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Background: Femoral head osteonecrosis is a progressive disease with disabling outcomes in hip joint if not treated.This study was designed to compare the effects of zoledronic acid plus vitamin E versus zoledronic acid alone insurgical induced femoral head osteonecrosis in rabbits.Methods: 26 Japanese white adult normal male rabbits at 28-32 weeks old were undertaken surgical femoraldislocation to devastate the femoral neck vessels; the femoral neck vessels were ligated and the hip was relocated.Next, the first 10 rabbits received zoledronic acid injections at 1st and the 4th weeks; the second group (10 rabbits)received zoledronic acid injections at 1st and the 4th week along with daily oral vitamin E for 12 weeks; and thethird group was considered as non-treated control group. Radiographic and postmortem pathological assessmentsincluding the Ficat classification, epiphyseal quotient (EQ), new bone formation, and residual necrotic bone (RNB)were performed and compared after week 12.Results: A significant difference was found between the combination therapy group and the control group in Ficatclassification at 12th weeks (P=0.048), but, the difference between monotherapy and combination therapy groups at12th weeks was nonsignificant (P=0.37). Also, both treated groups had significant difference with the control group forRNB (P=0.015). There were no significant differences between the three groups for Ficat classification at the 6th week(P=0.65); EQ at 6th (P=0.59) and 12th week (P=0.64); and NBF (P=0.55).Conclusion: Although zoledronic acid therapy along with vitamin E could improve some radiologic and pathologicalindices related to femoral head osteonecrosis, vitamin E showed a relative impact.Level of evidence: I