Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model.

BACKGROUND: After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. OBJECTIVE: The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. STUDY DESIGN AND METHODS: In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed. RESULTS: Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, p<0.01) and the percentage area of myofibroblasts (losartan: 2.8±1.8% [p<0.05], atorvastatin: 2.5±1.7% [p<0.01], vs control [6.4±4%], respectively). BSP was detectable in equivalent amounts in the joint capsules of all groups with only a trend toward a reduction of the BSP-stained area by atorvastatin. CONCLUSION: Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.

A novel rat model of stable posttraumatic joint stiffness of the knee.

BACKGROUND: Animal models of posttraumatic joint stiffness (PTJS) are helpful in understanding underlying mechanisms, which is important for developing specific treatments and prophylactic therapies. Existing rat models of PTJS in the knee failed to show that the created contracture does not resolve through subsequent remobilization. Our objective was to establish a rat model of persisting PTJS of the knee and compare it to existing models. METHODS: Thirty skeletally immature male Sprague Dawley rats underwent surgical intervention with knee hyperextension, extracartilaginous femoral condyle defect, and Kirschner (K)-wire transfixation for 4 weeks with the knee joint in 146.7° ± 7.7° of flexion (n = 10 per group, groups I-III). After K-wire removal, group I underwent joint angle measurements and group II and group III were allowed for 4 or 8 weeks of free cage activity, respectively, before joint angles were measured. Eighteen rats (n = 6 per group, groups Ic-IIIc) served as untreated control. RESULTS: Arthrogenic contracture was largest in group I (55.2°). After 4 weeks of remobilization, the contracture decreased to 25.7° in group II (p < 0.05 vs. group I), whereas 8 weeks of remobilization did not reduce the contracture significantly (group III, 26.5°, p = 0.06 vs. group I). Between 4 and 8 weeks of remobilization, no increase in extension (26.5° in group III, p = 0.99 vs. group II) was observed. Interestingly, muscles did not contribute to the development of contracture. CONCLUSION: In our new rat model of PTJS of the knee joint, we were able to create a significant joint contracture with an immobilization time of only 4 weeks after trauma. Remobilization of up to 8 weeks alone did not result in full recovery of the range of motion. This model represents a powerful tool for further investigations on prevention and treatment of PTJS. Future studies of our group will use this new model to analyze medical treatment options for PTJS.