Zoledronic Acid Improves Femoral Head Sphericity in a Rat Model of Perthes Disease

We hypothesized that the bisphosphonate zoledronic acid (ZA) could improve femoral head sphericity in Perthes disease by changing the balance between bone resorption and new bone formation. This study tests the effect of ZA in an established model of Perthes disease, the spontaneously hypertensive rat (SHR). One hundred and twenty 4-week old SHR rats were divided into three groups of 40: saline monthly, 0.015 mg/kg ZA weekly, or 0.05 mg/kg ZA monthly. At 15 weeks DXA measurements documented that femoral head BMD was increased by 18% in ZA weekly and 21% in ZA monthly compared to controls (p<0.01). Femoral head sphericity in animals with osteonecrosis was improved in ZA-treatment groups (p<0.01) as measured by epiphyseal quotient (EQ). The proportion of "flat" heads (EQ0.40) was significantly reduced from 32% in saline-treated animals to 12% in weekly ZA and 3% in monthly ZA (p<0.01). Histologically there was a similar prevalence of osteonecrosis in all groups. The prevalence of ossification delay was significantly reduced by ZA treatment (p<0.01). Zoledronic acid favorably altered femoral head shape in this spontaneous model of osteonecrosis in growing rats. Translation of these results to Perthes disease could mean that deformity of the femoral head may be modified in children, perhaps reducing the need for surgical intervention in childhood and adult life.