Interleukin-6 receptor blockade improves bone healing following ischemic osteonecrosis in adolescent mice
Gen Kuroyanagi, Nobuhiro Kamiya, Ryosuke Yamaguchi, Harry K.W. Kim
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.