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

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.
Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by a grant from the National Research Foundation of Korea (NRF), funded by the Republic of Korea government (MSIT) (NRF-2022R1A2C1005374). This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant No. HR22C1832). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. All animal procedures were approved by the Institutional Animal Care and Use Committee of Kyungpook National University, Daegu, Republic of Korea (IACUC No. KNU 2023-0210).