Do meta-analyses reveal time-dependent differences between the clinical outcomes achieved by microfracture and autologous chondrocyte implantation in the treatment of cartilage defects of the knee?
OBJECTIVE
To test the hypothesis that autologous chondrocyte implantation (ACI) has a better treatment effect than microfracture (MF), and increasing superiority over the years, when performed under similar patient-specific and defect-specific conditions.


METHODS
We scanned four electronic databases for controlled clinical trials or controlled prospective observational studies. We conducted random-effects meta-analyses of equivalent data using standardized mean differences as the outcome measure of choice at 1, 2, and 5-year follow-up. We assessed heterogeneity with the I (2) index and publication bias with funnel plots and Kendall's tests.


RESULTS
Our literature search revealed six study populations (nine papers) which satisfied our eligibility criteria. Overall, 399 patients aged between 16 and 60 years with 1-10 cm(2) chondral defects were available. The MF and the ACI study groups were well matched regarding patient baseline characteristics. For all papers, microfracture was performed according to Steadman, whereas three generations of ACI were applied. When all were combined, non-significant superiority of ACI over MF was revealed; surprisingly, this superiority decreased over the years. However, our meta-analyses combining solely second and third-generation ACI revealed significant standardized differences, becoming smaller over the years, but always representing a large effect. Nevertheless, our approximate estimate of the difference between the treatment effects provoked by second and third-generation ACI and by MF is not indicative of clinically relevant superiority of ACI over MF at 5-year follow-up.


CONCLUSIONS
Both series of meta-analyses (combining either all ACI modifications or solely the second and third generations of ACI) suggest that the treatment effects resulting from ACI and MF converge over the years.
Department of Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria, lukas.negrin@meduniwien.ac.at.
Lukas Leopold
LL
Negrin
Vilmos
V
Vécsei
D000293:Adolescent; D000328:Adult; D054544:Arthroplasty, Subchondral / Q000379:methods*; D002357:Cartilage Diseases / Q000175:diagnosis / Q000601:surgery*; D002358:Cartilage, Articular / Q000503:physiopathology / Q000601:surgery; D019902:Chondrocytes / Q000637:transplantation*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007718:Knee Injuries / Q000175:diagnosis / Q000601:surgery; D007719:Knee Joint / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016059:Range of Motion, Articular / Q000502:physiology; D018570:Risk Assessment; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult