Cyclooxygenase-2 inhibitor delays fracture healing in rats

Endo, Kenji; Sairyo, Koichi; Komatsubara, Shinji; Sasa, Takahiro; Egawa, Hiroshi; Ogawa, Takayuki; Yonekura, Daisuke; Murakami, Ri-ichi; Yasui, Natsuo

doi:10.1080/17453670510041439

Cited by 57 publications

(49 citation statements)

References 14 publications

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“…During the last few years, several studies have demonstrated that COX-2 inhibitors impair fracture healing and suppress bone formation [6,21,30,59,60,69]. Controversies still exist, however, regarding the potentially negative effects of the COX-2 inhibitors compared to the conventional COX inhibitors on bone healing and bone repair.…”

Section: Discussionmentioning

confidence: 99%

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Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats

Dimmen

Nordsletten

Madsen

2009

Clinical Orthopaedics &Amp; Related Research

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Nonsteroidal antiinflammatory drugs (NSAIDs) are used to reduce inflammatory response and pain. These drugs have been reported to impair bone metabolism. Parecoxib, a specific COX-2 inhibitor, exerts an inhibitory effect on the mineralization of fracture callus after a tibial fracture in rats. Decreased bone mineral density (BMD) at a fracture site may indicate impairment of early healing, casting doubt on the safety of using COX-2 inhibitors during the early treatment of diaphyseal fractures. Fortytwo female Wistar rats were randomly allocated to three groups. They were given parecoxib, indomethacin, or saline intraperitoneally for 7 days after being subjected to a closed tibial fracture stabilized with an intramedullary nail. Two and 3 weeks after surgery, the bone density at the fracture site was measured using dual energy xray absorptiometry (DEXA). Three weeks after the operation the rats were euthanized and the healing fractures were mechanically tested in three-point cantilever bending.Parecoxib decreased BMD at the fracture site for 3 weeks after fracture, indomethacin for 2 weeks. Both parecoxib and indomethacin reduced the ultimate bending moment and the bending stiffness of the healing fractures after 3 weeks. These results suggest COX inhibitors should be avoided in the early phase after fractures.

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Section: Discussionmentioning

confidence: 99%

“…53rd Annual Meeting of the Orthopaedic Research Society 2007; Poster no 0416). Several studies indicate that COX-2 inhibitors may delay fracture healing [6,21,22,28,30,60], and concerns have been raised using COX inhibitors in orthopaedic fracture treatment due to these possible negative effects [3,5,12,19].…”

Section: Introductionmentioning

confidence: 99%

Parecoxib and Indomethacin Delay Early Fracture Healing: A Study in Rats

Dimmen

Nordsletten

Madsen

2009

Clinical Orthopaedics &Amp; Related Research

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“…3 There is convincing evidence that selective COX-2 inhibitors and non-selective NSAIDs compromise the healing of complete fractures. [4][5][6][7][8] Yet, very little is known about the effect of NSAIDs on stress fracture (SFx) healing. 9 SFxs are a common injury affecting children, adolescents and adults participating at all levels of sport and other athletic endeavors.…”

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confidence: 99%

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

Kidd

Cowling

et al. 2012

Journal Orthopaedic Research

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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. ß

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“…[28][29][30] Studies evaluating fracture healing in mice treated with NSAIDs or in mice lacking the COX-2 gene demonstrate that deficiency of COX-2 impairs bone healing. [31][32][33] Limited clinical data also support the notion that COX-2 agents delay bone healing. 34 However, this finding has not been replicated in all studies.…”

Section: Bone Injurymentioning

confidence: 90%