## 1 Introduction  
Osteoarthritis is a local inflammatory joint disease marked by cartilage degeneration, synovitis and altered subchondral bone remodelling. Pathological changes in other parts of the joints, including ligaments, meniscus and infrapatellar fat pad, are also reported [1, 2]. Patients with osteoarthritis often suffer from joint swelling, tenderness and pain, limiting the joint motion [3, 4]. According to the Global Burden of Disease Study in 2019, the worldwide prevalence of osteoarthritis was 528 million, representing a 27.5% increase from 2010 [5]. Although osteoarthritis does not contribute to mortality directly, it was the top 15 th major contributor of years lived with disability globally in 2019 [5]. If it is not managed appropriately, patients with late-stage osteoarthritis will undergo costly and invasive total arthroplasty associated with possible side effects, such as infection and bleeding [6].  
The conventional pharmacological treatment agents for osteoarthritis, such as intra-articular corticosteroid and hyaluron injections and oral analgesics, place emphasise on relieving the patients' symptoms [7,8]. Glucosamine sulphate, a substrate for proteoglycan synthesis, is one of the common alternative agents used for preventing osteoarthritis [9]. Multiple meta-analyses have reported that glucosamine sulphate could reduce pain due to osteoarthritis, with limited effects on patients' knee functions [10,11]. In addition, glucosamine sulphate exerts potent anti-inflammatory properties by suppressing translocation of nuclear factor kappa B and facilitating the degradation of cyclooxygenase enzyme [12].  
Tocotrienol is a group of less common tocochromanols (Vitamin E), with four isomers (\(\alpha\), \(\beta\), \(\gamma\), and \(\delta\)-tocotrienol) based on the position of the side chain. It can be found abundantly in palm oil, annatto bean and rice bran in varying composition [13]. Tocotrienol and its metabolites possess biological activities, notably anti-inflammatory effects [14]. The joint protective effects of vitamin E have been widely reported (summarised in [15]). Some previous studies have reported that \(\gamma\)-tocotrienol [16], \(\delta\)-tocotrienol [17] and palm TRF [18] protect against inflammatory arthritis and rheumatoid arthritis in rats. However, only one animal study ever reported the effectiveness of annatto cocotrienol rich in \(\delta\)-tocotrienol in preventing cartilage and subchondral bone changes [19]. Palm TRF supplementation has been attempted in an open-labelled study, with some positive outcomes in pain and functional scores, but joint structural outcomes were not tested [20]. The therapeutic potential of palm TRF in combination with other joint protective agents like glucosamine sulphate has not been assessed previously.  
The current study aimed to compare the protective effects of palm TRF, glucosamine sulphate, and the combination of both agents in rats with osteoarthritis induced with monosodium iodoacetate (MIA). The parameters assessed included the body weight, grip strength, cartilage structure and serum cartilage oligomeric matrix protein (COMP) of the rats. It was hypothesised that the combination of palm TRF and glucosamine sulphate would perform better than individual agents in preventing osteoarthritis. This research will pave the way for the development of a better pharmacological regimen for reducing the morbidity caused by osteoarthritis.