High Tibial Osteotomy versus Unicompartmental Knee Arthroplasty for Compartmental Knee Osteoarthritis: A Systematic Review and Meta-Analysis

Purpose High tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) are commonly performed procedures for the treatment of compartmental knee osteoarthritis. However, the optimal procedure remains controversial. Therefore, we conducted this systematic review and meta-analysis to compare the functional outcomes, complications, and revision between the two techniques. Methods We searched electronic databases for relevant studies comparing HTO versus UKA for unicompartmental knee osteoarthritis. Continuous data as visual analogue scale (VAS), range of motion, and free walking speed were pooled as mean differences (MDs). Dichotomous data as functional knee outcomes, complications, and revision were pooled as odds ratios (ORs), with 95% condence interval (CI), using R software for windows. Results Twenty-ve studies involving 8185 patients were included. Meta-analysis showed that HTO was associated with higher risk of complications (OR= 2.47, 95% CI [1.52, 4.04]), poor functional results (excellent/good) (OR= 0.32, 95% CI [0.21, 0.49]), and larger range of motion (MD= 7.05, 95% CI [2.41, 11.68]) compared to UKA. No signicant differences were found between the compared groups in terms of VAS (MD= 0.14, 95% CI [-0.08, 0.36]), revision (OR= 1.30, 95% CI [0.65, 2.60]), and free walking speed (MD= -0.05, 95% CI [-0.11, 0.00]). Conclusion This study showed that UKA achieved fewer complications, better functional outcomes, and less range of motion compared to HTO. No signicant differences were detected between HTO and UKA in terms of VAS and revision rate. the degenerative compartment persists. Formerly, patients undergoing HTO were placed in a plaster cast from the groin to the ankle for six weeks, and the osteotomy took several months to heal postoperatively. Compared to UKA, a resurfacing technique, in which the degenerative compartment is replaced while the normal compartments are preserved. Some studies reported on the use of modern techniques such as TomoFix plate in the HTO group compared to UKA. Koh et al. enrolled patients with OWHTO performed using TomoFix plate vs UKA. The study reported that patient satisfaction was higher in the UKA group than the HTO group in active patients 30 . Kim et al. used TomoFix plate in OWHTO vs UKA and reported that HTO and UKA had similar pain and functional outcomes at 12 and 24 months postoperative 31 These results accord with the ndings of Takeuchi et al 32 , Jeon et al. 33 , Ryu et al. 34 .


Introduction
Knee osteoarthritis is a widespread source of knee pain that causes health and nancial burdens 1 . Despite multifactorial causes, mechanical axis deviation of the knee often causes compartmental knee osteoarthritis 2 . Thus, unloading the diseased compartment might relieve the deterioration of that compartment. The initial management of knee osteoarthritis includes non-operative treatment such as patient education, weight reduction, physical therapy, and pain relieving medications 3 . In addition, knee braces are other non-surgical options that may alter the alignment of the lower extremity 3 . If non-operative treatments fail, surgical treatment may be indicated that consists of high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA).
High tibial osteotomy is a known procedure for the treatment of patients with medial compartment knee osteoarthritis due to mechanical axis deviation 4 . Several methods have been developed to treat this condition, such as opening wedge (OW), closing wedge (CW), dome, and "en chevron" osteotomies; while, the most frequently used methods are medial (opening) and lateral (closing) wedge osteotomies 5 . It is reported that HTO is the rst surgical choice for active young patients with a preserved joint stability and single compartmental knee osteoarthritis 6 . Although overall HTO outcomes demonstrate the e cacy of procedure 7 , there is still debate regarding osteotomies.
Growing evidence has shown an interest in UKA that achieves excellent outcomes with a low risk of complications in single compartmental osteoarthritis 8 . UKA is used for less active elderly patients with a preserved range of motion, absence of ligament instability, and compartmental knee osteoarthritis 9 . Nowadays, these indications have become less de ned, especially in patients more than 50 years old.
Advances in surgical procedures, along with similar indications for both HTO and UKA, make the decision-making challenging. Previous studies have shown that both HTO and UKA are established solutions for compartmental knee osteoarthritis 6,10 ; however, the optimal intervention remains controversial. In the literature, there is a lack of evidence concerning the role of HTO compared to UKA for compartmental knee osteoarthritis 11 . Therefore, an updated systematic review and meta-analysis of clinical trials and comparative study was conducted to assess the role of HTO versus UKA for compartmental knee osteoarthritis. The current study aimed to compare the functional outcomes, complications, and revision between the two surgical techniques.

Materials And Methods
All steps of this study were conducted in accordance with the Cochrane handbook of systematic reviews of interventions in addition to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines 12 . The protocol of this meta-analysis was published online at the International Prospective Register of Systematic Reviews (PROSPERO) under registration number (CRD42021243076).

Literature search strategy
We searched Medline (via PubMed), Embase, the Cochrane Library, Clinicaltrial.gov, google scholar, up to March 2021, for randomized clinical trials (RCTs) and comparative studies comparing HTO to UKA. We used the possible combinations of the keywords: "knee osteoarthritis", "knee arthritis", "degenerative knee", "unicompartmental knee arthroplasty", "unicondylar knee arthroplasty", "partial knee arthroplasty", "high tibial osteotomy", and osteotomies, including variant spellings and endings. Additionally, the reference lists of identi ed articles were checked manually.

Eligibility criteria:
We included RCTs and comparative studies that compared HTO with UKA for the treatment of patients with compartmental knee osteoarthritis. The included outcomes were complications (infection, leg length discrepancy, deep vein thrombosis, and pain), functional outcomes (patients have excellent/good results), visual analogue scale (VAS), revision, range of motion, and free walking speed (velocity).
We excluded animal models, reviews, case reports, case series, non-English articles, and duplicate references.

Study selection
First, title/abstract screening for eligibility for the current study was conducted. Second, full-text screening was conducted. Each step was performed by three independent reviewers and disagreements were resolved upon consensus.

Data Extraction
Requisite data were extracted by three independent authors into a data extraction form. The extracted data included the following items: a) baseline characteristics of enrolled patients, b) general characteristics of study design, c) included outcomes. In case of missing the mean or standard deviation (SD), we calculated them from the equations provided in the Cochrane handbook of systematic reviews of interventions 13 .

Risk of bias assessment and quality assessment
We used Cochrane collaboration's tool for assessing the risk of bias of included RCTs 12 . Risk of bias assessment included: 1) sequence generation, 2) allocation sequence concealment, 3) blinding of participants and personnel, 4) blinding of outcome assessment, 5) incomplete outcome data, 6) selective outcome reporting and 7) other potential sources of bias; the authors' judgment is categorized as 'Low risk', 'High risk' or 'Unclear risk' of bias. To assess the risk of bias across included studies, we compared the reported outcomes between all studies to exclude selective reporting of outcomes. Newcastle Ottawa scale (NOS) was used to assess the quality of observational studies and each included study was assessed based on reporting of three essential domains: a) selection of the study subjects, b) comparability of groups on demographic characteristics and important potential confounders, and c) ascertainment of the included outcome (exposure/treatment) 14 .

Data Synthesis
Continuous data were pooled as mean difference (MD). Dichotomous data were pooled as odds ratio (OR), with a 95% con dence interval (CI). We used R software (meta-package 4.9-0) for windows during data synthesis. Heterogeneity was assessed by visual inspection of the forest plots and measured by Q statistic and I 2 statistic. Signi cant statistical heterogeneity was indicated by Q statistic P-value less than 0.1 or by I 2 more than 50%. In case of signi cant heterogeneity, we conducted a random effect model. Otherwise, the xed effect model was used. Sensitivity analysis was used to resolve the heterogeneity. The funnel plot method was used to assess publication bias for outcomes with more than 10 included studies.

Search strategy results
Our literature search yielded 2392 unique records. After title/abstract screening, 45 were retrieved and screened for eligibility. Finally, 25 studies were included in the meta-analysis. The ow of the study selection process is shown in the PRISMA ow diagram, Fig. 1.

Characteristic of included studies
Twenty-ve studies involving 8185 patients were included. Of them, 11 studies were RCTs and 14 were observational comparative studies. A total of 1996 patients had HTO, and 6189 patients had UKA. The follow-up period ranged from 12 to 793.6 months. The age ranged from 30 to 84 years old. All articles were published in English from 1982 to 2020. A summary of the design and baseline characteristics of enrolled patients is presented in Table 1. The risk of bias and quality assessment of included studies with the references were reported in Appendix Tables 1 and 2.

Discussion
The present study compared HTO to UKA for the treatment of compartmental knee osteoarthritis. This meta-analysis of 25 studies showed that UKA achieved fewer complications, better functional outcomes (excellent/good), and reduced knee range of motion compared to HTO.
No signi cant differences were detected between HTO and UKA in terms of visual analogue scale, revision rate, and free walking speed.
Conventionally, UKA has been used for patients over 60 years, less than 82 kg, single compartment osteoarthritis, less than 15-degree angular deformity, and more than 90-degree range of motion 9,15 . UKA is contraindicated in active patients with in ammatory arthritis and less than 60 years old. However, some studies showed that UKA provided promising outcomes in younger and obese patients 16,17 . A retrospective series of 41 patients showed that UKA achieved a 92% survival rate at 11 years in patients ranged from 35 to 60 years old 18 .
Another study including 62 patients, with 11.2 years follow-up, reported that UKA was associated with favourable outcomes and a 94% survival rate at 12 years in patients aged 60 years or younger 19 . Advances in the surgical procedures and implant designs, besides increased experience with the technique, have extended the surgical indications for UKA.
Both HTO and UKA share similar indications, such as patients aged 55 to 65 years, patients without obesity, patients with moderate activity, mild varus malalignment, joint stability, good range of motion, and moderate single compartmental osteoarthritis. The selection of suitable patients, accurate osteotomy types, and speci c surgical techniques are important in the success of HTO 20 . HTO is used for young patients less than 60 years, normal weight, active patients with radiographic single-compartment osteoarthritis, stable/unstable joint, range of motion with exion more than 120 degrees, and localized pain to the tibiofemoral joint line 21 22 . Furthermore, a prospective study including 132 patients demonstrated that a preoperative BMI of more than 27.5 kg/m2 was a risk factor for early failure of HTO 4 . Another investigation utilized a Markov model to simulate theoretical groups of patients 40, 50, 60, and 70 years of age undertaking primary HTO or UKA. The results demonstrated higher revision risks at follow-up durations of 5 and 10 years in the HTO compared to the UKA group for patients ≥ 50 years 23 . A large retrospective review in the USA showed that HTO was performed more commonly in patients aged 40 to 44 years and UKA was more common in patients aged 60 to 64 years 24 . Selecting the correct patient is the key to success. In the present meta-analysis, the included patients' ages ranged from 30 to 84 years, which might explain why the revision rate did not differ signi cantly between the HTO and UKA groups.
Several techniques of HTO have been developed including opening wedge, closing wedge, dome, and "en chevron" osteotomies. Opening wedge and closing wedge are the most frequently used techniques. No differences in most of the clinical outcomes were found except the operation time 25 . Currently, HTO seems common again; however, there were more post-surgical complications in the HTO group compared to the UKA group in the current meta-analysis. These ndings accord with previous meta-analyses 26,27 . The postoperative complications included the rate of infection, venous thrombosis, cortical fracture, and peroneal nerve injury. A systematic review of 12 HTO studies showed that HTO had a complication rate up to 47% postoperatively 28 . The signi cantly higher proportion of complications after HTO may be due to surgical techniques, long-standing cast immobilization, late limb load, and inadequate xation following HTO operation.
Regarding the knee functional outcomes, the current meta-analysis showed that the rate of excellent/good outcomes was signi cantly higher in the UKA group versus the HTO group, while the range of motion was higher in the HTO group versus the UKA group. However, there were no signi cant differences between the compared groups regarding the visual pain scale. The differences in functional outcomes and range of motion results indicate that further factors might impact functional results. Osteotomy targets transferring the mechanical axis from the abnormal position to the normal area 29 , which leads to improved pain and better gait, delaying the progression of osteoarthritis 20 .
Nevertheless, the degenerative compartment persists. Formerly, patients undergoing HTO were placed in a plaster cast from the groin to the ankle for six weeks, and the osteotomy took several months to heal postoperatively. Compared to UKA, a resurfacing technique, in which the degenerative compartment is replaced while the normal compartments are preserved. Some studies reported on the use of modern techniques such as TomoFix plate in the HTO group compared to UKA. Koh et al. enrolled patients with OWHTO performed using TomoFix plate vs UKA. The study reported that patient satisfaction was higher in the UKA group than the HTO group in active patients 30  UKA is associated with less perioperative blood loss, quicker recovery, and no immobilisation. A report by Jeon et al. showed a better postoperative activity level following UKA compared to HTO at 6 months, whereas at 12 months and 2-year follow-up no signi cant differences were reported in the compared groups 33 . A study by Borjesson et al. reported an increased free walking speed from 1.07 to 1.16 m/s in the UKA group compared to the HTO group which was associated with decreased free walking speed from 1.07 to 0.94 m/s three months postoperatively. However, comparable results were observed between the two groups at the follow-up durations of 1 and 5 years 35 . Based on the previous reasons, UKA offers improved postoperative functional outcomes than HTO in short-term follow-up while no difference was found in long-term results.

Strengths and limitations
The current meta-analysis included some new studies up to 2021 30,31,36−39 ; thus, our results are more up to date. We determined search methods and performed a comprehensive search using many electronic databases and we followed the PRISMA checklist when reporting this manuscript. However, a limitation of our meta-analysis is the heterogeneity in some of the included outcomes. The heterogeneity might be due to the included different study designs, matching criteria, sample size, operative techniques, and measurement of outcomes. These variances may lead to signi cant between-study heterogeneity, which can impact the results in the current study. We used the random effects model to decrease the impact of heterogeneity; however, it does not eliminate it.

Conclusion
This meta-analysis of 25 studies showed that UKA achieved less rate of complications, better functional outcomes (excellent/good), and less range of motion compared to HTO. No signi cant differences were detected between HTO and UKA in terms of visual analogue scale, revision rate, and free walking speed. Nimish Seth declares that he has no con ict of interest.
Gabriella Bulloch declares that she has no con ict of interest.
Damien Gibson declares that he has no con ict of interest.
Kirk Lower declares that he has no con ict of interest.
Aaron Rodwell declares that he has no con ict of interest.
Warwick Bruce declares that he has no con ict of interest.
Availability of data and material The raw extracted data are available upon requested