Methotrexate-loaded polymethylmethacrylate bone cement for local bone metastasis therapy: pilot animal study in the rabbit patellar groove

Abstract

Local chemotherapy is an option in bone metastasis treatment. On the other hand, evaluation of side effects on bone is a difficult issue in drug development and biomaterials research. Most animal models to date are inappropriate or not feasible. Rabbits are an alternative to other bigger mammals and have an appropriate bone structure compared to rats and mice. The patellar groove model of the rabbit offers a standardized and sensitive model to evaluate bone-compromising drug effects. We tested the system with a reproducible polymethacrylate implant as carrier and loaded this system with methotrexate. Three methotrexate concentrations were used in the test samples (250 mg, 1 g and 4 g per 40 g polymethacrylate bone cement; 2 per group) for a descriptive histology approach. Eight German giant rabbits were operated on both knees and received test and control implants in a randomized manner in this bilateral study design. The histological results after 35 days were convincing, encouraging the use in preclinical drug development and biomaterials research and warranting further development of this metastasis treatment approach.