all fractures, host factors need to be carefully considered but certain relatively novel agents such as bisphosphonates are of particular relevance to rigidly fixed fractures, as they inhibit the osteoclasts leading the process of primary bone repair [43]. Mechanical factors often have a role in creating the nonunion either because of excess rigidity (e.g. Locked plates with short working length) or insufficient rigidity (e.g. Failure of plate construct resulting in hypertrophic non-union). If non-unions are identified early whilst there is still sufficient mechanical stability, they can be managed by stimulation of callus. Late presenting non-unions typically require revision of the fixation construct and stimulation of the callus to induce fracture union.
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