Simvastatin Exposure and Rotator Cuff Repair in a Rat Model

Abstract

Simvastatin is a common medication prescribed for hypercholesterolemia that accelerates local bone formation. It is unclear whether simvastatin can accelerate healing at the tendon-bone interface after rotator cuff repair. This study was conducted to investigate whether local and systemic administration of simvastatin increased tendon-bone healing of the rotator cuff as detected by maximum load to failure in a controlled animal-based model. Supraspinatus tendon repair was performed on 120 Sprague-Dawley rats. Sixty rats had a polylactic acid membrane overlying the repair site. Of these, 30 contained simvastatin and 30 did not contain medication. Sixty rats underwent repair without a polylactic acid membrane. Of these, 30 received oral simvastatin (25 mg/kg/d) and 30 received a regular diet. At 4 weeks, 5 rats from each group were killed for histologic analysis. At 8 weeks, 5 rats from each group were killed for histologic analysis and the remaining 20 rats were killed for biomechanical analysis. One rat that received oral simvastatin died of muscle necrosis. Average maximum load to failure was 35.2±6.2 N for those receiving oral simvastatin, 36.8±9.0 N for oral control subjects, 39.5±12.8 N for those receiving local simvastatin, and 39.1±9.3 N for control subjects with a polylactic acid membrane. No statistically significant differences were found between any of the 4 groups (P>.05). Qualitative histologic findings showed that all groups showed increased collagen formation and organization at 8 weeks compared with 4 weeks, with no differences between the 4 groups at each time point. The use of systemic and local simvastatin offered no benefit over control groups. [Orthopedics. 2017; 40(2):e288-e292.].

Does statin-treated hyperlipidemia affect rotator cuff healing or muscle fatty infiltration after rotator cuff repair?

“…7,11,27 Dolkart et al 14 studied 48 healthy (non-hyperlipidemic) rats and found enhanced biomechanical properties (maximal load to repair failure and stiffness) of repaired cuff tendon in statintreated rats compared to saline-treated rats (P < 0.001). In contrast, Deren et al, 13 in their study of 80 healthy (non-hyperlipidemic) rats, found similar strength (maximum load to repair failure) and histology (collagen organization, cellularity, vascularity, cartilage formation, new bony matrix deposition) at the tendon-bone healing site in rats treated with local or systemic statin versus non-treated rats (P > 0.05). The results of these contradictory studies make it difficult to draw firm conclusions regarding the effect of statin.…”

Simvastatin-Loaded Nanofibrous Membrane Efficiency on the Repair of Achilles Tendons

“…Differences in revascularization, collagenization, and inflammatory cell infiltration were also observed histologically, but did not reach statistical significance. Deren et al 26 showed that locally used simvastatin-loaded polylactic acid membrane or oral administration of simvastatin were not beneficial to healing after rotator cuff repair. Eliasson et al 25 conducted an in vitro cell culture experiment, showing that simvastatin and atorvastatin decreased the cell proliferation and mechanical strength of the tendon construct.…”

The effects of hyperlipidemia on rotator cuff diseases: a systematic review

“…The effect of statins on the healing after rotator cuff repair was widely explored [ 11 , 17 ]. Muscle atrophy, fibrosis, and fatty infiltration of the supraspinatus muscle usually occurred following rotator cuff tears.…”

“…Although these studies have showed positive effects of statin use on the healing after rotator cuff repair, different results have been reported. Deren et al [ 11 ] investigated whether local and systemic administration of simvastatin increased tendon-bone healing in a rat rotator cuff repair model and indicated that the use of systemic and local simvastatin offered no benefit. In addition, Garcia et al [ 26 ] showed that type and dosage of statin medication did not significantly affect the incidence of retear after rotator cuff repair.…”

“…In hyperlipidemia environments, lipids could accumulate within the extracellular matrix of the tendon and thus affect the mechanical properties of the tendon [ 7 ]. Several studies have explored the relationship between hyperlipidemia and rotator cuff disease [ 8 – 11 ]. Animal studies indicated that high levels of lipids would lead to poorer mechanical properties and adversely affect tendon-to-bone healing after surgical repair of rotator cuff tears [ 9 – 11 ], while clinical studies showed inconsistent results on the association between hyperlipidemia and rotator cuff disease [ 8 , 12 ].…”