Ezetimibe/Atorvastatin, a Treatment for Hyperlipidemia, Inhibits Supraspinatus Fatty Infiltration and Improves Bone-Tendon Interface Healing in a Rotator Cuff Tear Rat Model

Abstract

Background: Multiple factors, such as muscle fatty infiltration (FI), tendon collagen content, and collagen arrangement, determine bone-tendon interface (BTI) healing after rotator cuff (RC) repair.

Purpose: To evaluate the effects of systemic administration of ezetimibe-atorvastatin (EZE/ATZ) combination on muscle FI and tendon collagen density and arrangement in an RC repair rat model.

Study design: Controlled laboratory study.

Methods: A total of 26 male Sprague-Dawley rats were randomly divided equally into control and EZE/ATZ groups and subjected to RC tendon repair surgery. Postoperatively, the EZE/ATZ group rats received a combination of EZE (10 mg/kg/d) and ATZ (20 mg/kg/d) for 4 weeks, after which they were sacrificed. Oil Red O staining was used to assess FI in the supraspinatus muscle. The expression of biomarkers related to muscle atrophy and FI was measured using quantitative real-time polymerase chain reaction. For the qualitative and quantitative analysis of FI-related biomarkers, immunohistochemical staining was performed. Biomechanical and histological analyses were performed to evaluate the quality of BTI healing after RC repair.

Results: The EZE/ATZ group showed significantly lower FI compared with the control group (P < .001) and significantly downregulated expression of gene markers related to muscle atrophy and FI. On histological analysis, the EZE/ATZ group exhibited increased collagen type I contents, consistent collagen arrangement (P = .005), and significantly higher collagen density (P = .003) compared with the control group. Biomechanical analysis of the BTI healing revealed that the EZE/ATZ group had significantly increased ultimate strength (P = .006) compared with the control group.

Conclusion: Systemic EZE/ATZ administration suppressed supraspinatus FI by downregulating muscle atrophy–related and FI-related genes after RC repair. Additionally, EZE/ATZ use improved collagen biosynthesis, density, and arrangement at the BTI and significantly increased tensile strength.

Clinical Relevance: The results of the current study strongly advocate the use of EZE/ATZ to improve shoulder function and tendon healing after RC repair.