Knee-to-Talus Donor-Site Morbidity Following Autologous Osteochondral Transplantation: A Meta-Analysis with Best-case and Worst-case Analysis
Authors: Shimozono Yoshiharu , Seow Dexter , Yasui Youichi , Fields Kara , Kennedy John G. 
Published: May 2019

Abstract

Background
Despite the promising clinical results of autologous osteochondral transplantation in the treatment of osteochondral lesions of the talus, the occurrence of knee donor-site morbidity remains a concern. However, the proportion of patients experiencing donor-site morbidity is not well established because of important variations in estimates drawn by heterogeneous studies with loss to followup, often made at short-term (< 1 year). Therefore, both a meta-analysis of studies that assumed no patients lost to followup had donor-site morbidity and assumed all patients lost to followup had donor-site morbidity may help to estimate the true risk of donor-site morbidity.

Questions/purposes
To evaluate the proportion of patients who developed knee donor-site morbidity after autologous osteochondral transplantation for osteochondral lesion of the talus, by (1) meta-analysis of the proportion of patients experiencing donor-site morbidity in the best-case scenario as reported, in which no patients lost to followup were assumed to have donor-site morbidity and (2) meta-analysis of the percentage of patients who had donor-site morbidity in the worst-case scenario, in which all patients lost to followup were assumed to have donor-site morbidity and (3) present the characteristics of studies associated with the reporting of donor-site morbidity.

Methods
A systematic search of the PubMed, Embase and The Cochrane Library databases was performed from their inception to October 2017 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria were clinical studies that reported knee donor-site morbidity after autologous osteochondral transplantation for osteochondral lesion of the talus, mean followup ≥ 1 year, full-text studies published in a peer-review journal and written in English. Quality of evidence (Case Series Quality Appraisal Checklist), sample size, mean patient age, study design, mean followup time, and observed rate of knee donor-site morbidity were evaluated. Twenty-six studies with 915 ankles (904 patients) were included in the systematic review and meta-analysis. Approximately half of the included studies were of small cohort (n < 30, 12 studies), and 12 of 26 studies did not report at all on loss to followup. In the studies that reported loss to followup (14 of 26), a total of 32 patients (35 ankles) were reported lost. Random-effects models were used to estimate the risk of donor-site morbidity as between-study heterogeneity was determined to be high in both meta-analyses that assumed that no patients lost to followup experienced donor-site morbidity (I2 = 82.1%) and the one that assumed all patients lost to followup experienced donor-site morbidity (I2 = 88.7%). Multivariable metaregression was used to estimate the association between study characteristics and the observed proportion of patients who experienced of donor-site morbidity. If there was evidence of an association between a study characteristic and proportion, a subgroup analysis was performed.

Results
The estimated proportion of donor-site morbidity was 6.7% (95% confidence interval [CI], 2.8–11.8), assuming that no patients lost to followup experienced donor-site morbidity and 10.8% (95% CI, 4.8–18.3) assuming that all patients lost to followup experienced donor-site morbidity after a mean followup of 43.8 ± 24.7 months (range, 15.9–120 months). There was a negative association between study sample size and proportion of donor-site morbidity (β = -0.26; 95% CI, -0.39 to -0.12; p < 0.001 assuming that no patients lost to followup experienced donor-site morbidity and β = -0.31; 95% CI, -0.48 to -0.13; p < 0.001 assuming that all patients lost to followup experienced donor-site morbidity); that is, as study size increased, the proportion of patients reported with donor-site morbidity decreased. In larger studies (n ≥ 30), the estimated percentage of donor-site morbidity was 2.8% (95% CI, 1.2%–5.0%; I2 = 47.6%) assuming that no patients lost to followup experienced donor-site morbidity, and 5.0% (95% CI, 2.1%–9.0%; I2 = 74.5%) assuming all patients lost to followup experienced donor-site morbidity. High between-study heterogeneity (differences in methodology) could not be completely explained by variability in study sample size, mean patient age, design, or mean followup time, and may be attributable to other factors such as inconsistent definitions of donor-site morbidity.

Conclusions
The estimated proportion of donor-site morbidity after autologous osteochondral transplantation for osteochondral lesion of the talus ranged from 6.7% to 10.8% in the current meta-analysis. However, subgroup analysis demonstrated that larger studies (n ≥ 30) estimated a lower donor-site morbidity risk (< 5.0%) than smaller studies (n < 30). This estimate should be interpreted in light of the fact that nearly half of the included studies did not report on loss to followup, and so their estimates of donor-site morbidity may be low. In addition, high between-study heterogeneity and the inclusion of predominantly retrospective studies with small sample sizes likely contributed to estimates that suffered from a high risk of bias, probably in favor of the surgical treatment being studied.

Level of Evidence
Level IV, therapeutic study.