Osteonecrosis of the femoral head (ONFH) is a devastating disease affecting young adults, resulting in significant pain, articular surface collapse, and disabling dysfunction. ONFH can be divided into two broad categories: traumatic and non-traumatic. It has been established that ONFH results from an inadequate blood supply that causes the death of osteocytes and bone marrow cells. Nonetheless, the precise mechanism of ONFH remains to be elucidated. In this regard, preclinical animal and cell models to study ONFH have been established to assess the efficacy of various modalities for preventing and treating ONFH. Nevertheless, it should be borne in mind that many models do not share the same physiologic and metabolic characteristics as humans. Therefore, it is necessary to establish a reproducible model that better mimics human disease.

We systematically reviewed the literatures in regard to ONFH experimental models over the past 30 years. The search was performed in PubMed and Web of Science. Original animal, cell studies with available full-text were included. This review summarizes different methods for developing animal and cell experimental models of ONFH. The advantages, disadvantages and success rates of ONFH models are also discussed. Finally, we provide experimental ONFH model schemes as a reference.

According to the recent literatures, animal models of ONFH include traumatic, non-traumatic and traumatic combined with non-traumatic models. Most researchers prefer to use small animals to establish non-traumatic ONFH models. Indeed, small animal-based non-traumatic ONFH modeling can more easily meet ethical requirements with large samples. Otherwise, gradient concentration or a particular concentration of steroids to induce MSCs or EPCs, through which researchers can develop cell models to study ONFH.

Glucocorticoids in combination with LPS to induce ONFH animal models, which can guarantee a success rate of more than 60% in large samples. Traumatic vascular deprivation combines with non-traumatic steroids to induce ONFH, obtaining success rates ranging from 80% to 100%. However, animals that undergo vascular deprivation surgery may not survive the glucocorticoid induction process. As for cell models, 10-6mol/L Dexamethasone (Dex) to treat bone marrow stem cells, which is optimal for establishing cell models to study ONFH.

This review aims to summarize recent development in experimental models of ONFH and recommended the modeling schemes to verify new models, mechanisms, drugs, surgeries, and biomaterials of ONFH to contribute to the prevention and treatment of ONFH.