title: Methotrexate loaded acrylic cement in the management of skeletal metastases. Biomechanical, biological, and systemic effect.
abstract: Skeletal metastases occur commonly, and frequently are complicated by the development of an impending or pathologic fracture. In the majority of instances, these patients are best treated by internal stabilization, frequently supplemented by methylmethacrylate, to relieve pain and maintain the patient's mobility. The underlying tumor may continue to grow, and if this occurs the progressive lysis may result in loosening and subsequent failure of the implant. To prevent additional local growth, postoperative radiotherapy is recommended, and many patients also receive endocrine or chemotherapy, but the adjuvant therapy is not always successful in preventing progressive local tumor induced osteolysis. It is possible that the addition of chemotherapeutic agents to the methylmethacrylate may inhibit local growth. This study was performed to determine the biomechanical, biologic, and systemic effects of adding methotrexate to methylmethacrylate. The results show that the addition of methotrexate in as much as a concentration of 2 g methotrexate per 40 g cement did not significantly alter the biomechanical characteristics of the bone cement. The incorporated methotrexate was released continuously from the loaded bone cement, and in the amount and concentration used did not have any toxic effects on the host animal. The methotrexate did not appear to be affected by the heat of polymerization and had a significant systemic effect. There was a significant reduction in pulmonary metastases with methotrexate loaded cement as compared with unloaded cement, the effect being dependent on the concentration of methotrexate in the cement. The results of these studies indicate that methotrexate loaded cement may have an important role to play as part of the orthopaedic management of impending and pathologic fractures.
authors.affiliation: Department of Orthopaedic Surgery, University of Manchester, United Kingdom.
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
authors.forename: C S
authors.initials: CS
authors.lastname: Galasko
authors.forename: S
authors.initials: S
authors.lastname: Crank
authors.forename: G
authors.initials: G
authors.lastname: Oliver
authors.forename: C A
authors.initials: CA
authors.lastname: Ward
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001843:Bone Cements; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005598:Fractures, Spontaneous / Q000517:prevention & control; D008175:Lung Neoplasms / Q000556:secondary; D008727:Methotrexate / Q000008:administration & dosage* / Q000097:blood; D020366:Methylmethacrylate; D008768:Methylmethacrylates; D011817:Rabbits
chemical_list: D001843:Bone Cements; D008768:Methylmethacrylates; D020366:Methylmethacrylate; D008727:Methotrexate