No Reduction in Revision Risk Associated With Highly Cross-linked Polyethylene With or Without Antioxidants Over Conventional Polyetheylene in TKA: An Analysis From the American Joint Replacement Registry

Abstract

Background

Highly cross-linked polyethylene (HXLPE) can improve wear properties in TKA, but it can also lead to decreased mechanical properties. Antioxidants were added to HXLPE to improve its mechanical properties while retaining the improved wear characteristics. However, it remains unclear whether these modifications to conventional polytheylene used in TKA have resulted in a change in the revision risk.

Questions/purposes

We used American Joint Replacement Registry data to ask: (1) Is there a difference in all-cause revision in patients who underwent TKA using HXLPE with or without an antioxidant doping compared with conventional polyethylene? (2) Is there a difference in revision for aseptic failure in patients who underwent TKA using HXLPE with or without an antioxidant doping compared with conventional polyethylene?

Methods

We analyzed American Joint Replacement Registry data from 2012 to 2019. We identified 339,366 primary TKAs over the study period in patients older than 65 years and linked procedures to supplemental Centers for Medicare & Medicaid data where available. Patient total number of reported comorbidities, gender, age, region, polyethylene characteristics, procedure dates, and indication for revision were recorded. Median follow-up was 34 months. We compared HXLPE with or without antioxidants to conventional polyethylene. Event-free percent survival curves and Cox proportional hazard regression modeling was used for all-cause revision and revision for aseptic failure.

Results

Compared with conventional polyethylene, there was no difference in all-cause revision with HXLPE with an antioxidant (HR 1.06 [95% CI 0.98 to 1.14]; p = 0.13) or HXLPE without an antioxidant (HR 1.04 [95% CI 0.97 to 1.11]; p = 0.28). Compared with conventional polyethylene, there was no difference in revision for aseptic failure with HXLPE with an antioxidant (HR 1.07 [95% CI 0.99 to 1.14]; p = 0.08) or HXLPE without an antioxidant (HR 1.03 [95% CI 0.97 to 1.01]; p = 0.30).

Conclusion

We found no difference in revision risk between HXLPE with or without an antioxidant and conventional polyethylene during this time frame. HXLPE polyethylene, with or without an antioxidant, should not be widely adopted until or unless it is shown to be superior to conventional polyethylene in TKA.

Level of Evidence

Level III, therapeutic study.

Introduction

Despite the success of TKA, revision TKA represented more than 7% of all TKAs in the United States in 2020 [1]. According to pooled registry data, the TKA revision rate is less than 5%, and aseptic loosening is the most common cause for revision [9]. The ramifications of revision surgery for the patient can be devastating, and ongoing efforts to limit the occurrence of TKA revision remain important. Highly cross-linked polyethylene (HXLPE), with or without the addition of an antioxidant (“doping”), can improve wear properties in TKA. HXLPE was introduced in THA, and its success in reducing wear, osteolysis, and subsequent revision spurred the adoption of its use in TKA [3, 11]. However, there are different wear characteristics for TKA related to the less conforming nature of round-on-flat geometries in the knee, compared with the round-on-round geometry in THA [11]. Polyethylene implants in TKA are subjected to various pivoting, sliding, and rolling motions, as well as forces related to posterior cruciate ligament stabilization or substitution that are not seen in THA. Additionally, there are concerns for modular locking mechanisms or backside wear in TKA [11].

Manufacturers utilize various polyethylene manufacturing and processing strategies for TKA. Differences may exist in the polyethylene resin, the subsequent consolidation process, articular surface treatment, type or dose of radiation, thermal processing, and sterilization [8]. Following consolidation of the resin and machining, most modern polyethylene bearings for TKA receive some level of either gamma or warm electron beam radiation leading to various levels of crosslinking [3, 8]. Previous literature has typically classified conventional polyetheylene or HXLPE based on the total radiation kilogray (kGy) dose [8]. Radiation occurs either before or at the time of terminal sterilization. For those that receive radiation before sterilization, they may also undergo a thermal processing step that involves remelting or annealing to reduce free radicals created by radiation in the crosslinking step [10, 12]. However, this thermal processing step can decrease the mechanical properties of the polyethylene and as an alternative to thermal processing, some polyethylene bearings use antioxidants in the form of vitamin E or pentaerythritol tetrakis (PBHP) as an alternative strategy to reduce free radicals and improve oxidation resistance [16].

Benefits to the use of HXLPE with or without an antioxidant in TKA have not been as clear as in THA. The addition of an antioxidant to HXLPE has also not been proven to have obvious clinical benefits outside of laboratory testing [5, 13]. National registry-level data have been inconsistent, with lower prosthesis-specific survivorship with HXLPE seen in the Australian Orthopaedic National Joint Replacement Registry (AOANJRR) [4] and investigations from the National Joint Registry (NJR) for England, Wales, and Northern Ireland demonstrating no survival benefit of HXLPE [14]. However, these registry analyses are derived from regions that use HXLPE with or without an antioxidant less frequently than in the United States, and they may be inherently limited because of concerns about selection bias. In the United States, the use of HXLPE with an antioxidant represents 31.8% of primary TKA inserts, and HXLPE without an antioxidant represents 46.3% [8]. Additionally, there is a paucity of data in large-scale registry investigations regarding the risk of revision TKA with HXLPE with antioxidant inserts. The American Joint Replacement Registry (AJRR) collects data on more than 2.1 million arthroplasty procedures from more than 1300 sites in the United States [1]. The AJRR thus provides a unique opportunity to evaluate whether there are increased revision risks with HXLPE with or without antioxidants compared with conventional polyethylene.

We therefore asked: (1) Is there a difference in all-cause revision in patients who underwent TKA using HXLPE with or without antioxidant doping compared with conventional polyethylene? (2) Is there a difference in revision for aseptic failure in patients who underwent TKA using HXLPE with or without antioxidant doping compared with conventional polyethylene?

Patients and Methods

Study Design and Setting

We retrospectively analyzed data on primary TKAs in the AJRR database from January 2012 to December 2019. We identified all primary TKA procedures in patients 65 years and older during the study period and linked these procedures to Centers for Medicare & Medicaid (CMS) claims data to supplement revision events occurring outside of AJRR reporting institutions, where available. The study was limited to patient 65 years and older as a way to supplement AJRR outcomes data with CMS claims data to capture a revision of a primary TKA even if the revision was done at a non-AJRR facility. Catalog numbers from each TKA were identified and recorded to classify procedures into target component categories. The study was limited to the 65 years and older population to limit the confounding that can be produced from non-Medicare patients. The Internet-only Manuals estimates that 96% of patients 65 years and older utilize Medicare benefits. The AJRR and Medicare databases were merged and crossvalidated so that it was not easy to distinguish which of the cases were identified from each source, but our methods do consider patient identification, joint, procedure date sequence, and laterality to ensure reliable outcome linking [7].

Participants

Each identified procedure in the AJRR was assessed for a linked revision surgery in the AJRR or CMS database. A surgery was labeled as a revision if it met four criteria: surgical date after the index procedure, matched patient identification number, matched surgical site, and matched laterality. Revision codes included CPT (27486, 27487, 27488) ICD-9 (00.80, 00.81, 00.82, 00.83, 00.84, 80.06, 81.55), and ICD-10 (0SHC08Z, 0SHD08Z, 0SPC08Z, 0SPC09Z, 0SPC0JZ, 0SPD08Z, 0SPD09Z, 0SUC09C, 0SUC09Z, 0SUC0JZ, 0SUD09C, 0SUD09Z, 0SUD0JZ, 0SUT09Z, 0SUU09Z, 0SUV09Z, 0SUW09Z, 0SWC09Z, 0SWC0JZ, 0SWD09Z, 0SWD0JZ, 0SPU0JZ, 0QRx0JZ, 0SPC0xx, 0SPD0xx, 0SWC0xx, 0SWD0xx, 0SRC0EZ, 0SRD0EZ, 0SUx09Z). In addition, ICD-10 codes were used to infer laterality, along with a discrete laterality field in the AJRR database for older procedures. Because of coding issues, we could not reliably limit this analysis to revisions for aseptic loosening alone, and rather used codes for aseptic failure. These codes include not only aseptic loosening, but also revisions for mechanical complications of internal knee prostheses, such as including revisions performed for instability, malrotation, or polyethylene post or locking mechanism fracture.

We identified 994,535 primary TKAs over the study period; 622 cases were excluded due to no gender classification and 202,680 were excluded because they had incomplete device data, leaving 791,233 TKAs over the study period that had complete device data available. Linking this group to CMS with age 65 years or older left a final cohort of 339,366 TKA cases included in the analysis. There were 110,724 in the conventional polyethylene group, 91,301 in the HXLPE with antioxidant group, and 137,341 in the HXLPE without antioxidant group (Fig. 1).

Fig. 1.

Flow chart demonstrating exclusion and allocation of primary TKA cases into cohorts: conventional polyethylene, HXLPE with antioxidant, and HXLPE without antioxidant.

Patients’ Baseline Data

Patients in the conventional polyethylene group were more likely to have a lower mean number of reported comorbidities, were more likely to be female, and were more likely to be older than 75 years (Table 1). Additionally, we noted different regional use: Conventional polyethylene use was more common in the midwestern United States, HXLPE with an antioxidant was more common in the West, and HXLPE without an antioxidant was the most common in the South (Table 1).

Table 1.

Demographics of patients with conventional polyethylene and HXLPE, with or without an antioxidant (n = 339,366)

	Conventional polyethylene	HXLPE with antioxidanta	HXLPE with no antioxidant	p value
Total	33 (110,724)	27 (91,301)	40 (137,341)
Female	63 (69,858)	61 (55,642)	62 (84,749)	< 0.001
Age in years
65-74	60 (66,484)	66 (59,832)	64 (88,572)	< 0.001
75-84	35 (38,415)	30 (27,548)	31 (42,864)
85 and older	5 (5825)	4 (3921)	4 (5905)
Region
Midwest	33 (36,853)	23 (20,911)	27 (37,554)	< 0.001
Northeast	26 (28,781)	14 (12,776)	15 (20,305)
South	20 (22,134)	27 (24,533)	30 (40,614)
West	21 (22,956)	36 (33,081)	28 (38,868)

Data presented as % (n). The percentages in the first row are based on the total population (n = 339,366); the remaining demographic breakdown variables are the percentage of the column total to show the distribution of the variable per study group.

^aHXLPE antioxidants include vitamin E blended, vitamin E infused, and pentaerythritol tetrakis.

Primary and Secondary Study Outcomes

Our primary and secondary study goal was to evaluate all-cause revision and revision due to aseptic failure after TKA comparing HXLPE with or without antioxidant doping to conventional polyethylene. To achieve this, we created event-free percent survival curves and Cox proportional hazard regression modeling. Hazard models and event-free survival curves are risk-adjusted, and they also adjust for competing risk, which enables us to assess cause-specific outcome.

Demographics, Description of Study Population

Data collected included patient age, gender, surgery dates, number of reported comorbidities, and region (Table 1). The reason for revision was also recorded, and outcomes were stratified into three groups based on polyethylene crosslinking. Crosslinking level was categorized as conventional polyethylene 0 kGy to 49 kGy, moderately crosslinked 50 kGy to 74 kGy, or highly crosslinked 75 + kGy, based on the total radiation dose [8]. There was relatively little use of moderately crosslinked polyethylene, and these were grouped into the HXLPE classification for analysis. The addition of an antioxidant, either pentaerythritol tetrakis or vitamin E, was also recorded.

Ethical Approval

We obtained ethical review board approval for this study.

Statistical Analysis, Study Size

For all-cause revision and revision for aseptic failure outcomes, we created event-free percent survival curves and Cox proportional hazard regression modeling. Hazard models and event-free survival curves are risk-adjusted and also adjust for competing risk; this enables us to assess cause-specific outcomes. The hazard model is the quantitative version of the result, whereas the event-free surival curves are the qualitative visual representation of the results.

Results

All-cause Revision

Compared with conventional polyethylene, there was no difference in all-cause revision with HXLPE with an antioxidant (HR 1.06 [95% CI 0.98 to 1.14]; p = 0.13) or HXLPE without an antioxidant (HR 1.04 [95% CI 0.97 to 1.11]; p = 0.28). Event-free percent survival curves demonstrated similar estimates for conventional polyethylene compared with HXLPE with or without an antioxidant with overlapping confidence limits (Fig. 2).

Fig. 2.

Event-free survival curve of all-cause revision for patients who underwent TKA using HXLPE with or without antioxidant doping compared with conventional polyethylene.

Revision for Aseptic Failure

Compared with conventional polyethylene, there was no difference in revision for aseptic failure with HXLPE with an antioxidant (HR 1.07 [95% CI 0.99 to 1.14]; p = 0.08) or HXLPE without an antioxidant (HR 1.03 [95% CI 0.97 to 1.01]; p = 0.30). Event-free percent survival curves demonstrate similar estimates for conventional polyethylene compared with HXLPE with or without antioxidant with overlapping confidence limits (Fig. 3).

Fig. 3.

Event-free survival curve of revision for aseptic failure of patients who underwent TKA using HXLPE with or without antioxidant doping compared with conventional polyethylene.

Discussion

The use of HXLPE with or without antioxidants in TKA continues to increase in the United States, but concerns persist regarding the potential of polyethylene fracture because of decreased mechanical properties. The United States is unique among large, national registries in the high frequency of HXLPE use and antioxidant doping, and the AJRR dataset allowed us to evaluate the risk of revision across these groups. We found no difference in the risk of all-cause revision or revision for aseptic loosening for HXLPE with or without antioxidant doping compared with conventional polyetheylene in TKA in the AJRR Medicare population.

Limitations

There are several limitations to this study. This is a retrospective study and therefore has the potential for selection bias and administrative error. However, the AJRR contains data representing more than 2.1 million procedures from more than 1300 sites in the United States and is the largest orthopaedic registry globally per annual procedure count [1]. Many types of practice settings are captured in this dataset. In addition to the size and variety of institutional capture in the AJRR, a recent study found distributions across hospital volume, age, and geography to be proportionally similar between the AJRR and the National Inpatient Sample database, further supporting the generalizability of AJRR data to the overall US population [15]. Additionally, we limited our population to patients 65 years and older to allow linkage to CMS data to ensure we captured a revision TKA if it was performed at a non-AJRR institution. Without supplemental CMS data, the AJRR is limited in its capture of outcomes data if a revision were to occur at a non-AJRR institution, but this limited our study population. Younger patients may have different results, and our results may not be generalizable to this population because younger patients may have higher activity levels or demands placed on a TKA polyetheylene bearing leading to different outcomes. Despite this, we captured more than 300,000 patients for our analysis, making this a very robust and encompassing group size.

To create a robust capture for analysis, we were unable to consider other factors such as obesity, bearing design, presence of inflammatory arthropathy, or comorbidities that may have played a role in each revision scenario. We could not rule out the presence of mechanical failures related to elevated radiation dosage within specific size-thickness variations of individual systems. As noted in the methods, because of issues related to coding of revision TKAs, we were unable to evaluate aseptic loosening as a separate entity and instead chose the outcome of aseptic failure as a broader category. This means our study may include revisions for other aseptic indications, such as instability, malrotation, or polyethylene post or locking mechanism fracture, which could confound our results. Additionally, we were unable to compare results with different variations of polyethylene within the same manufacturer’s systems. Finally, because the AJRR began collecting data in 2012, the ability to display long-term outcome data is limited. Although issues related to decreased mechanical properties with HXLPE might be expected to manifest at earlier points, wear-related complications will likely require longer-term follow-up than is currently available in the AJRR database and thus unavailable for the present study.

All-cause Revision

We found no difference in the risk of all-cause revision in patients who underwent TKA using HXLPE with or without antioxidant doping compared with conventional polyethylene. This finding is similar to previously published results including those of Partridge et al. [14], who evaluated the risk of revision with use of HXLPE compared with conventional polyethylene and found no differences between adjusted revision rates in individual analyses of the most common TKA systems. Their study used data from the NJR, and despite the high total number of procedures, the frequency of HXLPE use in that study population was lower than in our present study: only 6.7% (36,914 of 550,658) had HXLPE. Our results are similar to the findings from another European investigation; Boyer et al. [2] compared HXLPE with conventional polyethylene for TKA and found no difference in all-cause survival. Additionally, a US-based study evaluating results from the Kaiser Permanente registry showed no difference in all-cause revision for HXLPE versus conventional polyethylene [6]. In our present study, we used AJRR data to include a large patient population with a high frequency of HXLPE use, both with or without antioxidants. This factor helped mitigate some of the concerns of selection bias, allowing us to provide further insight into these bearings.

There is conflicting evidence from the AOANJRR; an investigation showed lower 10-year cumulative revision risk for HXLPE compared with conventional polyethylene [4]. The authors of that study noted that their findings appeared to be prosthesis-specific and most evident in patients younger than 65 years. The differences in the all-cause revision risk in our study may be because we included patients only 65 years or older, and there was a shorter-term follow-up period in the AJRR data. In addition, the AOANJRR, with more historical data, includes legacy TKA systems, which may include variations in the type of polyetheylene manufacturing and do not distinguish between antioxidant use or not in HXLPE.

Revision for Aseptic Failure

We found no difference in the revision risk for aseptic loosening in patients who underwent TKA using HXLPE with or without antioxidant doping compared with conventional polyethylene. Our finding is similar to the previously mentioned Kaiser Permanente registry investigation that evaluated the risk of aseptic revision for HXLPE compared with conventional polyethylene and also found no difference [6]. Our findings are also similar to the Italian registry experience in which the authors also found no difference in aseptic loosening comparing HXLPE with conventional polyethylene [2]. Our findings contrast with those from the NJR in which conventional polyethylene was found to have a superior unadjusted aseptic survival rate at 10 years [14]. However, they found no significant differences between adjusted revision rates of HXLPE compared with conventional polyethyelene. Additionally, the superior unadjusted aseptic survival rate could be a result of greater selection bias in the NJR as there is lower overall use of HXPLE. We feel that the higher incidence of HXPLE use in the present study helped mitigate the potential of selection bias.

Conclusion

Using AJRR data, we found no difference in all-cause revision or revision for aseptic loosening when comparing HXLPE with or without an antioxidant to conventional polyethylene for TKA. As the use of these modern polyethylene bearings for TKA has increased, our findings may help to mitigate concerns about the potential of polyethylene fracture because of decreased mechanical properties. However, longer-term follow-up, especially in younger patients, is required to demonstrate any potential benefits associated with HXLPE with or without the addition of an antioxidant. As the less time-tested and more costly alternative, HXLPE polyethylene, with or without an antioxidant, should not be widely adopted in TKA until or unless it is shown to be superior to conventional polyethylene.