title: The cyclooxygenase-2 selective inhibitor NS-398 does not influence trabecular or cortical bone gain resulting from repeated mechanical loading in female mice.
abstract: A single injection of the cyclooxygenase-2 (COX-2) selective inhibitor NS-398 reduces bone's osteogenic response to a single period of mechanical loading in female rats, while women taking COX-2 selective inhibitors do not have lower bone mass. We show that daily NS-398 injection does not influence bone gain from repeated loading in female mice.
  
  
  BACKGROUND
  Prostaglandins are mediators of bone cells' early response to mechanical stimulation. COX-2 expression is up-regulated by exposure of these cells to mechanical strain or fluid flow, and the osteogenic response to a single loading period is reduced by COX-2 inhibition. This study determined, in female mice in vivo, the effect of longer term COX-2 inhibition on adaptive (re)modelling of cortical and trabecular bone in response to repeated loading.
  
  
  METHODS
  Nineteen-week-old female C57BL/6 mice were injected with vehicle or NS-398 (5 mg/kg/day) 5 days a week for 2 weeks. On three alternate days each week, the right tibiae/fibulae were axially loaded [40 cycles (7 min)/day] three hours after injection. Left limbs acted as internal controls. Changes in three-dimensional bone architecture were analysed by high-resolution micro-computed tomography.
  
  
  RESULTS
  In control limbs NS-398 was associated with reduced trabecular number but had no influence on cortical bone. In loaded limbs trabecular thickness and cortical periosteally enclosed volume increased. NS-398 showed no effect on this response.
  
  
  CONCLUSIONS
  Pharmacological inhibition of COX-2 by NS-398 does not affect trabecular or cortical bone's response to repeated mechanical loading in female mice and thus would not be expected to impair the functional adaptation of bone to physical activity in women.
authors.affiliation: Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, London, UK. Toshihiro.Sugiyama@bristol.ac.uk
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
authors.forename: L B
authors.initials: LB
authors.lastname: Meakin
authors.forename: G L
authors.initials: GL
authors.lastname: Galea
authors.forename: L E
authors.initials: LE
authors.lastname: Lanyon
authors.forename: J S
authors.initials: JS
authors.lastname: Price
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005260:Female; D005360:Fibula / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009578:Nitrobenzenes / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D013314:Stress, Mechanical; D013449:Sulfonamides / Q000494:pharmacology*; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide