The generalized estimating equation analysis of the effect of the sex of the patient on femoral head penetration rates revealed a significant difference among the four polyethylene groups (men and women treated with conventional polyethylene and men and women treated with highly cross-linked polyethylene). In particular, a significant difference was found between men and women treated with conventional polyethylene (p = 0.014) but not between men and women treated with cross-linked polyethylene (p = 0.604). In addition, the polyethylene type had a strong effect in the male cohort but not in the female cohort—that is, the femoral head penetration rate in the male group treated with the highly cross-linked polyethylene was significantly lower than that in the male group treated with the conventional polyethylene (p = 0.003), but no significant difference was found between the female group treated with the conventional polyethylene and the female group treated with the highly cross-linked polyethylene (p = 0.091).
This randomized controlled trial demonstrated that, after a minimum of five years of follow-up, there were no clinical differences between patients treated with an acetabular liner made of conventional polyethylene and those treated with a cross-linked polyethylene liner. This finding was not unexpected as it is likely that the clinical benefits of highly cross-linked polyethylene, if they exist, would not be apparent until ten years postoperatively and beyond. Our findings are similar to those of other studies comparing the early and midterm clinical results between patients treated with highly cross-linked polyethylene and those treated with conventional polyethylene18,24-29. We did not find any significant difference between cohorts with regard to radiographic changes or the presence of osteolysis. Once again, it is unlikely that any difference, if one exists, would be seen at the time of midterm follow-up, especially since both cohorts had average wear rates that were well below the so-called “osteolysis threshold” of 0.1 mm/yr as proposed by Dumbleton et al.30. Interestingly, Leung et al.31 recently demonstrated that patients treated with a highly cross-linked polyethylene acetabular liner had a decreased incidence and volume of pelvic osteolysis, as shown by computed tomography, compared with patients treated with a conventional liner.
In our clinical trial, steady-state femoral head penetration rates were significantly lower in the group treated with the highly cross-linked polyethylene than they were in the group treated with the conventional polyethylene. The steady-state head penetration rate in the highly cross-linked polyethylene group was 0.003 mm/yr (95% confidence interval, −0.024 to 0.030), representing a reduction in head penetration of >95% as compared with the conventional polyethylene group. This very low wear rate is likely a result of the substantial number of negative wear rates seen in the highly cross-linked polyethylene group, as indicated by the negative lower bound of the 95% confidence interval. The low wear rate and the prevalence of negative wear rates compare well with the findings in a number of recent series in which the steady-state wear of highly cross-linked polyethylene was examined13,14,18,24,32-34. It is important to note that while the present study showed a trend suggesting decreased wear of highly cross-linked polyethylene at two to three years postoperatively, it was only after five years of follow-up, when steady-state rates could be calculated, that we were able to detect a difference between the cohorts at a significance level below 0.05. This finding is consistent with the fact that a number of earlier investigators who reported on total head penetration, and therefore did not take into account the bedding-in process, generally observed little improvement with highly cross-linked polyethylene as compared with conventional polyethylene25-28,35-38. Our study supports the concept that more than five years in vivo is required to show the true difference between the mean wear rates of these materials39.
We believe that the use of generalized estimating equations is the most appropriate method of analysis for this type of study23. We contend that it may be inappropriate to represent the wear rate by creating a regression line for the entire polyethylene group (containing all data points at various time intervals for all patients), as was done in previous studies13,14,16,17,40, because all data points within the group are not independent of one another23,41-44. Similarly, although the method of averaging individual patient regressions (i.e., the regression lines representing the wear rates for each patient)18,24 is a reasonable way to provide a visual comparison between groups, the method may be problematic statistically as it does not account for each patient's five data points (i.e., one for each year of follow-up) but instead applies statistical testing of the interpolated line of best fit41,43. In comparison, statistical analysis with generalized estimating equations accounts for the potential dependence between the related observations23,42,44. This issue is applicable to our data since repeated measurements were performed for each patient at various time intervals. A major strength of generalized estimating equations as compared with other repeated-measures approaches, such as analysis of variance, is that the generalized estimating equation model allows inclusion of several covariates (in our case, sex, polyethylene group, and time) whereas analysis of variance analysis allows only one explanatory variable. Therefore, the generalized estimating equation approach was used to determine if there were statistical differences between polyethylene groups and between polyethylene/sex groups.
To our knowledge, we are the first to examine the effect of the sex of the patient on the steady-state rate of femoral head penetration into highly cross-linked polyethylene. All analysis methods demonstrated significantly higher wear rates in male patients who had conventional polyethylene than in either male or female patients treated with highly cross-linked polyethylene. These findings are in agreement with the previous observations by Schmalzried et al.45, who demonstrated that polyethylene wear was related to use and was higher in male patients. While our data support this concept, with the relatively small numbers and the limitations of the edge-detection technique, one might still question the validity of this finding. A larger study with utilization of more precise tools, such as radiostereometric analysis, is probably required to confirm the effect of the patient's sex on wear of these new highly cross-linked polymers.
While this prospective, randomized, controlled trial provides Level-I evidence to support the concept that first-generation highly cross-linked polyethylene is associated with decreased femoral head penetration at the time of midterm follow-up, the study had several potential limitations. First, the numbers of patients were not large, and, although they were sufficient to demonstrate a clear difference in head penetration rates, the study was likely underpowered to show more subtle differences in clinical performance or the prevalence of osteolysis. Also, the addition of more sophisticated tools, such as computed tomography, is probably required to accurately assess osteolysis. Of note, the decision to use a cemented stem for the femoral reconstruction led to a tendency for older patients (those with Dorr type-B or C femoral bone46) to be enrolled in the study, which limited our follow-up (nine deaths occurred prior to the five-year follow-up point). In addition, we had no detailed activity scores with which to demonstrate the potential lower activity of these elderly patients, which may in turn have influenced their wear rates45.
Our decision to use edge-detection techniques as our primary wear-measurement tool is potentially problematic. There remains little doubt that the steady-state wear rate of highly cross-linked polyethylene is below the limit of detection of this technique. This is evidenced by the substantial number of patients who demonstrated negative wear values. This phenomenon of negative wear has been noted by several authors and there is no clear consensus on how to deal with it13,14,18,39. Lastly, because of image-quality issues, only approximately 78% of all available radiographs could be used for the analysis. While this is potentially worrisome, it is typical of the inclusion and exclusion rates in other investigations involving use of this technique12-15. Future work involving the prospective evaluation of these low-wear materials probably requires the use of radiostereometric analysis, the accuracy and precision of which exceed those of conventional edge-detection techniques32,39.
In summary, this prospective, randomized, controlled trial, which had a 98% rate of clinical follow-up and was performed at a single center, demonstrated, after the longest average duration of follow-up reported in this type of study in the literature, a clear decrease in femoral head penetration with the use of this first-generation highly cross-linked polyethylene. Our data confirm our initial hypothesis and strongly support the earlier laboratory and in vitro work4-7 that predicted a marked improvement in wear with this highly cross-linked polymer. Longer follow-up is required to determine if this will translate into improved clinical performance and longevity of these implants. To confound the issue further, because of concerns about ongoing oxidation47-50 and/or mechanical changes51-54, several manufacturers have now produced second-generation highly cross-linked polyethylene, which is already in clinical use55,56. These new materials should undergo the same rigorous in vivo testing to confirm their benefit.
NOTE: The authors thank Dr. John Martell for his help and guidance in the analysis of the head penetration data and Dr. Jan Brandt for his guidance regarding the interpretation of the individual patient regression analyses and correlated statistics. They also acknowledge the Biostatistics Consulting Unit at the University of Western Ontario for conducting the advanced statistical analyses utilized in this study.
A commentary is available with the electronic versions of this article, on our web site (www.jbjs.org) and on our quarterly CD-ROM/DVD (call our subscription department, at 781-449-9780, to order the CD-ROM or DVD).
Investigation performed at University Hospital, University of Western Ontario, London, Ontario, Canada
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