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Published on: August 31, 2022
Ketorolac administration does not delay early fracture healing in a juvenile rat model: a pilot study
Teresa Cappello1, Julia A V Nuelle, Nicolas Katsantonis
1Department of Orthopaedic Surgery and Rehabilitation, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA. tcappello@lumc.edu
Insights
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ketorolac did not inhibit fracture healing in juvenile rats. This finding supports the use of NSAIDs for pain relief in pediatric fracture cases.
Area of Science:
- Orthopedics
- Pharmacology
- Developmental Biology
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management in pediatric fractures.
- Conflicting evidence exists regarding NSAID effects on fracture healing in adult models.
- Limited data exists on NSAID impact on bone formation in juvenile animals.
Purpose of the Study:
- To investigate the effects of ketorolac, a common NSAID, on fracture healing in a juvenile rat model.
- To assess the impact of ketorolac on bone formation and healing at the early stages.
Main Methods:
- Surgically induced tibial shaft fractures in juvenile rats (3-4 weeks old).
- Administration of ketorolac (5 mg/kg) or saline (control) for 6 days/week.
- Biomechanical testing (4-point bending) and histological evaluation at 7, 14, and 21 days post-fracture.
Main Results:
- Fracture callus strength and stiffness increased over time in both ketorolac and saline groups.
- No statistically significant differences in strength, stiffness, or callus quality were observed between groups at any time point.
- Histological evaluation showed similar fracture callus characteristics in both treatment groups.
Conclusions:
- Ketorolac administration did not negatively affect early fracture healing (strength, stiffness, histology) in juvenile rats.
- These findings support the continued use of NSAIDs for analgesia in children with long bone fractures.
- The study provides evidence that ketorolac does not inhibit early bone healing in a juvenile animal model.
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.

