Bone–brain crosstalk in osteoarthritis: pathophysiology and interventions

The emerging concept of the ‘bone–brain axis’ represents a paradigm in our understanding of osteoarthritis (OA), moving from a purely peripheral perspective to recognizing the central role of the brain.Neuronal pathways are essential for transmitting OA pain signals, directly linking the skeletal system and brain.Bidirectional communication between bone and brain occurs through molecular signaling. Brain-derived and bone-derived mediators contribute to this communication, and play direct or indirect roles in the development and progression of OA.Circadian rhythms play a significant role in bone homeostasis and have implications for OA development.Emerging treatments that target bone–brain crosstalk – such as non-invasive brain stimulation (NIBS), neuropeptides, neurotransmitter drugs, and circadian rhythms regulation – hold promise for improving OA therapeutic outcomes. Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone–brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone–brain axis to the development of effective interventions for managing OA. Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone–brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone–bra