Abstract 21

ZOLEDRONIC ACID IMPROVES FEMORAL HEAD SPHERICITY IN A RAT MODEL OF PERTHES DISEASE

McDonald MM, Sharpe IT, Peat RA, Williams PR, McEvoy A, Little DG

The Children's Hospital at Westmead, Sydney, NSW, Australia

As the optimal treatment for Perthes disease remains controversial, a pharmaceutical therapy would be of great benefit. We hypothesized that the bisphosphonate, zoledronic acid (ZA) could maintain femoral head sphericity by changing the balance between bone resorption and new bone formation. In this investigation we test the effect of ZA in an established model of Perthes disease - the spontaneously hypertensive rat (SHR).

120 4-week old rats were divided into three groups of 40: 3 doses of saline monthly, 3 doses of 0.05 mg/kg ZA monthly, or 10 doses of 0.015 mg/kg ZA weekly. At harvest, 15 weeks of age, radiographs were taken and a modified epiphyseal quotient (EQ) measured by a blinded observer. Specimens were DXA scanned and processed for histology.

Radiographs revealed increased mineralization and improved sphericity of femoral heads in ZA groups. DXA measurements documented ZA femoral head BMD was increased by 18% to 21% over controls (p<0.01). Overall EQ was improved in ZA-treatment groups (p<0.01). The proportion of "flat" heads (EQ < 0.40) was significantly reduced from 45% to 16% with ZA treatment (p<0.01). On histology, affected femoral heads showed osteonecrosis, ossification delay, or both. There was a similar prevalence of osteonecrosis in control and ZA groups however the prevalence of ossification delay was significantly reduced by ZA (p<0.01). Analysis of EQ revealed the largest improvement in sphericity was in femoral heads with both osteonecrosis and ossification delay (p<0.01).

Zoledronic acid favourably altered femoral head shape in this spontaneous model of osteonecrosis in growing rats.

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