Dose and Time-Dependent Effects of Cyclooxygenase-2 Inhibition on Fracture Healing

Author(s): Simon AM, O’Connor JP

Source: J  Bone Joint Surg 89A (3): 500-511, 2007.


This study evaluated the effect of COX-2 inhibitors on fracture healing.  Female Sprague-Dawley rats were provided a femoral fracture and treated with varying dosages and at different time periods of celecoxib.  At eight weeks after fracture, healing was assessed with radiography and destructive torsional mechanical testing.  Celecoxib treatment effect on fracture healing was assessed by measuring prostaglandin E2 and F2 levels.  Celecoxib dosages as low as 2 mg/kg/day reduced fracture callus mechanical properties and caused a significant increase in the proportion of nonunions.  In addition, celecoxib dosages of 4 mg/kg/day for 5 days reduced fracture callus mechanical properties and significantly increased proportions of nonunions.  Celecoxib therapy prior to fracture or initiated 14 days after fracture did not significantly increase the proportion of nonunions.  Celecoxib treatment at a dose of 4 mg./kg./day reduced fracture callus prostaglandin E2 and F2 levels by greater than 60 %. 

This study confirms that COX-2 selective nonsteroidal anti-inflammatory medications can significantly effect fracture callus formation and increase the potential for nonunion formation.  However, evidence suggests that the timing of administration of the COX-2 inhibitor can be a significant factor.  However, until further studies are performed in humans, the use of COX-2 inhibitors in patients being treated for a fracture should be used cautiously.

Cox, Inhibitors, Fracture, Healing, Cyclooxygenase

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