Targeting subchondral osteoporosis in osteoarthritis: biomechanical crosstalk and the therapeutic rationale for inflammatory microenvironment remodeling.

Current osteoarthritis (OA) management remains largely symptom-directed, while the contribution of osteoporosis (OP)-related and OA-associated subchondral remodeling to disease heterogeneity remains uncertain. This review integrates macroscopic load redistribution and lower-limb malalignment with local osteoimmune processes, including macrophage-state heterogeneity, Th17/Treg imbalance, senescence-associated secretory signaling, and bone-vascular coupling. We propose a bidirectional, phenotype-dependent framework in which abnormal loading may initiate compartment-specific subchondral remodeling, whereas high-turnover bone loss may reduce trabecular competence and amplify stress concentration; late OA may instead exhibit a low-turnover sclerotic phenotype. Existing evidence supports biological links among bone remodeling, inflammatory signaling, and osteochondral crosstalk but does not establish that anti-osteoporotic therapy reverses malalignment or consistently modifies OA progression. Bone-targeting treatment should therefore be considered a hypothesis requiring turnover- and phenotype-stratified clinical evaluation. The proposed time-window model is intended to organize future studies rather than provide current treatment recommendations.