Protective effects of Apelin-13 on steroid-induced osteonecrosis of the femoral head in rats.

PURPOSE: Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by bone tissue necrosis due to vascular insufficiency, often triggered by corticosteroid use. Steroids are commonly employed in the management of autoimmune diseases, organ transplantation, and COVID-19. Early detection is crucial, as ONFH primarily affects young and middle-aged individuals and often progresses to femoral head collapse if untreated. The objective is to evaluate the protective effects of Apelin-13 (Ap-13) on steroid-induced ONFH (SONFH) in a rat model.

METHODS

Thirty-two female Sprague-Dawley rats were randomized into four groups: Control, Ap-13 only, ONFH, and ONFH + Ap-13. SONFH was induced using lipopolysaccharide (LPS) and methylprednisolone (MPS). The treatment group received daily intraperitoneal Ap-13 injections. At the fourth week, radiological, histopathological, immunohistochemical, and biochemical analyses were conducted on femoral heads.

RESULTS

Micro-CT showed no significant differences in bone mineral density or trabecular parameters. Histopathology revealed increased osteonecrosis, empty lacunae, and vascular thrombosis in the ONFH group, which were significantly reduced in the ONFH + Ap-13 group (p < 0.05). Ap-13 decreased serum malondialdehyde (MDA) levels (p = 0.0002), reduced caspase-3 expression (p < 0.05), and elevated VEGF expression (p = 0.046), indicating reduced oxidative stress, apoptosis, and enhanced vascularization. Additionally, LDL and triglyceride levels were significantly lower in the Ap-13 treated group (p < 0.05).

CONCLUSIONS

Apelin-13 demonstrates protective effects against SONFH by reducing oxidative stress, apoptosis, and improving vascularization. It may represent a promising noninvasive therapeutic strategy for early-stage ONFH.