The Long-Term Survivorship and Incidence of ARMD

The excellent mid- and long-term outcomes of MoM THA using 28 mm Metasul bearings have been reported. The survival rates were 90%–96% with revision surgery as the endpoint4-8. Besides, the revision rates associated with ARMD have been reported as 0%–3% only within 15 years following small-head MoM THA5, 6, 8, 17, 36. A recent study of AOANJRR data showed a significantly lower revision rate after small-head MoM THA than after large-head (>32 mm) MoM THA17. The revision rates were 27.4% and 8.5% at a 14-year follow-up period of large-head MoM THA and a 15-year follow-up period of small-head MoM THA with a hazard ratio of 5.18 (95% CI, 4.1–6.5; P < 0.001); additionally, the cumulative percentages of revision surgeries for ARMD at 15 years were 0.8% (95% CI, 0.8–1.4) for small heads and 12.4% (95% CI, 11.4–13.7) for large heads. Nevertheless, even using small-head MoM bearings, other recent studies have cautioned elevated metal ion levels and the late onset of ARMD after a long-term in vivo service30-32. Lombardi et al.31 reported the outcomes of small-head MoM THA using the M2a Taper system (Zimmer-Biomet), whose survival rates at 10, 15, and 19 years were 96%, 92%, and 73%, respectively. Revision THAs were performed in 14/20 hips (70%) due to ARMD. Reiner et al.32 reported that ARMD was found in 41% of the patients implanted with Metasul followed up at a mean period of 15.5 years. In this study, ARMD was found in 20% of the patients implanted with Metasul. Accordingly, the revision rate increased rapidly from 4% to 20% between 15 and 20 years after THA, and the survival rate decreased from 84.8% to 70.3% (Fig. 1). Our results suggest that ARMD is a major postoperative complication beyond 15 years even after small-head MoM THA.

The Long-Term Behavior of Metal Ions and Diagnostic Potential of ARMD

Most investigations on the association between serum metal ion levels and ARMD have involved large-head MoM THA10, 11, 23. Bosker et al.23 reported that patients with elevated serum metal ion levels had a four-times greater risk of developing a pseudotumor following large-head MoM THA. Conversely, the long-term behavior of serum metal ion levels after small-head MoM THA is not fully understood. Waldstein et al.37 showed that the median serum Co ion level remained low (1.04 μg/L [IQR, 0.64–1.70]) 21 years after implantation of 28 mm Metasul bearing, which was not significantly different from that at 5 years (0.70 μg/L [IQR, 0.2–1.8])38. In this study, serum Co ion levels at ≥15 years were also as low as those at <5 years although serum Cr ion levels were significantly higher (Table 3). Note that the Co ion level peaked at 5–10 years, which was significantly higher than that at <5 years, but it decreased to the initial level after 15 years. Alternatively, Cr ion levels increased significantly at 5–10 years and remained almost constant. This trend should reflect a time-dependent change in the balance between ion release from the device and ion excretion or storage (or potential consumption for tissue reactions)28, 29. Renal excretion is the primary clearance mode of Co and Cr ions, but the kidney reportedly eliminates Co ions at a higher rate compared with Cr ions28, 29. Furthermore, Cr ions bind more readily to proteins than Co ions, allowing Cr accumulation in local soft tissues and precipitation as chromium orthophosphate39. In these contexts, Cr ions might last longer in vivo than Co ions, suggesting the potential of Cr ion level as a more stable indicator. According to the current guideline40, serum Co and Cr ion levels of <2.0 μg/L are of no clinical concern. Possible biological effects of high Cr ion levels are DNA and chromosomal damage, reduction in CD8+ lymphocyte levels, and ARMD, although these effects remain controversial41.

Besides the serum ion levels, the Co/Cr ratio is an informative parameter to understand the long-term behavior of the released metal ions in the serum. The Co/Cr ratio of the base material within the ASTM guidelines ranges from 1.9 to 2.6 depending on the exact composition of the alloy used by the manufacturer42. Numerous studies19-21, 43-45 have reported that, in large-head MoM THA, ARMD onset is associated with mechanically assisted (fretting) corrosion at the head–neck interfaces and its related metal ion release. The fretting corrosion is an irreversible interfacial reaction of material, often resulting in an active metal ion release. Under such circumstances, ion release might continuously occur at a faster rate than excretion and tissue reaction, increasing serum Co levels and the Co/Cr ratio in large-head MoM components being susceptible to large frictional torque at the modular head–neck interfaces19-21. Nevertheless, the fact that our results obtained from the small-head MoM THA did not follow the previously reported trend is interesting. The median Co/Cr ratio (5.0 [IQR, 4.8–7.3]) was highest within the first 5 years after THA, a value higher than that of the base material, and then decreased thereafter (Table 3, Fig. 2C). In fact, no obvious fretting corrosion was intraoperatively confirmed in the three ARMD patients during the revision surgeries, which might be due to less frictional torque at the head–neck junction associated with the use of the small-head bearings17. Thus, in our cases, articulating surfaces were probably a primary source of metal ion release rather than the head–neck interfaces. Because the wear rates of Metasul MoM articulation decreased with implantation time46, the Co/Cr ratio peaked within the first 5 years possibly due to the initial wear and then decreased possibly due to the reduced wear rate and increased ion excretion (primarily Co ion) and/or tissue reaction.

The overall trend of the Co/Cr ratio can be associated with the difference in ion release–excretion behavior between Co and Cr (i.e. a faster excretion of Co than Cr ion). Renner et al.47 have reported that Co/Cr ratios above 1.71 were predictive of osteolysis; however, ARMD was not studied as an outcome. In our study on small-head Metasul bearings, most ARMD patients had Co/Cr ratios below 1.71 and a lower median Co/Cr ratio than non-ARMD patients. In fact, Fehring et al.42 have highlighted that the interplay between ion release and excretion makes the use of this ratio difficult as a diagnostic tool. Nevertheless, in our cases, the Co/Cr ratio succeeded in obtaining the statistical significances between non-ARMD and ARMD patients after long-term follow-up (Table 4, Fig. 5). Thus, compared with the initial Co/Cr ratio at <5 years, its significant decrease might be associated with an increased risk of ARMD after small-head MoM THA. Additionally, the Co/Cr ratio may be a more sensitive predictor than serum Co levels alone, showing no significance at ≥15 years. These results suggest that, in small-head MoM THA, monitoring both Co and Cr ion levels is important for a more stable prediction of the ARMD risk.

Limitations of the Study

This study had the following limitations. First, the number of patients followed up over 15 years was relatively small (35 patients). Second, the infection rate was relatively high (Table 2), contributing to the reduced overall survival rate of the patients implanted with Metasul bearings. MoM bearings have been noted to be associated with a higher risk of periprosthetic infection than metal-on-polyethylene and ceramic-on-ceramic bearings48. However, in the patients with infections in this study, the serum Co and Cr levels at the time of infection onset (within 5–6 years) remained below the level of clinical concern (<2.0 μg/L)40. All three revision cases due to infection were at high risk of infection; two cases of idiopathic osteonecrosis of the femoral head (Cases 1 and 2 in Table 2) were on high-dose steroids, and the other case of osteoarthritis (Case 4 in Table 2) was complicated with severe diabetes mellitus. Thus, metal ions released from Metasul bearings are unlikely to be associated with infection.

Conclusion

The risk of ARMD-related revision surgery significantly increased following MoM THA using 28 mm Metasul bearings beyond the postoperative period of 15 years. The long-term in vivo behavior differs between Co and Cr, and increased Cr ion levels and decreased Co/Cr ratio may be signs of ARMD. Our results suggest that careful screening is needed not only for large-head MoM patients but also for small-head MoM patients according to metal ion levels and clinical imaging findings.