Açan Ahmet Emrah, Aydın Mert Emre, Bulmuş Özgür, Özcan Emrah, Karakılıç Aslı, Turan Gülay, Reşit Buğra Hüsemoğlu Reşit Buğra Hüsemoğlu Reşit Buğra Hüsemoğlu
Balıkesir Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Anabilim Dalı, 10185 Altıeylül, Balıkesir, Türkiye.
Jt Dis Relat Surg. 2025 Jan 2;36(1):200-209. doi: 10.52312/jdrs.2025.2042. Epub 2024 Dec 18.
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.
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.
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).
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.
本研究在大鼠股骨干模型中评估不同剂量加巴喷丁和普瑞巴林对骨折愈合的影响，并进行组织学、放射学和生物力学评估。
根据人体等效剂量，将70只雄性Wistar白化大鼠分为五组：对照组、低剂量加巴喷丁组（GBP-L，300毫克/天）、高剂量加巴喷丁组（GBP-H，3600毫克/天）、低剂量普瑞巴林组（PRG-L，150毫克/天）和高剂量普瑞巴林组（PRG-H，600毫克/天）。诱导双侧股骨骨折；右侧股骨用于通过显微断层扫描进行放射学检查，随后进行组织学分析，而左侧股骨用于生物力学测试。术前3周开始给药，持续至2周或4周处死。组织学评估包括炎症和转化评分以及显微断层扫描测量的骨痂体积。生物力学测试评估最大力和刚度。
在第4周时，GBP-H组、PRG-L组和PRG-H组的炎症水平与对照组相比显著更高（p<0.01、p<0.05和p<0.01），而这些组的转化评分显著更低（p<0.01、p<0.05和p<0.001）。低剂量普瑞巴林显示出临界转化差异（p=0.051）。显微断层扫描分析显示，GBP-H组在第2周时骨痂体积与对照组相比显著减小（p<0.01），在第4周时仍以较低的显著性持续减小（p<0.05）。到第4周时，PRG-H组的骨痂体积也减小了（p<0.05）。与对照组相比，GBP-L组、GBP-H组和PRG-H组在第4周时的最大力值显著更低（GBP-L组p<0.05；GBP-H组和PRG-H组p<0.01）。
这些发现表明，这些药物，尤其是高剂量应用时，可能导致炎症持续时间延长，并通过减小骨痂体积和生物力学完整性来阻碍骨折愈合，潜在地破坏从愈合的炎症阶段到修复阶段的转变。
