title: Effect of the antineoplastic agent methotrexate on experimental heterotopic new bone formation in rats.
abstract: Heterotopic new bone formation was induced by implanting pieces of demineralized bone matrix in the abdominal wall of 22 growing Sprague-Dawley rats. The animals were divided into three groups and were given, 24 hr after initiation of the bone induction process, a single i.v. injection of methotrexate, 100 or 250 mg/kg body weight, or placebo, followed after 2 hr by leucovorin rescue. A slight and transient arrest in weight gain was noted in the methotrexate-treated animals. New bone formation during 3 weeks after implantation was analyzed by the amount of ash in implants, and as a measure of bone formation at the end of the experiment, short-time incorporation of 45Ca and [3H]proline was used. The ash content of implants was reduced by 56 and 68% in the two methotrexate groups. Uptake of both nucleotides was also greatly reduced in heterotopic bone, whereas metaphysial and diaphysial tibia and teeth were not affected. The results indicate a pronounced inhibition of methotrexate on bone induction, persisting for at least 3 weeks. Methotrexate reduces the bone-forming potential, with possible consequences for the success of limb-saving surgery and fracture healing.
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D016025:Bone Transplantation; D001842:Bone and Bones / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002118:Calcium; D008727:Methotrexate