Effects of diclofenac and tenoxicam on distraction osteogenesis

In the management of bone defects, pseudoarthrosis, deformities, chronic osteomyelitis and in extremity lengthening procedures, the technique of distraction osteogenesis (DO) has been frequently used. In this experimental animal study, the effects of two non-steroidal anti-inflammatory drugs, i.e., diclofenac and tenoxicam, on the outcomes of distraction osteogenesis are investigated.

In this study, 30 mature New Zealand-type male rabbits (2.5-4.5 kg) were used. The rabbits were randomized into three groups, each consisting of ten animals. Under optimal operating conditions, a pre-reconstructed circular external fixator was applied on the right tibias of rabbits, and osteotomy was performed with a Gigli saw just below the tibial tuberosity. After seven postoperative days, distraction was initiated at a rhythm of 2 x 0.5 mm/day. During the 10 days of distraction, adjunctive therapy was not instituted for group I (control group). For 10 days, group II received i.m. diclofenac sodium (0.5 mg/kg per day) and group III was treated with tenoxicam (8 mg/kg per day i.m.). At the end of 3 weeks postoperatively, five rabbits from each group were killed for histologic examinations. The remaining rabbits were killed at the end of eight postoperative weeks for biomechanical and histological analysis. Besides, radiological examinations were performed at the end of 3, 6 and 8 weeks postoperatively for the radiologic evaluation of calluses. For statistical evaluations between groups, Kruskal-Wallis variance analysis, and for intergroup assessments, Mann-Whitney test were performed.

For radiological evaluations, the scoring system developed by Lane and Sandhu, and for histopathological assessments, the grading system of Huddlestone et al. were used. Biomechanical tests were realized using torsional loading. During the first 3 weeks, the groups did not differ much in the radiological parameters. However, in the diclofenac group and in especially the tenoxicam group, the histological scores were lower than in the control group. Radiological images obtained at the end of 6 weeks demonstrated inadequate consolidation in the diclofenac and tenoxicam groups when compared with the control group. At the end of 8 weeks postoperatively, in consideration of biomechanical, radiological and histological tests, significantly worse regenerates were obtained in the diclofenac and tenoxicam groups.

During the distraction osteogenesis period, diclofenac and tenoxicam affected the quality of regenerate unfavorably. This effect is sustained during all periods of bone healing. However, this finding should be supported by experimental and human studies.