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The cyclooxygenase-2 selective inhibitor NS-398 does not influence trabecular or cortical bone gain resulting from
T Sugiyama1, L B Meakin, G L Galea
1Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, London, UK. Toshihiro.Sugiyama@bristol.ac.uk
Unlabelled:
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.
Introduction:
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.
Conclusion:
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.
Insights
Daily cyclooxygenase-2 (COX-2) inhibition with NS-398 did not affect bone
Area of Science:
- Bone biology
- Pharmacology
- Skeletal adaptation
Background:
- Prostaglandins mediate early bone cell responses to mechanical stimuli.
- Cyclooxygenase-2 (COX-2) expression increases with mechanical strain.
- COX-2 inhibition reduces osteogenic response to single mechanical loading events.
Purpose of the Study:
- To investigate the long-term effects of COX-2 inhibition on bone remodeling in response to repeated mechanical loading in female mice.
- To determine if daily COX-2 inhibition impacts adaptive bone changes from mechanical loading.
Main Methods:
- Female mice received daily injections of NS-398 (a COX-2 inhibitor) or vehicle for two weeks.
- Skeletal limbs underwent axial mechanical loading on alternate days.
- Bone architecture was analyzed using micro-computed tomography.
Main Results:
- In unloaded limbs, NS-398 reduced trabecular number but not cortical bone.
- In loaded limbs, NS-398 did not alter the increases in trabecular thickness and cortical bone volume.
- Repeated mechanical loading increased bone mass in control limbs.
Conclusions:
- Daily pharmacological inhibition of COX-2 does not impede the adaptive response of trabecular or cortical bone to repeated mechanical loading in female mice.
- These findings suggest that COX-2 inhibition may not impair bone's functional adaptation to physical activity in women.
