As representatives of degenerative orthopedic diseases, intervertebral disc degenerative disease (IVDD) and osteoarthritis (OA) involve the spine and peripheral articular cartilage, respectively. Their comorbidity rate in individuals over 60 years exceeds 40%, suggesting overlapping pathological and physiological features. Age-related "inflammaging" and cellular senescence, obesity-mediated mechanical load and metabolic disorders, and genetic/epigenetic abnormalities (e.g., COL2A1, ADAMTS5) constitute a shared risk factor network. Extracellular matrix (ECM) imbalance is a core initiating event: the MMPs/ADAMTS enzyme system, together with inflammatory cytokines such as IL-1β and TNF-α, drives excessive degradation of type II collagen and aggrecan, forming a "degradation-inflammation" positive feedback loop. In the chronic inflammatory microenvironment, damage-associated molecules activate TLR/NLRP3 pathways, triggering M1 macrophage polarization and Th17 cell infiltration, further disrupting ECM and inducing cell apoptosis. Cellular senescence releases pro-inflammatory mediators and degradation enzymes via the senescence-associated secretory phenotype (SASP). Abnormal mechanical loading exacerbates mechanobiological dysregulation through the integrin-YAP/TAZ signaling axis, while hypoxia/acidification-induced mitochondrial dysfunction creates a "mechanical-metabolic" double hit. Innate and adaptive immune cells recognize degenerated fragments and amplify local tissue damage. The interweaving of these mechanisms contributes to the comorbid progression of IVDD and OA through mechanical conduction, inflammatory diffusion, and neural sensitization. Importantly, we also discuss key differences between the two diseases, including the avascular nature of the intervertebral disc, the distinct roles of nutrient supply and disc herniation subtypes, and the etiological heterogeneity of OA across different joints. Future research should move beyond single-disease frameworks, analyze multi-tissue interactions from a systemic degeneration perspective, and develop combined strategies targeting senescent cell clearance, inflammatory blockade, and ECM repair. The concept of "spine-joint integrated diagnosis" - defined as concurrent evaluation of spinal and peripheral joint degeneration - is proposed to guide integrated management and improve clinical outcomes in comorbid patients.
