Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis...

This narrative review explores the role of subchondral bone in the pathophysiology of osteoarthritis (OA), emphasizing the biomechanical and biochemical contributions that it makes to disease progression. A fresh perspective is presented by the authors in the form of a novel hypothesis that implicates mechano-inflammatory disruption of the bone marrow (BM) microenvironmental ecosystem (BM niche), unresolved inflammation, and fibrosis as key drivers of OA pathogenesis and pain. BMLs, detectable via magnetic resonance imaging (MRI), serve as dynamic imaging biomarkers that correlate with pain severity and structural deterioration, making them valuable in patient stratification for enhanced clinical trials and more effective therapeutic monitoring. Persistent inflammation within the BM microenvironmental niche exacerbates nociceptive signaling and structural joint damage. The parallels between OA, hematopoietic malignancies and immunological disorders of the BM underscore the potential for targeting inflammatory and fibrotic pathways within the BM niche as novel therapeutic strategies. Additionally, obesity-associated BM dysfunction raises the prospect of weight-loss interventions, including GLP-1 receptor agonists, as potential disease-modifying approaches for OA. We propose that the future research agenda should focus on integrating imaging biomarkers with genomic, molecular and clinical data to explore alterations in the BM microenvironmental ecosystem. This new knowledge may refine precision medicine strategies, improve early detection, enhance prognostic monitoring and develop targeted therapies aimed at successful modification of OA progression and effective control of pain mechanisms.