Administration of erythropoietin exerts protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats

Abstract

Accumulating evidence has indicated that erythropoietin (EPO) plays a role in anti-apoptosis and tissue protection in a number of human diseases. The present study was implemented to evaluate these anti-apoptotic and tissue-protective effects in glucocorticoid-induced osteonecrosis in rats. Osteonecrosis was induced by low-dose lipopolysaccharide and subsequent high-dose methylprednisolone pulse. Rats in the preventive group were treated with 500 U/kg/day recombinant human EPO (rhuEPO) for 1 week. Hematological and histomorphometric methods were then used to determine the effects of the administration of rhuEPO. An analysis of trabecular bone architecture was performed to evaluate bone mass change in the osteonecrosis zone. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was performed to determine the apoptotic index of osteoblasts and osteocytes. Immunoblot analysis was performed to assess the expression of caspase-3 and vascular endothelial growth factor (VEGF) in the femoral head. Treatment with rhuEPO greatly improved the histological performance. Additionally, the incidence of osteonecrosis markedly decreased in the rats in the rhuEPO-treated group (22.2%) compared with the control group (66.7%). Furthermore, the expression of caspase-3 markedly decreased in the rhuEPO-treated group. Consistently, the apoptosis of osteoblasts and osteocytes, as determined by TUNEL assays, was inhibited following the administration of rhuEPO. By contrast, the expression of VEGF increased in the osteonecrosis zone in the rats treated with rhuEPO. The results from the present study demonstrate that EPO exerts prominent protective effects against glucocorticoid-induced osteonecrosis of the femoral head in rats by inhibiting the apoptosis of osteoblasts and osteocytes and increasing the expression of VEGF.

Nitric oxide content and apoptosis rate in steroid-induced avascular necrosis of the femoral head

“…These two free radicals have very strong oxidizing activity and cytotoxicity, resulting in bone damage. NO has a dual function in bone absorption and inhibits the growth of osteoblasts or even has toxic effects during bone formation (1). However, the effect of NO on the process of SANFH development is unclear.…”

“…Previous clinical studies have found that the primary cause of femoral head necrosis is steroid hormones, which is the main reason for the disease (1). The occurrence of femoral head necrosis is associated with the administration method and dose of the hormones, and is affected by individual differences and sensitivities (2).…”

Bilateral Idiopathic Osteonecrosis of the Femoral Head: A Case Report With an Emphasis on Differential Diagnosis, Imaging, and Treatment

“…7 Recent data using an animal model also supports the use of exogenous erythropoietin in the treatment of corticosteroid induced ONFH. 23 Operative treatment of ONFH consists of core decompression, nonvascularized bone grafting, vascularized bone grafting, and administration of bone morphogenetic proteins, stem cell therapy, proximal femoral osteotomies, and hip arthroplasty. 7 The patient in this case report had advanced ONFH on the left (Ficat and Arlet stage III) and was treated with a total hip arthroplasty.…”

The Effect of Cape on Steroid Induced Osteonecrosis of the Femoral Head in Rat Model

“…We divided all rats into four groups: control group (7 rats), methylprednisolone treatment group (MPS, 8 rats), CAPE treatment group (8 rats) and MPS+CAPE administered group (8 rats). The rats of group MPS and CAPE+MPS, On days 2, 3 and 4 were treated with 20 mg/kg/day methylprednisolone (MPS; Pfizer Pharmaceutical, Puurs, Belgium) intramuscularly 22) . 10 μmol/kg/day CAPE was intraperitoneally injected to the rats of group CAPE from 13 weeks of age for 4 weeks 23) .…”