Abstract
Non-steroidal anti-rheumatics (NSAR) are often used in patients with fractured bones for analgetic reasons. This animal experiment was performed to determine the influence of NSAR on the process of fracture healing. As an alternative central acting analgetic without peripheral effect Tramadol was included in this experiment.
Wistar rats were operated by a transverse osteotomy of the proximal tibia of the left leg, fracture was stabilized by intramedullary nailing (healing period 21 days). All therapeutics were applied orally, twice a day. The animals were divided in 4 groups, 10 rats each: Group 1 was treated with placebo, group2 with tramadol (20mg/kg bodyweight/day), group3 with Diclofenac-Colestyramin (5mg/kg/bw./day) over 7 days followed by 14 days placebo, group4 with Diclofenac-Colestyramin (5mg/kg/bw./day) over 21 days. On day 21 the rats were sacrificed and each leg was examined by x-ray, than the tibia was examined by CT-Scan, three-point-bending and histological evaluation.
There were no significant differences between group1 and 2 and between group3 and 4, respectively. Therefore the data of group1 and 2 as well as group3 and 4 are put together.
The results of CT and 3-point-bending showed, that rats treated by Diclofenac presented with delayed fracture healing compared to those treated by placebo or Tramadol. Bone density was 30% lower (p = 0,0001) in animals treated with Diclofenac (mean = 577mg/ccm, SD:53,1 in group1 and 2 vs. mean = 404,3mg/ccm, SD:27,3 in group3 and 4).
The breaking force was 45% (p = 0,0009) lower (mean = 42,4N, SD:14,2 vs. mean = 23,3N, SD:8,2) and the bending stiffness 56% (p = 0,0039) lower (mean = 1218,9Nmm/mm, SD:477,9 vs. mean = 532,6Nmm/mm, SD:389,9) in animals, treated with diclofenac. Diclofenacserumlevels on day 21 in rats with longtime diclofenac application (mean = 242ng/ml, SD:47,7) were comparable to those in humans.
Oral application of Diclofenac significantly delayed fracture healing in rats. This effect might be comparable to other NSAR and fracture healing in humans.
