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Effectiveness of rosiglitazone in reducing flexion contracture in a novel rabbit model of arthrofibrosis with surgical capsular release| a biomechanical, histological, and genetic analysis

<p> <b>Introduction:</b> Animal models of joint contracture induced by capsular injury and prolonged immobilization are used to elucidate the mechanisms of arthrofibrosis. Clinically, patients with joint contracture commonly undergo surgical capsular release. Peroxisome proliferator-activated receptor gamma (PPAR&gamma;) agonists (such as rosiglitazone) hold promise as antifibrogenic agents that may be used as an adjunct to capsular release. </p><p> <b>Methods:</b> A surgically induced capsular contracture was created in thirty skeletally mature female rabbits. Twenty rabbits underwent a limited capsular release, which consisted of elevation of the posterior capsule through a lateral femoral incision under tension. Ten of these received rosiglitazone, while ten received placebo. Ten rabbits had a similar sham incision, without elevation of the capsule or joint extension (control group). Flexion contracture was measured using intraoperative fluoroscopy. All animals were allowed free cage activity for 16 weeks following this procedure. Joint contracture was measured using a custom device.</p><p> <b>Results:</b> All animals survived both operations without operative complications. At the time of surgical release or sham surgery, the average flexion contracture was 129&deg; &plusmn; 11&deg; in the control group versus 30&deg; &plusmn; 8&deg; in the release group (p=0.0002). Following sixteen weeks of remobilization, the animals that had a capsular release had significantly decreased flexion contractures compared to the control animals: 37&deg; &plusmn; 14&deg; and 49&deg; &plusmn; 13&deg; respectively (p=0.035). Following sixteen weeks of remobilization, the difference in flexion contracture between the rosiglitazone and capsular release groups was not statistically significant (rosiglitazone 33&deg; &plusmn; 11&deg;; control, 37&deg; &plusmn; 14&deg;; p = 0.39). Several gene products were significantly affected by rosiglitazone administration.</p><p> <b>Discussion:</b> In this animal model, a limited capsular release decreased flexion contracture immediately after surgery as well as following sixteen weeks of remobilization. This resembles clinical experience. Rosiglitazone did not prevent flexion contracture in this model, but did modulate gene expression in the joint capsule.</p>

Identiferoai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:1541020
Date17 August 2013
CreatorsBarlow, Jonathan David
PublisherCollege of Medicine - Mayo Clinic
Source SetsProQuest.com
LanguageEnglish
Detected LanguageEnglish
Typethesis

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