A Novel Murine Model to Study the Early Biological Events of Corticosteroid-Associated Osteonecrosis of the Femoral Head

This study establishes a murine model of corticosteroid-associated osteonecrosis of the femoral head (ONFH) using a sustained-release prednisolone pellet and evaluates mitochondrial stress using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and changes in key histologic markers of bone over a 6-week period. Sixteen 12-week-old Balb/C mice were divided into two groups: a prednisolone group (PRED) and a control group (SHAM). The PRED group received a subcutaneous 60-day sustained-release pellet containing 2.5 mg of prednisolone, while the SHAM group received placebo pellets. PET/CT imaging was performed at 1, 3, and 6 weeks. Bone mineral density (BMD) measurements, and histomorphological analyses for the number of empty lacunae, osteoblasts, osteoclasts, and NADPH oxidase (NOX) 2, a marker for oxidative stress, were conducted at 4 or 6 weeks. PET/CT imaging demonstrated increased uptake in the femoral head at 3 weeks in the PRED group. This was accompanied by increased numbers of empty lacunae and osteoclasts, increased oxidative stress, and decreased alkaline phosphatase staining at 4 weeks in the PRED group. We have successfully established and validated a small murine model of ONFH. The findings of this preclinical study suggest a critical timeline for potential interventions to mitigate the early adverse effects of continuous corticosteroid exposure on bone.