Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview)

Xie, Xin-Hui; Wang, Xin-Luan; Yang, Hui-Lin; Zhao, De-Wei; Qin, Ling

In conclusion, ON is a challenging orthopaedic condition which resulted from unwanted adverse effects of corticosteroids administration. Normally, no single factor is involved in the pathophysiology of SAON initiation and its development. Evaluation of approaches developed for prevention and treatment of ON in both animal and human studies indicated that a certain pathophysiology resulted in ON, including abnormality of BMSCs pool, bone matrix and cartilage degeneration cell apoptosis, abnormality of lipid metabolism and clotting disorders, decreased angiogenesis and elevated vasoconstriction, and oxidation injury. Orthopaedic surgery is important for the treatment of SAON, yet its prognosis is rather poor. This implies the importance of prevention in two aspects, including: (1) to prevent the happening of SAON after the administration of steroid; and (2) to prevent the development of SAON from early stage to late stage. Based on the possible pathophysiology and the effective prevention or therapy performed in animals and humans with steroid administration, much more bench to clinic translational work shall be done in the future to promote efficiency of early prevention, diagnosis, and treatment of SAON. Good prevention requires good predictive diagnosis. Gene analysis or hypercoagulability of plasma might be earlier methods to predict ON development, although dynamic perfusion MRI is another advanced and promising bioimaging approach. Chinese herb and statins treatment produced significantly lower incidences of SAON both in humans and animal models, implying that they might be promising alternatives for prevention and eventually treatment of SAON. The apoptosis of osteoblasts, osteoclasts, and osteocytes suggested a new mechanism for the effect of steroids, giving a new insight into mechanisms responsible for bone loss in patients with SAON. Core decompression combined with bone grafting, bone marrow or cells transplantation, and growth factors is the best documented therapy for early SAON stage(s). The newly tested osteopromotive porous composite scaffolds were also promising for enhancing repair of ON lesions after core decompression [87, 88] . Gene therapy was proven to be effective in animal models, but its safety and ethical issues are still controversial. Despite all treatments, joint replacement is still advocated for patients at the late ON stage(s). How to improve postoperative prognosis after joint replacement therapy remains a challenging topic for not only orthopaedic surgeons, but also biomedical engineers and biomaterial scientists. We hope that with all collective efforts, more scientifically confirmed approaches will be available for clinical applications and will benefit patients suffering from ON, especially SAON.