High-Dose Statins Preserve Tendon-Bone Interface Healing Without Adversely Affecting Fatty Infiltration in a Rotator Cuff Repair Rat Model.

Abstract

To evaluate the effects of high-dose atorvastatin (hATZ) on histologic and biomechanical tendon-bone interface (TBI) healing and fatty infiltration following rotator cuff (RC) repair in a rat model. Twenty Sprague-Dawley rats underwent RC repair surgery on both shoulders, after which hATZ was administered orally for 4 weeks postoperatively. The effects of hATZ on TBI healing were assessed macroscopically, histologically, and biomechanically. Fatty infiltration was evaluated using Oil-Red-O staining and immunohistochemical analysis of gene marker expressions. Expression levels of muscle RING-finger protein 1 (MuRF-1) and muscle atrophy F-box protein, markers of muscle atrophy, and peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α, transcription factors involved in adipogenesis, were assessed by quantitative real-time polymerase chain reaction to evaluate molecular changes related to muscle degeneration. Biomechanical tendon healing was measured using a universal testing machine, and histologic analysis was performed using hematoxylin and eosin and Masson's trichrome staining. At 4 weeks postoperatively, systemic administration of hATZ did not negatively affect TBI healing following RC repair. Fatty infiltration analysis showed no significant difference between the hATZ group (3,322.16 ± 1,117.59 μm²) and the control group (3,946.94 ± 1,843.96 μm²) (P = .415). However, immunohistochemical analysis revealed that hATZ significantly inhibited the expression of MuRF-1 (P < .001), a key regulator of muscle atrophy, while the expression levels of muscle atrophy F-box protein (P = .803), peroxisome proliferator-activated receptor γ (P = .200), and CCAAT/enhancer-binding protein α (P = .909) remained unchanged. Histologic analysis confirmed no significant differences in collagen density (P = .142) or arrangement (P = .164) between the groups, and biomechanical testing showed comparable ultimate strength (P = .398) and load to failure (P = .464). High-dose atorvastatin did not impair histologic and biomechanical healing of the TBI in a rat model of RC repair. It also did not accelerate fatty infiltration of the muscle and led to a significant downregulation of the muscle atrophy-related marker MuRF-1. This study shows that hATZ does not negatively affect TBI healing or muscle recovery following RC repair, supporting its continued use in patients requiring long-term statin therapy.