Results of tibia nailing with Angular Stable Locking Screws (ASLS); A retrospective study of 107 patients with distal tibia fracture.

Results of tibia nailing with Angular Stable Locking Screws (ASLS); A retrospective study of 107 patients with distal tibia fracture. stud. med. David Andreas Lunde Hatfield stud. med. Mohammed Sherif Supervisor M.D. Michael Brix, Department of Orthopaedic Surgery, Odense University Hospital, Denmark Words: 3452

Abstract Aim of project The aim of the study was to present early and mid-term experiences and results of tibial nailing combined with angular stable locking screws (ASLS) in distal tibial fractures. Fracture types AO42 and AO43 were included except AO43 B2,B3 and C3. To explore whether this treatment provides stable conditions, which has been shown in biomechanical studies. Furthermore, to show whether ASLS provides a favourable postoperative course with fewer complications, optimal healing, high union rate and lower rate of secondary loss of reduction. Background Therapy with ASLS is widely used. At present there are no published clinical data to be found in the relevant literature. Several biomechanical studies have been carried out showing positive results and capacities of the ASLS. Due to the lack of clinical data presented in the literature the study is considered to be highly relevant to promote quality assurance as well as evidence of effectiveness and safety of the method. Current standard treatment of tibia fractures involves a high rate of unwanted complications and non-unions. The most distally located fractures, as well as intraarticular fractures are commonly treated with tibial plate. Alternatively, a treatment with intramedullary nailing together with fibula plate is chosen. Both these methods are followed by a high rate of non-union and complications. Methods During the period from September 2009 until June 2014 a consecutive series of 107 patients with AO42 and AO43 fractures were treated with Synthes Expert Tibial Nail combined with ASLS screws. One patient was lost to follow up. Two patients were excluded due to earlier operation on the affected bone. All fractures except 14 were preoperatively CT scanned analysing the presence of intraarticular fracture involvement as well as the pattern of the fracture. The patients followed a post-operative control programme including X-ray and clinical control until healing. The average follow-up time was 38,3 months. All patients except eight were followed for at least a year. However, these eight patients have confirmed healing at present. Results All 104 patients experienced healing. No patients had non-union. 37 patients were reoperated; 34 patients because of minor complications and three patients because of major complications. Two patients had perioperative complications. Two patients had malunion. One patient missed the follow-up X-ray. Conclusion We found 100% union with an average of 5,1 months to healing and a low rate of complications. In particular, a low rate of infection (one patient) was found. However, 37 of 104 patients were re-operated, mostly due to local irritation around the osteosynthesis material. This suggests that the treatment could possibly become a standard procedure in the future for distal tibia fractures. Such fractures are traditionally treated with plating and external fixation methods, which has shown relative high rates of reoperation and complications. 2

Index Abstract...2 Introduction...4 Objectives...4 Tibia fracture...4 Current research...5 ASLS; technique and method...5 Materials and method...6 Results...7 Discussion...7 Missing data...7 Study limitations...8 Conclusion...8 Figure and charts...9 References...14 3

Introduction Treatment with Angular Stable Locking Screws (ASLS) has in recent years been introduced as an alternative to current standard treatment of distal tibia fractures. At present (November 20, 2014) there are no published clinical data to be found in the relevant literature (PubMed, Cochrane Library). Several biomechanical studies have been carried out showing positive results and capacities of the ASLS 6 7 9. Due to the lack of clinical data presented in the literature this study is considered to be highly relevant to promote quality assurance as well as evidence of effectiveness and safety of the method. Current standard treatment of tibia fractures involves a high rate of unwanted complications and non-unions 3. The most distally located fractures, as well as intra-articular fractures are commonly treated with tibial plate. Alternatively, a treatment with intramedullary nailing together with fibula plate is chosen. Both these methods are followed by a high rate of non-union and complications 3 10. Objectives The aim of the study was to present early and mid-term experiences and results of tibial nailing combined with angular stable locking screws (ASLS) in distal tibia fractures. Fracture types AO42 and AO43 were included except AO43 B2, B3 and C3. The study aims to explore whether this treatment provides stable conditions, which has been shown in biomechanical studies 6 7 9. Furthermore, to show whether ASLS provides a favourable post-operative course with fewer complications, optimal healing, high union rate and lower rate of secondary loss of reduction. Tibia fracture Tibia fractures are among the commonest of long bone fractures accounting for an estimated 40% of all lower limb fractures 1. With approximately 500.000 cases per year and an average incidence of 26 tibia fractures per 100.000 per year in the USA it represents a major burden on the health care system 2. The following epidemiological data show particular age and sex differences 2. The overall average age of patients with tibia fracture is 37 years, with an average age of 31 years among men and 54 years among women. Interestingly, there are two peaks in the incidence distribution. The first peak represents dominance among young males aged 15-19 with an incidence of 109 cases per 100.000. A second peak is seen among the female population older than 80 years. This second peak is commonly acknowledged to be related with osteoporosis. Tibia fractures are regarded as one of the most challenging to be treated by the orthopedic surgeon. As a common injury it does present with a great variability, and the final individual outcome is often unpredictable. Therefor, it is a subject of continuous discussion, however, still without reaching consensus. This emphasizes a need for further innovation. Treatment with ASLS represents another such innovative initiative, which adds useful arguments and experience to the debate. Lastly, tibia fractures cause substantial impact on morbidity, health care use and costs. Non-unions after tibia fractures are, in particular, a relevant factor to this, often requiring secondary surgery to achieve satisfactory union. One study found a reoperation rate of 35,8% 3.Of these 13,2% tibiae required minor revision surgery and 22.6% tibiae required major revision surgery 3. As such, non-union represents a core challenge with treatment of tibia fractures and accounts for a significant cost and use of health care resources as well as high use of strong opioids. Furthermore, patients with non-union are at greater risk of having additional subsequent injuries in the affected limb, trunk, spine or skull 4. A median total care cost for a patient with non-union is estimated to be 65% higher than those without non-union 4. 4

Current research Therapy with intramedullary nailing has become widely used in the management of distal tibia fractures. With such method follows an increased risk of weakened biomechanical stability. During the past several years the indication for intramedullary nailing has expanded and the use of ASLS screws has been introduced as an alternative to conventional screws with the aim of providing increased stability. However, as of November 20, 2014 there are no clinical data to be found in the relevant literature (PubMed, Cochrane Library) that can confirm this. Several biomechanical studies have been carried out showing positive results and capacities of the ASLS 5 6 7. One biomechanical study showed no significant difference in terms of construct stability capacities when comparing a four-screw ASLS configuration and a standard solution with five locking screws 8. The same study found in the ASLS solution a higher stiffness of the construct and less motion in the fracture gap during early loading. Thus one might conclude that the ASLS solution offers sufficient fixation stability of distal tibia fractures with fewer locking screws, consequently reducing the risk of intraoperative nerve and vessel injury as well as reducing operating time and cost. Another biomechanical study evaluated the long-term stability comparing conventional locking screws and the ASLS screws 9. This study evaluated biomechanical testing over a period of 12 weeks, finding a significantly higher long-term stability with the ASLS system compared with conventional locking screws. It concludes the finding of increased stability and resistance to torsional loading to have clinical relevance. Furthermore, it suggests the overall mechanical capacities of the ASLS system to have the potential to reduce common complications such as secondary loss of reduction and mal-/non-union. All these studies show promising results. Due to the lack of clinical data presented in the literature this study is considered to be highly relevant to promote quality assurance as well as evidence of effectiveness and safety of the method. We found one multi-centre on-going randomized control trial with ClinicalTrials.gov identifier: NCT00875992. This study aims to evaluate the effectiveness of ASLS. According to ClinicalTrials.gov the study has been completed and thus published results should be expected to present in the very near future. ASLS technique Synthes intramedullary nails are designed to anatomically fit the medullary canal, allowing indirect reduction. ASLS reduces the risk of secondary loss of reduction by providing axial and angular stability between nail and screws, by using resorbable sleeves as dowels in the nail locking holes. Intramedullary nailing has become an alternative treatment choice for the most displaced diaphyseal tibia fractures. It provides increased mechanical stability 6 7 9. However, fractures of the most distal one third of the tibia treated with intramedullary nailing and conventional screws often results in delayed union and non-unions 10. To improve the mechanical stability of intramedullary nailed tibia fractures, ASLS have been developed. The use of ASLS in tibial nailing results in fixation stiffness comparable with that of external fixation 6 7 9. Indications and Contraindications ASLS is compatible with all Synthes Expert Tibial cannulated titanium nails. It is used as an alternative to standard locking screws. ASLS is used for the operative treatment and stabilization of long bones in the upper and lower extremities, according to specific indications. ASLS is particularly indicated in cases where stability is needed, for example, in fractures close to the metaphyseal area. The contraindications of the nail system are applicable, e.g in patients with acute or chronic infections, poor bone quality, reduced blood circulation, allergy, or in situations where internal fixation is contraindicated for other reasons. 5

Product information - Screws: The ASLS-screws are made up of about 90% titanium. They have blunt tips, 4 or 5 mm in diameter. The Screw shaft has three diameters [D]; D1 provides fixation in near cortex D2 expands sleeve, thus providing angular stability D3 - provides fixation in the far cortex - Sleeves: Made up of biodegradable polylacatide material. Its purpose is to decrease fracture site motion during first 12 weeks of healing, by expanding in the nail locking hole. They are resorbable within two years. - Nail: Expert Tibial Nail (9 or 11 mm in diameter). Traditional screws (B) have one single and continuous diameter and attach only to the near and distant cortex. ASLS, on the other hand, (B) has three different diameters and attach to the near and distant cortex as well as the intramedullary nail, creating angular stability. See figure 1 for in vivo installation. (A) (B) Materials and Method The study is designed as a retrospective study of a consecutive series of 107 patients, 57 male patients and 50 female patients. During the period from September 2009 until June 2014 a consecutive series of 107 patients with Müller AO42 and AO43 fractures were treated at Odense University Hospital with Synthes Expert Tibial Nail combined with ASLS screws. See figure 2 for a flow chart of the study process. The distribution of the Müller AO classification among the patients is showed in figure 3. Figure 4 shows the most commonly occurring fractures in the study. The following material is summarized in figure 5. All fractures except 14 were preoperatively CT-scanned analysing the presence of intra-articular fracture involvement as well as the pattern of the fracture. 41 of 93 patients with such pre-operative CT-scan had their Müller AO fracture code modified after the CT-scan. 13 patients were treated as trauma patients. All patients were operated after an average of 3,1 days after the injury. 19 patients were operated on the same day as the injury. The longest interval between injury and operation was 14 days. 46 patients were found to have intra-articular fracture. 30 of these intra-articular fractures were identified only after the pre-operative CT-scan. 63 patients had an additional fracture of the most distal one third of fibula. 35 of these fibula fractures were treated with osteosynthesis. 40 patients were treated with additional screws in the proximity of a joint. 7 patients were treated with additional Poller screws. Each patient was treated with an average of 2,6 ASLS screws. The average postoperative hospitalization was 5,1 days. Evaluation of fracture union and time to healing was performed by assessment of radiographs. Healing is most commonly defined as cortical bridging of at least 3 out of 4 cortices 11 The patients followed a post-operative control programme including X-ray and 6

clinical control every 6 weeks until healing. The average follow-up time was 38,3 months. All patients except eight (operated in 2014) were followed for at least a year. However, these eight patients have confirmed healing at present. One patient was lost to follow up. Two patients were excluded due to earlier operation on the affected bone. Results All 104 patients included in the study experienced healing. No patients had non-union 1 year post-operatively. Two patients had mal-union. Average time to healing was 5,1 months. 37 patients were re-operated; o 34 patients because of minor complications, These 34 patients represent a relatively homogenous group requiring removal of the osteosynthesis material. We found that these patients experienced local irritation around the osteosynthesis material and therefore qualified for the indication for its removal; 16 patients underwent removal of only screws. 18 patients removed both the intramedullary nail and screws. Among the 34 patients, 28 patients (82%) had an additional fibula fracture. 10 (35%) of these 28 patients had an additional fibula ostesynthesis whereas the remaining 18 patients (65%) o had not. Three patients because of major complications. One patient with confirmed deep infection, one patient with suspected deep infection (not found) and one patient had autograft bone transplantation. One patient had minor perioperative complications. o Tibial splinting. Discussion We found 100% union with an average of 5,1 months to healing and a low rate of complications. No patients had secondary loss of reduction. In particular, a low rate of infection (one patient) was found. However, 37 of 104 patients were re-operated, mostly (34 patients) due to local irritation around the osteosynthesis material. 28 (82%) of the 34 patients re-operated due to local irritation around the osteosynthesis material had an additional fibula fracture, as shown in figure 7. This may suggest fibula fracture as a complicating factor in the healing process. Figure 7 also shows that local irritation followed by removal of the osteosynthesis material among patients with fibula fracture was more common if the an additional osteosynthesis of the fibula was not applied. These results suggest that treatment with ASLS could possibly become a standard procedure for distal tibia fractures in the future. ASLS offers all the advantage of an intramedullary approach. Stable fixation, provided by ASLS, permits controlled, early and active rehabilitation, which is pivotal to optimal recovery. Finally, the results of our study correlates with the promising results of biomechanical studies performed on ASLS. Tibial intramedullary nailing combined with ASLS screws seems to be a secure and effective treatment method for distal fractures in the tibia. Our study suggests that the treatment could possibly become a standard procedure for distal tibia fractures in the future. Missing data One patient was lost to the study due to missed follow up X-ray. 14 patients were operated without a pre-operative CT-scan, but had only a pre-operative X-ray. We found that 41 (44%) of the 93 patients with a pre-operative CT-scan changed the Müller AO classification of their fracture. Therefor, the group of patients without a pre-operative CT- 7

scan may not have been classified as precisely as possible according to the Müller AO classification. Smokers/previous smokers, chronic alcoholism, diabetes, cardiovascular disease and other chronic comorbidities are all parameters that were not registered and assessed in this study. They are all confounding factors that possibly could affect other parameters such as time to healing and mal-union. Study limitations 40 patients were treated with additional screws and 7 patients with Poller screws. These may influence as external factors adding stability to the main construction of intramedullary nail and ASLS. Quite a substantial number of the patients (63) also had a fracture in the most distal one third of fibula. This might also influence the result in terms of additional pain, edema and decreased stability of the crus. For coming studies of the ASLS we suggest to add these to the exclusion criteria in order to obtain a more precise evaluation of the ASLS. Alternatively, the importance of an additional osteosynthesis in the fibula may be evaluated by performing a randomized controlled trial. Some of the patients missed some of the X-ray and clinical control programme every 6 weeks. However, all patients included in the study had X-ray which confirmed healing within 12 months post-operatively. Finding a precise time to healing was challenged by this component. An X-ray, which confirms healing, cannot reveal for how long time healing has been present. Therefor, patients who only underwent the 12 months X-ray might have had healing already for up to 8-9 months. It is likely to suggest that the real time to healing is less than the average 5,1 months we found in this study. Conclusion 1. We found 100% union with an average of 5,1 months to healing and a low rate of complications. In particular, a low rate of infection (one patient) was found. However, 37 of 104 patients were re-operated, mostly due to local irritation around the osteosynthesis material. This suggests that the treatment could possibly become a standard procedure in the future for distal tibia fractures, replacing traditional methods, which carry relative high rates of reoperation and complications 3. 2. A coincidental finding in the study emphasizes the importance of a pre-operative CT scan in order to obtain the most precise diagnosis. The pre-operative CT scan of the 93 patients resulted in a change of Müller AO classification code for a total of 41 patients (44%), as shown in figure 8. Furthermore, 30 (65%) of the 46 patients found with intra-articular fracture had their intra-articular fracture involvement confirmed only after the CT-scan. Hence, one may conclude that the CT-scan instrumental in precise diagnosis, and particularly effective in identifying an intra-articular involvement of the fracture. 8

Tables and graphs Figure 1. In vivo installation of the ASLS system. 9

Figure 2. Flow chart of study process. 10

Figure 3. Overview of all fracture types. Figure 4. Most common fracture types found in the study. 11

Figure 5. Materials, summarized. Figure 6. Selected variables. 12

Figure 7. Implant removal among patients with additional fibula fracture. Figure 8. Change of diagnosis after pre-operative CT-scan. 13

References 1 C.M. Court-Brown, S. Rimmer, U.Prakash, M.M. McQueen. Injury: International Journal of the Care of the Injured Vol. 29, No. 7,1998 2 Murali Poduval, MBBS, MS, DNB, article on Diaphyseal Tibial Fracture from www.medscape.com, updated on May 13, 2014. Link available at: http://emedicine.medscape.com/article/1248857-overview#a0199 3 Harris I, Lyons M. Reoperation rate in diaphyseal tibia fractures. ANZ Journal of Surgery, 2005 Dec;75(12):1041-4 4 Antonova et al. Tibia shaft fractures: costly burden of nonunions BMC Musculoskeletal Disorders 2013, 14:42 5 Hoegel et al - J Trauma Acute Care Surg. 2012 Oct;73(4):933-8 6 Horn J, Linke B, Höntzsch D, Georguiev B, Schwieger K. Angle stable interlocking screws improve construct stability of intramedullary nailing of distal tibia fractures: A biomechanical study. Injury, Int. J. Care Injured 40 (2009) 767 771 7 Gueorguiev B, Ockert B, Schwieger K, Wähnert D, Lawson-Smith M, Windolf M, Stoffel K. Angular Stability Potentially Permits Fewer Locking Screws Compared With Conventional Locking in Intramedullary Nailed Distal Tibia Fractures: A Biomechanical Study. J Orthop Trauma,Volume 25, Number 6, June 2011 8 Gueorguiev B, Ockert B, Schwieger K, Wähnert D, Lawson-Smith M, Windolf M, Stoffel K. Angular Stability Potentially Permits Fewer Locking Screws Compared With Conventional Locking in Intramedullary Nailed Distal Tibia Fractures: A Biomechanical Study. J Orthop Trauma,Volume 25, Number 6, June 2011 9 Dirk Wähnert, Yves Stolarczyk, Konrad L Hoffmeier et al. Long-term stability of angle-stable versus conventional locked intramedullary nails in distal tibia fractures. BMC Musculoskeletal Disorders 2013, 14:66 10 Attal R. Hansen M. Kirjavainen M. et al. A multicentre case series of tibia fractures treated with the Expert Tibia Nail (ETN) Arch Orthop Trauma Surg (2012) 132:975 984 11 Shisha T. Parameters for defining efficacy in fracture healing. Clin Cases Miner Bone Metab. 2010 Jan-Apr; 7(1): 15 16 14