Previous studies have shown that the activity of the cytostatic drug methotrexate (MTX) embedded in acrylic cement is not affected by thermal changes in the cement. MTX is slowly released from the cement for several months and remains biologically active throughout this period. Our aim was to determine whether MTX embedded in cement would control the local growth of a tumour.In 15 rabbits we injected 0.1 ml of VX 2 tumour suspension into the proximal tibia. At 3, 5, 7, 10 and 14 days three animals were killed and the tibiae removed and examined histologically. With increasing growth of the VX 2 carcinoma there was increased bone destruction and a rise in the numbers of osteoclasts, but after 14 days the numbers of osteoclasts had decreased.We then injected VX 2 into the tibiae of another 45 rabbits. After 5 days most of the tumour was curetted out and the defect filled with cement containing either 0 g, 0.1 g, 0.5 g, 1.0 g or 2.0 g MTX/40 g cement. The rabbits were divided into three groups and killed at 3, 7 or 10 days after implantation of cement. The number of osteoclasts and the amount of bone destruction were measured in each tibia. In all three groups bone destruction and osteoclast proliferation were markedly decreased with higher doses of MTX, but bone destruction was not eliminated.Our findings show that in the higher doses used, which were not toxic to the animal, MTX-embedded cement may be of value in minimising the amount of tumour-induced osteolysis and may be a useful adjunct in the surgical management of pathological fractures.J Bone Joint Surg [Br] 1996;78-B:14-17. Received 28 April 1995; Accepted 21 June 1995 Pathological and impending fractures, secondary to metastatic cancer, are usually treated by internal fixation, often supplemented by methylmethacrylate. In other cases such as pathological fractures of the proximal femur, the lesion is treated by replacement arthroplasty which is cemented in place. Patients are given postoperative radiotherapy and adjuvant endocrine or chemotherapy depending on the primary tumour, in an attempt to keep the tumour under control. Progressive growth of the tumour leads to further osteolysis, loosening and failure of the implant.Our aim was to determine whether methotrexate (MTX) embedded in the cement would help to control local growth of the tumour. Previous experiments in vitro have shown that cytostatic drugs such as MTX are released from acrylic cement for at least four to six months. The released MTX remains biologically active throughout this period (Hernigou et al 1989;Marshall et al 1990;Wang et al 1995), and the addition of MTX does not appear to alter the mechanical properties of Palacos-R cement. It has been shown in the VX 2 carcinoma rabbit model that the local administration of MTX-loaded cement reduced the number of pulmonary metastases with no detectable toxic effect (Wang et al 1995). Administration of MTX-loaded Palacos-R acrylic cement may reduce the amount of tumour-induced local bone destruction.Most tumour-induced osteolysis is media...
The EAR (Excision, Alcoholization, Replantation) method consists of a proper tumor resection, removal of tumor tissue extracorporally, soaking the residual bone shell in 95% alcohol for half an hour, and replantation in situ, the cavity being filled with bone graft or bone cement. Eighty-three cases were treated in this manner, of which 95% were followed for 2 years or more, with complete success in cases with IA lesions and no recurrence in two-thirds of those with IB-IIB lesions. Experimentally, it is proved that alcohol can kill tumor cells completely without interfering with osteogenesis. The joint cartilage, although degenerated, is replaced by newly formed fibrocartilage, thus preserving joint function.
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