Acta Biomed 2020; Vol. 91, Supplement 14: e2020012 10.23750/abm.v91i14-S.10890 © Mattioli 1885 Review Management of acute bone loss following high grade open tibia fractures. Review of evidence on distraction osteogenesis and induced membrane techniques Crt Benulic1, Gianluca Canton2, Iztok Gril1, Luigi Murena2, Anze Kristan1 1 Department of traumatology, UMC Ljubljana, Slovenia, 2 Orthopaedics and Traumatology Unit, Cattinara Hospital - ASU- GI, Department of Medical, Surgical and Life Sciences, Trieste University, Trieste (Italy). Summary. Introduction: Optimal treatment for acute post-traumatic bone loss in the tibia remains unclear. Distraction osteogenesis (DO) and induced membrane technique (IM) have been established as the main- stays of treatment. Aim of this article is to review the current evidence regarding the use of these two meth- ods. Methods: A review of the MEDLINE database was performed with strict inclusion and exclusion criteria focusing on treatment of the acute bone loss after open tibia fractures with DO and IM. Bone union rate was taken as the primary outcome and infection rate as secondary outcome. Results: Four studies out of 78 on the use of the DO and three studies out of 18 on the use of the IM technique matched the inclusion criteria. Union rate in the DO group ranged between 92% and 100%, with infection rates between 0 and 4%. In the IM group, union was reached in 42% to 100% of cases, with septic complications occurring in 12% to 43%. Differences in union rate and infection rate reached statistical significance. Discussion: We found a consider- able evidence gap regarding treatment of bone loss in high grade open tibia fractures. The limitations of our study prevented us from drawing clear causative conclusions on the results. Although our study points to higher union rates and lower infection rate with the use of the DO technique, the results remain preliminary and further high-level evidence is needed to establish the roles of DO and IM in treatment of acute bone loss in open tibia fractures. (www.actabiomedica.it) Key words: tibia, bone loss, infection, union, distraction osteogenesis, induced membrane Introduction injuries, compartment syndrome and injuries to other organ systems. Open fractures with associated bone loss are rare Prevention of infection with systematic debride- injuries. They represent approximately 0,4 % of all ment and early soft tissue coverage in a mechanically fractures and 11,4 % of all open fractures (1). Most stable environment, supported by systemic antibiotic of them are high degree Gustilo-Anderson (GA) frac- therapy, is the most important treatment in the early tures affecting primarily the tibia, which represents the phase. Guidelines established by the British Orthope- site of 25% of all open fractures (2, 3). Mechanisms of dic Association / British Association of Plastic Sur- these injuries usually involve high energy transfers (1). geons (BOA/BAPRAS) address these crucial first Apart from bone loss, these injuries are further compli- steps of treatment (4,5). cated by soft tissue loss, contamination, neurovascular The optimal treatment regime for acute post- traumatic bone defects in the tibia remains unclear. 10890.indd 1 10/12/20 9:30 AM 2 C. Benulic, G. Canton, et al. A critical-size bone defect is qualitatively defined as recently been challenged in the use of post-traumatic the smallest osseous defect that will not heal spontane- defects in the lower limb (19-21). ously during the lifetime (6). A quantitative definition Aim of the present paper is to review and critically is still lacking since many factors beyond the extent of evaluate the current evidence regarding the treatment the bone defect affect its ability to heal. Factors regard- of acute post-traumatic bone loss in the tibia. Focus ing bone status, soft tissue envelope and host need to will be given to the two most established techniques: be considered (7,8). The broad spectrum of injury distraction osteogenesis and induced membrane tech- patterns and complexities have so far precluded the nique. establishment of clear guidelines for treatment. Rec- ognition of the problem led to the development of the “diamond concept” of bone healing (9,10). This con- Methods ceptual framework, however, gives no clear guidelines on which surgical technique is to be used for optimal A review of the MEDLINE database in agree- healing of the bone defect. ment with the Preferred Reported Items for Systematic In the absence of clear suggestions many tech- Reviews and Meta-Analyses Statement for Individual niques have been proposed. Historically, autologous Patient Data (PRISMA-IPD) was performed. bone grafting has been the gold standard of bone defect treatment (11). Its use has been challenged in the Search strategy management of larger bone defects, where increased rates of graft resorption have been observed8. With A search strategy was developed, involving key- the development of microsurgical techniques, the free words for the three key concepts (bone defect, open frac- vascularized fibular graft has been popularized. Due ture, tibia) and two interventions of interest (DO, IM). to the technical complexity, donor site morbidity and Keywords bone defect*” OR “bone loss” AND “Frac- high rate of refractures in weight-bearing bones, it has tures, Open”[Mesh] OR “open fracture*” OR “com- been mostly limited to treatment of bone defects in the pound fracture*” AND “Tibia”[Mesh] OR “tibia*”were upper extremity (1,12). combined with the Boolean operator AND either Following its conception in the 1950s, Ilizarov’s with “Osteogenesis, Distraction”[Mesh] OR “Ilizarov distraction osteogenesis (DO) has revolutionized the Technique”[Mesh] OR “Bone Transplantation”[Mesh] treatment of bone defects. The concept of new bone OR “Bone Lengthening”[Mesh] OR “bone transport” formation under controlled tension stress with the use OR “segmental bone transport” OR “Ilizarov bone of a circular external fixator has led to the development transport” for distraction ostegenesis or with “induced of a versatile system, which enables simultaneous or membrane” OR “induced membrane technique” OR sequential limb shortening, lengthening and deform- “pseudo-membrane” OR “pseudo-membrane tech- ity correction (13,14). High rates of bone union (60 nique” OR “Masquelet technique” OR “Masquelet to 100%) are to a certain extent off-balanced by a method” OR “Masquelet” for the induced membrane long duration of treatment and a broad spectrum of technique. frequent complications (15,16). To overcome certain drawbacks of the Ilizarov technique, a two-stage pro- Inclusion and exclusion criteria cedure has been introduced by Masquelet in 2000 (17). Following debridement, the bone defect is filled with a Studies were included when focused on the treat- cement (PMMA) spacer. The latter induces formation ment of acute bone loss in the setting of an open tibia of a well-vascularized pseudo membrane. After resto- fracture. Articles reporting on bone defects in differ- ration of the soft tissues, the cement spacer is removed ent body regions were included only if outcomes of and fresh autologous bone graft implanted into the interest were given separately for the tibia. Our evalu- envelope created by the induced membrane (IM) (18). ation focused on adult patients (>18 years old) and on Previously reported high union rates around 90%, have studies presenting results of at least 5 cases. A mean 10890.indd 2 10/12/20 9:30 AM Bone loss, open tibia fractures, review 3 follow-up of at least one year was a prerequisite for Results inclusion. Treatment modalities included were distrac- tion osteogenesis or the induced membrane technique, For DO treatment modality, the search resulted in combined either with external or internal fixation 73 articles. Based on the title and abstract, 23 articles methods. Studies published between 1990 and 2020 in were chosen for detailed reading. Additional 5 relevant English or German language were eligible. We filtered articles were identified from the reference lists. Of the our search to studies on humans and those contain- 28 articles, 4 studies met our inclusion criteria (Fig. 1). ing a full text. Primary outcome was bone union, while For the IM technique, the search resulted in 18 deep infection rate represented the secondary out- articles. Based on the title and abstract, 9 were elected come. Studies were included if reporting at least one for further reading. Additional 2 relevant studies were outcome of interest (Table 1). identified from the reference lists. Of the total of 11 Studies were excluded if the etiology of the bone studies, 3 met our inclusion criteria (Fig. 2). defect was infection, bone tumor or nonunion. Bone We found 4 articles reporting the results of DO periprosthetic and peri-implant fractures were also treatment of bone defects in open tibia fractures which excluded, as were case reports and small case studies met our inclusion criteria. Number of patients per regarding less than 5 patients or having an inadequate study ranged from 5 to 24. Mean patients age ranged follow up (Table 1). between 31 and 34 years. All fractures were grade III open tibia fractures according to the Gustilo-Ander- son classification. Mean length of bone defects ranged Analysis from 5 to 11 cm. Bony union was achieved in 92 to 100% of cases, with deep infection rates between 0 and Narrative synthesis was used to describe the main 4% (Table 2). results of each study and summarize the findings. In the IM group 3 articles were found in the Comparisons between the two approaches (DO and MEDLINE database that met the inclusion and IM) were done using independent samples’ t-test or exclusion criteria. Number of cases per study ranged Fisher’s exact count test. Meta-analysis was not per- from 8 to 12. Mean patient age was between 25 and formed due to high heterogeneity of studies, lack of 37 years. All fractures were grade III open tibia frac- control groups, or incomplete data reported in the tures according to the Gustilo-Anderson classification.