Selective and non-selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna

Kidd, Lisa J., Cowling, Nick R., Wu, Andy C., Kelly, Wendy L. and Forwood, Mark R. (2013) Selective and non-selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna. Journal of Orthopaedic Research, 31 2: 235-242. doi:10.1002/jor.22203

Author Kidd, Lisa J.
Cowling, Nick R.
Wu, Andy C.
Kelly, Wendy L.
Forwood, Mark R.
Title Selective and non-selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna
Journal name Journal of Orthopaedic Research   Check publisher's open access policy
ISSN 0736-0266
Publication date 2013-02-01
Year available 2012
Sub-type Article (original research)
DOI 10.1002/jor.22203
Volume 31
Issue 2
Start page 235
End page 242
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract Anti-inflammatory drugs are widely used to manage pain associated with stress fractures (SFxs), but little is known about their effects on healing of those injuries. We hypothesized that selective and non-selective anti-inflammatory treatments would retard the healing of SFx in the rat ulna. SFxs were created by cyclic loading of the ulna in Wistar rats. Ulnae were harvested 2, 4 or 6 weeks following loading. Rats were treated with non-selective NSAID, ibuprofen (30 mg/kg/day); selective COX-2 inhibition, [5,5-dimethyl-3-3 (3 fluorophenyl)-4-(4 methylsulfonal) phenyl-2 (5H)-furanone] (DFU) (2.0 mg/kg/day); or the novel c5a anatagonist PMX53 (10 mg/kg/day, 4 and 6 weeks only); with appropriate vehicle as control. Quantitative histomorphometric measurements of SFx healing were undertaken. Treatment with the selective COX-2 inhibitor, DFU, reduced the area of resorption along the fracture line at 2 weeks, without affecting bone formation at later stages. Treatment with the non-selective, NSAID, ibuprofen decreased both bone resorption and bone formation so that there was significantly reduced length and area of remodeling and lamellar bone formation within the remodeling unit at 6 weeks after fracture. The C5a receptor antagonist PMX53 had no effect on SFx healing at 4 or 6 weeks after loading, suggesting that PMX53 would not delay SFx healing. Both selective COX-2 inhibitors and non-selective NSAIDs have the potential to compromise SFx healing, and should be used with caution when SFx is diagnosed or suspected.
Keyword Stress fracture
Fracture healing
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 30 July 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Veterinary Science Publications
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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