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

Cappello, Teresa MD*; Nuelle, Julia A.V. MD; Katsantonis, Nicolas BS*; Nauer, Rachel K. BS; Lauing, Kristen L. PhD§; Jagodzinski, Jason E. MD*; Callaci, John J. PhD

Journal of Pediatric Orthopaedics: June 2013 - Volume 33 - Issue 4 - p 415–421
doi: 10.1097/BPO.0b013e318288b46f

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective at controlling pain in children, especially in the treatment of fractures. Adult animal and adult clinical studies demonstrate conflicting evidence for the inhibitory relationship between NSAIDs and fracture healing. Published pediatric orthopaedic clinical studies do not demonstrate an inhibitory effect of ketorolac on bone healing. Little is known about the effects of any NSAID on bone formation in juvenile animals. This study investigates the effects of the NSAID ketorolac on fracture healing in a juvenile rat model.

Methods: Unilateral surgically induced and stabilized tibial shaft fractures were created in 45 juvenile (3 to 4 wk old) male Sprague-Dawley rats. Either ketorolac (5 mg/kg; n=24) or saline (0.9% normal saline; n=21) was then administered to the rats 6 d/wk by intraperitoneal injections. Animals were then randomly assigned into time groups and euthanized at 7 days (n=8 ketorolac, n=7 saline), 14 days (n=8 ketorolac, n=7 saline), or 21 days (n=8 ketorolac, n=7 saline) postfracture. Biomechanical analysis was performed using a custom-designed 4-point bending loading apparatus. Statistics for tibial stiffness and strength data were performed using software package Systat 11. Specimens were also evaluated histologically using hematoxylin and eosin staining.

Results: Strength and stiffness of all fractured tibiae increased over time from day 7 to day 21 regardless of treatment type. No statistical difference was found between the fractured tibiae strength or stiffness in the ketorolac or control-treated specimens at the same time point. In addition, the quality of the fracture callus was similar in both groups at each of the time points.

Conclusions: In this study of a juvenile rat model with a stabilized tibia fracture, fracture callus strength, stiffness, and histologic characteristics were not affected by the administration of ketorolac during the first 21 days of fracture healing.

Clinical Relevance: The absence of inhibitory effects of ketorolac on early juvenile rat fracture healing supports the clinical practice of utilizing NSAIDs for analgesia in children with long bone fractures.

*Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine

Burn and Shock Trauma Institute

Department of Orthopaedic Surgery and Rehabilitation, Alcohol Research Program, Loyola University Stritch School of Medicine, Maywood

§Department of Pediatrics, University of Chicago, Chicago, IL

Department of Orthopaedic Surgery, University of Missouri School of Medicine, Colombia, MO

Supported by the Loyola Department of Orthopaedic Surgery Faculty Research Start-Up Fund and The Orthopaedic Research and Education Foundation.

The authors declare no conflict of interest.

Reprints: Teresa Cappello, MD, Department of Orthopaedic Surgery, Loyola Stritch School of Medicine, 2160 S. First Avenue, Maguire Suite 1700, Maywood, IL 60153. E-mail:

© 2013 by Lippincott Williams & Wilkins