Fracture Repair and the Role of Anti-Inflammatory Drugs: Deleterious Effects of Diclofenac but not of Dexamethasone

Abstract

Anti-inflammatory drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), are routinely used in traumatology for reduction of pain and swelling after injury. Though these beneficial effects are proven beyond doubt, the concern remains that these drugs might impair fracture healing. To test this hypothesis, fracture healing was studied in 100 mice treated with either anti-inflammatory drugs (i. e., diclofenac, dexamethasone) or placebo. Anti-inflammatory drugs were given in doses (per kg) similar to the ones used in humans and for different periods of time to mimic chronic or acute use of these drugs. To make mouse models accessible to fracture modulation studies that also allow biomechanical analysis, we modified the Einhorn tibial fracture model and developed a standardized closed femur fracture model. Analysis included biomechanics, contact radiography, microCT analysis, undecalcified histology, histomorphometry and immunocytochemical analysis. Mice treated with diclofenac showed a significant impairment of fracture healing, whereas treatment with dexamethasone had no discernible effect. This study shows that NSAIDs can impair the fracture healing process in vivo, leading to significantly reduced biomechanical stability. As these drugs are widely used in patients with fractures, it seems important that further experimental and clinical studies clarify the role of these substances in fracture healing.

Key words

NSAIDs - biomechanics - fracture repair

References

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1 * These authors contributed equally and therefore share first authorship.