# Evaluation of the Effects of Locally Applied Resveratrol and Cigarette Smoking on Bone Healing
## 4 Discussion
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline  & **Proliferation** & **Control** & **RES** & **CS + RS** & **CS** & **\(p\)** \\  & **(\%)** & **(\(n_{t}\), \%)** & **(\%)** & **(\(n_{t}\), \%)** & **(\(n_{t}\), \%)** & **(\(n_{t}\), \%)** & **\(p\)** \\ \hline \multirow{4}{*}{**Proliferation** & None & 8 (80.0) & 3 (27.3) & 3 (30.0) & 6 (60.0) & \\ \cline{2-6}  & 0–1\% & 2 (20.0) & 3 (27.3) & 5 (50.0) & 4 (40.0) & \\ \cline{1-1} \cline{2-6}  & 1–3\% & 0 (0.0) & 2 (18.2) & 2 (20.0) & 0 (0.0) & \\ \cline{1-1} \cline{2-6}  & 3+\% & 0 (0.0) & 3 (27.3) & 0 (0.0) & 0 (0.0) & \\ \hline \hline \end{tabular} Fisher–Freeman–Halton Exact Test: 13.12. RES: resveratrol; CS: cigarette smoking. Values are presented as numbers (%). There is no statistically significant difference detected between the groups (\(p>0.05\)).  
\end{table} 
Table 5: Comparison of proliferation. non-smokers. In a meta-analysis evaluating the relationship between smoking and bone mass, [PERSON] and [PERSON] [39] reported that smokers experienced significantly reduced bone mass in all regions compared with non-smokers. Consistent with the literature, the results of our study show that new bone area, macroscopic bone filling rate, and osteoblast number in rats exposed to cigarettes were significantly lower than those of the control group. [PERSON] et al. [40] evaluated bone healing in calvarial defects created in rats exposed to CS, administered 10 mg/kg oral RES to rats for 30 days, and found a decrease in the expression of RANKL/OPG, Dkk1, which plays a role in osteoblast differentiation, and an increase in the expression of RUNX2 gene, which plays important functions in osteoblast differentiation and bone mineralization. The effects of RES on bone healing and the effect of osteogenic markers on gene expression were also researched by [PERSON] et al. [21] In the study, two defects were created in the tibia of rats to which 10 mg/kg/RES was administered via gavage for 30 days, and a screw-shaped titanium implant was placed. As a result of the histomorphometric analysis, it was seen that the number of defects healed was the highest in the RES group. Additionally, immunohistochemical results showed that the expression of bone morphogenetic proteins (BMP)-2, BMP-7, and osteepontin (OPN) increased in the RES group [21]. [PERSON] et al. [4] evaluated bone healing in critical size defects in the femur of CS-exposed rats preoperatively for 28 days. After the surgical operation, CS exposure was continued postoperatively for 28 days, after which the rats were sacrificed and bone healing in the defects was evaluated. They reported that the number of osteoblasts in the defect area was the fewest in the smoking group and that the new bone area formed was less in the smoking group. They reported that the number of osteoblasts and new bone area increased in the groups that had been administered 20 mg/kg RES via oral gavage compared with the control and smoking groups [4]. [PERSON] et al. injected a single dose of 10 umol/kg resveratrol 24 h after the orthodontic device was placed on the interpermeillary suture line of rats in which widening was performed. They evaluated the bone healing in the suture histomorphometrically and reported a significant increase in the new bone area and the osteoblast numbers in the resveratrol group [28]. [PERSON] et al. evaluated the extraction socket and administered intraperitoneal RES injection to rats at 10 umol/kg per day, and at the end of the study, they observed an increase in osteepontin, new bone formation, and epithelialization and a decrease in inflammation [41]. In our study, similar to these studies, the highest osteoblast numbers and the most new bone areas were found in the RES group than in the RES + CS and control groups, respectively, and the lowest osteoblast numbers were found in the CS group.