Clinical Effectiveness of Various Treatments for Cartilage Defects Compared to Microfracture: a Network Meta-analysis of Randomized Controlled Trials

Background Advancements have been made in the realm of cartilage regenerative techniques in the past decades. However, their comparative advantage has not yet been fully studied. Objectives To comparatively analyze the functional, radiological and histological outcomes, and complications of various procedures available for the treatment of cartilage defects. Data sources PubMed, Embase, Web of Science, Cochrane, and Scopus Study eligibility criteria Randomized controlled trials(RCTs) reporting functional, radiological, histological outcomes or complications of various methods utilized in the management of cartilage defects. Participants Patients with cartilage defects Interventions Treatment methods including microfracture(MFX), Autologous Chondrocyte Implantation(ACI), Osteochondral Allo/Autograft transplantation(OAT), mosaicplasty or acellular implants Study appraisal Cochranes CINeMA approach Synthesis methods Network meta-analysis was conducted in Stata. Random effects model was used for forest plots. Results 3,193 patients from 54 RCTs were included in the analysis. The mean age of included patients was 37.9(±9.46) years. MFX-I was used as a constant comparator. Among the restorative methods, OAT-II offered significantly better functional outcome at 5 yearsWMD=16.00, 95\% CI(11.66,20.34), p{\textless}0.001, and 10-yearsWMD=16.00, 95\% CI(10.42,21.58), p{\textless}0.001 while OAT-I offered significantly better pain relief WMD=-1.74, 95\% CI(-3.45,-0.02), p=0.042, and retained hyaline histology OR=8.12, 95\% CI(4.17,12.07), p=0.001 at 1 year with least reported adverse events and failures. Among the regenerative methods, MFX-IIIWMD=-10.0, 95\% CI(-13.07,-6.93), p=0.008offered significantly better functional outcomes at 5-years while ACI-IIIOR=0.89, 95\% CI (0.03,1.76), p=0.032 demonstrated significantly better radiological outcomes at 2-years. Limitations Heterogeneity in reporting of diverse functional outcome measures. Conclusions and implications of key findings Compared to MFX-I, OAT-II demonstrated significantly better long term functional outcome(10-years), while ACI-III, and MFX-III demonstrated significantly better functional outcomes only till mid- term(5-years), and there is a paucity of long term data on these treatment methods. Systematic review registration number CRD42022338329 Level of Evidence Level I