The effects of gabapentin and pregabalin on fracture healing: A histological, radiological, and biomechanical analysis

Abstract

Objectives: This study evaluated the impact of different doses of gabapentin and pregabalin on fracture healing in a rat femoral shaft model, with histological, radiological, and biomechanical assessments.

Materials and methods: Seventy male Wistar albino rats were divided into five groups: control, low-dose gabapentin (GBP-L, 300 mg/day), high-dose gabapentin (GBP-H, 3600 mg/day), low-dose pregabalin (PRG-L, 150 mg/day), and high-dose pregabalin (PRG-H, 600 mg/day), based on human equivalent doses. Bilateral femoral fractures were induced; the right femurs were prepared for radiological examination using microtomography, followed by histological analysis, whereas the left femurs were allocated for biomechanical testing. Drug administration began three weeks preoperatively and continued until sacrifice at either two or four weeks. Histological assessments included inflammation and transformation scoring and microtomography-measured callus volume. Biomechanical testing assessed maximum force and stiffness.

Results: At the fourth week, inflammation levels were significantly higher in the GBP-H, PRG-L, and PRG-H groups compared to control (p<0.01, p<0.05, and p<0.01), while transformation scores were significantly lower in these groups (p<0.01, p<0.05, and p<0.001). Low-dose pregabalin showed a borderline transformation difference (p=0.051). Microtomography analysis showed that the GBP-H group had significantly reduced callus volume versus control by the second week (p<0.01), persisting at a lower significance by week four (p<0.05). By the fourth week, PRG-H also had reduced callus volume (p<0.05). Maximum force values by the fourth week were significantly lower in the GBP-L, GBP-H, and PRG-H groups compared to control (p<0.05 for GBP-L; p<0.01 for GBP-H and PRG-H).

Conclusion: These findings suggest that these drugs, particularly with their high-dose applications, may lead to prolonged inflammation and hinder fracture healing by reducing callus volume and biomechanical integrity, potentially disrupting the transition from the inflammatory to reparative phases of healing.

Citation: Açan AE, Aydın ME, Bulmuş Ö, Özcan E, Karakılıç A, Turan G, et al. The effects of gabapentin and pregabalin on fracture healing: A histological, radiological, and biomechanical analysis. Jt Dis Relat Surg 2025;36(1):200-209. doi: 10.52312/jdrs.2025.2042.

Idea/concept, literature review, design, conducted the study and writing the article: A.E.A.; Materials and conducted the study: A.M.E.; Materials, supervision of the study and critical review of the manuscript: B.Ö.; Data collection, analysis and interpretation: Ö.E., K.A., T.G., T.N., H.R.B. All authors read and approved the final manuscript.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

This study was supported solely by our university’s scientific research fund. No author has any professional or financial relationships that could be perceived as influencing the impartiality of the presentation.

The statistics were performed by Prof. Sinan Saraçlı, Department of Biostatistics, Faculty of Medicine, Balıkesir University.

The data that support the findings of this study are available from the corresponding author upon reasonable request.