Abstract
Hypothesis: Early initiation of COX-2 inhibition is more detrimental to fracture healing than later, irrespective of the analgesia-permitted biomechanical stimulation of the fracture by movement.
Model: A validated externally fixated murine femoral fracture model.
Intervention: Left femoral osteotomies, immobilised with sagittal uniplanar external fixators. Treated mice received 4mg/kg meloxicam from the day of surgery, day 4 or day 8 post op until sacrifice, by gavage. Control mice received carrier alone.
Outcome Measurements: Mouse movement was quantified each day until sacrifice. Fracture geometry was determined from post-sacrifice orthogonal x-rays. Animals were sacrificed on day 4,8,16 and 24. Blind computer aided histomorphometric analysis was performed, on six coronal sections per specimen, determining the medial, intramedullary and lateral areas of total callus, mesenchymal tissue, cartilage and new bone.
Results: No difference existed between the treated groups and control fracture fragments overlap or alignment nor in post-operative movement. Meloxicam treated groups showed decreased callus areas on day 4, 8, and 16, although it was noted that callus remodelling had commenced after day 16 in the control specimens only. New bone areas were reduced in all treated groups at all time points examined relative to the controls with the reduction being proportional to duration of COX-2 inhibition. Mesenchymal tissue differentiation was maximally affected in the earliest treatment group.
On day 24, day 0 treated specimens demonstrated significantly more mesenchymal tissue. No correlation was demonstrated between post-operative motion and callus area or new bone area. The care of cartilage present however, was significantly correlated to the amount of post-operative movement in all groups.
Conclusions: COX-2 inhibition inhibits new bone formation in proportion to the proximity of its commencement the fractures occurrence, irrespective of fracture stimulation by motion. Cartilage production in the healing fracture is not altered by COX-2 inhibition but is proportional to fracture stimulation by motion.
The abstracts were prepared by Mr Ray Moran. Correspondence should be addressed to him at the Irish Orthopaedic Association, Secretariat, c/o Cappagh Orthopaedic Hospital, Finglas, Dublin
