Effects of external application of Xiaozhong Zhitong San combined with oral etoricoxib on serum inflammatory mediators and bone metabolic molecules in patients with knee osteoarthritis

Wei Aichun; Zhou Yongjin; Xu Xudong; Wei Xiaobing; Dong Yuqi; Huan Dawei; Li Wanhong; Yang Xiaojian; Chen Ling

doi:10.11986/j.issn.1673-873X.2025.06.05

Abstract：Objective To investigate the clinical efficacy of external application of Xiaozhong Zhitong San combined with oral etoricoxib in treating knee osteoarthritis(KOA)and its effects on patients' serum inflammatory mediators and bone meta-bolic molecule levels,so as to provide a reference for optimizing KOA treatment strategies.Methods From March 2021 to March 2024,148 KOA patients admitted to Haian Traditional Chinese Medicine Hospital were enrolled and randomized by sealed-envelope method into a monotherapy group(n=74)and a combination group(n=74).The monotherapy group re-ceived oral etoricoxib,while the combination group received external application of Xiaozhong Zhitong San plus oral etoricox-ib;both regimens were given for 4 weeks.Clinical efficacy,knee pain,serum inflammatory mediators,bone metabolic mol-ecule levels,and adverse events were compared between the two groups.Results The overall response rate in the combina-tion group was significantly higher than that in the monotherapy group(93.24％[69/74]vs.81.08％[60/74];x2=4.891,P=0.027).Baseline knee pain assessed by the visual analogue scale(VAS)did not differ significantly between groups(P＞0.05);after treatment,VAS scores in both groups decreased from baseline,and the combination group's scores were lower than those of the monotherapy group,with statistically significant differences(P＜0.05).Baseline serum levels of tumor necrosis factor-α(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),and matrix metalloproteinase-3(MMP-3)did not differ significantly between groups(P＞0.05);after treatment,these inflammatory markers decreased in both groups and were lower in the combination group than in the monotherapy group,with statistically significant differ-ences(P＜0.05).Baseline serum osteocalcin(OC),bone-specific alkaline phosphatase(BALP)and total procollagen type Ⅰ N-terminal propeptide(PINP)levels were similar between groups(P＞0.05);after treatment,OC,BALP and PINP in-creased in both groups and were higher in the combination group than in the monotherapy group,with statistically signifi-cant differences(P＜0.05).Adverse event rates were 9.46％(7/74)in the monotherapy group and 14.86％(11/74)in the combination group,with no statistically significant difference(x2=1.012,P=0.314).Conclusion External application of Xiaozhong Zhitong San combined with oral etoricoxib in KO A patients promotes overall clinical efficacy,relieves knee pain,favorably modulates serum inflammatory mediators and bone metabolic molecule levels,and does not increase the risk of ad-verse events,justifying its wider clinical application.