To investigate the role of the nervous system of bone in steroid-induced osteonecrosis in rabbits

Abstract

Glucocorticoid treatment frequently causes osteonecrosis of the femoral head. The precise mechanism in the pathogenesis of osteonecrosis remains highly controversial. Normal bone metabolism requires a coordinated interaction between the sensory/sympathetic nervous system and cells within the bone tissue. So we speculated that neural lesions may be involved in osteonecrosis. using a rabbit model, we investigated the relationship between neural factors and steroid-induced osteonecrosis of the femoral head. Japanese white rabbits weighing about 3.5 kg each were injected with a single intramuscular dose of methylprednisolone 4 mg/kg and then divided into three groups (groups A, B and C) consisting of 15 rabbits each. The rabbits of group A were killed after 3 days, those of group B after 1 week, and those of group C after 2 weeks. As a control group, 10 rabbits (group N) were fed under the same conditions but did not receive a steroid injection. An immunohistochemical study of the femoral heads was conducted using the monoclonal antibodies CGRP, SP, VIP, NPY and NGF. Also, using the software Image Pro Plus, the areas showing positive immunoreactivity in each group were calculated and the four groups were compared. significant changes were seen in the expression of CGRP, SP, VIP and NPY nerve fibres and of NGF immunoreactivity in the subchondral bone of the femoral head and these changes were associated with the process of osteonecrosis. Furthermore, CGRP, SP, NPY and NGF (but not VIP) showed marked changes in expression 1 week after steroid administration, and this is the time when osteonecrosis is thought to occur in this model. This study showed that osteonecrosis in rabbits is chronologically associated with changes in neural factors.