Effects of Tissue-Bone Homeostasis Manipulation at Different Time Points on Pain and Brain Mechanisms in Patients with Knee Osteoarthritis Based on Circadian Rhythm: Study Protocol for a Randomized Controlled Trial.

Background: Knee osteoarthritis (KOA) is characterized by pain and dysfunction. Tissue-bone homeostasis manipulation (TBHM) has been shown to have a good effect on KOA. However, its optimal application time and related mechanism of action are still unclear. Therefore, this study will explore the efficacy and brain mechanism of TBHM at different time points in patients with KOA.

Methods: The experiment is designed as a randomized controlled single-blind study, aiming to recruit 100 patients with KOA. These patients will be divided into four groups using stratified random sampling: the TBHM group at 8 a.m. the TBHM group at 1 p.m. the TBHM group at 6 p.m. and the Joint Mobilization group. The intervention will last for 4 weeks, once a day, 5 days per week. All outcome indicators will be measured at baseline and 4 weeks after the intervention, with the efficacy indicators measured additionally during follow-up visits at the 3rd and 6th months. The efficacy results include the Visual Analog Scale, Active range of motion, SF-36, electroencephalogram (EEG) and the Hamilton Anxiety Rating Scale. The mechanism part mainly focuses on changes in melatonin content in saliva. Two-way repeated measures analysis of variance (ANOVA) will be used to measure and statistically analyze all quantitative scores, while MatLab 2022b will be utilized for the analysis of EEG data.

Discussion: This study, based on "circadian rhythm", innovatively combines different treatment times with TBHM to treat KOA pain. It will delve into the differences in the impact of this approach on KOA pain relief at different time points and clarify its potential mechanism of action. This will not only enhance the scientific understanding of the treatment effect of this manipulation but also provide new strategies and references for clinical treatment of KOA.

Trial Registration: The study was registered in Chinese Clinical Trial Registry (No. ChiCTR2400080820). Registered on Feb. 07, 2024, https://www.chictr.org.cn/showproj.html?proj=220404.