Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

Abstract 

Introduction

Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate (¹⁵³Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic ¹⁵³Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of ¹⁵³Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of ¹⁵³Sm-EDTMP on growth of long bones.

Methods

Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of ¹⁵³Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P<.05.

Results

Significant differences in lengths of multiple bones were detected between the high-dose group and other treatment groups and controls at each time interval. A significant difference in lengths of the tibias was also noted in the medium-treatment group, compared to controls. Mean reduction of bone length was first detected at 4 months and did not increase significantly over time.

Conclusions

These data suggest that clinically significant bone shortening may occur as a result of high-dosage administration of ¹⁵³Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted.

Keywords: Samarium-153-ethylenediaminetetramethylene phosphonate, Osteosarcoma, Physeal cartilage, Bone growth