Background: Nonsteroidal anti-inflammatory medications have been
shown to delay fracture-healing. COX-2-specific inhibitors such as celecoxib
have recently been approved for human use. Our goal was to determine,
mechanically, histologically, morphologically, and radiographically, whether
COX-2-specific inhibition affects bone-healing.
Methods: A nondisplaced unilateral fracture was created in the right
femur of fifty-seven adult male rats. Rats were given no drug, indomethacin (1
mg/kg/day), or celecoxib (3 mg/kg/day) daily, starting on postoperative day 1.
Fractures were analyzed at four, eight, and twelve weeks after creation of the
fracture. Callus and bridging bone formation was assessed radiographically.
The amounts of fibrous tissue, cartilage, woven bone, and mature bone
formation were determined histologically. Morphological changes were assessed
to determine fibrous healing, callus formation, and bone-remodeling. Callus
strength and stiffness were assessed biomechanically with three-point bending
Results: At four weeks, only the indomethacin group showed
biomechanical and radiographic evidence of delayed healing. Although femora
from rats treated with celecoxib appeared to have more fibrous tissue than
those from untreated rats at four and eight weeks, radiographic signs of
callus formation, mechanical strength, and stiffness did not differ
significantly between the groups. By twelve weeks, there were no significant
differences among the three groups.
Conclusions: Postoperative administration of celecoxib, a
COX-2-specific inhibitor, did not delay healing as seen at twelve weeks
following fracture in adult rat femora. At four and eight weeks, fibrous
healing predominated in the celecoxib group as compared with the findings in
the untreated group; however, mechanical strength and radiographic signs of
healing were not significantly inhibited.
Clinical Relevance: Many orthopaedists rely on narcotic analgesia
for postfracture and postoperative pain, despite deleterious side effects and
morbidity. Traditional nonsteroidal anti-inflammatory medications have been
shown to delay fracture union. This effect may be smaller with COX-2-specific