Mechano-biological mechanisms of femoral head collapse in osteonecrosis: a multiscale zonal analysis

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a progressive disorder characterised by vascular compromise, osteocyte loss, and regional structural deterioration that ultimately leads to femoral head collapse. Because ONFH affects the femoral head heterogeneously, understanding zone-specific structural and mechanical alterations is essential for clarifying mechanisms of structural failure. METHODS: 15 femoral heads obtained during total hip arthroplasty were analyzed using a patient-matched multiscale approach. Trabecular cores from necrotic, sclerotic, and preserved regions within the same femoral heads were evaluated using micro-computed tomography, uniaxial compression testing, nanoindentation, Fourier-transform infrared spectroscopy, x-ray diffraction, and histology to assess microarchitecture, mechanical behaviour, mineral composition, and osteocyte viability. In contrast, the sclerotic zone demonstrated increased trabecular density and stiffness but reduced post-yield deformation, indicating a stiff yet brittle mechanical phenotype. These findings reveal a mechanical paradox in which dense sclerotic bone surrounds structurally compromised necrotic tissue. CONCLUSIONS: This zonal heterogeneity in microarchitecture, composition, and mechanical behavior may generate stiffness gradients within the femoral head and may contribute to localised stress concentration and mechanical imbalance during ONFH progression. These findings provide a mechano-biological framework for understanding femoral head failure and highlight the importance of considering zonal bone quality in evaluating structural collapse.