Modulation of Tocotrienol's Bone Effects by Osteocytes: A Perspective

Nurul Nabihah Zahanordin¹Pei Yuen Ng^2*Kok-Yong Chin^1*

• ¹Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Malaysia
• ²Centre of Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

Osteocytes function as central regulators of skeletal health by acting as mechanosensors that control bone remodelling mediated by osteoblasts and osteoclasts. Disrupted osteocyte function, often driven by oxidative stress and linked to ageing and osteoporosis, contributes to pathological bone remodelling. Tocotrienols (TTs), a family of vitamin E, are intensively investigated for their bone-protective effects, with mechanisms that involve reducing intracellular reactive oxygen species, enhancing antioxidant defences, and modulating signalling pathways of bone remodelling. Preliminary studies suggest that TTs exert protective and anabolic effects by influencing osteocytes, including shielding them from oxidative damage. In vivo models using ovariectomised or metabolic syndrome rats demonstrated that TT supplementation modulated key osteocyte-secreted factors, including sclerostin, dentin matrix protein-1, Dickkopf-related protein 1, fibroblast growth factor 23, and receptor activator of nuclear factor κB ligand. However, the current evidence is limited by the use of models that may not fully represent degenerative osteoporosis, restricted dose-dependent studies, and the challenge of real-time in vivo monitoring. This perspective summarises the reported effects of TTs on osteocytes' function and emphasises the critical need for future research to employ more representative animal models, advanced imaging techniques, and complex 3D co-culture or bone explant systems to accurately define the mechanism of action of TTs and their resulting functional outcomes on overall bone quality.