Osteoimmune microenvironmental failure in osteonecrosis of the femoral head: a necrosis-inflammation-repair loop and immune-editing-inspired framework for hip preservation.

Osteonecrosis of the femoral head (ONFH) is traditionally framed as structural failure after interrupted blood supply, yet this linear model does not explain why patients with similar radiographic stage may show markedly different pain trajectories, collapse kinetics, and hip-preservation outcomes. We propose that ONFH is better interpreted as an osteoimmune microenvironmental failure sustained by a self-reinforcing loop: ongoing cell-death input, maladaptive inflammatory reprogramming, bone-marrow niche dysfunction, and mechanical destabilization. In this framework, early sterile inflammation may support debris clearance, but persistent danger signaling can shift the lesion border into chronic, repair-incompetent inflammation. The marrow niche then transitions from a regenerative interface to a maladaptive state characterized by impaired stromal osteogenesis, endothelial dysfunction, uncoupled remodeling, and reduced load tolerance. To translate this model clinically, we organize intervention into three coordinated axes: entry blockade, niche reprogramming, and reconstruction. We further propose a dynamic decision path integrating stage, risk-factor burden, and niche activity, with serial imaging, biomarker trajectories, and functional outcomes guiding escalation.