RANTES Concentration at the Time of Surgery Is Associated With Postoperative Stiffness in Patients Undergoing ACL Reconstruction

Abstract

Background: Patients undergoing anterior cruciate ligament (ACL) reconstruction have been shown to be at risk for postoperative arthrofibrosis. Diagnostic biomarkers associated with the development of postoperative stiffness are unknown.

Hypothesis: Biomarkers found in the synovial fluid at the time of surgery are associated with the development of postoperative arthrofibrosis in a cohort of patients undergoing ACL reconstruction.

Study design: Case-control study; Level of evidence, 3.

Methods: Patients undergoing ACL reconstruction were prospectively enrolled. Synovial fluid was collected before surgical incision. A cohort of patients with postoperative stiffness requiring manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA) was retrospectively identified. Matching of cases to controls was performed using a 1:2 pair matching algorithm. Risk factor-adjusted single-biomarker and multivariable models were used to assess the association of synovial fluid biomarkers with postoperative stiffness requiring MUA/LOA. Stepwise logistic regression controlling for clinical risk factors was used to identify biomarkers that are possible predictors of postoperative stiffness.

Results: A total of 11 cases (3 male, 8 female) were identified and matched with 21 controls (6 male, 15 female) with no significant differences in age, sex, smoking history, or days from injury to surgery. Concentrations of the biomarker regulated upon activation, normal T-cell expressed and presumably secreted (RANTES) were significantly higher in patients requiring MUA/LOA versus controls (694.20 pg/mL [interquartile range, 214.75-3428.79] vs 113.04 pg/mL [interquartile range, 32.81-517.91], respectively; P = .034). On single-biomarker models, RANTES (odds ratio, 2.28; 95% CI, 1.29-5.37; P = .019) and basic fibroblast growth factor (bFGF) (odds ratio, 1.91; 95% CI, 1.07-3.99; P = .047) were associated with increased risk of postoperative stiffness requiring MUA/LOA after ACL reconstruction. Stepwise logistic regression identified 3 biomarkers that are possible predictors of postoperative stiffness, which were included in the final model: Interleukin 1 receptor antagonist (IL-1RA) (P = .198), bFGF (P = .157), and RANTES (P = .046).

Conclusion: Higher concentrations of synovial fluid biomarkers bFGF and RANTES were associated with increased risk for stiffness requiring intervention after ACL reconstruction. Interleukin 6 (IL-6), vascular endothelial growth factor A (VEGF-A), tissue inhibitor of metalloproteinases 1 (TIMP-1), interleukin 1 receptor antagonist (IL-1RA), matrix metalloproteinase 3 (MMP-3), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1B (MIP-1B) were not associated with the development of postoperative arthrofibrosis.

Keywords: anterior cruciate ligament; arthrofibrosis; biomarkers; stiffness; synovial fluid.