Ketorolac Administration Does Not Delay Early Fracture Healing in a Juvenile Rat Model: A Pilot Study

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective at controlling pain in the pediatric population, especially in the treatment of postoperative pain and orthopaedic injuries.1–8 These analgesics also have fewer side effects than narcotics in the pediatric population. 1,7,9–11 Narcotics are known to have common side effects such as nausea, vomiting, respiratory depression, and constipation, which can be especially problematic in pediatric patients.1,6,10,12 Despite this, NSAID use in the treatment of pain associated with bony injury and healing in children is now considered controversial. This controversy arises from the theory that NSAIDs delay bone healing, especially in adults. Several studies in various adult mammals including the rat, mouse, and rabbit have demonstrated an inhibition of bony repair with the use of various NSAIDs.13–28 However, there are also animal studies showing no effect of NSAIDs on bone formation or fracture healing.29–33 The published adult clinical studies are also conflicting. Some human adult studies investigating the effects of the NSAID ketorolac on spinal fusion have demonstrated an inhibition to bone healing34–36 but one larger clinical study did not.37 The effect of NSAIDs on bone healing in human adults after fracture or osteotomy is less clear, with some studies demonstrating increased rates of nonunion with NSAID use,38,39 whereas other studies finding no correlation.40,41 There is no evidence in the clinical pediatric orthopaedic literature suggesting NSAIDs delay bone healing in children. Clinical retrospective studies in the pediatric population do not demonstrate these inhibitory effects of the NSAID ketorolac on bone healing for posterior spinal fusion4,42,43 or operative fracture care44 or osteotomy healing.45 Furthermore, to our knowledge, there are no published studies investigating the effects of ketorolac in a juvenile animal model. The present study was performed to evaluate the effect of ketorolac administration on the healing of surgically induced and stabilized tibia shaft fractures in a juvenile rat model. Ketorolac was chosen because it is practically utilized in orthopaedic surgery, has been studied in both adults34–37 and children,4,42–45 and there is evidence that it delays bone formation in adult rats13 and adult rabbits.14,22,27 We hypothesized that the NSAID ketorolac would not lead to delayed union or failure of bone formation in healing tibia fractures in these juvenile rats.