Short-term survivorship of antioxidant highly cross-linked polyethylene liners in total hip arthroplasty reported in American Joint Replacement Registry

Abstract

BACKGROUND

Total hip arthroplasty is a safe and effective procedure. To improve survivorship, ultrahigh molecular weight polyethylene hip liners with antioxidants have been developed. Additive antioxidant was deployed to reduce oxidation and consequential wear, loosening, or osteolysis. A unique manufacturing process was utilized for two such hip liners, the Novation^® and Alteon^® XLE hip liners and this research represents the first large series on this specific material. The study hypothesis was that Novation and Alteon XLE hip liners have similar short-term survivorship as other manufacturers’ antioxidant liners according to procedure and outcome data from the American Joint Replacement Registry (AJRR).

AIM

To demonstrate similar short-term survivorship of XLE antioxidant hip liners compared to all antioxidant hip liners in AJRR.

METHODS

Utilizing total hip arthroplasty data from the AJRR, a retrospective review was performed for subjects who underwent implantation of Novation XLE (n = 461), Alteon XLE (n = 989), or any other antioxidant hip liner (termed the aggregate antioxidant group; n = 39964) as of March 31, 2022. Survivorship at three years and revision rates were compared statistically between the Novation group and the aggregate antioxidant group as well as the Alteon group and the aggregate antioxidant group.

RESULTS

Survivorship at three years post-surgery was 99.09% for Novation, 97.73% for Alteon, and 97.69% for the aggregate antioxidant group. There were no reports of failure due to wear in either the Novation or Alteon groups. Among the revision categories (fracture, infection, aseptic loosening, instability, mechanical complications, wear, pain, hematoma/wound complications, or other), there were no significant differences identified in either comparison. There were also no significant differences in cumulative percent revision rates up to three years post-surgery for the Novation vs aggregate antioxidant group or the Alteon vs aggregate antioxidant group.

CONCLUSION

Novation and Alteon XLE hip liner revision rate and survivorship are equivalent to other antioxidant hip liners in the short term.

Key Words: Total hip arthroplasty; Hip liner; Blended vitamin E; Antioxidant; Safety; Survivorship; American Joint Replacement Registry; XLE; Novation; Alteon

Core Tip: Short-term data from the American Joint Replacement Registry on the Novation and Alteon XLE hip liners reveal similar survivorship and reasons for revision compared to an aggregate group of all other antioxidant liners. Within this dataset there were no failures due to wear in the Novation and Alteon XLE groups.

INTRODUCTION

Total hip arthroplasty (THA) is performed using several components. The hemispherical acetabular cup component allows for screw fixation into the bones of the pelvis. A liner is then affixed to the acetabular cup component and serves as the articulating interface between the cup and the femoral head component. The hip liner provides stability and distributes forces within the hip joint, ensuring smooth articulation and is developed to minimize wear due to the articulation.

Traditionally, hip liners have been exclusively made of materials such as ultrahigh molecular weight polyethylene (UHMWPE). Modern hip liners incorporate advanced designs and material processing to enhance longevity and reduce the risk of complications such as dislocation and loosening. A major advancement in liner technology has come in the form of highly cross-linked polyethylene, which has demonstrated improved wear resistance and decreased the likelihood of osteolysis, a condition associated with macrophage infiltration following particle debris from wear[1-3].

The newest advancements in liner technology include highly crosslinked, antioxidant-stabilized UHMWPEs (VE-HXLPE)[4], which provide protection against oxidation, a prominent factor in implant failure[5]. The earliest form of VE-HXLPE hip liners, first released in 2007, utilized diffusion of vitamin E as part of post-processing[6,7]. VE-HXLPE has demonstrated reduced wear debris generation and associated osteolysis compared to conventional polyethylene liners[8,9]. Several studies have shown promising results regarding the improved wear resistance and reduced liner wear rates of VE-HXLPE in laboratory simulations and clinical studies[10,11]. The implementation of VE-HXLPE in hip liners for THA has contributed to improved implant longevity, thereby reducing the need for revision surgery and improving the long-term success of total hip arthroplasty procedures[12].

The XLE Vitamin E Liner, a type of VE-HXLPE developed by polymer scientists at Massachusetts General Hospital and licensed to and manufactured by Exactech, Inc. for use in both the Novation^® and Alteon^® acetabular cup systems, uses UHMWPE blended with vitamin E (1000 ppm) prior to consolidation and crosslinking. This method provides the benefits of a uniform distribution of vitamin E and minimizes the elution effect found in diffused vitamin E liners. It also protects the polymer against oxidation during manufacturing by scavenging the free radicals generated during cross-linking[4,13]. Furthermore, the proprietary process includes gamma irradiation, and mechanical deformation and annealing below the melting temperature, before the material is machined to its final shape. The unique process has two benefits: (1) To reduce the free radical content of the vitamin E-containing material, further protecting the polymer against oxidation; and (2) to graft the vitamin E to the polymer, which results in a highly crosslinked material with excellent oxidative stability[14]. Quenching free radicals using mechanical deformation and annealing without melting the cross-linked polymer[15] results in reduced wear and improved mechanical strength compared to traditional polyethylene[4].

While previous research has demonstrated the early clinical safety and efficacy of Vitamin E-containing hip liners[16,17], the goal of this study was to compare how XLE hip liners made with the unique process perform relative to other commercially available antioxidant liners. The American Joint Replacement Registry (AJRR) was utilized to achieve the study goal. Although results of such blended Vitamin E-containing UHMWPE hip liners have been published previously[18-20], this is the first publication to report short-term survivorship in more than 100 subjects.

MATERIALS AND METHODS

All primary THA cases from January 2012 – March 2022 submitted to AJRR as of December 31, 2022, were queried. Only Medicare patients aged 65 and older were eligible for analysis. Subjects implanted with the Novation XLE liner and cup (Exactech) were included as the first comparison group, subjects implanted with the Alteon XLE liner and cup (Exactech) were included as the second comparison group, and the third group was made up of subjects implanted with any other antioxidant-containing liner. This group was termed the ‘aggregate antioxidant liner group’.

Cases submitted to AJRR that had patient ID, laterality, and site data met the inclusion criteria for analyses of post-operative outcomes, including percent revision. Cases submitted to AJRR without all of these data points were excluded. These exclusion criteria are critical to ensure the validity of the revision data whereby incorrect coding of a procedure as a revision would cause false positives in the data. Centers for Medicare & Medicaid Services (CMS) data from January 2, 2012 through March 31, 2022 was merged with AJRR data for a comprehensive survival analysis which is presented as cumulative percent revision curves. CMS data allowed for revision procedures to be linked to the index procedure when a subsequent THA procedure was performed with matching patient ID, laterality, and site. Exclusions were made for linked outcome cases if laterality could not be verified within AJRR or CMS or if the primary procedure date came after the revision date.

Statistical analysis

Continuous data were analyzed using t tests and categorical data (including reason for revision) were compared using either χ² tests with Yates’s continuity correction or Fisher’s exact test. Fisher’s exact test was utilized when any cell in the comparison matrix had fewer than six counts. The analyses focused on the Novation group vs the aggregate antioxidant liner group comparison and the Alteon group vs the aggregate antioxidant liner group comparison. For each comparison a hazard ratio adjusted for age and sex was produced with the 95% confidence interval and P value to determine statistical significance. A P value of less than 0.05 was set as the threshold for statistical significance. A Cox proportional hazard (PH) regression model was run for all cases where an index procedure and revision procedure were linked in the AJRR database. Since the earliest relevant XLE case in AJRR occurred in 2018, index and revision procedures were tracked for up to 3 years, which represents the maximum full year of follow-up that was available for the XLE groups when data were pulled in March 2022. Case information from AJRR is not registered down to the component level so if, for example, four components were implanted, and that subject had a subsequent revision, it is not known which of the four components failed, if any.

This study was exempt from Institutional Review Board review and approval based on the exemption criteria included in 45 CFR 46.104. Statistical review of the study was performed by biomedical statisticians at both the American Academy of Orthopaedic Surgeons and Exactech.

RESULTS

According to the AJRR, a total of 461 Novation XLE, 989 Alteon XLE, and 39964 aggregate antioxidant liners were implanted prior to the data cutoff date in March 2022. The mean ages across the three groups ranged from 72.6 to 74.0 years (Table 1). Statistical comparisons using t test found a significant difference in age in the Alteon vs that in the aggregate antioxidant liner group, with the Alteon group being older. There was no significant difference in mean age in the Novation vs the aggregate antioxidant liner group. The proportion of females in each group ranged from 57.8% to 63.3% (Table 1). There were no significant differences in proportions of males and females in either comparison. The Charlson Index, a calculated score based on a set of comorbidities, was significantly different in the two comparisons. Subjects in the Novation group had a significantly lower Charlson Index score compared to the aggregate antioxidant liner group whereas the Alteon group had a significantly higher Charlson Index score compared to the aggregate antioxidant liner group. The duration of follow-up varied widely across the three groups from 15 months (Alteon group), 33 months (Novation group), and 53 months (aggregate antioxidant liner group). Statistical analyses using t test found significant differences in follow-up duration for both comparisons (Table 1).

Table 1 Subject demographics of Novation, Alteon, and aggregate antioxidant groups, n (%).

	Novation (n = 461)	Alteon (n = 989)	Aggregate antioxidant (n = 39964)	Novation vs aggregate, P value	Alteon vs aggregate, P value
Age - mean (SD)	72.55 (5.92)	74.01 (6.43)	72.92 (6.30)	0.21	< 0.0001
Follow-up (months) - mean (SD)	33.07 (8.59)	14.84 (8.20)	53.21 (24.01)	< 0.0001	< 0.0001
Sex				0.12	0.30
Female	291 (63.26)	572 (57.84)	23722 (59.54)	-	-
Male	169 (36.74)	417 (42.16)	16121 (40.46)	-	-
Unknown	1	0	121	-	-
Charlson index – mean (SD)	2.89 (0.91)	3.18 (1.16)	3.00 (1.09)	0.01	< 0.0001
Primary OA diagnosis				0.40	< 0.0001
Yes	439 (95.85)	838 (88.68)	37305 (94.88)	-	-
No	19 (4.15)	107 (11.32)	2014 (5.12)	-	-
Unknown	3	44	645	-	-

OA: Osteoarthritis.

The all-cause revision rate was 2.47% for the aggregate antioxidant liner group, 1.82% for the Alteon group and 0.87% for the Novation group. Proportion analyses found no significant difference in the revision rate for the Alteon group vs that for the aggregate antioxidant liner group whereas the difference in the revision rate was statistically significant for the Novation group vs that for the aggregate antioxidant liner group (Table 2). The two most common reasons for revision in the aggregate antioxidant group were instability and fracture (including periprosthetic fracture; Table 2). For the Alteon group, fracture (including periprosthetic fracture) and infection were the most common reasons for revision (Table 2). Fracture (including periprosthetic fracture) was also one of the most common causes for revision in the Novation group (Table 2). Proportion analyses found no significant differences in the reason for revision across groups. There were no reports of failure due to wear in the Alteon and Novation groups. Similarly, failure due to wear was rare, only 3 cases of 39964 subjects, in the aggregate antioxidant liner group.

Table 2 Revision rate and reason for revision rates for Novation, Alteon, and aggregate antioxidant groups, n (%).

Revisions	Novation (n = 461)	Alteon (n = 989)	Aggregate antioxidant (n = 39964)	Novation vs aggregate, P value	Alteon vs aggregate, P value
All-cause	4 (0.87)	18 (1.82)	986 (2.47)	0.02	0.23
Fracture (including periprosthetic fracture)	2 (0.43)	6 (0.61)	247 (0.62)	0.99	0.99
Infection	0 (0.00)	6 (0.61)	205 (0.51)	0.18	0.86
Aseptic loosening	0 (0.00)	2 (0.20)	116 (0.29)	0.65	0.99
Instability	0 (0.00)	3 (0.30)	248 (0.62)	0.12	0.30
Mechanical complications	0 (0.00)	2 (0.20)	101 (0.25)	0.63	0.33
Hematoma or wound complications	0 (0.00)	1 (0.10)	24 (0.06)	0.99	0.46
Wear	0 (0.00)	0 (0.00)	3 (0.01)	0.99	0.99
Pain	0 (0.00)	2 (0.20)	80 (0.20)	0.99	0.99
Revisions for all other reasons	2 (0.43)	1 (0.10)	229 (0.57)	0.19	0.05

F¹ “Other” reasons include non-specific or possibly irrelevant/erroneous diagnoses including cardiac conditions, hypertension, obesity, etc.

Cumulative percent revision rate was calculated for post-operative years 1, 2, and 3 for all groups (Table 3). The cumulative percent revision rates for both the Novation and the Alteon groups were less than or equal to that of the aggregate antioxidant liner group at all years (Table 3). Survivorship at three years post-surgery was 99.09% for Novation, 97.73% for Alteon, and 97.69% for the aggregate antioxidant liner group. The age- and sex-adjusted hazard ratios for statistical comparison of survivorship indicate no statistical difference in the survivorship of Novation compared to the aggregate antioxidant liner group, nor Alteon compared to the aggregate antioxidant liner group (Table 4). The Cox PH regression model of cumulative percent revision rates is shown in Figure 1 as a visual representation of the comparison between groups.

Figure 1 Cumulative percent revision curves for Novation, Alteon, and aggregate antioxidant liner groups. THA: Total hip arthroplasty; PH: Proportional hazard.

Table 3 Cumulative percent revision rates for Novation, Alteon, and aggregate antioxidant liner groups.

	Novation (n = 461)	Alteon (n = 989)	Aggregate antioxidant (n = 39964)
Years to Revision	Cumulative Percent Revision% [95%CI] (Number at risk)
0	0.10% [0.00-0.19] (460)	0.25% [0.12-0.37] (989)	0.25% [0.20-0.30] (39843)
1	0.71% [0.01-1.40] (443)	1.79% [0.97-2.60] (584)	1.82% [1.69-1.95] (37561)
2	0.83% [0.02-1.64] (394)	2.09% [1.13-3.03] (162)	2.12% [1.98-2.27] (35337)
3	0.91% [0.02-1.79] (186)	2.27% [1.23-3.31] (2)	2.31% [2.16-2.46] (27951)

Table 4 Hazard ratios for statistical comparison of survivorship.

Comparison	Hazard ratio	Confidence interval	P value
Novation vs aggregate antioxidant	0.389	0.146-1.04	0.060
Alteon vs aggregate antioxidant	0.982	0.615-1.567	0.940

DISCUSSION

Traditionally, reasons for THA failure have included dislocation/instability, periprosthetic fracture, prosthetic joint infection, wear, and aseptic loosening[21-23]. Thankfully for patients with modern implants, the risk of any of these is small, which causes even large series to have relatively low numbers of implants that have failed via any individual failure mechanism. This may be due to appropriate hip liner selection, which should be based on factors such as patient age, activity level, surgeon preference, and implant design. In this study, there were no differences in the proportion of subjects revised for any of the individual reasons categorized in the Novation vs the aggregate antioxidant group comparison or the Alteon vs aggregate antioxidant liner group comparison.

The oxidative and wear performances of the XLE liners are expected to be similar to other antioxidant-containing, highly cross-linked liners, thus differences in their longevity or reasons for revision from others is not expected. The main findings of this study, substantiated by the hazard ratios, support this expectation for both the Novation and Alteon XLE liners out to three years of post-operative follow up. While some of the indicators are trending better than the aggregate antioxidant liner AJRR data, a statistical claim cannot yet be made that the Novation or Alteon XLE liners perform better than the aggregate antioxidant liner data due to the current small number of revision cases and short follow-up durations available from the AJRR. However, there are equivalent hazard ratios of the XLE liners in relation to the large aggregate antioxidant liner data in the AJRR database at three years. Long-term survivorship analysis will be critical to determine whether blended vitamin-E liners made using the proprietary process described previously will lead to differences in terms of patient outcomes.

Registry research has limitations. Follow-up durations were significantly different across the two comparisons, though the Novation group had a longer follow-up with an average of 33 months than that of the Alteon group with an average of 15 months. Differences in follow-up duration can impact the revision rate, but were controlled for in the hazard ratio analyses by limiting the data to three years of follow-up duration. Furthermore, despite populations with almost 1,000 (Alteon XLE) and 500 (Novation XLE) implants per liner type, the numbers of revisions for even the most common modes of failure are very low (due to the generally low revision rates in THA) and thus will be subject to further study with greater numbers and longer-term follow-up. Failures are not reported at the component level so failures reported in this study may be related the other components in the hip construct or may not be related to the hip liner implants themselves. Registry research also has the limitation of potential selection bias; AJRR is a voluntary registry. The dataset may also have unmeasured confounding variables both within and across liner groups.

CONCLUSION

This study demonstrates for the first time that the proprietary blended antioxidant process developed for XLE hip liners is associated with revision rates equivalent to the aggregate antioxidant-containing liners available in the AJRR. Further studies will be able to assess if XLE liners perform better than other antioxidant liners as well as report on other clinical parameters such as patient-reported outcomes and longer term follow up. Limitations include the retrospective design, potentially unmeasured confounding variables and selection bias.

ACKNOWLEDGEMENTS

The authors would like to acknowledge and thank the American Academy of Orthopaedic Surgeons (AAOS) and the American Joint Replacement Registry (AJRR) for providing the data and statistical analyses that made this publication possible.