PDGF-BB improves cortical bone quality through restoring the osteogenic microenvironment in the steroid-associated osteonecrosis of rabbits

Objective

Steroid-associated osteonecrosis of the femoral head (SONFH) is a refractory disease characterized by progressive bone destruction. Clinical evidence suggests that SONFH may extend beyond the intra-capital region to the femoral neck, metaphysis, and even diaphysis, increasing the risk of subtrochanteric fractures and implant loosening post-surgery. While our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) promotes reparative osteogenesis in the femoral head, its effects on cortical bone quality in the extended diaphyseal regions under steroid-associated osteonecrosis (SAON) remain unclear. This study aims to investigate whether PDGF-BB could mitigate cortical bone deterioration in the femoral diaphysis during SAON progression.

Methods

SAON was induced by repeated lipopolysaccharide (LPS) and methylprednisolone (MPS) injections in rabbits. At 2, 4, and 6 weeks after SAON induction, PDGF-BB was intramedullary injected into the proximal femur. Xylenol orange and Calcein green were injected subcutaneously into rabbits on days 14 and 4 before euthanasia. At 3 days after last PDGF-BB treatment, micro-fil perfusion was performed for angiography. Then the femur shaft was dissected for micro-computed tomography (μCT)-based angiography, μCT-based cortical bone geometry, and histological analysis. With regard to the macrophage infiltration and activated osteoclast function in osteonecrosis regions during SAON progression, RAW 264.7 cells were utilized to evaluate the effect of PDGF-BB on macrophage polarization and osteoclasts activity in vitro.

Results

In this study, osteonecrosis extended to the femoral diaphysis, accompanied by vascular disruption (reduced CD31+ vessels), sensory nerve degeneration (decreased CGRP + fibers), and cortical bone destruction, at 6 weeks post-SAON induction. While PDGF-BB treatment significantly attenuated SAON progression in the femoral diaphysis, restoring blood supply (angiography) and improving cortical bone geometry (μCT). Histologically, PDGF-BB enhanced periosteal and endosteal osteogenesis while suppressing osteoclastic resorption. In vitro, PDGF-BB not only could modulate M1-type macrophages polarization to reduce inflammatory response, but also subsequently afford a secondary source of bioactivity factors during osteoclasts formation process to restore the osteogenic microenvironment, suggesting a dual role in resolving inflammation and enhancing bone remodeling.

Conclusion

SAON progression leads to diaphyseal cortical bone deterioration, while PDGF-BB application could restore the osteogenic microenvironment and drive cortical bone remodeling during SAON progression.

The translational potential of this article

These findings suggest that PDGF-BB could serve as a potential candidate for attenuating the progression of SAON. Local delivery of PDGF-BB during surgical interventions for SONFH may enhance cortical bone repair and improve mechanical stability, offering a clinically viable strategy to achieve better long-term outcomes.