Pathological mechanisms of osteoarthritis in the network of geriatric comorbidities: Emerging insights from organs-crosstalk

With the rapid progression of global population aging, osteoarthritis (OA), a common degenerative joint disease, increasingly affects the quality of life and functional status of the elderly. OA often coexists with other chronic diseases in elderly patients, forming a complex comorbidity network. However, the interactions between OA and other geriatric comorbidities and their effects on disease progression have not been fully explored. This review investigates the pathological mechanisms of OA within the geriatric comorbidity network, focusing on its bidirectional interactions with osteoporosis, obesity, diabetes, and hypertension, and examines the effects of commonly used medications in elderly patients with comorbidities. The findings reveal that these chronic conditions contribute to OA through mechanisms such as mechanical stress, metabolic dysregulation, and inflammation. Additionally, OA exacerbates other comorbidities, further worsening the overall health of patients. The review emphasizes the need for integrated treatment strategies that address both OA and its comorbidities, and highlights the importance of further research into the molecular interactions between OA and comorbidities for more effective treatment strategies, particularly targeting shared pathways. Translational Potential of this Article : This review defines osteoarthritis (OA) as a systemic disease driven by organ crosstalk within the geriatric comorbidity network. Interactions among bone, adipose, vascular, and metabolic systems converge on shared pathways, including inflammation, metabolic dysregulation, and biomechanical imbalance. This framework supports a shift toward mechanism-based, multi-organ management and highlights opportunities for drug repurposing, biomarker-guided risk stratification, and precision medicine, ultimately improving outcomes in elderly patients with OA and multimorbidity.