Effect of Local Simvastatin on the Healing of Surgically Created Critical-Sized Bone Defects: An experimental Study on sheep.

Abstract

Background and objective: the role of simvastatin in lowering serum cholesterol levels is well described. However, recent findings suggest they have a role in bone formation as well. The study aims to determine the effect of local simvastatin application on bone defect healing and compare the amount of new bone produced by a simvastatin-treated defect with that produced by a bone graft (biphasic calcium phosphate) and non-treated defects (left empty) histologically. Methods: Forty-five critical-size defects were created (8mm in diameter and depth) in the iliac bone of 6 sheep. For the first three sheep (5 defects/ilium), the five defects on the right ilium were left empty as a Control group, while the five defects on the left ilium were filled with biphasic calcium phosphate as Test 1 group. For the other three sheep, 5 defects were created on the right ilium, the defects were filled with 10mg crushed simvastatin tablet with gelfoam (as a carrier) as Test 2 group. The animals were sacrificed over periods of 1, 2, and 3 months. Histopathological studies were done for all the samples. SPSS version 28 was used to analyze the results. The numerical variables were checked for normality using Smirnov – Kolmogorov test, then analyzed using ANOVA and unpaired t-test (p–values ≤ 0.05 were considered statistically significant). Results: All 6 adult male sheep passed the scheduled periods uneventfully. During the wound healing period, there was no complication such as infection, excessive hematoma, or wound dehiscence. All 45 standardized iliac bone defects were included in the final analysis (n= 45). The histologic results showed that Test 2 group (defect filled with simvastatin) in the 1st, 2nd, and 3rd months had significantly higher bone formation at the surface and depth of the defects than Test 1 and Control group with P values (<0.0001) at all period intervals. Conclusion: Simvastatin enhances bone formation and accelerates the healing process of the bony defect. Keywords: Bone formation, Bone graft, Bone healing, Simvastatin, Statin.