Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model

Brian Mullis, Spencer T. Copland, Paul S. Weinhold, Theodore Miclau, Gayle E. Lester, Gary D. Bos

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

A randomised, blinded, prospective animal study with 296 male C57BL/6N mice was performed to evaluate the biomechanical, biomolecular, biochemical, and histological impact of anti-inflammatory medications on fracture healing. A reproducible closed tibia fracture was created and stabilised with an intramedullary pin. Animals were randomised to placebo, ketorolac, ibuprofen, celecoxib, or rofecoxib treatment groups with biomechanical and biochemical testing at 4, 8, and 12 weeks. A second arm of the study was conducted in which animals were randomised to indomethacin or placebo treatment with biomechanical testing at 12 weeks. Histological and biomolecular studies were performed at 2 weeks on all groups in the first arm of the study. Biomechanical testing consisted of three-point bending evaluating maximum load, energy absorbed to maximum load, and stiffness. Safranin O-Fast Green stain was performed for histology. Biochemical quantifications of chondroitin and dermatan sulphate, hydroxyproline, total protein, and DNA content were performed. Osteocalcin and collagen types II and X were evaluated by in situ hybridisation. Some mechanical differences were seen between ketorolac and placebo at 4 weeks with respect to energy absorbed, but there were no differences in maximum load or stiffness seen between any treatment group and placebo at any time point. Indomethacin, celecoxib, rofecoxib, ibuprofen, and ketorolac did not significantly affect fracture healing in this young murine model.

Original languageEnglish (US)
Pages (from-to)827-837
Number of pages11
JournalInjury
Volume37
Issue number9
DOIs
StatePublished - Sep 2006
Externally publishedYes

Fingerprint

Cyclooxygenase 2 Inhibitors
Celecoxib
Ketorolac
Anti-Inflammatory Agents
Placebos
Fracture Healing
Ibuprofen
Indomethacin
Pharmaceutical Preparations
Collagen Type X
Closed Fractures
Dermatan Sulfate
Collagen Type II
Chondroitin Sulfates
Hydroxyproline
Osteocalcin
Tibia
Inbred C57BL Mouse
In Situ Hybridization
Histology

Keywords

  • Animal
  • Celecoxib
  • COX-2
  • Fracture
  • Ibuprofen
  • Indomethacin
  • Ketorolac
  • Model
  • NSAIDs
  • Rofecoxib

ASJC Scopus subject areas

  • Emergency Medicine
  • Orthopedics and Sports Medicine

Cite this

Mullis, B., Copland, S. T., Weinhold, P. S., Miclau, T., Lester, G. E., & Bos, G. D. (2006). Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model. Injury, 37(9), 827-837. https://doi.org/10.1016/j.injury.2005.12.018

Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model. / Mullis, Brian; Copland, Spencer T.; Weinhold, Paul S.; Miclau, Theodore; Lester, Gayle E.; Bos, Gary D.

In: Injury, Vol. 37, No. 9, 09.2006, p. 827-837.

Research output: Contribution to journalArticle

Mullis, B, Copland, ST, Weinhold, PS, Miclau, T, Lester, GE & Bos, GD 2006, 'Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model', Injury, vol. 37, no. 9, pp. 827-837. https://doi.org/10.1016/j.injury.2005.12.018
Mullis, Brian ; Copland, Spencer T. ; Weinhold, Paul S. ; Miclau, Theodore ; Lester, Gayle E. ; Bos, Gary D. / Effect of COX-2 inhibitors and non-steroidal anti-inflammatory drugs on a mouse fracture model. In: Injury. 2006 ; Vol. 37, No. 9. pp. 827-837.
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