Combined Treatment with an Anticoagulant and a Vasodilator Prevents Steroid-Associated Osteonecrosis of Rabbit Femoral Heads by Improving Hypercoagulability.

Fang Cao,Fan Yang,Dewei Zhao,Benjie Wang,Yongxuan Wang,Xiaowei Wei,Wei Wang,Kai Kang,Jiahui Yang,Faqiang Lu,Ge Liu,Kairong Qin

doi:10.1155/2017/1624074

Abstract

Steroid-associated osteonecrosis of the femoral head remains a challenging problem in orthopedics worldwide. One pathomechanism is ischemia of the femoral head, as a result of thrombus formation and vasoconstriction. The present study investigates the effects of combination prevention with enoxaparin and EGb 761 on steroid-associated ONFH in rabbits. Rabbits were randomly divided into 5 groups (control group, model group, enoxaparin group, ginkgo group, and combination group). With the exception of the control group, the groups of rabbits were modeled with lipopolysaccharide and methylprednisolone acetate. Starting with modeling, the enoxaparin group and ginkgo group were injected with 1 μg/kg/day enoxaparin subcutaneously and orally given 40 mg/kg/day EGb 761 for 4 weeks, respectively; the combination group received both treatments. After modeling for 6 weeks, the hematology data indicated prolonged PT and APTT in the three prevention groups. The micro-CT examination revealed higher bone density and better structure; histomorphometry revealed significant pathological changes. Immunohistochemistry revealed higher expression of BMP-2 and VEGF, thus revealing better osteogenesis and angiogenesis activities. Among the three prevention groups, the combination group had the most efficient results. In conclusion, the combined prevention with an anticoagulant and a vasodilator has the potential to decrease the incidence of steroid-associated ONFH in rabbits.

Highlights

Osteonecrosis of the femoral head (ONFH) has been reported to occur in patients who undergo long-term or heavy glucocorticoid use as a treatment for underlying diseases, such as systemic lupus erythematosus, nephrotic syndrome, and renal transplantation [1]
To investigate the coagulation state of the model group and the potential effects of enoxaparin and EGb 761, the coagulation states were evaluated by measuring the prothrombin time (PT) and activated partial thromboplastin time (APTT)
Enoxaparin group and ginkgo group resulted in a prolongation of PT but not significant, which was 7.82 ± 0.23 s (p = 0.1662) and 7.30 ± 0.19 s (p = 0.8436), respectively; the combination group showed the best results: the PT reached 8.08 ± 0.27 s, representing a significant prolongation compared with model group (p = 0.0418 < 0.05) (Figure 1(a))

Summary

Introduction

Osteonecrosis of the femoral head (ONFH) has been reported to occur in patients who undergo long-term or heavy glucocorticoid use as a treatment for underlying diseases, such as systemic lupus erythematosus, nephrotic syndrome, and renal transplantation [1]. ONFH, as a progressive and degenerative bone disease, leads to the collapse of the femoral head, which subsequently destroys the hip joint and affects the patient’s activities [2]. Several possible factors relating to the pathogenesis of ONFH have been suggested on the basis of both human and animal studies, including coagulation abnormalities, hyperlipidemia, endothelial dysfunction, and oxidative stress [5,6,7,8,9]. These factors have been thought to be related to an interruption of the bone vascular circulation and to result in bone ischemia. Many experimental studies have revealed that glucocorticoids directly injure endothelial cells, resulting in vasoconstriction, disturbance of the coagulation-fibrinolysis system, and thrombus formation in the femoral head, which decrease the blood circulation of the trabecular bone and lead to BioMed Research International

Methods

Results

Conclusion