title: Cyclooxygenase-2 inhibition delays the attainment of peak woven bone formation following four-point bending in the rat.
abstract: Fracture healing is retarded in the presence of cyclooxygenase-2 (COX-2) inhibitors, demonstrating an important role of COX-2 in trauma-induced woven bone adaptation. The aim of this experiment was to determine the influence of COX-2 inhibition on the remodeling and consolidation of nontraumatic woven bone produced by mechanical loading. A periosteal woven bone callus was initiated in the right tibia of female Wistar rats following a single bout of four-point bending, applied as a haversine wave for 300 cycles at a frequency of 2 Hz and a magnitude of 65 N. Daily injections of vehicle (VEH, polyethylene glycol) or the COX-2 inhibitor 5,5-dimethyl-3-3(3 fluorophenyl)-4-(4-methylsulfonal)phenyl-2(5H)-furanone (DFU, 2.0 mg . kg(-1) and 0.02 mg . kg(-1) i.p.), commenced 7 days postloading, and tibiae were examined 2, 3, 4, and 5 weeks postloading. Tibiae were dissected, embedded in polymethylmethacrylate, and sectioned for histomorphometric analysis of periosteal woven bone. No significant difference in peak woven bone area was observed between DFU-treated and VEH rats. However, treatment with DFU resulted in a temporal defect in woven bone formation, where the achievement of peak woven bone area was delayed by 1 week. Woven bone remodeling was observed in DFU-treated rats at 21 days postloading, demonstrating that remodeling of the periosteal callus is not prevented in the presence of a COX-2 inhibitor in the rat. We conclude that COX-2 inhibition does not significantly disrupt the mechanism of woven bone remodeling but alters its timing.
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, The University of Queensland, Brisbane, Qld, 4072, Australia. l.gregory@qut.edu.au
authors.forename: L S
authors.initials: LS
authors.lastname: Gregory
authors.forename: M R
authors.initials: MR
authors.lastname: Forwood
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D017102:Fracture Healing; D008297:Male; D010012:Osteogenesis; D010521:Periosteum / Q000473:pathology; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000473:pathology; D013997:Time Factors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D020033:Protein Isoforms; D051546:Cyclooxygenase 2