MusculoskeletalThe Effectiveness of Two COX-2 Inhibitors in the Prophylaxis Against Heterotopic New Bone Formation: An Experimental Study in Rabbits
Introduction
The incidence of heterotopic ossification (HO) is variable, affecting mainly total hip arthroplasty (6–50%) [1, 2, 3], internal fixation of acetabular fractures (14–90%) [4, 5], as well as patients with head (10–20%) [6] or spinal cord injuries (20–30%) [7]. Since there is no current medical treatment for the established HO, prophylaxis is the only way to avoid the consequences of this serious complication. Over the past years it has been shown that radiotherapy [8] and nonsteroidal anti-inflammatory drugs (NSAIDs) [9] are both effective in preventing the development of HO. Postoperative radiotherapy may not always be available and poses concerns regarding wound healing, loosening of implants, or even malignancy [10]. A wide range of NSAIDs have been proposed as an effective prophylactic modality, with indomethasin being the most extensively studied drug [11]. Nevertheless, NSAIDs have been associated with a high incidence of gastrointestinal complications and low patient compliance [12].
The advantages offered by the cyclooxygenase-2 (COX-2) inhibitors are that these drugs are equally effective in their anti-inflammatory action, while demonstrating lower incidence of gastrointestinal side effects [13, 14, 15] compared to the traditional NSAIDs. There are also reports that COX-2 inhibitors might not affect bone union as negatively as other NSAIDs [16, 17].
Although COX-2 inhibitors have been available for some time, there are few reports that they can prevent HO like other nonselective NSAIDS [12, 18, 19, 20, 21, 22].
The purpose of this study was to present the effectiveness of 2 COX-2 inhibitors, the “preferential” COX-2 inhibitor meloxicam, as well as the injectable COX-2-specific inhibitor parecoxib, in the prevention of HO. A historical comparison with indomethacin was also performed.
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Materials and Methods
For the purposes of the experiment, the Michelsson [23] model for mechanical induction of heterotopic new bone formation was applied. The experiment was held in the Laboratory for Research of the Musculoskeletal System “Th. Garofalidis” (University of Athens, KAT Hospital, Athens, Greece). Once approval was obtained from the Veterinary Directorate of the Prefecture of Athens, Greece (protocol Number K/1898), 18 male sexually mature New Zealand white rabbits of similar age and weight were used.
Results
All of the radiographs were evaluated using the method of Scott et al. [24]. The graded results (Table 1) of the 10th wk were analyzed using the Wilcoxon's rank-sum test, which is a nonparametric test for assessing whether the difference in means between 2 independent samples of observations is statistically significant. The radiographic rating scale represents a variable that has been organized into ranked categories. Two-tailed P values less than 0.05 were considered to be significant. The
Discussion
The results from this study were compared to those from a similar experiment by Moed et al. [25], where it was shown that indomethasin was effective in decreasing the formation of heterotopic new bone. In this comparison we found no statistical difference between the results of the indomethasin group and the meloxicam (P = 0.12) or parecoxib (P = 0.08) groups of animals.
The Michelsson model was selected because it consistently leads to the formation of heterotopic new bone in rabbits, which is
Acknowledgments
All authors certify that they have not signed any agreement with any commercial interest, related to this study, that would in any way limit publication of any and all data generated by the study.
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