title: Selective and non-selective cyclooxygenase inhibitors delay stress fracture healing in the rat ulna.
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.
authors: School of Veterinary Science, The University of Queensland, Gatton, QLD 4343, Australia.
authors: Lisa J
authors: LJ
authors: Kidd
authors: Nick R
authors: NR
authors: Cowling
authors: Andy C
authors: AC
authors: Wu
authors: Wendy L
authors: WL
authors: Kelly
authors: Mark R
authors: MR
authors: Forwood
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy; D015936:Complement C5a / Q000037:antagonists & inhibitors; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D017102:Fracture Healing / Q000187:drug effects; D050723:Fractures, Bone / Q000188:drug therapy; D015775:Fractures, Stress / Q000188:drug therapy* / Q000473:pathology; D005663:Furans / Q000009:adverse effects / Q000494:pharmacology*; D007052:Ibuprofen / Q000009:adverse effects / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014457:Ulna / Q000293:injuries* / Q000473:pathology
chemical_list: C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D005663:Furans; D010456:Peptides, Cyclic; D015936:Complement C5a; D007052:Ibuprofen