Rate of revision and wear penetration in different polyethylene liner compositions in total hip arthroplasty: a Bayesian network meta-analysis

The present Bayesian network meta-analysis compared different types of polyethylene liners in total hip arthroplasty (THA) in terms of wear penetration (mm/year) and rate of revision. The type of liners compared were the crosslinked ultra-high molecular weight polyethylene (CPE/UHMWPE), Vitamin E infused highly cross-linked polyethylene (HXLPE-VEPE), modified cross-linked polyethylene (MXLPE), highly cross-linked polyethylene (HXLPE), Cross-linked polyethylene (XLPE). This study was conducted according to the PRISMA extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions. In June 2024, PubMed, Scopus, Embase, Google Scholar, and Cochrane databases were accessed. A time constraint was set from January 2000. All investigations which compared two or more types of polyethylene liners for THA were accessed. Only studies that clearly stated the nature of the liner were included. Data from 60 studies (37,352 THAs) were collected. 56% of patients were women. The mean age of patients was 60.0 ± 6.6 years, the mean BMI was 27.5 ± 2.0 kg/m2. The mean length of follow-up was 81.6 ± 44.4 months. Comparability was found at baseline between groups. XLPE and HXLPE liners in THA are associated with the lowest wear penetration (mm/year) and the lowest revision rate at approximately 7 years of follow-up.


Search strategy
This study followed the PRISMA extension statement for reporting systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations 21 .The PICOD algorithm was established: In July 2024, PubMed, Scopus, Embase, Google Scholar, and Cochrane databases were accessed.A time constraint was set from January 2000.Medical subject headings (MeSH) used for the database search are reported in the appendix.

Synthesis methods
The main author (FM) performed the statistical analyses following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions 27 .Mean and standard deviation were used for descriptive statistics.For baseline comparability, the IBM SPSS software was used.The sum of squares and mean of squares were evaluated.Comparability was assessed through the analysis of variance (ANOVA), with P ANOVA > 0.1 considered satisfactory.The network meta-analyses were made through the STATA/MP software (Stata Corporation, College Station, Texas, USA).Only studies which clearly stated the nature of the type of polyethylene of the liner were included in the analyses.The analyses were performed using the STATA routine for Bayesian hierarchical random-effects model analysis.Continuous variables were analysed using the inverse variance method, using the standardised mean difference (SMD) effect measure.Binary data were analysed through the Mantel-Haenszel method, with the Log Odd Ratio (LOR) effect measure.Edge, interval, and funnel plots were performed and analysed.The overall transitivity, consistency, heterogeneity, and the size of the treatment effect of interest within-study variance were evaluated.The overall inconsistency was evaluated through the equation for global linearity via the Wald test.In P Wald values > 0.05, the null hypothesis could not be rejected, and the consistency assumption could be accepted at the overall level of each treatment.Confidence and percentile intervals (CI a d PrI, respectively) were each set at 95%.Edge, interval, and funnel plots were performed.Egger's test assessed plot asymmetry, with values of P Egger < 0.05 indicating statistically significant asymmetry.The Egger test is a linear regression of the intervention effect estimates on their standard errors weighted by their inverse variance.

Study selection
The systematic literature search resulted in 1541 articles.Of them, 1061 were identified as duplicates and therefore excluded.After reviewing the abstracts, a further 384 articles were discarded because they did not match the defined eligibility criteria: study design (N = 191), low level of evidence (N = 104), not comparing two or more types of polyethylene liners (N = 41), not clearly stated the nature of the liner (N = 31), and language limitations (N = 17).A further 36 studies were excluded as they missed quantitative data under the outcomes of interests.In conclusion, 60 comparative studies were included in the present investigation: 16 RCTs, 23 prospective, and 21 retrospective clinical trials.52 (83.3%) of these investigations compared CPE/UHMWPE liner with HXLPE liner.The results of the literature research are shown in Fig. 1.

Risk of bias assessment
To investigate the risk of bias for RCTs included in the present meta-analysis, the revised Risk of Bias assessment tool (RoB2) was performed.27% (16 of 60) of the studies reviewed were RCTs.Most authors reported highquality allocation concealments, resulting in comparable study groups at baseline, leading to an almost low risk of bias arising from the randomisation process.Some concerns about deviations from the intended intervention, missing outcome data, and selection of the reported outcome were detected in a few studies, leading to a low to moderate risk of bias.Given the lack of blinded assessors to intervention status, a high risk of bias was identified in the outcome measurement in two of the included investigations.In summary, the risk of bias graph indicates a low to moderate quality of methodological assessment of RCTs (Fig. 2).
The ROBINS-I was applied to investigate the risk of bias of non-RCTs.73% (44 of 60) of the included investigation were NRSIs.23% (10 of 44) studies were rated as having a serious risk of bias in at least one domain, but no critical risk of bias in any domain.One study was identified with a critical risk of bias in the domain of participant selection, but all other domains had a low to moderate risk of bias.Given the mainly good methodological quality of the included studies, the overall risk of bias was low to moderate (Fig. 3).

Study characteristics
Data from 37,352 THAs were collected.56% of patients were women.The mean patient age was 60.0 ± 6.6 years, the mean BMI was 27.5 ± 2.0 kg/m 2 .The mean length of follow-up was 81.6 ± 44.4 months.The generalities and demographic data of the included studies are shown in Table 1.

Baseline comparability
Between groups, baseline comparability in mean age, mean BMI, women:men ratio, side, length of the follow-up, and HHS was evidenced (Table 2).

Synthesis of results
XLPE, followed by HXLPE, demonstrated the lowest wear penetration (Fig. 4).The equation of global linearity found no statistically significant inconsistency in all comparisons (P Wald = 0.2).The Egger test found no statistically significant asymmetry (P Egger = 0.9).XLPE, followed by HXLPE, demonstrated the lowest rate of revision at the last follow-up (Fig. 5).The equation of global linearity evidenced no statistically significant inconsistency in all comparisons (P Wald = 0.9).The Egger test found no statistically significant asymmetry (P Egger = 0.07).

Discussion
The present study shows that XLPE followed by HXLPE demonstrated the lowest wear penetration and the lowest rate of revision after THA at a mean follow-up of 81.6 ± 44.4 months compared to other polyethylene liners (CPE/UHMWPE), HXLPE-VEPE, MXLPE).
Polyethylene is a complex material, and its morphological and mechanical properties are temporal and dependent on functional loading and environmental conditions 85 .UHMWPE is a linear (non-branching) semicrystalline polymer, which can be described as a two-phase composite of crystalline and amorphous phases, which both influence the mechanical properties of the polymer 85 .While the crystalline phase provides modulus or stiffness to the material, the amorphous phase provides ductility and toughness 13 .Given its excellent wear resistance, high strength and biological inertness, UHMWPE remains the most commonly used bearing material in THA since its introduction in 1962 2,86,87 .However, particulate wear and the consequent osteolysis related to its wear debris and delamination wear from oxidation reduced the longevity of the UHMWPE implants, with subsequent aseptic loosening, with the need for revision surgery 13,86 .In light of these increasing demands in revisions, the necessity to develop longer-lasting, more resilient formulations of UHMWPE was obvious 85 .Osteolysis is an inflammatory process induced by exposure to wear particles of UHMWPE, which is in part consequent to the oxidation process and is even more evident when using gamma sterilisation in air.This has led to introducing gamma irradiation in an inert environment, using ethylene oxide and gas plasma 88 , significantly decreasing the wear rates in conventional UHMWPE.
Additionally, gamma radiation can break the C-C bonds of the polyethylene chain and induce cross-linking, which can potentially increase wear resistance 13,88 .Therefore, in the late 1990s, cross-linked-UHMWPEs (XPLE) were proposed for joint arthroplasties 13 .The initially used sterilisation dose of 25-40 kGy of gamma radiation was increased up to 100 kGy with a linear correlation to the degree cross-linking obtained 12,89 .With higher doses of radiation, the cross-link density did not increase further, and the mechanical properties of UHMWPE were affected, compromising toughness, ultimate mechanical properties, stiffness, and hardness, mainly caused by possible formation of free radicals during the manufacturing process, leading to oxidative changes in the XLPE 8 .For this reason, all first-generation XLPE were irradiated with a dose between 50 and 100 KGy 12 .Improvements in XLPE were achieved by increasing the irradiation dose and removing the free radicals trapped in the crystalline phase 89 .Two thermal treatments were used to remove free radicals in XLPE: remelting or annealing 89 .With remelting, it is possible to remove all free radicals.However, the process decreases its mechanical properties.Annealing does not alter the mechanical properties significantly, but it cannot remove all free radicals, and the oxidative process continues during storage and in vivo after implantation 13 .
Oral et al. showed promising early in vitro results compared with irradiated UHMWPE 101,102 .HXLPE-VEPE showed some oxidation on the surface, which stayed constant thereafter, UHMWPE exhibited substantial oxidation in the subsurface region, which increased over time 102 .The hip simulator wear rate of HXLPE-VEPE showed a fourfold to tenfold decrease from that of conventional UHMWPE 101 .Studies comparing HXLPE-VEPE with UHMWPE or MXLPE showed similar results 78,79 .Six-year results in a recent RCT including 199 patients reported superior results of vitamin E blended HXLPE (0.028 mm/ year) compared with UHMWPE (0.035 mm/year) 65 .Significantly decreased wear rates of vitamin E-diffused HXLPE compared to a moderately cross-linked and mechanically annealed UHMWPE coupled with metal and ceramic femoral heads were shown within the first 5 years after THA 18 .However, both liners showed very low rates of wear (0.00-0.07 mm/year), with osteolysis or implant failure from aseptic loosening 18 .Similar results were shown when polyethylene wear of MXLPE and HXLPE was compared with HXLPE-VEPE over 5 years 19 .A prospective, randomised, controlled, multicenter study also compared the mid-term results of HXLPE with HXLPE-VEPE, with no significant differences between the two cohorts regarding wear rate (HXLPE: 23.2 μm/ year vs HXLPE-VEPE: 24.0 μm/year, p = 0.73) after 5-years follow up 34 .The antioxidative benefit of vitamin E is expected to become evident in long-term follow-up.However, the results of this present network meta-analysis indicate better performance of XLPE and HXLPE after 7 years of follow-up.Skoldenberg reported a significantly higher total migration and continuous proximal migration of the component in the VEPE group compared to conventional argon-gas gamma-sterilized PE, with a difference at 2 years of a mean of 0.21 mm 80 .
This network meta-analysis has several limitations.First, there is no consistency in the liner/head coupling, and different implants were used in the various studies.Metal-on-polyethylene (MOP) is the most widely used THA bearings.At the same time, ceramic-on-polyethene (COP) may provide better mechanical properties, but has higher costs and is susceptible to femoral head fractures 8 .There was also a high level of heterogeneity between the studies regarding surgical approaches, which is considered a source of bias.Most studies did not report data separately according to the femoral head size or did not report information on the size of the head.Therefore, it was not possible to conduct additional analyses based on head sizes.Several techniques exist to investigate wear penetration (e.g.radiostereometry, Martell method, Polyware 104,105 ).However, given the between-studies heterogeneity in these techniques, the analyses were not conducted separately according to each method.The mean follow-up of the included studies was 81.6 ± 44.4 months, allowing only short to midterm conclusions about the wear rates and revision rates of each liner.Although aseptic loosening caused by polyethylene wear is frequent 3,4 , there is a lack of large prospective long-term clinical trials.In addition, different study types were analysed: 16 RCTs, 23 prospective, and 21 retrospective clinical trials.83% (52 of 60) of these investigations compared CPE/ UHMWPE liner with HXLPE liner.Second-generation HXLPE stabilised with vitamin E is underrepresented.

Fig. 4 .
Fig. 4. From left to right: edge, funnel, and interval plots of the comparison: wear penetration (mm/year).

Fig. 5 .
Fig. 5. From left to right: edge, funnel, and interval plots of the comparison: revision.

Table 1 .
Generalities and patient baseline data of the included studies.RCT, randomised controlled trial;