Rat rotator cuff tendon-to-bone healing properties are adversely affected by hypercholesterolemia

Abstract

Background Rotator cuff tendon tears represent a major component of reported orthopaedic injuries. In addition, more than one quarter of U.S. adults either currently have high cholesterol levels or have reduced their previously high cholesterol levels through the use of pharmaceuticals. Our clinical data have already linked hypercholesterolemia to full-thickness rotator cuff tears, and experimental data from our laboratory have shown effects on native tendon properties in multiple species. The objective of this study was to evaluate healing of supraspinatus tendons in our rat rotator cuff injury model. We hypothesized that tendon healing would be inferior in rats receiving a high-cholesterol diet for 6 months compared with those receiving standard chow. Methods All animals were subjected to a unilateral supraspinatus detachment and repair surgery, with contralateral limbs serving as within-animal comparative data. Animals continued their respective diet courses, and their supraspinatus tendons were biomechanically or histologically evaluated at 2, 4, and 8 weeks postoperatively. Results Biomechanical testing revealed a significant reduction in normalized stiffness in hypercholesterolemic rats compared with controls at 4 weeks after injury, whereas histologic analyses showed no significant differences in collagen organization, cellularity, or cell shape between groups. Conclusion On the basis of our findings, hypercholesterolemia may have a detrimental biomechanical effect on tendon healing in our rat rotator cuff injury and repair model. Level of evidence Basic Science Study, Animal Model.

Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear

“…In mice, chronic hypercholesterolemia decreased the elastic modulus of patellar tendons, which can increase the susceptibility of tendons to rupture 3 . For rats that received a rotator cuff tear and repair, a high cholesterol diet was associated with decreased healing stiffness one month after repair 4 . While Abboud and colleagues did not directly explore statins in their studies, they postulated that these medications may have a positive impact on tendon-bone healing.…”

“…These medications are most commonly used in the treatment of hypercholesterolemia, as they are very effective at lowering low-density lipoprotein cholesterol and improving clinical outcomes of patients with coronary artery disease and other cardiovascular conditions 6; 31 . In addition to promoting cardiovascular disease, hypercholesterolemia is associated with a greater risk for rotator cuff tendon tear and impaired tendon-bone regeneration 1; 4 . Aside from their efficacy in treating hypercholesterolemia, there are emerging roles for statins in the treatment of inflammatory diseases 6; 31 .…”

Factors affecting healing after arthroscopic rotator cuff repair

“…This data would support hypercholesterolemia likely plays a role not only in the development of rotator cuff tearing but also on the ability for a tendon to heal after repair. Similarly, diabetes has been found to have a detrimental effect on tendon healing using a rat rotator cuff tear model [39] . Modification of serum cholesterol levels and blood glucose levels may play a role in improving healing after repairs.…”

“…Consequently, patients with cuff tears are more likely to have hypercholesterolemia compared to controls. Beason et al [39] evaluated the effects of hypercholesterolemia on tendon healing in a rat rotator cuff tear model. These authors determined that there was a significant reduction in rotator cuff repair stiffness in hypercholesterolemic rats compared with controls [40] .…”

Dyslipidaemia is associated with an increased risk of rotator cuff disease: a systematic review

“…Rabbits with elevated cholesterol had significantly different mechanical tendon properties, with lower load-to-failure and diminished elasticity, and increased tendon fat-to-muscle ratio compared with the control groups (p<0.05) 13. Beason et al 12 identified statistically significant abnormalities in tendon stiffness in high-cholesterol rats versus control rats at the short-term, 4-week mark. This relationship disappeared at the 8-week mark, and no significant histological differences in the rotator cuff tendons at the 8-week mark were identified.…”