Comparative Effectiveness of Circular Frames, Plate Fixation, and Intramedullary Nailing in Distal-Third Tibial Fractures: A Systematic Review and Meta-Analysis

Comparative Effectiveness of Circular Frames, Plate Fixation, and Intramedullary Nailing in Distal-Third Tibial Fractures: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Comparative Effectiveness of Circular Frames, Plate Fixation, and Intramedullary Nailing in Distal-Third Tibial Fractures: A Systematic Review and Meta-Analysis Jules Deruelle, Henry Clark, Peyman Bakhshayesh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8501129/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Distal-third tibial fractures are surgically challenging due to limited soft-tissue coverage and a high risk of complications. The optimal fixation method remains uncertain. This systematic review and meta-analysis compared intramedullary nailing, plate fixation, and circular external fixation for distal-third tibial fractures. A comprehensive search identified 54 studies, including 15 randomised controlled trials. Meta-analyses of randomised evidence demonstrated that intramedullary nailing was associated with a modest but statistically significant reduction in time to fracture union and a lower rate of superficial infections compared with plating, without significant differences in deep infection rates, functional outcomes, or overall complications. Functional scores were broadly comparable between techniques. Evidence for circular external fixation was limited and largely derived from non-randomised studies, which suggested longer union times and higher complication rates compared with internal fixation. Overall, intramedullary nailing offers a favourable balance between fracture healing and infection risk for distal-third tibial fractures, particularly extra-articular patterns, while achieving similar functional outcomes to plating. Plate fixation remains an appropriate alternative when nailing is contraindicated. The role of circular external fixation appears more selective and warrants further high-quality comparative trials. Health sciences/Anatomy Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Fractures of the distal-third of the tibia represent a common and clinically challenging injury, owing to the limited soft-tissue envelope, compromised blood supply, and proximity to the ankle joint 46 ,56 . These anatomical characteristics contribute to an increased risk of delayed union, infection, malalignment, and functional impairment following surgical fixation 56 . As a result, the optimal management of distal tibial fractures remains an area of ongoing clinical uncertainty. Three principal surgical strategies are currently employed: intramedullary nailing (IMN), plate fixation, and circular external fixation (CEF). IMN is widely used due to its minimally invasive nature, preservation of periosteal blood supply, and potential for early mobilisation. Plate fixation allows accurate fracture reduction and alignment and may facilitate early functional recovery, but is associated with soft-tissue complications, especially in the distal tibia where surgical exposure is limited 56, 57 . CEF offers stable fixation with minimal disruption of the fracture biology and permits early weight-bearing, yet it has been associated with pin tract infections, patient discomfort, and prolonged treatment duration 60 ,63 . Despite the availability of randomised controlled trials and observational studies comparing these techniques, the existing evidence base remains fragmented. Most prior systematic reviews and meta-analyses have focused on pairwise comparisons: most commonly IMN versus plate fixation 57 , 58 ,59 . There has been minimal incorporation of CEF 60 and limited distinction between superficial and deep infection outcomes, which have differing clinical implications. Consequently, clinicians lack a comprehensive synthesis of evidence comparing all three fixation strategies across clinically relevant outcomes. A systematic review evaluating all three fixation techniques is therefore warranted to better inform surgical decision-making for the management of these fractures. The objective of this systematic review and meta-analysis was to compare the effectiveness and safety of intramedullary nailing, plate fixation, and circular external fixation for all distal-third tibial fractures. Specifically, we aimed to evaluate differences between fixation strategies with respect to union times, superficial and deep infections, functional outcomes, and other reported complications, meta-analysing evidence from randomised controlled trials where available and contextualising findings using non-randomised studies. Results Screening and selection process Among the 1463 retrieved articles, 669 were automatically deleted by the Rayyan software (version 1.4.3) and 13 were deleted manually. Following title and abstract screening, 115 articles remained. These articles’ full-texts were retrieved and scrutinised against the inclusion criteria ( SI1.1 ). Finally, 54 articles were included in this review 1 – 54 (Fig. 1 ). Some articles appeared to meet all eligibility criteria but were excluded because their results were unavailable. This was particularly noted for some clinical trial registrations, where published results could not be identified despite searching their NCT numbers across registries and other databases. Baseline characteristics All the 54 articles had their baseline characteristics summarised in tables (SI2: SI2.1.1 and SI2.2.1 ). Fifteen randomised control trials (RCTs) and thirty-nine non-randomised studies (NRSs) were identified. The distribution of the fracture types investigated was substantially skewed towards extra-articular distal tibia fractures (AO43A). Approximately 80% of RCTs and 67% of NRSs only included extra-articular fractures; around 6.7% of RCTs and 17% of NRSs only included intra-articular fractures (AO43B/C). The remaining 15% of studies included both fracture types. Most investigations were performed in tertiary settings. The only study that involved a combination of tertiary and “regional trauma units” was the UK FixDT 8 trial: a RCT which included 321 patients from 28 acute trauma centres in the United Kingdom. Only 19% of the included studies compared circular external fixation (CEF) with the alternative techniques, and notably, just two of these were RCTs. In contrast, comparisons between plating and intramedullary nailing (IMN) were far more common, investigated in 87% of studies. Risk of Bias – quality assessment Risk of bias was evaluated across fifteen RCTs using the RoB 2 tool. Three studies 2 , 6 , 11 were judged to have a high risk of bias. In two trials 2 , 11 , concerns arose in Domain 1 (randomisation process) because treatment allocation was performed using non-random methods such as “every other participant” 2 or a “coin flip,” 11 introducing potential selection bias. The third study 6 was rated high risk in Domain 3 (missing outcome data) due to incomplete reporting: the authors did not specify which intervention groups participants lost to follow-up belonged to, nor did they provide reasons for attrition. Consequently, the proportion of missing data per group was unclear: different reasons for missingness between groups could not be ruled out. Most RCTs had no trial registration numbers available so they automatically ranked at “some concerns” in Domain 5 (selection of the reported result). The same judgement was apparent for the second part of Domain 2 (deviations from intended interventions) because very few studies had performed ITT or mITT analyses. By use of traffic-light and summary plots, distribution of judgements by domain and outcome category were displayed in the Supplementary Information ( SI3.1 ). Precise RoB2 tool decision pathways and reasoning for judgements were compiled in tables ( SI3.1.1.3 , SI3.1.2.3 and SI3.1.3.3 ). Misreporting of standard deviations Due to inconsistent reporting of standard deviations (SDs) for continuous outcomes, conversions were used as previously described in the Methods section. Im 6 et al., 2005, reported ranges for times to union. These were converted from “12–64” into ± 13 (IMN) and “12–72” into ± 15 (plate). Guo 5 et al., 2010, reported 95% confidence intervals (CIs) and these were converted to standard errors (SE) and subsequently to SDs. For “time to union” (weeks) the 95% CIs were converted from “16.7–18.6” into ± 3.127 (IMN) and “16.9–18.3” into ± 2.219 (plate). AOFAS’, at 12 months post-operatively, 95% CIs we converted from “83.7–88.6” to ± 8.064 (IMN) and “81.7–86.1” to ± 6.975. A similar conversion method was used when another trial 51 had, likely, mislabelled their SEs as SDs. This was noted when it was meta-analysed with a much larger trial by Costa 8 et al., 2018, and it was being weighted disproportionately highly due to an unnaturally minute standard deviation value. Its mislabelled SE for “time to union” (weeks) was converted from 0.58 to ± 3.23 (IMN) and 0.53 to ± 3.09 (plate). The same conversion done for OMAS, at 3 months (m) and 6 months: 1.05 to ± 5.85 (IMN 3 m), 1.07 to ± 6.24 (plate 3 m), 1.32 to ± 7.35 (IMN 6 m) and 1.14 to ± 6.65 (plate 6 m) respectively 51 . One trial 3 , describing investigations for mean times to full weight bearing in IMN versus plating, had to be excluded completely from meta-analysis due to insufficient data for SD derivation. Primary meta-analyses The quantity of RCTs included in each outcome’s meta-analysis depended on the number of studies investigating it, under the same technique comparison. A summary of their findings was reported in Fig. 5 , including: pooled risk ratios (RR) and mean differences (MD), 95% confidence intervals (CI), sample sizes, I 2 heterogeneity values, risk of bias summaries, and certainty of evidence judgements. IMN was the intervention and plating was the comparator in all rows. There were insufficient RCTs for meta-analysis of CEF compared to the other interventions. All meta-analyses, heterogeneity and overall effect calculations were displayed on forest plots in the Supplementary Information 4 ( SI4 ). Significantly faster union times and lower superficial infection rates (Fig. 2 , 3 ) were found in IMN versus plating (Z=-2.76 and p = 0.0221; Z=-3.29 and p = 0.0113). As the only outcome with ≥ 10 studies available for meta-analysis, Egger’s test 55 could be performed for times to union. This confirmed insignificant publication bias (p = 0.6038). Further details and a corresponding funnel plot were compiled ( SI3.2 ). No significant difference was found in time to full-weight bearing in IMN versus plating. However, the pooled MD favoured IMN at -0.87. The 95% confidence interval was calculated using the classical normal approximation since the HK random-effects model produced degenerate values (Z=-Inf). This was prespecified in the Methods section. Sensitivity analyses As mentioned in the methods, exclusions were made for various reasons: studies at a high risk of methodological bias and outcomes requiring SD retrieval via calculation or unit conversion (days to weeks). This unit conversion was done in one trial 10 , and it resulted with an artificially small SD and a consequently exaggerated weight. Six 2 , 5 , 6 , 10 , 11 , 51 trials reporting time to union were excluded from the sensitivity analysis: three 5 , 6 , 51 for SD retrieval by calculation, one 10 for SD unit conversion and the two 2 , 11 remaining were at a high risk of bias. The four 3 , 7 , 52 , 53 , remaining, showed no significant difference between IMN and plating techniques (Z= -0.05 and p = 0.964) and low heterogeneity (I 2 = 0.0%). The pooled MD favoured IMN at -0.02 but the 95% CI was − 1.59 to 1.54. Three 2 , 6 , 11 trials reporting superficial infections were excluded for being at a high risk of methodological bias. Five 3 , 7 , 10 , 52 , 53 trials remained for sensitivity analysis. These showed no significant difference between IMN and plating techniques (Z= -2.13 and p = 0.1) and a slightly higher heterogeneity compared to primary meta-analysis (I 2 = 24.7%). The pooled RR favoured IMN at 0.37 but the 95% CI was 0.10 to 1.36. One 6 trial reporting deep infections was excluded for being at a high risk of methodological bias. Seven 3 , 7 , 8 , 9 , 51 , 52 , 53 trials remained for sensitivity analysis. These showed no significant difference between IMN and plating techniques (Z= -1.96 and p = 0.0982) and an equally low heterogeneity compared to primary meta-analysis (I 2 = 0.0%). The pooled RR favoured IMN at 0.49 but the 95% CI was 0.20 to 1.19. No exclusions were warranted for the sensitivity analysis of “overall complications”. All other outcomes only had two trials in their meta-analysis and at least one trial was excluded in each. Thus, only four outcomes could have a sensitivity analysis out of the nine initially meta-analysed. *Time to full weight-bearing was the only outcome whose confidence interval had to be calculated using the Common effect model rather than Random effect model (HK). Descriptive analyses of extracted data All the 54 articles had their outcome results extracted and compiled into tables, available in the Supplementary Information ( SI2 ). 75% of NRSs found shorter mean times to union in IMN versus plating. Seven 15 , 24 , 25 , 31 , 33 , 38 , 43 out of the eight 15 , 24 , 25 , 31 , 33 , 38 , 39 , 43 studies, identifying a statistical significance in this difference, favoured IMN. NRSs and RCTs suggested shorter mean times to union in plating versus CEF as six out of nine studies favoured plating techniques. Four 13 , 24 , 37 , 48 out of the five 13 , 24 , 29 , 37 , 48 studies, identifying a statistical significance in this difference, favoured plating. Both studies comparing mean times to union in all 3 techniques were NRSs 24 , 37 . These showed significantly longer mean times to union in CEF versus plating or IMN. Tukade 24 (2023) summarised this finding with a single p-value by ANOVA (p = 0.002). Jöstl 37 et al. (2015) outlined the significantly shorter times to union in plating compared to CEF (p = 0.01) and IMN compared to CEF (p = 0.001). Sixteen out of eighteen NRSs investigating mean times to partial or full weight-bearing found IMN faster than plating. The remaining two studies 18 , 19 , showing otherwise, reported no significant differences. CEF was also found to be faster than plating in all four studies making this comparison. The only three-way comparison which compared the times to full-weight bearing was the NRS by Tukade 24 (2023). This found the time to full weight-bearing in IMN to be significantly faster than CEF and in CEF to be significantly faster than plating. The reported p-value was “p < 0.00001” 24 . Thirteen out of nineteen NRSs found a decrease in superficial infections when using IMN compared to plating. Two 18 , 41 found IMN to be no different to plating and the remaining four 24 , 32 , 39 , 45 NRSs actually favoured plating. Tests for statistical significance were sparse and the only identification of a significant difference, favoured IMN (p = 0.031) 38 . Nevertheless, plating was found to have a reduced incidence of superficial infections when compared to CEF in most studies: four 13 , 36 , 40 , 48 , out of six NRSs. One 24 found no difference in infection rates and the only identification of a significant difference between techniques favoured plating over CEF (p = 0.031) 13 . Tukade 24 (2023) was the only study to compare infection rates between all three techniques. One superficial infection was found in the IMN group and none in CEF nor plating. Deep infections were only noted for one patient in the plating group and none in IMN nor CEF. The sample sizes were eleven (IMN), four (CEF) and fifteen (plating). No tests for statistical significance were conducted. Similar patterns for deep infections were evident in other studies. Three out of nineteen NRSs found no deep infections in neither plating nor IMN. 94% of the remaining studies showed decreased deep infections in IMN compared to plating. Only one study 49 found the contrary, but there was no significance in this difference (p = 0.46) 49 . Plating and CEF were found to have similar deep infection rates. Three 36 , 40 , 48 of seven NRSs favoured plating, one 29 of six found no difference, and the remaining three 13 , 24 , 54 NRSs - along with the only 12 RCT - favoured CEF. Overall infection rates were substantially lower in IMN compared to plating in 100% of studies investigating this outcome. These included six 14 , 30 , 35 , 39 , 42 , 47 NRSs and one 52 RCT. The same was found when investigating overall complication rates where all six out of six NRSs 21 , 30 , 34 , 37 , 41 , 46 noted decreased overall complications in IMN compared to plating. Overall infections for CEF were compared in only one study 54 and found to be higher than plating. Only three 13 , 36 , 37 NRSs compared CEF’s overall complications to plating groups’. Three out of three NRSs found reduced overall complications in plating versus CEF. One 36 found significantly reduced overall complications in plating compared to CEF (p = 0.007) and a second NRS 13 found no significant difference (p = 0.520). Jöstl et al. (2015) 37 compared the overall complications in all three surgical techniques and found the greatest rates in CEF followed by plating and then IMN. The NRSs showed very similar American Orthopaedic Foot & Ankle Scores (AOFAS) in comparisons between IMN and plating. Seven 17 , 21 , 34 , 35 , 38 , 45 , 46 out of eleven studies showed no significant differences and two 28 , 41 NRSs showed significantly better AOFAS in IMN (p = 0.0219 28 and p = 0.019 41 ). The remaining two NRSs 20 , 22 compared all three techniques, showing significantly better AOFAS scores in plating followed by IMN and finally CEF (p = 0.05 20 and p < 0.001 22 ). Only one study found significantly better long-term AOFAS in CEF compared to plating (p = 0.001) 48 . Another study 25 reported the distribution of patients’ AOFAS; no significance analyses were performed but outcomes were considerably more favourable in IMN compared to plating ( see SI2.2.3 ). Olerud-Molander Ankle Scores (OMAS) also showed very similar results. Six 15 , 16 , 24 , 31 , 43 , 50 out of eight NRSs showed no significant differences between IMN and plating and one 24 of these also found no significant difference between them and CEF (p = 0.59) 24 . The two 19 , 42 remaining studies found significantly better outcomes in IMN compared to plating (p = 0.013 19 and p = 0.008 42 ). Teeny and Wiss scores were only compared between plating and IMN. Three 14 , 18 , 32 NRSs found no significant differences between the mean total scores for these techniques (p = 0.767 14 , p = 0.451 18 and “p > 0.05” 32 ). Kaya 41 et al. (2023) reported the distribution of Teeny and Wiss scores rather than a mean total value and found significantly better results in IMN compared to plating (p = 0.03). Discussion This systematic review and meta-analysis synthesised evidence from 54 studies, including 15 RCTs, to compare intramedullary nailing (IMN), plate fixation, and circular external fixation (CEF) for fractures of the distal third of the tibia. The principal findings from pooled RCT data were that IMN was associated with a modest but statistically significant reduction in time to union and superficial infections when compared with plating. These were supported by the minimal heterogeneity between studies along with high and moderate certainties of evidence 68 , respectively. These findings are concordant with existing literature 6 ,56 suggesting that fracture healing and infection control is improved through better preservation of periosteal blood supply and reduced disruption of the soft-tissue envelope. This highlights the benefits of methods, like IMN and CEF, which are less disruptive to regions adjacent to the fracture site. Importantly, the consistency of this result across randomised and non-randomised studies in the present review, and others 57 ,59 , supports its robustness. Despite not reaching statistical significance, the pooled effect estimates for deep infection rates also favoured IMN (Fig. 4 ). This aligns with the hypothesis that less invasive surgical approaches reduce the risk of soft-tissue complications in the distal tibia, a region characterised by its limited soft-tissue coverage. Most reviews meta-analysed overall infections without discriminating between superficial and deep. These consistently found significantly decreased infections in IMN versus plating like that by Bleeker 57 et al. (2021): the pooled odds ratio (OR) was 2.41 and 95% CI = 1.52 to 3.81. Zhou 58 et al. (2025), who compared IMN only to the minimally invasive percutaneous plate osteosynthesis (MIPPO), still found IMN to have significantly reduced infections: pooled OR = 2.86 and 95% CI = 1.91 to 4.28. No statistically significant differences were identified between IMN and plating for functional outcomes, including AOFAS, OMAS, and Foot Function Index scores, upon follow-up. However, these analyses were limited by small sample sizes and wide confidence intervals, resulting in lower certainties of evidence 68 . Despite point estimates consistently favouring IMN, functional equivalence rather than superiority is, currently, the most defensible interpretation. These findings are consistent with other reviews 57 , 58 which also combined all functional outcomes together and still found no significant differences (pooled MD=-0.39 and 95% CI = -0.86 to 0.08 57 ; pooled MD=-0.06 and 95% CI = -0.19 to 0.07 58 ). Some reviews also investigated the specific functional challenges that patients experienced, like the significantly increased ankle stiffness in plating (pooled OR = 2.33 and 95% CI = 1.05 to 5.18 58 ) and anterior knee pain in IMN (pooled OR = 0.08 and 95% CI = 0.03 to 0.18 58 ; pooled OR = 3.94 and 95% CI = 1.68 to 9.28 59 ). Evidence comparing circular external fixation (CEF) with internal fixation techniques was sparse and predominantly from NRSs. Descriptive analysis suggested longer times to union, more infections and higher overall complication rates with circular frames compared with IMN or plating. The absence of adequately powered randomised comparisons and limited meta-analyses precludes definitive conclusions regarding the relative effectiveness of CEF. These few studies focused on the use of CEF in more severe distal tibia fractures such as open or intra-articular types. Some meta-analyses supported the conclusions made in this review’s descriptive analysis. For example, Liu 61 et al. (2023) compared IMN to external fixators (EF) in open tibial fractures and found significantly faster union times in IMN (pooled MD = 2.12 and 95% CI = 0.94 to 3.29) on sensitivity analysis, reduced superficial infections (pooled RR = 3.15 and 95% CI = 2.03 to 4.88), and no difference in deep infections (pooled RR = 1.33 and 95% CI = 0.68 to 2.59). This concluded in favour for IMN over EF, even for these severe injuries. However, it 61 does not fully translate into the scope of this review: neither did they focus on distal tibia fractures nor CEF specifically. However, these differences were possibly unimpacted by the inclusion of (monolateral) ankle-spanning EF as they have shown to be no different to their ankle-sparing (circular) counterparts 62 in these domains. Malik-Tabassum 60 et al. (2020) conducted a meta-analysis focusing specifically on intra-articular distal tibia fractures and compared CEF with open-reduction internal fixation (ORIF) plating. They found no significant difference in infective complications (pooled RR = 0.30 and 95% CI = 0.06 to 1.58). However, this could be due to the invasive nature of ORIF operations balancing against the pin tract infection risks of the external fixator. Our review’s descriptive analyses highlighted the reduced infection rates in plating versus CEF, by including investigations of less invasive plating techniques (MIPPO). Union times were not investigated in the review by Malik-Tabassum 60 et al. (2020), but our review’s descriptive analysis deemed them to be faster in plating 24 , 37 . They 60 concluded that both techniques were comparable and they also noted the trend in treating more severe injuries with CEF to “minimise the risk of iatrogenic soft tissue injury (with ORIF)” 60 . An advantage of CEF is the potential for immediate weight-bearing, which is generally contraindicated in other techniques due to risks like hardware failure 61 . This feature has been reported 63 to be particularly beneficial for patients with “cognitive or behavioural disorders”, who may struggle to adhere to postoperative weight-bearing restrictions. However, it is important to note that these same patients may also have difficulty complying with essential postoperative frame-hygiene instructions, increasing the risk of complications such as pin tract infections. A limitation of this review’s design was its focus on outcomes that were favoured in IMN over other techniques such as union times and infection rates. Over the course of this review some disadvantages in IMN were noted like misalignment and the aforementioned knee pain 58 ,59 . Misalignment and malunion were assessed in approximately two-thirds of RCTs and three-quarters of NRSs. Most studies reported a higher incidence of malunion or misalignment with IMN and CEF compared to plating. However, in NRSs, the differences between groups were often minimal and failed to reach statistical significance. For example, Vaienti 42 et al. (2019) conducted a prospective NRS involving 183 patients and found no significant differences in rotational, varus, or valgus deformities. In contrast, most RCTs reported statistically significant differences between groups. For ethical reasons, no p-values or quantitative data were extracted for this outcome in accordance with the review protocol, representing a limitation. Other meta-analyses 58 noted significantly increased rates of malalignment in IMN compared to plating (pooled OR = 0.58 and 95% CI = 0.40 to 0.84) 58 . Despite these findings, it has been shown 64 that nail positioning can significantly impact the quality of alignment and this must be considered before concluding that misalignment is consistently increased in all IMN. Garbano 64 et al. (2023) found that “distal positioning of the nail … (zone 2–2) allows high alignment percentages to be obtained” 64 , while “nail positioning in the 3 − 2 zone generated a significant risk of misalignment (OR 18.55; p = 0.009)” 64 . Another consideration is the “clinical” or functional significance of the malalignment rather than simply using statistical significances to discredit IMN. This could be calculated by identifying the needs for re-intervention following misalignment or malunion from IMN. Bleeker 57 et al. (2021) noted no significant differences in numbers of re-interventions for IMN versus plating (weighted OR = 1.3 and 95% CI = 0.8 to 1.9). However, this could be masked by other indications for re-intervention in both groups and highlights a key research gap. We aim to fill this with a retrospective study investigating the rates of reintervention for misalignment or malunion, following IMN for distal tibia fractures. Another limitation of this review is the breadth of its scope. Including all distal tibia fractures, rather than analysing open, closed, intra-articular, and extra-articular types separately, provides a broad overview of fixation methods and allows for sufficiently powered meta-analyses. However, this also introduces potential bias, such as the disproportionately higher number of extra-articular fractures, which may influence pooled estimates. Consequently, the generalisability of the findings is limited, despite what the title suggests. This was somewhat clarified by availability of baseline characteristics along with the extracted outcome data in the Supplementary information (SI2: SI2.1.1 and SI2.2.1 ). Variations also existed in surgical technique (e.g. minimally invasive versus open plating), post-operative rehabilitation protocols, and outcome definitions. These factors likely contributed to some clinical heterogeneity not fully captured by statistical measures. Although fifteen RCTs were included, many outcomes were informed by only two trials, leading to imprecise estimates and lower certainties of evidence 68 . This was particularly evident for functional outcomes and times to full weight-bearing. Additionally, some trials were small and underpowered, increasing the risk of type II error. Therefore, their conclusions were reinforced by descriptive analysis of NRSs. Furthermore, outcome reporting was inconsistent, with occasional misreporting or omission of standard deviations, necessitating data conversions that may have introduced additional imprecision. Although sensitivity analyses were conducted to mitigate this, the exclusions attenuated the significance of findings. Consequently, definitive conclusions were mainly drawn from primary meta-analyses with moderate or high certainties of evidence 68 due to their greater statistical power, at the cost of minor potential biases. Finally, the evidence base for circular external fixation was dominated by non-randomised studies with small sample sizes, limiting confidence in comparative effectiveness estimates for this technique. This review also had methodological limitations. Despite a comprehensive search strategy and rigorous screening process, unpublished or selectively reported trials may have been missed, particularly among registered clinical trials without available results. Although publication bias was formally assessed for time to union (found insignificant and unlikely), this could not be evaluated for most outcomes due to the limited number of studies. The decision to restrict quantitative synthesis to RCTs enhanced internal validity but reduced statistical power for less frequently reported outcomes. Additionally, while sensitivity analyses were prespecified and transparently conducted, the exclusion of studies with converted or imputed variance data reduced the number of eligible trials and may have obscured true effects. Once more highlighting our reasons for deriving conclusions from primary meta-analyses with moderate or high certainties of evidence 68 . From a clinical perspective, the findings of this review support intramedullary nailing as a first-line surgical option for extra-articular distal third tibial fractures, given its association with faster union and lower infection rates without compromise in functional outcomes. Plating remains a valid alternative in cases where IMN is contraindicated or technically unsuitable, but surgeons should remain mindful of its higher soft-tissue complication risks. The role of circular external fixation appears more limited and should likely be reserved for specific indications such as compromised soft tissues, infection, or complex fracture patterns, pending higher-quality comparative evidence. Reductions in specific complications may be more beneficial to different patient demographics and injury types. For example, a younger, more active, patient may be better suited to plating techniques, to minimise the risk of chronic knee pain from IMN, at the cost of an increased risk of superficial infection. An older, more vulnerable patient may prioritise the reduced infection risk demonstrated by IMN at the cost of knee pain or minor misalignment. At a policy level, these findings may inform evidence-based treatment algorithms and training priorities, particularly in high-volume trauma centres where distal tibial fractures are commonly encountered. Future research should focus on well-powered randomised comparisons between all three surgical techniques. We also aim to explore the clinical and functional significance of the noted misalignment in IMN through a retrospective study, as was discussed previously. Qualitative research may also give a better understanding on what specific difficulties are faced following misalignment and how acceptable these are in different demographics (e.g. age, activity-status, or job-type). This will help tailor surgical treatment plans for future patients, based on their unique preferences and priorities. In summary, intramedullary nailing demonstrates a favourable balance between fracture healing, infection risk, and functional recovery when compared with plate fixation for distal-third tibial fractures, particularly in extra-articular patterns. While circular external fixation remains a valuable technique in selected clinical scenarios, its comparative effectiveness relative to internal fixation remains insufficiently defined. This underscores the need for high-quality comparative trials in this challenging fracture population. These conclusions reinforce the need for individualised surgical decision-making. Notably, although malalignment was more frequently reported following intramedullary nailing, the clinical relevance of these radiographic findings remains unclear. Future research should therefore focus on determining whether malalignment translates into increased rates of reintervention or functional impairment, through retrospective analyses of reoperation following intramedullary fixation. Addressing these uncertainties will be essential to refine treatment selection and optimise patient-centred outcomes. Materials and methods The systematic review and meta-analyses were conducted in accordance with the 2020 PRISMA guidelines and the prespecified protocol, registered on PROSPERO. Search strategies Two independent researchers (JD and HC) searched the following databases: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Allied and Complementary Medicine Database (AMED - EBSCO) and ClinicalTrials.gov (for grey literature). Consistent MeSH terms and Boolean operators were used ( SI1.2 ). No restrictions were applied based on the publication date of studies; all available studies, published in English, were considered. All searches were conducted on the 23/7/25 except for the Scopus search which had to be performed on the 24/7/25 due to technical difficulties. Screening and eligibility criteria Two reviewers independently screened articles in two phases: title/abstract screening followed by full-text screening. Disagreements were resolved by in-person discussions at the end of each phase. If a consensus could not be reached, a third reviewer was consulted (senior author - PB). Rayyan software was used for both automated and manual deletion of duplicate search results before beginning the title/abstract screening. The inclusion and exclusion criteria were specified in SI1.2 , with no deviation from the PROSPERO registration. In the second conflict-resolution meeting, it was agreed that all conference abstracts were to also be excluded due to insufficient information. The same was decided for certain pieces of grey literature, identified on ClinicalTrials.gov, which had unpublished results. The screening process was documented using the PRISMA 2020 flow diagram template, which was adapted to suit the specifics of our review. For example, boxes related to previous reviews were removed as no prior, identical, systematic reviews were identified. Data extraction Two reviewers independently extracted data from the included studies, using the prespecified set of outcomes: time to union (weeks), time to partial weight-bearing (weeks), time to full weight-bearing (weeks), rate of superficial infections (%), rate of deep infections (%), overall infection rate (%), overall complication rate (%), American Orthopaedic Foot & Ankle Society (AOFAS) scoring system 69 , Olerud-Molander Ankle Scores (OMAS) 72 , and the Teeny and Wiss score 73 . Additional functional or radiological measures, such as the Disability Rating Index (DRI) 70 and the Foot Function Index (FFI) 71 , were also recorded. No automation tools were used and discrepancies in extracted data were resolved through discussion. Baseline characteristics, including the country and clinical setting of each study, were systematically recorded alongside detailed descriptions of the surgical interventions. Particular attention was given to variations in plating techniques, such as the use of minimally invasive plate osteosynthesis (MIPO) compared with the more traditional open reduction and internal fixation (ORIF), to capture differences in operative approach across studies. The outcome “Overall complication rate (%)” was considered ambiguous and was inconsistently calculated between studies. To ensure consistency, it was collected only when explicitly defined as including the following complications: superficial infections, deep infections, malunion, non-union, and delayed union. Most time-related outcomes were already reported in weeks. If expressed in other units, they were converted to weeks for consistency. Days were converted to weeks by dividing by seven. Months were converted by multiplying by 52 and dividing by 12. Infection and complication rates were reported as either percentages or dichotomous events. These were extracted as percentages to contextualise the events within their sample sizes and, consequently, enhance readability. An additional column titled “Points of Interest” was included in the data extraction table to record comments on outcomes not prespecified in the PROSPERO registration. No numerical data were entered in this column to prevent introduction of bias. Randomised controlled trials (RCTs) and non-randomised studies (NRSs) were organised into separate tables (see Results). Meta-analysis was performed exclusively on RCTs with two or more studies measuring a given outcome, due to their higher certainty of evidence. No assumptions were made for missing data, and some studies were excluded from meta-analyses if they measured outcomes too inconsistently with other studies. For example, time-related outcomes were meta-analysed as a continuous measure; studies reporting these outcomes as “rates at a given time point”, were excluded from meta-analysis. Studies with unclear or inconsistent reporting were excluded from this systematic review altogether. Handling Missing or Misreported Standard Deviations When studies did not report standard deviations (SDs), established imputation methods were applied to assist the meta-analyses. If only the range was available, SD was estimated using the Wan 67 et al. (2014) approach for sample sizes of ≥ 25 participants: SD ≈ (max-min) / 4. For studies reporting means with 95% confidence intervals (CIs) but not SDs, advice from the Cochrane Handbook 66 (Section 6.5.2.3) was used. The standard error (SE) was first derived as: SE = (Upper CI – Lower CI) / (2 * t 0.975,n−1 ), and SD was subsequently calculated as : SD = SE * (√n). In one instance, it was noted that one study’s weighting was unusually high compared to another’s. On closer inspection of its results, it was noted that it had probably mislabelled its standard error of the mean (SEM) as SD. This was also corrected using: SD = SE * (√n). Studies lacking sufficient data to derive SDs were excluded from the meta-analysis. All collected SDs were audited for consistency, and unusually small SDs were investigated for unit conversion issues and presented in the Results (e.g. days to weeks). Risk of Bias assessment Two reviewers independently assessed the risk of bias for all included RCTs using the RoB 2 tool. Risk of bias assessment was limited to RCTs, as these were the only study designs included in the meta-analyses and subsequent sensitivity analyses. Discrepancies were resolved through discussion, and final judgments were summarised, using the Robvis tool, in traffic-light and distribution summary plots (see Results ). RoB2 tool decision pathways were reported in detail along with the plots to ensure transparency within decision making processes. Each was assessed for risk of bias by category of outcome. These categories were split based on the assessor of each outcome: radiographically-assessed, patient-assessed and clinician-assessed. If an outcome was measured by two assessor categories, such as AOFAS scores, it was assigned to the category with the greater risk of bias. For meta-analysed outcomes with ≥ 10 studies, publication bias was evaluated using Egger’s test 55 and illustrated with a funnel plot (see Results ). For outcomes with fewer than 10 contributing studies, formal statistical assessment of reporting bias was not feasible due to insufficient power, and therefore the presence of reporting bias could not be reliably evaluated. Finally, the certainty of evidence for each meta-analysed outcome was appraised using the GRADE 68 approach across five domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Ratings were categorised as high, moderate, low, or very low (see Results ). Statistical analysis Statistical synthesis followed a two-stage approach. Where sufficient homogeneity and data availability permitted, outcomes from randomised controlled trials were quantitatively synthesised using meta-analysis. Where quantitative pooling was inappropriate due to study design, outcome heterogeneity, or limited data, findings were summarised using structured descriptive analyses. Meta-analyses The meta-analysed RCTs’ outcomes were divided into two groups: continuous and dichotomous outcomes. Continuous outcomes – time to union, time to weight bearing and functional/radiological scores – were compared using mean differences. Dichotomous outcomes – infections and complications – were measured as events and consequently compared using risk ratios. These mean differences and risk ratios were displayed along with I 2 tests for heterogeneity, 95% CIs, weighting and overall effect calculations (Z-values) in forest plot formats (see Results ). These were all completed under the conditions of a common and random effects model. Random-effects meta-analyses were performed using the Hartung-Knapp-Sidik-Jonkman (HK) adjustment for confidence intervals. For comparisons where the HK method produced degenerate estimates (e.g., zero-width confidence intervals or infinite test statistics), the classic normal approximation was applied instead. This occurred only in cases with very few studies and zero between-study variance. This was evident in the meta-analysis of the “Time to full weight bearing” outcome. All effect sizes were pooled on the log scale for statistical analysis but back-transformed for presentation as risk ratios to improve interpretability, as recommended by the Cochrane Handbook 65 . All statistical calculations and plots were generated using R (version 4.5.2) within the RStudio software environment (version 2025.09.2 + 418), using the ‘meta’ package (version 8.2.1). Sensitivity analyses were performed using the same statistical approach, applying the following exclusion criteria: (i) studies judged to have a high risk of bias for the outcome of interest, and (ii) studies in which standard deviations were derived through unit conversions or imputation. Subgroup analyses (e.g. extra- versus intra-articular fractures) and meta-regression were not conducted because each outcome included too few studies to support reliable between-study comparisons. Conducting these analyses with such limited numbers would risk producing unstable or spurious findings. Descriptive analyses Data from NRSs were presented in tabular form (Supplementary Information: SI2.2 ) and synthesised descriptively. Owing to the limited literature on circular external fixation, findings from both RCTs and NRSs evaluating this technique were summarised descriptively where quantitative, meta-analytic pooling was not feasible. For outcomes where sufficient RCT data were available to support meta-analysis, descriptive summaries of NRS findings were provided for contextual purposes only and did not contribute to quantitative inference. They served to reinforce conclusions already drawn through meta-analysis. In contrast, for outcomes with insufficient RCT data to permit reliable meta-analysis, more detailed descriptive synthesis of NRS findings was undertaken. This involved reference to the statistical significance of a given outcome comparison. Decisions regarding the depth of descriptive synthesis were assisted by the certainty of evidence 68 assigned to outcomes (GRADE framework). If a significant or insignificant difference was described, p-values, statistical tests and sample sizes were presented in the Supplementary information tables ( SI2 ) to ensure transparency. Other Information This review was registered on PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ) with the following ID: CRD420251108552. No amendments were made to the registered protocol, apart from a minor change to the title phrasing (“frame” changed to “frames”). All supplementary materials such as search terms, data extraction tables, or forest plots were compiled into four separate Supplementary Information documents ( SI1-4 ). Data supporting the findings of this study are available within the article and its Supplementary Information files. The PRISMA 2020 checklist is duly filled in SI5 . Funding Declaration No financial support or funding sponsored this review and none of the authors had competing interests to declare. Declarations Author Contribution J.D. led all stages of the review from protocol registration to manuscript submission. J.D. and H.C. independently screened studies, extracted data, and assessed risk of bias. J.D. performed the statistical analyses and prepared the manuscript text and much of the Supplementary Information. HC contributed to the preparation and formatting of the Supplementary Information. PB conceived the study, developed the protocol, and provided ongoing supervision and critical feedback throughout the review process. All authors reviewed and approved the final manuscript. Data Availability Data supporting the findings of this study are available within the article and its Supplementary Information files. References Rayan, A. et al. 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Bakhshayesh","email":"","orcid":"","institution":"University of Leeds","correspondingAuthor":false,"prefix":"","firstName":"Peyman","middleName":"","lastName":"Bakhshayesh","suffix":""}],"badges":[],"createdAt":"2026-01-02 13:09:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8501129/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8501129/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102347342,"identity":"2d0af402-6f53-48bf-83fa-d53917702d54","added_by":"auto","created_at":"2026-02-10 17:42:17","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":114357,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ePRISMA flowchart depicting the selection process\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/b820b677a18d5bc0513bb4fd.jpg"},{"id":102347379,"identity":"699a18a3-7090-4889-a16f-6f76078050b1","added_by":"auto","created_at":"2026-02-10 17:42:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120543,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eTime to union upon primary meta-analysis\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/2627f5177618f1003c9eb010.jpg"},{"id":102347296,"identity":"7df1162e-70ed-408d-b992-55a5f7fa5870","added_by":"auto","created_at":"2026-02-10 17:42:07","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":126525,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eSuperficial infections upon primary meta-analysis\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/020d4a643cb48486629d258d.jpg"},{"id":102347380,"identity":"ca3cb4cd-a177-4efe-90ff-b29570328108","added_by":"auto","created_at":"2026-02-10 17:42:21","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":136342,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eDeep infections upon primary meta-analysis\u003c/em\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/dc3320b271fd95ac0253deb3.jpg"},{"id":102347384,"identity":"c741b361-79e2-4587-8d5f-7d487ae78bc9","added_by":"auto","created_at":"2026-02-10 17:42:23","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":254408,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003esummary of primary meta-analytic findings\u003cbr\u003e\n *Time to full weight-bearing was the only outcome whose confidence interval had to be calculated using the Common effect model rather than Random effect model (HK).\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage12.png","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/482143663aaa4d2c34fda209.png"},{"id":102397949,"identity":"e4a8048c-427e-4cff-b8ba-83ebb7a6716c","added_by":"auto","created_at":"2026-02-11 10:20:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1759405,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/89d83503-1830-4c3a-95c6-ce29c7882c23.pdf"},{"id":102347200,"identity":"3beadbb0-83c4-4c85-9f4a-f0eab291afab","added_by":"auto","created_at":"2026-02-10 17:41:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":4641120,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8501129/v1/16c63c185cc6243a7c96a9a4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative Effectiveness of Circular Frames, Plate Fixation, and Intramedullary Nailing in Distal-Third Tibial Fractures: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFractures of the distal-third of the tibia represent a common and clinically challenging injury, owing to the limited soft-tissue envelope, compromised blood supply, and proximity to the ankle joint\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e,56\u003c/sup\u003e. These anatomical characteristics contribute to an increased risk of delayed union, infection, malalignment, and functional impairment following surgical fixation\u003csup\u003e56\u003c/sup\u003e. As a result, the optimal management of distal tibial fractures remains an area of ongoing clinical uncertainty.\u003c/p\u003e \u003cp\u003eThree principal surgical strategies are currently employed: intramedullary nailing (IMN), plate fixation, and circular external fixation (CEF). IMN is widely used due to its minimally invasive nature, preservation of periosteal blood supply, and potential for early mobilisation. Plate fixation allows accurate fracture reduction and alignment and may facilitate early functional recovery, but is associated with soft-tissue complications, especially in the distal tibia where surgical exposure is limited\u003csup\u003e56,\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. CEF offers stable fixation with minimal disruption of the fracture biology and permits early weight-bearing, yet it has been associated with pin tract infections, patient discomfort, and prolonged treatment duration\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e60\u003c/span\u003e,63\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite the availability of randomised controlled trials and observational studies comparing these techniques, the existing evidence base remains fragmented. Most prior systematic reviews and meta-analyses have focused on pairwise comparisons: most commonly IMN versus plate fixation\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e57\u003c/span\u003e,\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e58\u003c/span\u003e,59\u003c/sup\u003e. There has been minimal incorporation of CEF\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e and limited distinction between superficial and deep infection outcomes, which have differing clinical implications. Consequently, clinicians lack a comprehensive synthesis of evidence comparing all three fixation strategies across clinically relevant outcomes.\u003c/p\u003e \u003cp\u003eA systematic review evaluating all three fixation techniques is therefore warranted to better inform surgical decision-making for the management of these fractures.\u003c/p\u003e \u003cp\u003eThe objective of this systematic review and meta-analysis was to compare the effectiveness and safety of intramedullary nailing, plate fixation, and circular external fixation for all distal-third tibial fractures. Specifically, we aimed to evaluate differences between fixation strategies with respect to union times, superficial and deep infections, functional outcomes, and other reported complications, meta-analysing evidence from randomised controlled trials where available and contextualising findings using non-randomised studies.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eScreening and selection process\u003c/h2\u003e \u003cp\u003eAmong the 1463 retrieved articles, 669 were automatically deleted by the Rayyan software (version 1.4.3) and 13 were deleted manually. Following title and abstract screening, 115 articles remained. These articles\u0026rsquo; full-texts were retrieved and scrutinised against the inclusion criteria (\u003cem\u003eSI1.1\u003c/em\u003e). Finally, 54 articles were included in this review\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSome articles appeared to meet all eligibility criteria but were excluded because their results were unavailable. This was particularly noted for some clinical trial registrations, where published results could not be identified despite searching their NCT numbers across registries and other databases.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eBaseline characteristics\u003c/h3\u003e\n\u003cp\u003eAll the 54 articles had their baseline characteristics summarised in tables (SI2: \u003cem\u003eSI2.1.1\u003c/em\u003e and \u003cem\u003eSI2.2.1\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eFifteen randomised control trials (RCTs) and thirty-nine non-randomised studies (NRSs) were identified. The distribution of the fracture types investigated was substantially skewed towards extra-articular distal tibia fractures (AO43A). Approximately 80% of RCTs and 67% of NRSs only included extra-articular fractures; around 6.7% of RCTs and 17% of NRSs only included intra-articular fractures (AO43B/C). The remaining 15% of studies included both fracture types. Most investigations were performed in tertiary settings. The only study that involved a combination of tertiary and \u0026ldquo;regional trauma units\u0026rdquo; was the UK FixDT\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e trial: a RCT which included 321 patients from 28 acute trauma centres in the United Kingdom.\u003c/p\u003e \u003cp\u003eOnly 19% of the included studies compared circular external fixation (CEF) with the alternative techniques, and notably, just two of these were RCTs. In contrast, comparisons between plating and intramedullary nailing (IMN) were far more common, investigated in 87% of studies.\u003c/p\u003e\n\u003ch3\u003eRisk of Bias – quality assessment\u003c/h3\u003e\n\u003cp\u003eRisk of bias was evaluated across fifteen RCTs using the RoB 2 tool. Three studies\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e were judged to have a high risk of bias. In two trials\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, concerns arose in Domain 1 (randomisation process) because treatment allocation was performed using non-random methods such as \u0026ldquo;every other participant\u0026rdquo;\u003csup\u003e2\u003c/sup\u003e or a \u0026ldquo;coin flip,\u0026rdquo;\u003csup\u003e11\u003c/sup\u003e introducing potential selection bias. The third study\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e was rated high risk in Domain 3 (missing outcome data) due to incomplete reporting: the authors did not specify which intervention groups participants lost to follow-up belonged to, nor did they provide reasons for attrition. Consequently, the proportion of missing data per group was unclear: different reasons for missingness between groups could not be ruled out.\u003c/p\u003e \u003cp\u003eMost RCTs had no trial registration numbers available so they automatically ranked at \u0026ldquo;some concerns\u0026rdquo; in Domain 5 (selection of the reported result). The same judgement was apparent for the second part of Domain 2 (deviations from intended interventions) because very few studies had performed ITT or mITT analyses.\u003c/p\u003e \u003cp\u003eBy use of traffic-light and summary plots, distribution of judgements by domain and outcome category were displayed in the Supplementary Information (\u003cem\u003eSI3.1\u003c/em\u003e). Precise RoB2 tool decision pathways and reasoning for judgements were compiled in tables (\u003cem\u003eSI3.1.1.3\u003c/em\u003e, \u003cem\u003eSI3.1.2.3\u003c/em\u003e and \u003cem\u003eSI3.1.3.3\u003c/em\u003e).\u003c/p\u003e\n\u003ch3\u003eMisreporting of standard deviations\u003c/h3\u003e\n\u003cp\u003eDue to inconsistent reporting of standard deviations (SDs) for continuous outcomes, conversions were used as previously described in the Methods section.\u003c/p\u003e \u003cp\u003eIm\u003csup\u003e6\u003c/sup\u003e et al., 2005, reported ranges for times to union. These were converted from \u0026ldquo;12\u0026ndash;64\u0026rdquo; into \u0026plusmn;\u0026thinsp;13 (IMN) and \u0026ldquo;12\u0026ndash;72\u0026rdquo; into \u0026plusmn;\u0026thinsp;15 (plate). Guo\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e et al., 2010, reported 95% confidence intervals (CIs) and these were converted to standard errors (SE) and subsequently to SDs. For \u0026ldquo;time to union\u0026rdquo; (weeks) the 95% CIs were converted from \u0026ldquo;16.7\u0026ndash;18.6\u0026rdquo; into \u0026plusmn;\u0026thinsp;3.127 (IMN) and \u0026ldquo;16.9\u0026ndash;18.3\u0026rdquo; into \u0026plusmn;\u0026thinsp;2.219 (plate). AOFAS\u0026rsquo;, at 12 months post-operatively, 95% CIs we converted from \u0026ldquo;83.7\u0026ndash;88.6\u0026rdquo; to \u0026plusmn;\u0026thinsp;8.064 (IMN) and \u0026ldquo;81.7\u0026ndash;86.1\u0026rdquo; to \u0026plusmn;\u0026thinsp;6.975. A similar conversion method was used when another trial\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e had, likely, mislabelled their SEs as SDs. This was noted when it was meta-analysed with a much larger trial by Costa\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e et al., 2018, and it was being weighted disproportionately highly due to an unnaturally minute standard deviation value. Its mislabelled SE for \u0026ldquo;time to union\u0026rdquo; (weeks) was converted from 0.58 to \u0026plusmn;\u0026thinsp;3.23 (IMN) and 0.53 to \u0026plusmn;\u0026thinsp;3.09 (plate). The same conversion done for OMAS, at 3 months (m) and 6 months: 1.05 to \u0026plusmn;\u0026thinsp;5.85 (IMN 3 m), 1.07 to \u0026plusmn;\u0026thinsp;6.24 (plate 3 m), 1.32 to \u0026plusmn;\u0026thinsp;7.35 (IMN 6 m) and 1.14 to \u0026plusmn;\u0026thinsp;6.65 (plate 6 m) respectively\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOne trial\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, describing investigations for mean times to full weight bearing in IMN versus plating, had to be excluded completely from meta-analysis due to insufficient data for SD derivation.\u003c/p\u003e\n\u003ch3\u003ePrimary meta-analyses\u003c/h3\u003e\n\u003cp\u003eThe quantity of RCTs included in each outcome\u0026rsquo;s meta-analysis depended on the number of studies investigating it, under the same technique comparison. A summary of their findings was reported in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, including: pooled risk ratios (RR) and mean differences (MD), 95% confidence intervals (CI), sample sizes, I\u003csup\u003e2\u003c/sup\u003e heterogeneity values, risk of bias summaries, and certainty of evidence judgements. IMN was the intervention and plating was the comparator in all rows. There were insufficient RCTs for meta-analysis of CEF compared to the other interventions. All meta-analyses, heterogeneity and overall effect calculations were displayed on forest plots in the Supplementary Information 4 (\u003cem\u003eSI4\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eSignificantly faster union times and lower superficial infection rates (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) were found in IMN versus plating (Z=-2.76 and p\u0026thinsp;=\u0026thinsp;0.0221; Z=-3.29 and p\u0026thinsp;=\u0026thinsp;0.0113). As the only outcome with \u0026ge;\u0026thinsp;10 studies available for meta-analysis, Egger\u0026rsquo;s test\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e could be performed for times to union. This confirmed insignificant publication bias (p\u0026thinsp;=\u0026thinsp;0.6038). Further details and a corresponding funnel plot were compiled (\u003cem\u003eSI3.2\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eNo significant difference was found in time to full-weight bearing in IMN versus plating. However, the pooled MD favoured IMN at -0.87. The 95% confidence interval was calculated using the classical normal approximation since the HK random-effects model produced degenerate values (Z=-Inf). This was prespecified in the Methods section.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analyses\u003c/h2\u003e \u003cp\u003eAs mentioned in the methods, exclusions were made for various reasons: studies at a high risk of methodological bias and outcomes requiring SD retrieval via calculation or unit conversion (days to weeks). This unit conversion was done in one trial\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, and it resulted with an artificially small SD and a consequently exaggerated weight.\u003c/p\u003e \u003cp\u003eSix\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e trials reporting time to union were excluded from the sensitivity analysis: three\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e for SD retrieval by calculation, one\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e for SD unit conversion and the two\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e remaining were at a high risk of bias. The four\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e, remaining, showed no significant difference between IMN and plating techniques (Z= -0.05 and p\u0026thinsp;=\u0026thinsp;0.964) and low heterogeneity (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%). The pooled MD favoured IMN at -0.02 but the 95% CI was \u0026minus;\u0026thinsp;1.59 to 1.54.\u003c/p\u003e \u003cp\u003eThree\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e trials reporting superficial infections were excluded for being at a high risk of methodological bias. Five\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e trials remained for sensitivity analysis. These showed no significant difference between IMN and plating techniques (Z= -2.13 and p\u0026thinsp;=\u0026thinsp;0.1) and a slightly higher heterogeneity compared to primary meta-analysis (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;24.7%). The pooled RR favoured IMN at 0.37 but the 95% CI was 0.10 to 1.36.\u003c/p\u003e \u003cp\u003eOne\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e trial reporting deep infections was excluded for being at a high risk of methodological bias. Seven\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e trials remained for sensitivity analysis. These showed no significant difference between IMN and plating techniques (Z= -1.96 and p\u0026thinsp;=\u0026thinsp;0.0982) and an equally low heterogeneity compared to primary meta-analysis (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0%). The pooled RR favoured IMN at 0.49 but the 95% CI was 0.20 to 1.19.\u003c/p\u003e \u003cp\u003eNo exclusions were warranted for the sensitivity analysis of \u0026ldquo;overall complications\u0026rdquo;. All other outcomes only had two trials in their meta-analysis and at least one trial was excluded in each. Thus, only four outcomes could have a sensitivity analysis out of the nine initially meta-analysed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e*Time to full weight-bearing was the only outcome whose confidence interval had to be calculated using the Common effect model rather than Random effect model (HK).\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDescriptive analyses of extracted data\u003c/h3\u003e\n\u003cp\u003eAll the 54 articles had their outcome results extracted and compiled into tables, available in the Supplementary Information (\u003cem\u003eSI2\u003c/em\u003e).\u003c/p\u003e \u003cp\u003e75% of NRSs found shorter mean times to union in IMN versus plating. Seven\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e out of the eight\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e studies, identifying a statistical significance in this difference, favoured IMN. NRSs and RCTs suggested shorter mean times to union in plating versus CEF as six out of nine studies favoured plating techniques. Four\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e out of the five\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e studies, identifying a statistical significance in this difference, favoured plating. Both studies comparing mean times to union in all 3 techniques were NRSs\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. These showed significantly longer mean times to union in CEF versus plating or IMN. Tukade\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e (2023) summarised this finding with a single p-value by ANOVA (p\u0026thinsp;=\u0026thinsp;0.002). J\u0026ouml;stl\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e et al. (2015) outlined the significantly shorter times to union in plating compared to CEF (p\u0026thinsp;=\u0026thinsp;0.01) and IMN compared to CEF (p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eSixteen out of eighteen NRSs investigating mean times to partial or full weight-bearing found IMN faster than plating. The remaining two studies\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, showing otherwise, reported no significant differences. CEF was also found to be faster than plating in all four studies making this comparison. The only three-way comparison which compared the times to full-weight bearing was the NRS by Tukade\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e (2023). This found the time to full weight-bearing in IMN to be significantly faster than CEF and in CEF to be significantly faster than plating. The reported p-value was \u0026ldquo;p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001\u0026rdquo; \u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThirteen out of nineteen NRSs found a decrease in superficial infections when using IMN compared to plating. Two\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e found IMN to be no different to plating and the remaining four\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e NRSs actually favoured plating. Tests for statistical significance were sparse and the only identification of a significant difference, favoured IMN (p\u0026thinsp;=\u0026thinsp;0.031)\u003csup\u003e38\u003c/sup\u003e. Nevertheless, plating was found to have a reduced incidence of superficial infections when compared to CEF in most studies: four\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003c/sup\u003e out of six NRSs. One\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e found no difference in infection rates and the only identification of a significant difference between techniques favoured plating over CEF (p\u0026thinsp;=\u0026thinsp;0.031)\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTukade\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e (2023) was the only study to compare infection rates between all three techniques. One superficial infection was found in the IMN group and none in CEF nor plating. Deep infections were only noted for one patient in the plating group and none in IMN nor CEF. The sample sizes were eleven (IMN), four (CEF) and fifteen (plating). No tests for statistical significance were conducted.\u003c/p\u003e \u003cp\u003eSimilar patterns for deep infections were evident in other studies. Three out of nineteen NRSs found no deep infections in neither plating nor IMN. 94% of the remaining studies showed decreased deep infections in IMN compared to plating. Only one study\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e found the contrary, but there was no significance in this difference (p\u0026thinsp;=\u0026thinsp;0.46)\u003csup\u003e49\u003c/sup\u003e. Plating and CEF were found to have similar deep infection rates. Three\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e of seven NRSs favoured plating, one\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e of six found no difference, and the remaining three\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e NRSs - along with the only\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e RCT - favoured CEF.\u003c/p\u003e \u003cp\u003eOverall infection rates were substantially lower in IMN compared to plating in 100% of studies investigating this outcome. These included six\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e NRSs and one\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e RCT. The same was found when investigating overall complication rates where all six out of six NRSs\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e noted decreased overall complications in IMN compared to plating. Overall infections for CEF were compared in only one study\u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e and found to be higher than plating. Only three\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e NRSs compared CEF\u0026rsquo;s overall complications to plating groups\u0026rsquo;.\u003c/p\u003e \u003cp\u003eThree out of three NRSs found reduced overall complications in plating versus CEF. One\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e found significantly reduced overall complications in plating compared to CEF (p\u0026thinsp;=\u0026thinsp;0.007) and a second NRS\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e found no significant difference (p\u0026thinsp;=\u0026thinsp;0.520). J\u0026ouml;stl et al. (2015)\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e compared the overall complications in all three surgical techniques and found the greatest rates in CEF followed by plating and then IMN.\u003c/p\u003e \u003cp\u003eThe NRSs showed very similar American Orthopaedic Foot \u0026amp; Ankle Scores (AOFAS) in comparisons between IMN and plating. Seven\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e out of eleven studies showed no significant differences and two\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e NRSs showed significantly better AOFAS in IMN (p\u0026thinsp;=\u0026thinsp;0.0219\u003csup\u003e28\u003c/sup\u003e and p\u0026thinsp;=\u0026thinsp;0.019\u003csup\u003e41\u003c/sup\u003e). The remaining two NRSs\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e compared all three techniques, showing significantly better AOFAS scores in plating followed by IMN and finally CEF (p\u0026thinsp;=\u0026thinsp;0.05\u003csup\u003e20\u003c/sup\u003e and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003csup\u003e22\u003c/sup\u003e). Only one study found significantly better long-term AOFAS in CEF compared to plating (p\u0026thinsp;=\u0026thinsp;0.001)\u003csup\u003e48\u003c/sup\u003e. Another study\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e reported the distribution of patients\u0026rsquo; AOFAS; no significance analyses were performed but outcomes were considerably more favourable in IMN compared to plating (\u003cem\u003esee SI2.2.3\u003c/em\u003e).\u003c/p\u003e \u003cp\u003eOlerud-Molander Ankle Scores (OMAS) also showed very similar results. Six\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e out of eight NRSs showed no significant differences between IMN and plating and one\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e of these also found no significant difference between them and CEF (p\u0026thinsp;=\u0026thinsp;0.59)\u003csup\u003e24\u003c/sup\u003e. The two\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e remaining studies found significantly better outcomes in IMN compared to plating (p\u0026thinsp;=\u0026thinsp;0.013\u003csup\u003e19\u003c/sup\u003e and p\u0026thinsp;=\u0026thinsp;0.008\u003csup\u003e42\u003c/sup\u003e).\u003c/p\u003e \u003cp\u003eTeeny and Wiss scores were only compared between plating and IMN. Three\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e NRSs found no significant differences between the mean total scores for these techniques (p\u0026thinsp;=\u0026thinsp;0.767\u003csup\u003e14\u003c/sup\u003e, p\u0026thinsp;=\u0026thinsp;0.451\u003csup\u003e18\u003c/sup\u003e and \u0026ldquo;p\u0026thinsp;\u0026gt;\u0026thinsp;0.05\u0026rdquo;\u003csup\u003e32\u003c/sup\u003e). Kaya\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e et al. (2023) reported the distribution of Teeny and Wiss scores rather than a mean total value and found significantly better results in IMN compared to plating (p\u0026thinsp;=\u0026thinsp;0.03).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review and meta-analysis synthesised evidence from 54 studies, including 15 RCTs, to compare intramedullary nailing (IMN), plate fixation, and circular external fixation (CEF) for fractures of the distal third of the tibia. The principal findings from pooled RCT data were that IMN was associated with a modest but statistically significant reduction in time to union and superficial infections when compared with plating. These were supported by the minimal heterogeneity between studies along with high and moderate certainties of evidence\u003csup\u003e68\u003c/sup\u003e, respectively.\u003c/p\u003e \u003cp\u003eThese findings are concordant with existing literature\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,56\u003c/sup\u003e suggesting that fracture healing and infection control is improved through better preservation of periosteal blood supply and reduced disruption of the soft-tissue envelope. This highlights the benefits of methods, like IMN and CEF, which are less disruptive to regions adjacent to the fracture site. Importantly, the consistency of this result across randomised and non-randomised studies in the present review, and others\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e57\u003c/span\u003e,59\u003c/sup\u003e, supports its robustness.\u003c/p\u003e \u003cp\u003eDespite not reaching statistical significance, the pooled effect estimates for deep infection rates also favoured IMN (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This aligns with the hypothesis that less invasive surgical approaches reduce the risk of soft-tissue complications in the distal tibia, a region characterised by its limited soft-tissue coverage. Most reviews meta-analysed overall infections without discriminating between superficial and deep. These consistently found significantly decreased infections in IMN versus plating like that by Bleeker\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e et al. (2021): the pooled odds ratio (OR) was 2.41 and 95% CI\u0026thinsp;=\u0026thinsp;1.52 to 3.81. Zhou\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e et al. (2025), who compared IMN only to the minimally invasive percutaneous plate osteosynthesis (MIPPO), still found IMN to have significantly reduced infections: pooled OR\u0026thinsp;=\u0026thinsp;2.86 and 95% CI\u0026thinsp;=\u0026thinsp;1.91 to 4.28.\u003c/p\u003e \u003cp\u003eNo statistically significant differences were identified between IMN and plating for functional outcomes, including AOFAS, OMAS, and Foot Function Index scores, upon follow-up. However, these analyses were limited by small sample sizes and wide confidence intervals, resulting in lower certainties of evidence\u003csup\u003e68\u003c/sup\u003e. Despite point estimates consistently favouring IMN, functional equivalence rather than superiority is, currently, the most defensible interpretation. These findings are consistent with other reviews\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e57\u003c/span\u003e,\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e which also combined all functional outcomes together and still found no significant differences (pooled MD=-0.39 and 95% CI = -0.86 to 0.08\u003csup\u003e57\u003c/sup\u003e; pooled MD=-0.06 and 95% CI = -0.19 to 0.07\u003csup\u003e58\u003c/sup\u003e). Some reviews also investigated the specific functional challenges that patients experienced, like the significantly increased ankle stiffness in plating (pooled OR\u0026thinsp;=\u0026thinsp;2.33 and 95% CI\u0026thinsp;=\u0026thinsp;1.05 to 5.18\u003csup\u003e58\u003c/sup\u003e) and anterior knee pain in IMN (pooled OR\u0026thinsp;=\u0026thinsp;0.08 and 95% CI\u0026thinsp;=\u0026thinsp;0.03 to 0.18\u003csup\u003e58\u003c/sup\u003e; pooled OR\u0026thinsp;=\u0026thinsp;3.94 and 95% CI\u0026thinsp;=\u0026thinsp;1.68 to 9.28\u003csup\u003e59\u003c/sup\u003e).\u003c/p\u003e \u003cp\u003eEvidence comparing circular external fixation (CEF) with internal fixation techniques was sparse and predominantly from NRSs. Descriptive analysis suggested longer times to union, more infections and higher overall complication rates with circular frames compared with IMN or plating. The absence of adequately powered randomised comparisons and limited meta-analyses precludes definitive conclusions regarding the relative effectiveness of CEF.\u003c/p\u003e \u003cp\u003eThese few studies focused on the use of CEF in more severe distal tibia fractures such as open or intra-articular types. Some meta-analyses supported the conclusions made in this review\u0026rsquo;s descriptive analysis. For example, Liu\u003csup\u003e\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e et al. (2023) compared IMN to external fixators (EF) in open tibial fractures and found significantly faster union times in IMN (pooled MD\u0026thinsp;=\u0026thinsp;2.12 and 95% CI\u0026thinsp;=\u0026thinsp;0.94 to 3.29) on sensitivity analysis, reduced superficial infections (pooled RR\u0026thinsp;=\u0026thinsp;3.15 and 95% CI\u0026thinsp;=\u0026thinsp;2.03 to 4.88), and no difference in deep infections (pooled RR\u0026thinsp;=\u0026thinsp;1.33 and 95% CI\u0026thinsp;=\u0026thinsp;0.68 to 2.59). This concluded in favour for IMN over EF, even for these severe injuries. However, it\u003csup\u003e61\u003c/sup\u003e does not fully translate into the scope of this review: neither did they focus on distal tibia fractures nor CEF specifically. However, these differences were possibly unimpacted by the inclusion of (monolateral) ankle-spanning EF as they have shown to be no different to their ankle-sparing (circular) counterparts\u003csup\u003e\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u003c/sup\u003e in these domains.\u003c/p\u003e \u003cp\u003eMalik-Tabassum\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e et al. (2020) conducted a meta-analysis focusing specifically on intra-articular distal tibia fractures and compared CEF with open-reduction internal fixation (ORIF) plating. They found no significant difference in infective complications (pooled RR\u0026thinsp;=\u0026thinsp;0.30 and 95% CI\u0026thinsp;=\u0026thinsp;0.06 to 1.58). However, this could be due to the invasive nature of ORIF operations balancing against the pin tract infection risks of the external fixator. Our review\u0026rsquo;s descriptive analyses highlighted the reduced infection rates in plating versus CEF, by including investigations of less invasive plating techniques (MIPPO). Union times were not investigated in the review by Malik-Tabassum\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e et al. (2020), but our review\u0026rsquo;s descriptive analysis deemed them to be faster in plating\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. They\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e concluded that both techniques were comparable and they also noted the trend in treating more severe injuries with CEF to \u0026ldquo;minimise the risk of iatrogenic soft tissue injury (with ORIF)\u0026rdquo;\u003csup\u003e60\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAn advantage of CEF is the potential for immediate weight-bearing, which is generally contraindicated in other techniques due to risks like hardware failure\u003csup\u003e\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e. This feature has been reported\u003csup\u003e63\u003c/sup\u003e to be particularly beneficial for patients with \u0026ldquo;cognitive or behavioural disorders\u0026rdquo;, who may struggle to adhere to postoperative weight-bearing restrictions. However, it is important to note that these same patients may also have difficulty complying with essential postoperative frame-hygiene instructions, increasing the risk of complications such as pin tract infections.\u003c/p\u003e \u003cp\u003eA limitation of this review\u0026rsquo;s design was its focus on outcomes that were favoured in IMN over other techniques such as union times and infection rates. Over the course of this review some disadvantages in IMN were noted like misalignment and the aforementioned knee pain\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e58\u003c/span\u003e,59\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMisalignment and malunion were assessed in approximately two-thirds of RCTs and three-quarters of NRSs. Most studies reported a higher incidence of malunion or misalignment with IMN and CEF compared to plating. However, in NRSs, the differences between groups were often minimal and failed to reach statistical significance. For example, Vaienti\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e et al. (2019) conducted a prospective NRS involving 183 patients and found no significant differences in rotational, varus, or valgus deformities. In contrast, most RCTs reported statistically significant differences between groups. For ethical reasons, no p-values or quantitative data were extracted for this outcome in accordance with the review protocol, representing a limitation. Other meta-analyses\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e noted significantly increased rates of malalignment in IMN compared to plating (pooled OR\u0026thinsp;=\u0026thinsp;0.58 and 95% CI\u0026thinsp;=\u0026thinsp;0.40 to 0.84)\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite these findings, it has been shown\u003csup\u003e\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e that nail positioning can significantly impact the quality of alignment and this must be considered before concluding that misalignment is consistently increased in all IMN. Garbano\u003csup\u003e\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e et al. (2023) found that \u0026ldquo;distal positioning of the nail \u0026hellip; (zone 2\u0026ndash;2) allows high alignment percentages to be obtained\u0026rdquo;\u003csup\u003e64\u003c/sup\u003e, while \u0026ldquo;nail positioning in the 3\u0026thinsp;\u0026minus;\u0026thinsp;2 zone generated a significant risk of misalignment (OR 18.55; p\u0026thinsp;=\u0026thinsp;0.009)\u0026rdquo;\u003csup\u003e64\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAnother consideration is the \u0026ldquo;clinical\u0026rdquo; or functional significance of the malalignment rather than simply using statistical significances to discredit IMN. This could be calculated by identifying the needs for re-intervention following misalignment or malunion from IMN. Bleeker\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e et al. (2021) noted no significant differences in numbers of re-interventions for IMN versus plating (weighted OR\u0026thinsp;=\u0026thinsp;1.3 and 95% CI\u0026thinsp;=\u0026thinsp;0.8 to 1.9). However, this could be masked by other indications for re-intervention in both groups and highlights a key research gap. We aim to fill this with a retrospective study investigating the rates of reintervention for misalignment or malunion, following IMN for distal tibia fractures.\u003c/p\u003e \u003cp\u003eAnother limitation of this review is the breadth of its scope. Including all distal tibia fractures, rather than analysing open, closed, intra-articular, and extra-articular types separately, provides a broad overview of fixation methods and allows for sufficiently powered meta-analyses. However, this also introduces potential bias, such as the disproportionately higher number of extra-articular fractures, which may influence pooled estimates. Consequently, the generalisability of the findings is limited, despite what the title suggests. This was somewhat clarified by availability of baseline characteristics along with the extracted outcome data in the Supplementary information (SI2: \u003cem\u003eSI2.1.1\u003c/em\u003e and \u003cem\u003eSI2.2.1\u003c/em\u003e). Variations also existed in surgical technique (e.g. minimally invasive versus open plating), post-operative rehabilitation protocols, and outcome definitions. These factors likely contributed to some clinical heterogeneity not fully captured by statistical measures.\u003c/p\u003e \u003cp\u003eAlthough fifteen RCTs were included, many outcomes were informed by only two trials, leading to imprecise estimates and lower certainties of evidence\u003csup\u003e68\u003c/sup\u003e. This was particularly evident for functional outcomes and times to full weight-bearing. Additionally, some trials were small and underpowered, increasing the risk of type II error. Therefore, their conclusions were reinforced by descriptive analysis of NRSs. Furthermore, outcome reporting was inconsistent, with occasional misreporting or omission of standard deviations, necessitating data conversions that may have introduced additional imprecision. Although sensitivity analyses were conducted to mitigate this, the exclusions attenuated the significance of findings. Consequently, definitive conclusions were mainly drawn from primary meta-analyses with moderate or high certainties of evidence\u003csup\u003e68\u003c/sup\u003e due to their greater statistical power, at the cost of minor potential biases.\u003c/p\u003e \u003cp\u003eFinally, the evidence base for circular external fixation was dominated by non-randomised studies with small sample sizes, limiting confidence in comparative effectiveness estimates for this technique.\u003c/p\u003e \u003cp\u003eThis review also had methodological limitations. Despite a comprehensive search strategy and rigorous screening process, unpublished or selectively reported trials may have been missed, particularly among registered clinical trials without available results. Although publication bias was formally assessed for time to union (found insignificant and unlikely), this could not be evaluated for most outcomes due to the limited number of studies.\u003c/p\u003e \u003cp\u003eThe decision to restrict quantitative synthesis to RCTs enhanced internal validity but reduced statistical power for less frequently reported outcomes. Additionally, while sensitivity analyses were prespecified and transparently conducted, the exclusion of studies with converted or imputed variance data reduced the number of eligible trials and may have obscured true effects. Once more highlighting our reasons for deriving conclusions from primary meta-analyses with moderate or high certainties of evidence\u003csup\u003e68\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFrom a clinical perspective, the findings of this review support intramedullary nailing as a first-line surgical option for extra-articular distal third tibial fractures, given its association with faster union and lower infection rates without compromise in functional outcomes. Plating remains a valid alternative in cases where IMN is contraindicated or technically unsuitable, but surgeons should remain mindful of its higher soft-tissue complication risks. The role of circular external fixation appears more limited and should likely be reserved for specific indications such as compromised soft tissues, infection, or complex fracture patterns, pending higher-quality comparative evidence.\u003c/p\u003e \u003cp\u003eReductions in specific complications may be more beneficial to different patient demographics and injury types. For example, a younger, more active, patient may be better suited to plating techniques, to minimise the risk of chronic knee pain from IMN, at the cost of an increased risk of superficial infection. An older, more vulnerable patient may prioritise the reduced infection risk demonstrated by IMN at the cost of knee pain or minor misalignment.\u003c/p\u003e \u003cp\u003eAt a policy level, these findings may inform evidence-based treatment algorithms and training priorities, particularly in high-volume trauma centres where distal tibial fractures are commonly encountered.\u003c/p\u003e \u003cp\u003eFuture research should focus on well-powered randomised comparisons between all three surgical techniques. We also aim to explore the clinical and functional significance of the noted misalignment in IMN through a retrospective study, as was discussed previously. Qualitative research may also give a better understanding on what specific difficulties are faced following misalignment and how acceptable these are in different demographics (e.g. age, activity-status, or job-type). This will help tailor surgical treatment plans for future patients, based on their unique preferences and priorities.\u003c/p\u003e \u003cp\u003eIn summary, intramedullary nailing demonstrates a favourable balance between fracture healing, infection risk, and functional recovery when compared with plate fixation for distal-third tibial fractures, particularly in extra-articular patterns. While circular external fixation remains a valuable technique in selected clinical scenarios, its comparative effectiveness relative to internal fixation remains insufficiently defined. This underscores the need for high-quality comparative trials in this challenging fracture population. These conclusions reinforce the need for individualised surgical decision-making.\u003c/p\u003e \u003cp\u003eNotably, although malalignment was more frequently reported following intramedullary nailing, the clinical relevance of these radiographic findings remains unclear. Future research should therefore focus on determining whether malalignment translates into increased rates of reintervention or functional impairment, through retrospective analyses of reoperation following intramedullary fixation. Addressing these uncertainties will be essential to refine treatment selection and optimise patient-centred outcomes.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eThe systematic review and meta-analyses were conducted in accordance with the 2020 PRISMA guidelines and the prespecified protocol, registered on PROSPERO.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategies\u003c/h2\u003e \u003cp\u003eTwo independent researchers (JD and HC) searched the following databases: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Allied and Complementary Medicine Database (AMED - EBSCO) and ClinicalTrials.gov (for grey literature). Consistent MeSH terms and Boolean operators were used (\u003cem\u003eSI1.2\u003c/em\u003e). No restrictions were applied based on the publication date of studies; all available studies, published in English, were considered.\u003c/p\u003e \u003cp\u003eAll searches were conducted on the 23/7/25 except for the Scopus search which had to be performed on the 24/7/25 due to technical difficulties.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eScreening and eligibility criteria\u003c/h2\u003e \u003cp\u003eTwo reviewers independently screened articles in two phases: title/abstract screening followed by full-text screening. Disagreements were resolved by in-person discussions at the end of each phase. If a consensus could not be reached, a third reviewer was consulted (senior author - PB). Rayyan software was used for both automated and manual deletion of duplicate search results before beginning the title/abstract screening.\u003c/p\u003e \u003cp\u003eThe inclusion and exclusion criteria were specified in \u003cem\u003eSI1.2\u003c/em\u003e, with no deviation from the PROSPERO registration. In the second conflict-resolution meeting, it was agreed that all conference abstracts were to also be excluded due to insufficient information. The same was decided for certain pieces of grey literature, identified on ClinicalTrials.gov, which had unpublished results.\u003c/p\u003e \u003cp\u003eThe screening process was documented using the PRISMA 2020 flow diagram template, which was adapted to suit the specifics of our review. For example, boxes related to previous reviews were removed as no prior, identical, systematic reviews were identified.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eTwo reviewers independently extracted data from the included studies, using the prespecified set of outcomes: time to union (weeks), time to partial weight-bearing (weeks), time to full weight-bearing (weeks), rate of superficial infections (%), rate of deep infections (%), overall infection rate (%), overall complication rate (%), American Orthopaedic Foot \u0026amp; Ankle Society (AOFAS) scoring system\u003csup\u003e\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e, Olerud-Molander Ankle Scores (OMAS)\u003csup\u003e\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e\u003c/sup\u003e, and the Teeny and Wiss score\u003csup\u003e73\u003c/sup\u003e. Additional functional or radiological measures, such as the Disability Rating Index (DRI)\u003csup\u003e\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e and the Foot Function Index (FFI)\u003csup\u003e\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e\u003c/sup\u003e, were also recorded. No automation tools were used and discrepancies in extracted data were resolved through discussion.\u003c/p\u003e \u003cp\u003eBaseline characteristics, including the country and clinical setting of each study, were systematically recorded alongside detailed descriptions of the surgical interventions. Particular attention was given to variations in plating techniques, such as the use of minimally invasive plate osteosynthesis (MIPO) compared with the more traditional open reduction and internal fixation (ORIF), to capture differences in operative approach across studies.\u003c/p\u003e \u003cp\u003eThe outcome \u0026ldquo;Overall complication rate (%)\u0026rdquo; was considered ambiguous and was inconsistently calculated between studies. To ensure consistency, it was collected only when explicitly defined as including the following complications: superficial infections, deep infections, malunion, non-union, and delayed union. Most time-related outcomes were already reported in weeks. If expressed in other units, they were converted to weeks for consistency. Days were converted to weeks by dividing by seven. Months were converted by multiplying by 52 and dividing by 12. Infection and complication rates were reported as either percentages or dichotomous events. These were extracted as percentages to contextualise the events within their sample sizes and, consequently, enhance readability. An additional column titled \u0026ldquo;Points of Interest\u0026rdquo; was included in the data extraction table to record comments on outcomes not prespecified in the PROSPERO registration. No numerical data were entered in this column to prevent introduction of bias.\u003c/p\u003e \u003cp\u003eRandomised controlled trials (RCTs) and non-randomised studies (NRSs) were organised into separate tables (see Results). Meta-analysis was performed exclusively on RCTs with two or more studies measuring a given outcome, due to their higher certainty of evidence.\u003c/p\u003e \u003cp\u003eNo assumptions were made for missing data, and some studies were excluded from meta-analyses if they measured outcomes too inconsistently with other studies. For example, time-related outcomes were meta-analysed as a continuous measure; studies reporting these outcomes as \u0026ldquo;rates at a given time point\u0026rdquo;, were excluded from meta-analysis. Studies with unclear or inconsistent reporting were excluded from this systematic review altogether.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eHandling Missing or Misreported Standard Deviations\u003c/h2\u003e \u003cp\u003eWhen studies did not report standard deviations (SDs), established imputation methods were applied to assist the meta-analyses. If only the range was available, SD was estimated using the Wan\u003csup\u003e\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e et al. (2014) approach for sample sizes of \u0026ge;\u0026thinsp;25 participants: SD \u0026asymp; (max-min) / 4.\u003c/p\u003e \u003cp\u003eFor studies reporting means with 95% confidence intervals (CIs) but not SDs, advice from the Cochrane Handbook\u003csup\u003e\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e (Section 6.5.2.3) was used. The standard error (SE) was first derived as:\u003c/p\u003e \u003cp\u003eSE = (Upper CI \u0026ndash; Lower CI) / (2 * t\u003csub\u003e0.975,n\u0026minus;1\u003c/sub\u003e),\u003c/p\u003e \u003cp\u003eand SD was subsequently calculated as : SD\u0026thinsp;=\u0026thinsp;SE * (\u0026radic;n).\u003c/p\u003e \u003cp\u003eIn one instance, it was noted that one study\u0026rsquo;s weighting was unusually high compared to another\u0026rsquo;s. On closer inspection of its results, it was noted that it had probably mislabelled its standard error of the mean (SEM) as SD. This was also corrected using: SD\u0026thinsp;=\u0026thinsp;SE * (\u0026radic;n).\u003c/p\u003e \u003cp\u003eStudies lacking sufficient data to derive SDs were excluded from the meta-analysis. All collected SDs were audited for consistency, and unusually small SDs were investigated for unit conversion issues and presented in the \u003cem\u003eResults\u003c/em\u003e (e.g. days to weeks).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRisk of Bias assessment\u003c/h2\u003e \u003cp\u003eTwo reviewers independently assessed the risk of bias for all included RCTs using the RoB 2 tool. Risk of bias assessment was limited to RCTs, as these were the only study designs included in the meta-analyses and subsequent sensitivity analyses. Discrepancies were resolved through discussion, and final judgments were summarised, using the Robvis tool, in traffic-light and distribution summary plots (see \u003cem\u003eResults\u003c/em\u003e). RoB2 tool decision pathways were reported in detail along with the plots to ensure transparency within decision making processes.\u003c/p\u003e \u003cp\u003eEach was assessed for risk of bias by category of outcome. These categories were split based on the assessor of each outcome: radiographically-assessed, patient-assessed and clinician-assessed. If an outcome was measured by two assessor categories, such as AOFAS scores, it was assigned to the category with the greater risk of bias.\u003c/p\u003e \u003cp\u003eFor meta-analysed outcomes with \u0026ge;\u0026thinsp;10 studies, publication bias was evaluated using Egger\u0026rsquo;s test\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e and illustrated with a funnel plot (see \u003cem\u003eResults\u003c/em\u003e). For outcomes with fewer than 10 contributing studies, formal statistical assessment of reporting bias was not feasible due to insufficient power, and therefore the presence of reporting bias could not be reliably evaluated. Finally, the certainty of evidence for each meta-analysed outcome was appraised using the GRADE\u003csup\u003e68\u003c/sup\u003e approach across five domains: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Ratings were categorised as high, moderate, low, or very low (see \u003cem\u003eResults\u003c/em\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical synthesis followed a two-stage approach. Where sufficient homogeneity and data availability permitted, outcomes from randomised controlled trials were quantitatively synthesised using meta-analysis. Where quantitative pooling was inappropriate due to study design, outcome heterogeneity, or limited data, findings were summarised using structured descriptive analyses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eMeta-analyses\u003c/h2\u003e \u003cp\u003eThe meta-analysed RCTs\u0026rsquo; outcomes were divided into two groups: continuous and dichotomous outcomes. Continuous outcomes \u0026ndash; time to union, time to weight bearing and functional/radiological scores \u0026ndash; were compared using mean differences. Dichotomous outcomes \u0026ndash; infections and complications \u0026ndash; were measured as events and consequently compared using risk ratios.\u003c/p\u003e \u003cp\u003eThese mean differences and risk ratios were displayed along with I\u003csup\u003e2\u003c/sup\u003e tests for heterogeneity, 95% CIs, weighting and overall effect calculations (Z-values) in forest plot formats (see \u003cem\u003eResults\u003c/em\u003e). These were all completed under the conditions of a common and random effects model.\u003c/p\u003e \u003cp\u003eRandom-effects meta-analyses were performed using the Hartung-Knapp-Sidik-Jonkman (HK) adjustment for confidence intervals. For comparisons where the HK method produced degenerate estimates (e.g., zero-width confidence intervals or infinite test statistics), the classic normal approximation was applied instead. This occurred only in cases with very few studies and zero between-study variance. This was evident in the meta-analysis of the \u0026ldquo;Time to full weight bearing\u0026rdquo; outcome. All effect sizes were pooled on the log scale for statistical analysis but back-transformed for presentation as risk ratios to improve interpretability, as recommended by the Cochrane Handbook\u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAll statistical calculations and plots were generated using R (version 4.5.2) within the RStudio software environment (version 2025.09.2\u0026thinsp;+\u0026thinsp;418), using the \u0026lsquo;meta\u0026rsquo; package (version 8.2.1).\u003c/p\u003e \u003cp\u003eSensitivity analyses were performed using the same statistical approach, applying the following exclusion criteria: (i) studies judged to have a high risk of bias for the outcome of interest, and (ii) studies in which standard deviations were derived through unit conversions or imputation. Subgroup analyses (e.g. extra- versus intra-articular fractures) and meta-regression were not conducted because each outcome included too few studies to support reliable between-study comparisons. Conducting these analyses with such limited numbers would risk producing unstable or spurious findings.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eDescriptive analyses\u003c/h2\u003e \u003cp\u003eData from NRSs were presented in tabular form (Supplementary Information: \u003cem\u003eSI2.2\u003c/em\u003e) and synthesised descriptively. Owing to the limited literature on circular external fixation, findings from both RCTs and NRSs evaluating this technique were summarised descriptively where quantitative, meta-analytic pooling was not feasible.\u003c/p\u003e \u003cp\u003eFor outcomes where sufficient RCT data were available to support meta-analysis, descriptive summaries of NRS findings were provided for contextual purposes only and did not contribute to quantitative inference. They served to reinforce conclusions already drawn through meta-analysis. In contrast, for outcomes with insufficient RCT data to permit reliable meta-analysis, more detailed descriptive synthesis of NRS findings was undertaken. This involved reference to the statistical significance of a given outcome comparison. Decisions regarding the depth of descriptive synthesis were assisted by the certainty of evidence\u003csup\u003e68\u003c/sup\u003e assigned to outcomes (GRADE framework). If a significant or insignificant difference was described, p-values, statistical tests and sample sizes were presented in the Supplementary information tables (\u003cem\u003eSI2\u003c/em\u003e) to ensure transparency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eOther Information\u003c/h2\u003e \u003cp\u003eThis review was registered on PROSPERO (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.crd.york.ac.uk/PROSPERO/\u003c/span\u003e\u003cspan address=\"https://www.crd.york.ac.uk/PROSPERO/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) with the following ID: CRD420251108552. No amendments were made to the registered protocol, apart from a minor change to the title phrasing (\u0026ldquo;frame\u0026rdquo; changed to \u0026ldquo;frames\u0026rdquo;).\u003c/p\u003e \u003cp\u003eAll supplementary materials such as search terms, data extraction tables, or forest plots were compiled into four separate Supplementary Information documents (\u003cem\u003eSI1-4\u003c/em\u003e). Data supporting the findings of this study are available within the article and its Supplementary Information files. The PRISMA 2020 checklist is duly filled in \u003cem\u003eSI5\u003c/em\u003e.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eFunding Declaration\u003c/span\u003e \u003c/p\u003e \u003cp\u003eNo financial support or funding sponsored this review and none of the authors had competing interests to declare.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.D. led all stages of the review from protocol registration to manuscript submission. J.D. and H.C. independently screened studies, extracted data, and assessed risk of bias. J.D. performed the statistical analyses and prepared the manuscript text and much of the Supplementary Information. HC contributed to the preparation and formatting of the Supplementary Information. PB conceived the study, developed the protocol, and provided ongoing supervision and critical feedback throughout the review process. All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData supporting the findings of this study are available within the article and its Supplementary Information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRayan, A. et al. Open reduction internal fixation versus external fixation with limited internal fixation for displaced comminuted closed pilon fractures: A randomised prospective study. \u003cem\u003eJ. Orthop. Trauma. Rehabilitation\u003c/em\u003e. \u003cb\u003e24\u003c/b\u003e, 84\u0026ndash;89 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmed, A., Ali, H., Aledanni, M. \u0026amp; Asadi, T. 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Res.\u003c/em\u003e \u003cb\u003e292\u003c/b\u003e, 108\u0026ndash;117 (1993).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8501129/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8501129/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDistal-third tibial fractures are surgically challenging due to limited soft-tissue coverage and a high risk of complications. The optimal fixation method remains uncertain. This systematic review and meta-analysis compared intramedullary nailing, plate fixation, and circular external fixation for distal-third tibial fractures. A comprehensive search identified 54 studies, including 15 randomised controlled trials. Meta-analyses of randomised evidence demonstrated that intramedullary nailing was associated with a modest but statistically significant reduction in time to fracture union and a lower rate of superficial infections compared with plating, without significant differences in deep infection rates, functional outcomes, or overall complications. Functional scores were broadly comparable between techniques. Evidence for circular external fixation was limited and largely derived from non-randomised studies, which suggested longer union times and higher complication rates compared with internal fixation. Overall, intramedullary nailing offers a favourable balance between fracture healing and infection risk for distal-third tibial fractures, particularly extra-articular patterns, while achieving similar functional outcomes to plating. Plate fixation remains an appropriate alternative when nailing is contraindicated. The role of circular external fixation appears more selective and warrants further high-quality comparative trials.\u003c/p\u003e","manuscriptTitle":"Comparative Effectiveness of Circular Frames, Plate Fixation, and Intramedullary Nailing in Distal-Third Tibial Fractures: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-10 17:40:47","doi":"10.21203/rs.3.rs-8501129/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-10T10:23:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-22T18:31:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T21:22:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197252738123637465923837408955576043920","date":"2026-02-11T17:12:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-09T18:45:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"193865583858002708630373200510782562794","date":"2026-02-09T18:25:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71520755387894308414958345466425074870","date":"2026-01-28T07:57:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-28T06:04:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-08T16:58:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T01:19:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-05T01:18:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-01-02T13:04:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8dc39f64-9d81-4c67-b893-62059b417b18","owner":[],"postedDate":"February 10th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":62613023,"name":"Health sciences/Anatomy"},{"id":62613024,"name":"Health sciences/Diseases"},{"id":62613025,"name":"Health sciences/Health care"},{"id":62613026,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-04-06T14:09:20+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-10 17:40:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8501129","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8501129","identity":"rs-8501129","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}