1. Experimental research on the change of subchondral bone microstructure in early stage of mouse osteoarthritis
Yonghui DONG ; Ang LI ; Zhipeng DAI ; Shengjie WANG ; Wendi ZHENG ; Weiyu PAN ; Yi JIN ; Ke LIU ; Jiajun ZHAO ; Jia ZHENG
Chinese Journal of Orthopaedics 2019;39(22):1392-1398
Objective:
To establish a mouse model of osteoarthritis (OA) and study the bone microarchitecture and bone metabolism of tibial subchondral bone in early stage of OA.
Methods:
The mouse model of post-traumatic osteoarthritis (PTOA) with anterior cruciate ligament (ACLT) was established by using c57 mice. The Sham operation group served as the control group. All mice were fed with conventional diet. All mice were sacrificed after 4 weeks. The degeneration of knee joint was observed by HE staining and Safranin O-Fast Green staining. The number of osteoclasts was counted by TRAP staining. Micro CT was used to analyze the quantitative parameters of the microstructure of tibia subchondral bone in mice. Serum levels of bone resorption biomarker CTX I and cartilage degeneration marker CTX II were determined.
Results:
After ACLT 4 weeks, the average score of OARSI in ACLT group was 3.2, which was higher than that in Sham group, and the joint degeneration occurred in mice, presenting the pathological characteristics of early OA. Compared with the sham operation phase, the total subchondral bone volume (TV) of ACLT group was 4.72 mm3, increased by 13.6%; the bone trabecular resolution (Tb.Sp) was 0.130 and 0.154 mm, respectively, and the ACLT group also increased by 18.8%; the bone volume/tissue volume (BV/TV) was 0.470 and 0.294, respectively, and the ACLT group decreased by 48.9%; the bone trabecular thickness (Tb.Th) was 0.162 and 0.083 mm groups, ACLT decreased by 37.5%. Trap staining showed that the number of osteoclasts per unit volume in ACLT group was 72, which was significantly higher than that in sham operation group. The CTX I of mice in the sham operated ACLT group and sham operated group were 20.9 ng/ml and 18.29 ng/ml, with an increase of 48.9% in the ACLT group; the CTX II of mice in the ACLT group and sham operated group were 35.5 ng/ml and 28.6 ng/ml, with an increase of 24.1% in the ACLT group.
Conclusion
ACLT Mouse model can successfully construct early OA, which confirms the early loss of osteochondral bone and the pathological changes of osteoclast activation in OA, and provides a new specific target for the treatment of OA.
2.Clinical Efficacy of Medication of Xibining Ⅱ Prescription in Treatment of Knee Osteoarthritis with Cold-dampness Blockage Syndrome: A Retrospective Cohort Study
Zifeng CAO ; Wei MEI ; Li ZHANG ; Wendi PAN ; Xiaochen LI ; Jun MAO ; Guojun LI ; Peimin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):122-129
ObjectiveTo retrospectively analyze the clinical efficacy of Xibining Ⅱ prescription in the treatment of knee osteoarthritis with cold-dampness blockage syndrome by oral medication and to explore the influencing factors of endpoint events. MethodA real-world retrospective cohort design was adopted, and medical records of knee osteoarthritis patients with cold-dampness blockage syndrome treated with oral medication from the orthopedics outpatient department of Jiangsu Province Hospital of Chinese Medicine were collected. All patients received conventional Western medicine treatment and were divided into non-exposure group (573 cases) and exposure group (427 cases) according to whether or not they received treatment with Xibining Ⅱ prescription. Descriptive analysis of the baseline data of the 1 000 screened cases was performed using IBM SPSS 27.0. According to the baseline data, 334 pairs were matched using the propensity score matching method, resulting in a total of 668 cases in both groups. The changes in visual analogous scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, Japanese Knee Osteoarthritis Measure (JKOM) score, and traditional Chinese medicine (TCM) syndrome score before treatment and at 2, 6, 12 weeks after treatment, as well as the incidence of adverse reactions, were compared between the two groups. A multivariate logistic regression analysis was conducted to analyze the influencing factors of endpoint events, with clinical cure judged based on the improvement rate of WOMAC total score before and after treatment. ResultAfter 12 weeks of treatment, compared to the results before treatment, the VAS, WOMAC total score, JKOM score, and TCM syndrome score of patients in both groups significantly decreased (P<0.01). Compared to the non-exposure group, the exposure group showed a more significant reduction in VAS, WOMAC total score, JKOM score, and TCM syndrome score (P<0.01). After 12 weeks of treatment, the clinical cure rate and significant efficiency were higher in the exposure group than in the non-exposure group (P<0.05). Compared to the results before treatment within each group, VAS, WOMAC pain, stiffness, function scores, JKOM score, and TCM syndrome score significantly decreased at 2, 6, 12 weeks after treatment in both groups (P<0.01). Compared to the non-exposure group at the same time points, the exposure group showed a reduction in VAS at 2, 12 weeks, WOMAC pain at 6, 12 weeks, and function scores at 12 weeks (P<0.05, P<0.01). The JKOM score decreased at 6, 12 weeks, and the TCM syndrome score significantly decreased at 2, 6, 12 weeks in the exposure group (P<0.05, P<0.01). Multivariate logistic regression analysis at 12 weeks showed that factors affecting clinical cure included the course of disease, history of alcohol consumption, hypertension, coronary heart disease, and the use of Xibining Ⅱ prescription (P<0.05, P<0.01). Compared to the non-exposure group at the same time points, the incidence of epigastric discomfort in the exposure group was lower at 2, 12 weeks (P<0.01), the incidence of diarrhea and vomiting was slightly higher than that in the non-exposure group, but the difference was not statistically significant. ConclusionThe clinical application of Xibining Ⅱ prescription combined with conventional Western medicine treatment in the treatment of knee osteoarthritis with cold-dampness blockage syndrome is more effective than conventional Western medicine treatment alone. It can significantly reduce VAS, WOMAC total score, JKOM score, and TCM syndrome score, with more pronounced long-term effects and a low incidence of adverse reactions.