Abstract
BackgroundSteroids such as glucocorticoid have been widely used for their excellent anti-inflammatory, anti-immune, and anti-shock properties. However, the long-term use in high doses has been found to cause necrosis of femoral head and other serious adverse reactions. Thus, it is of great importance to safely use these medications on patients without inducing bone necrosis.MethodsIn this preclinical study, we examined the effects of erythropoietin (EPO) to attenuate the induction of steroid-induced femoral bone necrosis using rats to build up the in-vivo models. Rats were randomly divided into three groups: negative control group (group A), disease group (group B), and EPO group (group C). 20 mg/kg methylprednisolone was administrated into group B and group C for 6 weeks with two intramuscular injections per week per rat. Group C was further given daily intraperitoneal injections of rHuEPO during this period. Group A received only injection of saline at the same schedule. 12 weeks after the initial drug administration, the rats’ femoral tissues were harvested for HE staining, immunohistochemistry studies for PECAM-1(also CD31) expression and Western Blotting for VEGF expression.ResultsHistology studies showed that compared with the disease group, EPO group had significant improvement and bone morphology being much closer to the negative control group. Immunohistochemical studies revealed that EPO group had statistically much more expression of PECAM-1 than the other groups did. Western Blot demonstrated that the EPO group had significantly higher VEGF expression than the disease group.ConclusionResults suggested that simultaneous injection of EPO could partially prevent steroid-induced ANFH.
Highlights
Steroids such as glucocorticoid have been widely used for their excellent anti-inflammatory, antiimmune, and anti-shock properties
Osteonecrosis is often observed in hips, knees, shoulders, and ankles, in which avascular necrosis of the femoral head (ANFH) is the most common one
These eighteen male rats and eighteen female rats were randomly assigned into three groups (6 male rats and 6 female rats for each group) using a random number table: the negative control group, disease group, and EPO group
Summary
Steroids such as glucocorticoid have been widely used for their excellent anti-inflammatory, antiimmune, and anti-shock properties. Osteonecrosis is often observed in hips, knees, shoulders, and ankles, in which avascular necrosis of the femoral head (ANFH) is the most common one. There are several hypotheses including fat embolization, intramedullary pressure changes, coagulation disorders, circulatory impairment and cell dysfunction and apoptosis [4,5,6]. Amongst these mechanisms, the vascular hypothesis, in which local microvascular impairment leads to a decrease in blood flow in the femoral head, has become more widely accepted [7,8,9,10,11]
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