Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice

Abstract

ObjectiveJuvenile ischemic osteonecrosis (JIO) of the femoral head is one of the most serious hip disorders causing a permanent deformity of the femoral head in childhood. We recently reported that interleukin 6 (IL-6) is significantly increased in the hip synovial fluid of patients with JIO and that articular chondrocytes are primary source of IL-6. Adolescent JIO is particularly challenging to treat and has poor outcome. This study determined if IL-6 receptor blockade prevents bone loss and improves the bone healing in adolescent JIO. MethodAdolescent mice (12-week-old) surgically induced with JIO were treated with either saline or MR16-1, an IL-6 receptor blocker. ResultsMicro-CT assessment showed significantly increased bone volume (p ​< ​0.001, Cohen's d ​= ​2.0) and trabecular bone thickness (p ​< ​0.001, d ​= ​2.3) after the MR16-1 treatment. Histomorphometric assessment showed significantly increased osteoblast number (p ​< ​0.01, d ​= ​2.3), bone formation rate (p ​< ​0.01, d ​= ​4.3), and mineral apposition rate (p ​< ​0.01, d ​= ​4.1) after the MR16-1 treatment. The number of osteoclasts was unchanged. Histologic assessment showed significantly increased revascularization (p ​< ​0.01) and restoration of the necrotic marrow with new hematopoietic bone marrow (p ​< ​0.01). Vascular endothelial growth factor (VEGF) expression was increased in the revascularized area and the articular cartilage, and in the cultured chondrocytes treated with IL-6 receptor inhibitor. ConclusionIL-6 blockade in adolescent mice with JIO enhanced bone formation and revascularization. The findings suggest IL-6 receptor blocker as a potential medical therapy for adolescent JIO.