Negative effect of parecoxib on bone mineral during fracture healing in rats.
OBJECTIVE
Non-steroidal anti-inflammatory drugs (NSAIDs) are conventional cyclooxygen-ase (cox) inhibitors commonly used in musculoskeletal trauma to reduce the inflammatory response and pain, but they also seem to affect bone metabolism. Parecoxib is a cox inhibitor that selectively inhibits cox-2. Through their selective mechanism of action, these newer drugs are supposed to reduce the gastrointestinal side effects of conventional cox inhibitors. The effects on bone metabolism and healing have, however, not been fully elucidated. Thus, there are reasons for concern regarding the potential negative effects of these drugs on bone metabolism and bone repair. We investigated the effects of short-term administration of parecoxib on bone mineral formation and bone healing in rats.


METHODS
26 female Wistar rats were given parecoxib intraperitoneally for 7 days after a closed tibial fracture that was stabilized with an intra-medullary nail, and 26 animals were given saline. At 2, 3, and 6 weeks after surgery bone mineral density (BMD) at the fracture site was measured using dualenergy X-ray absorptiometry (DEXA). 6 weeks after the fracture, 14 rats from the parecoxib group and 16 rats from the placebo group were killed for mechanical testing, and the rest of the animals were killed for tissue analysis. The healing fractures and the intact contralateral tibias were mechanically tested by three-point cantilever bending.


RESULTS
The BMD at the fracture site was calculated as the average of the results after 2,3, and 6 weeks. Mean BMD was lower in the parecoxib group, 0.23 (SD 0.06) g/ cm2, than in the control group, 0.27 (SD 0.05) g/cm2 (p = 0.01). There were no statistically significant differences in mechanical properties of the healing fractures after 6 weeks. However, the study may have lacked sufficient statistical power to determine whether a negative effect on healing had occurred.


CONCLUSIONS
No mechanical differences were detected between the control and treatment groups after 6 weeks, but they may have been present earlier in the fracture healing process. Our findings do, however, indicate that parecoxib given postoperatively for a week has a negative effect on mineralization during the early phase of fracture healing.
Dimmen
Sigbøjrn
S
Institute of Surgical Research and Biomechanics Laboratory, Orthopedics Department, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Norway. sidimmen@online.no
Nordsletten
Lars
L
Engebretsen
Lars
L
Steen
Harald
H
Madsen
Jan Erik
JE
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005593:Fracture Fixation, Internal; D017102:Fracture Healing / Q000187:drug effects*; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013978:Tibial Fractures / Q000378:metabolism / Q000601:surgery
D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; C409945:parecoxib