Effect of Fatty Acid-Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis.

BACKGROUND: A rotator cuff tear (RCT) induces fatty acid-binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. PURPOSE: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. RESULTS: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. CONCLUSION: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. CLINICAL RELEVANCE: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.

Effect of capsular release in the treatment of shoulder stiffness concomitant with rotator cuff repair: diabetes as a predisposing factor associated with treatment outcome.

BACKGROUND: In spite of the high prevalence of shoulder stiffness during rotator cuff repair, optimal management remains unclear. PURPOSE: To identify the effect of capsular release during rotator cuff repair on the outcomes of patients with both shoulder stiffness and a rotator cuff tear, based on subgroup analyses. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Forty-nine consecutive patients (mean age, 61.5 ± 8.3 years) were enrolled who underwent arthroscopic repair of a small- to large-sized full-thickness rotator cuff tear and manipulation for concomitant shoulder stiffness (passive forward flexion ≤120°, external rotation at the side ≤45°). The first 21 consecutive patients underwent manipulation alone to treat stiffness; the second 28 consecutive patients underwent capsular release with manipulation. Among the 49 patients, 25 showed severe stiffness (forward flexion ≤100°, external rotation at the side ≤30°; 11 in the first series and 14 in the second series), and 15 had diabetes mellitus (30.6%; 6 in the first series and 9 in the second series). Shoulder range of motion was measured 6 weeks, 3 months, 6 months, and 1 year postoperatively and at final follow-up visit. Simultaneously, functional outcome was evaluated by visual analog scale for pain, American Shoulder and Elbow Surgeons score, Constant score, and muscle strength ratio (involved/uninvolved), and cuff integrity was assessed ultrasonographically at least 1 year postoperatively. RESULTS: All range of motion measurements, functional scores, and muscle strength ratios significantly improved postoperatively regardless of the treatment method of stiffness. No outcome measure differed significantly between patients who did and did not undergo capsular release, regardless of the severity of stiffness, except for a temporary improvement in external rotation at side 3 months postoperatively in favor of those who underwent capsular release in cases with severe stiffness. Among patients with diabetes mellitus however, those who underwent capsular release showed greater improvement in forward flexion after 3 months and 1 year and in external rotation at the side for all time points (all P < .05), except for 6 weeks postoperatively; these patients also had a significantly higher final American Shoulder and Elbow Surgeons score (P = .03). Of 21 patients who underwent manipulation alone and of 28 who underwent capsular release and manipulation, 2 and 1 developed retears, respectively. CONCLUSION: Both manipulation and capsular release with manipulation significantly improved range of motion and produced satisfactory functional outcomes. The outcomes did not differ between treatment methods for stiffness regardless of the severity of stiffness. In patients with diabetes mellitus however, capsular release at the time of rotator cuff repair seems to be beneficial, especially for external rotation and final postoperative function.