A Comparison Between the Effects of Acetaminophen and Celecoxib on Bone Fracture Healing in Rats

Abstract

This study compared the acute treatment effects of systemic analgesics with (celecoxib) and without anti-inflammatory activity (acetaminophen) on bone fracture healing. Longitudinal time study of fracture healing in rats. Closed, mid diaphyseal femur fractures were produced in female Sprague-Dawley rats. The rats were treated for 10 days after fracture with 60 or 300 mg/kg of acetaminophen, 3 or 6 mg/kg of celecoxib, or vehicle by once-daily oral dosing. Fracture healing was measured after 8 weeks by radiographic examination, mechanical testing, and histology. Radiographic scoring indicated that acute celecoxib treatment significantly impaired fracture healing; acetaminophen treatment had no negative effect. Mechanical testing supported the radiographic observations. No negative effects of celecoxib or acetaminophen treatment on the structural properties (peak torque and torsional rigidity) of the healing femurs were detected. In contrast, celecoxib treatment, but not acetaminophen treatment, significantly reduced the material properties (maximum shear stress and shear modulus) of the healing femurs (P < 0.001). Post-mechanical testing examination of the healing femurs found that 73% of the vehicle-treated or acetaminophen-treated femurs had healed as unions (30/41), 27% failed as incomplete unions (11/41), and none failed as nonunions (0%). In contrast, only 21% of the fractured femurs from the celecoxib treated rats had healed as unions (7/34), 53% failed as incomplete unions (18/34), and 26% failed as nonunions (9/34). The proportion of nonunions among the celecoxib-treated rats was significantly higher compared with the control and acetaminophen-treated rats (P < 0.001). Histologic examination indicated that similar to previous studies, celecoxib treatment, but not acetaminophen treatment, altered normal fracture callus morphology in which cartilage rather than new bone abuts the fracture site. No negative effect from acute acetaminophen treatment on fracture healing was detected. In contrast, acute treatment with celecoxib, a selective cyclooxygenase-2 inhibitor with anti-inflammatory activity, significantly impaired fracture healing.