Circadian rhythm: The hidden “puppet master” behind musculoskeletal disorders

Circadian rhythm (CR), regulated by the central biological clock in the hypothalamus and synchronized with local clocks in peripheral tissues, orchestrates the physiology of localized tissues in response to the periodic rhythmic variations of the environment. Environmental cues and behavioral factors, such as light exposure, feeding, and exercise, can synchronize or desynchronize these rhythms, and abnormalities can lead to disruption of the human CR. Certain modern behaviors, such as traveling across time zones, shift work, and irregular eating patterns, disrupt the body's natural CR, thereby potentially contributing to the development of musculoskeletal disorders through multiple pathways. In this review, we summarize the role of CR in the physiology of the musculoskeletal system—encompassing bone, cartilage, tendons, and muscles—alongside the mechanisms by which CR disruption contributes to various musculoskeletal disorders. Additionally, we discuss interventions for treating musculoskeletal disorders based on CR, including resetting biological clocks or optimizing medication administration times. The translational potential of this article A comprehensive understanding of the role of CR in the physiology and pathology of the musculoskeletal system offers significant therapeutic and preventative opportunities for musculoskeletal disorders, holding considerable importance for advancing the prevention and treatment of such conditions.