Session II - Basic Science

Thurs., 10/18/01 Basic Science, Paper #10, 9:38 AM

The Influence of Diclofenac (Group of Nonsteroidal Antirheumatics) on Fracture Healing

Alexander Beck, MD; Florian Gebhard, MD, PhD; Peter Augat, MD; Tobias Sorg, MS; Lothar Kinzl, MD, Prof.; Lutz Claes, MD, Prof., University of Ulm, Ulm, Germany

Introduction: Nonsteroidal antirheumatics (NSAR) are often used for patients with fractured bones for analgesic purposes. An animal experiment was performed to determine the influence of NSAR on the process of fracture healing, and, as an alternative central-acting analgesic without peripheral effect, tramadol was included in this experiment.

Methods: A transverse osteotomy of the proximal tibia of the left leg was performed on Wistar rats. The fracture was stabilized by intramedullary nailing with a healing period of 21 days. All therapeutic agents were administered orally, twice daily. The animals were divided into four groups with 10 rats each: group 1 was treated with placebo, group 2 with tramadol (20mg/kg of body weight/day), and group 3 with diclofenac-cholestyramine (5 mg/kg of body weight/day) over 21 days. On day 21 the rats were sacrificed, and each leg was examined radiologically. The tibia was examined with a CT scan and three-point bending, and histological evaluation of the tissues was performed.

Results: There were no significant differences between group 1 and 2 and between group 3 and 4, respectively. Therefore the data from group 1 and 2 as well as that from group 3 and 4 were put together. The results of the CT scan and 3-point bending showed that rats treated by diclofenac had delayed fracture healing compared with those treated with placebo or with tramadol. Bone density was 30% lower (P = 0.0001) in animals treated with diclofenac (mean, 577 mg/ccm, SD 53.1 for group 1 and 2 compared with the mean = 40.3 mg/ccm, SD 27.3 of group 3 and 4). The breaking force was 45% (P = 0.0009) lower (mean = 42.4N, SD 14.2 compared with the mean = 23.3N, SD 8.2) and the bending stiffness was 56% (P = 0.0039) lower (mean =1218.9 Nmm/mm, SD 477. 9 compared with the mean = 5326 Nmm/mm, SD 389. 9) in animals treated with diclofenac. Diclofenac serum levels on day 21 in rats with long-term diclofenac application (mean = 242ng/ml, SD: 47, 7) were comparable to those in humans.

Conclusion: Oral administration of diclofenac significantly delayed fracture healing in rats. This effect might be comparable to the effect of other NSAR and fracture healing in humans.