At the same time point, approximately 50% of the patients who had not had a failure had early radiographic signs of osteoarthritis, defined as a Kellgren and Lawrence grade of ≥2. There was no significant difference between the groups, although the microfracture group had the lowest frequency of osteoarthritis (48% versus 57%). Among the survivors, 20 patients (13 in the ACI group and 7 in the microfracture group) had not had planned radiographs made because they did not return to the outpatient clinic; however, they were contacted by mail or telephone to determine the clinical scores.
In contrast to the earlier follow-up studies, 1 failure occurred in a patient in the group that had repair tissue with the best histological quality. This patient had an HTO performed 9 years after the ACI. As a result, the association between histological quality and risk for later failure seen at 5 years was no longer significant.
The most important finding in this prospective randomized study of large chronic cartilage defects was that there were no major differences between microfracture and ACI. Further, it is remarkable that 30 of the 80 patients had treatment failure and that approximately 50% of the remaining patients (excluding 20 who had not returned for the final radiographic evaluation) had radiographic signs of early osteoarthritis at the latest follow-up. These findings raise serious concerns regarding the efficacy of these procedures in delaying osteoarthritis and preventing further surgery in this patient group. At the start of this study, we included only relatively large (median, 4.5 cm2), chronic lesions (median, 36-month duration of symptoms). In contrast to the study by Steadman et al., this study did not include any acute lesions9. The frequency of radiographic evidence of osteoarthritis in our study should be evaluated in light of the chronicity and size of the defects treated. Information regarding osteochondritis dissecans and osteoarthritis was discussed in our first study28. At the long-term follow-up, we did not find more radiographic evidence of osteoarthritis in the osteochondritis dissecans group (using linear regression). For the previous follow-up evaluations, standing radiographs with the knee in extension were used. This time, the use of standardized, fixed flexion standing radiographs (Synaflexer) may have identified more patients with early osteoarthritis33; however, this discrepancy has not influenced the comparison between groups.
Most studies have described good clinical results in the short and mid-term follow-up after different types of cartilage repair surgery; however, to our knowledge, this RCT is the first to compare ACI and microfracture with a follow-up as long as 14 to 15 years6-9,11-13,15,16,18,20-22,24,27,34,35. Compared with other studies with >10 years of follow-up, few patients (2.5%) were lost to follow-up. In our report on the results at 5 years, we used the intention-to-treat principle. However, clinical scores were missing at the time of failure in some cases. In addition, 17 of the patients underwent major surgery such as total knee replacement and HTO so their final score after surgery could not been used for comparison in this RCT.
In the same period, microfracture gained popularity as a low-cost 1-stage procedure resulting in acceptable clinical results that seemed better than previous drilling procedures9,37.
Surgeons such as Haggart and Magnussen in the 1940s and Pridie in the 1950s used open debridement, abrasion, and drilling for cartilage repair38. The results reported by Pridie need to be compared with the results that we achieve today. He noted that 77% of his patients were satisfied with the result of their operation, and 64% rated the result as good at a mean follow-up of 6.5 years. Perhaps we need to realize that the progress since that time regarding clinical results is not so impressive.
Steadman et al. reported outcomes of microfracture for traumatic chondral defects of the knee after a mean of 11 years9. The mean Lysholm score had improved from 59 to 89, and 80% of the patients rated themselves as improved at 7 years postoperatively. This cohort (75 knees) consisted of 25% of the patients at their institution who were treated with microfracture during this period. Two patients were lost to follow-up, and 2 knees were considered treatment failures.
It is difficult to compare studies because of different design and patient characteristics. However, our study and the studies mentioned above do not indicate that one of the methods is better than the other.
Very few RCTs have described long-term results. In a mid-term outcome study comparing characterized chondrocyte implantation (CCI) and microfracture22, the clinical outcomes for CCI and microfracture at 5 years were comparable and in line with our findings. However, in the early treatment group, CCI was significantly better. No long-term results exist. So far, that study does not prove that the cell cultivation performed in vitro improves the outcome. The CCI study was very well designed and performed; however, it was conducted in cooperation with the cell-culture company TiGenix NV Belgium, which could be a potential bias.
At the 15-year follow-up, contrary to our 5-year results, we did not find a relationship between the likelihood of failure and the quality of the repair tissue evaluated after biopsies were performed at the 2-year follow-up. However, the numbers were small, and as mentioned above, the treatment failure in 1 patient in the group with the best-quality cartilage in the last follow-up period made the difference.
Our study has several limitations. The 2-year evaluation was performed by an independent observer, while the later follow-up examinations were performed by an author of the study. This may introduce a potential bias; however, as mentioned in our previous reports, this risk was reduced by using patient-based outcome questionnaires. Furthermore, the lack of a control group that was not treated with surgery is a limitation of our study. However, it is a major challenge to include such a group when the majority of patients have chronic pain and have already had some form of conservative treatment. External validity is problematic with RCTs, and in the future, register data could also help us in building up a better evidence base in this field. There is a need for innovation to reach our goal3.
The survivors in both groups had improved clinical scores at the short, intermediate, and long-term evaluations, and there was no significant difference between the ACI and microfracture groups at the long-term follow-up. The risk of treatment failure and the frequency of radiographic osteoarthritis are problematic. Our findings raise serious concerns regarding the efficacy of these procedures in delaying osteoarthritis and preventing further surgery. Continued basic and clinical research is needed in this field.
Tables showing the inclusion and exclusion criteria and the baseline data are available with the online version of this article as a data supplement at jbjs.org.
NOTE: The authors thank Tom Wilsgaard for statistical assistance and Ann Kristin Hansen for assistance with graphics.
Investigation performed at the University of Tromsø – The Arctic University of Norway and University Hospital North-Norway, Tromsø, St. Olav’s Hospital, Trondheim University Hospital, Trondheim, Oslo University Hospital, Olso, and Deaconess University Hospital Bergen, Bergen, Norway
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